View source for User:Immunize/Differential diagnosis for a fever

{{underconstruction}}
{{Expert-subject|Medicine|date=February 2010}}
{{very long|Date=March 2010}}
Fever is the elevation of the body temperature above the normal range of {{convert|36.5|–|37.5|C|F}}.<ref>{{cite journal |author=Karakitsos D, Karabinis A |title=Hypothermia therapy after traumatic brain injury in children |journal=N. Engl. J. Med. |volume=359 |issue=11 |pages=1179–80 |year=2008 |month=September |pmid=18788094 |doi= |url=}}</ref>

==Infectious==
=== Diptheria ===
{{main|Diptheria}}
Diphtheria<ref>{{cite web|url=http://emedicine.medscape.com/article/782051-overview |title=Diphtheria: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-10-05 |accessdate=2010-03-09}}</ref> is a contagious disease spread by direct physical contact or breathing the [[particulate|aerosolized]] secretions of infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations through widespread [[vaccination]]. In the [[United States]] for example, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007 there were only three cases<ref name = Pinkbook>{{cite book | author = Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. | title = Diphtheria. ''in:'' Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) | edition = 10 | pages = 59–70 | publisher = Washington DC: Public Health Foundation | year = 2007 | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/dip.pdf }}</ref> as the [[DTP vaccine|DPT]] (''Diphtheria–[[Pertussis]]–[[Tetanus]]'') vaccine is recommended for all school-age children. Boosters of the vaccine are recommended for adults since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

The respiratory form has an [[incubation period]] of 2–5 days. The onset of disease is usually gradual. Symptoms include fatigue, [[fever]], a mild sore throat and [[Dysphagia|problems swallowing]]. Children infected have symptoms that include nausea, vomiting, chills, and a high fever, although some do not show symptoms until the infection has progressed further. In 10% of cases, patients experience neck swelling, informally referred to as "bull neck." These cases are associated with a higher risk of death.

=== Tetanus ===
{{main|Tetanus}}
'''Tetanus''',<ref>https://health.google.com/health/ref/Tetanus</ref> also called '''lockjaw''', is a medical condition characterized by a prolonged contraction of [[skeletal muscle]] fibers. The primary symptoms are caused by [[tetanospasmin]], a [[neurotoxin]] produced by the [[Gram-positive]], [[Anaerobic organism|obligate anaerobic bacterium]] ''[[Clostridium tetani]]''. Infection generally occurs through wound contamination and often involves a cut or deep puncture wound. As the infection progresses, muscle [[spasms]] develop in the jaw (thus the name "lockjaw") and elsewhere in the body.<ref name="Baron">{{cite book | author = Wells CL, Wilkins TD | chapter = Clostridia: Sporeforming Anaerobic Bacilli | title = Baron's Medical Microbiology  | editor= Baron S, ''et alublisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1099  | isbn = 0-9631172-1-1 }}</ref> Infection can be prevented by proper immunization and by [[post-exposure prophylaxis]].<ref name="CDC">{{cite web | title=Tetanus | work=CDC Pink Book | url=http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf |format=PDF| accessdate=2007-01-26}}</ref> 
'''Generalized tetanus''' is the most common type of tetanus, representing about 80% of cases. The generalized form usually presents with a descending pattern. The first sign is [[trismus]], or lockjaw, and  the facial spasms called [[risus sardonicus]], followed by stiffness of the neck, difficulty in swallowing, and rigidity of pectoral and calf muscles. Other symptoms include elevated temperature, sweating, elevated [[blood pressure]], and episodic rapid heart rate. [[Spasm]]s may occur frequently and last for several minutes with the body shaped into a characteristic form called [[opisthotonos]]. Spasms continue for up to 4 weeks, and complete recovery may take months.

'''Neonatal tetanus''' is a form of generalized tetanus that occurs in newborns. Infants who have not acquired passive [[immunity (medical)|immunity]] because the mother has never been immunized are at risk. It usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with a non-sterile instrument. Neonatal tetanus is common in many developing countries and is responsible for about 14% (215,000) of all neonatal deaths, but is very rare in developed countries.<ref name="WHO_2000">{{cite web | title=Maternal and Neonatal Tetanus Elimination by 2005 | author=[[World Health Organization]] | date=2000-11-01 | url=http://www.unicef.org/immunization/files/MNTE_strategy_paper.pdf#search=%22neonatal%20tetanus%20rates%22 | accessdate=2007-01-26}}</ref>

The wound must be cleaned. Dead and infected tissue should be removed by surgical [[debridement]]. Administration of the antibiotic [[metronidazole]] decreases the number of [[bacteria]] but has no effect on the bacterial toxin. [[Penicillin]] was once used to treat tetanus, but is no longer the treatment of choice, owing to a theoretical risk of increased spasms. However, its use is recommended if metronidazole is not available. [[Passive immunization]] with human anti-[[tetanospasmin]] [[immunoglobulin]] or tetanus immunoglobulin is crucial. If specific anti-tetanospasmin immunoglobulin is not available, then normal human immunoglobulin may be given instead. All tetanus victims should be vaccinated against the disease or offered a booster shot.

=== Pertussis ===
{{main|Pertussis}}
*[[Pertussis]]<ref>https://health.google.com/health/ref/Pertussis</ref>
Treatment with an effective [[antibiotic]] ([[erythromycin]] or [[azithromycin]]) shortens the infectious period but does not generally alter the outcome of the disease; however, when treatment is initiated during the catarrhal stage, symptoms may be less severe. Three [[macrolide]]s ([[erythromycin]], [[azithromycin]] and [[clarithromycin]]) are used in the U.S. for treatment of pertussis; [[Co-trimoxazole|trimethoprim-sulfamethoxazole]] is generally used when a macrolide is ineffective or is contraindicated. Close contacts who receive appropriate antibiotics (''chemoprophylaxis'') during the 7–21 day incubation period may be protected from developing symptomatic disease. Close contacts are defined as anyone coming into contact with the respiratory secretions of an infected person in the 21 days before or after the infected person's cough began.

=== Influenza ===
{{main|Influenza}}
*[[Influenza]]<ref>{{cite web|url=http://www.who.int/topics/influenza/en/ |title=WHO &#124; Influenza |publisher=Who.int |date=2009-11-13 |accessdate=2010-03-09}}</ref>
'''Influenza''', commonly referred to as the '''flu''', is an [[infectious disease]] caused by [[RNA virus]]es of the [[biological family|family]] [[Orthomyxoviridae]] (the influenza viruses), that affects [[bird]]s and [[mammal]]s. The most common symptoms of the disease are [[chills]], [[fever]], [[sore throat]], [[myalgia|muscle pains]], severe [[headache]], [[cough]]ing, weakness/[[fatigue (medical)|fatigue]] and [[malaise|general discomfort]].<ref name=Merck>{{cite web
|url=http://www.merck.com/mmhe/sec17/ch198/ch198d.html
|title=Influenza: Viral Infections: Merck Manual Home Edition
|publisher=www.merck.com
|accessdate=2008-03-15
|last=
|first=
}}
</ref> Sore throat, fever and coughs are the most frequent symptoms. In more serious cases, influenza [[sequela|causes]] [[pneumonia]], which can be fatal, particularly for the young and the elderly. Although it is often confused with other [[influenza-like illness]]es, especially the [[common cold]], influenza is a much more severe disease than the common cold and is caused by a different type of virus.<ref name=Eccles>{{cite journal |last=Eccles |first=R |title=Understanding the symptoms of the common cold and influenza |journal=Lancet Infect Dis |volume=5 |issue=11 |pages=718–25 |year=2005 |pmid=16253889 |doi=10.1016/S1473-3099(05)70270-X}}</ref> Influenza may produce [[nausea]] and [[vomiting]], particularly in children,<ref name=Merck/> but these symptoms are more common in the unrelated [[gastroenteritis]], which is sometimes called "stomach flu" or "24-hour flu".<ref>[http://coldflu.about.com/od/flumisconceptions/f/stomachflu.htm Seasonal Flu vs. Stomach Flu] by Kristina Duda, R.N.; accessed 12 March 2007 (Website: "About, Inc., A part of The New York Times Company")</ref>

Typically, influenza is transmitted through the air by coughs or sneezes, creating [[aerosols]] containing the virus. Influenza can also be transmitted by direct contact with bird droppings or [[mucus|nasal secretions]], or through contact with contaminated surfaces. Airborne aerosols have been thought to cause most infections, although which means of transmission is most important is not absolutely clear.<ref name=Brankston/> Influenza viruses can be inactivated by [[sunlight]], [[disinfectant]]s and [[detergent]]s.<ref>{{cite journal |last=Suarez |first=D |coauthors=Spackman E, Senne D, Bulaga L, Welsch A, Froberg K |title=The effect of various disinfectants on detection of avian influenza virus by real time RT-PCR |journal=Avian Dis |volume=47 |issue=3 Suppl |pages=1091–5 |year=2003 |pmid=14575118 |doi=10.1637/0005-2086-47.s3.1091}}</ref><ref>[http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html Avian Influenza (Bird Flu)]: Implications for [[Disease|Human Disease]]. Physical characteristics of influenza A viruses. UMN CIDRAP.</ref> As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.

Influenza spreads around the world in [[flu season|seasonal epidemic]]s, resulting in the deaths of between {{nts|250000}} and {{nts|500000}} people every year,<ref>[http://www.who.int/mediacentre/factsheets/fs211/en/ Influenza (Seasonal)], [[World Heath Organization]], April 2009, retrieved 2010-02-13</ref> and millions in [[pandemic]] years. On average 41,400 people died each year in the [[United States]] between 1979 and 2001 from influenza.<ref>{{cite journal |url=http://aje.oxfordjournals.org/cgi/content/full/163/2/181 |title=Mortality due to Influenza in the United States — An Annualized Regression Approach Using Multiple-Cause Mortality Data  | author=[[Jonathan Dushoff]] | journal =[[American Journal of Epidemiology]] | volume = 163| issue = 2| pages = 181–7|accessdate=2009-10-29 |quote=The regression model attributes an annual average of 41,400 (95% confidence interval: 27,100, 55,700) deaths to influenza over the period 1979–2001.  |work= |pmid=16319291 |doi=10.1093/aje/kwj024 |year=2006 |first2=JB |first3=C |first4=DJ |first5=L |last2=Plotkin |last3=Viboud |last4=Earn |last5=Simonsen }}</ref> Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new [[strain (biology)|strain]] of the virus in humans. Often, these new strains appear when an existing flu virus spreads to humans from other animal [[species]], or when an existing human strain picks up new [[gene]]s from a virus that usually infects birds or pigs. An avian strain named [[H5N1]] raised the concern of a new [[influenza pandemic]], after it emerged in Asia in the 1990s, but it has not [[evolution|evolved]] to a form that spreads easily between people.<ref>{{cite web |title=Avian influenza ("bird flu") fact sheet |url=http://www.who.int/mediacentre/factsheets/avian_influenza/en/ |month=February | year=2006 |publisher=WHO |accessdate=2006-10-20}}</ref> In April 2009 a novel flu strain evolved that combined genes from human, pig, and bird flu, initially dubbed "[[swine flu]]" and also known as [[Influenza A virus subtype H1N1|influenza A/H1N1]], emerged in Mexico, the United States, and several other nations. The [[World Health Organization]] officially declared the outbreak to be a [[pandemic]] on June 11, 2009 (see [[2009 flu pandemic]]). The WHO's declaration of a pandemic level 6 was an indication of spread, not severity, the strain actually having a lower mortality rate than common flu outbreaks.<ref>World Health Organization. World now at the start of 2009 influenza pandemic. http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html</ref>

[[Vaccination]]s against influenza are usually given to people in [[developed country|developed countries]]<ref name=WHOvaccines>[http://www.who.int/wer/2005/wer8033.pdf WHO position paper: influenza vaccines] ''WHO weekly Epidemiological Record'' 19 August 2005, vol. 80, 33, pp. 277–288.</ref> and to farmed poultry.<ref>{{cite journal |last=Villegas |first=P |title=Viral diseases of the respiratory system |journal=Poult Sci |volume=77 |issue=8 |pages=1143–5 |year=1998 |pmid=9706079}}</ref> The most common human vaccine is the trivalent [[influenza vaccine]] (TIV) that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two [[influenzavirus A|influenza A virus]] subtypes and one [[Influenzavirus B|influenza B virus]] strain.<ref>{{cite journal |author=Horwood F, Macfarlane J |title=Pneumococcal and influenza vaccination: current situation and future prospects |journal=Thorax |volume=57 |issue=Suppl 2 |pages=II24–II30 |year=2002 |month=October |pmid=12364707 |pmc=1766003 |url=http://thorax.bmj.com/cgi/pmidlookup?view=long&pmid=12364707}}</ref> The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and new strains quickly replace the older ones. [[Antiviral drug]]s can be used to treat influenza, with [[neuraminidase inhibitor]]s being particularly effective.

=== Infectious Mononucleosis ===
{{main|Infectious Mononucleosis}}
[[Infectious Mononucleosis]]<ref>{{cite web|url=http://www.mayoclinic.com/health/mononucleosis/DS00352/DSECTION=symptoms |title=Mononucleosis: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
'''Infectious Mononucleosis''' '''(IM)''' (also known as '''EBV Infectious Mononucleosis''' or '''Pfeiffer's Disease''' or '''Filatov's Disease'''<ref name="wni1811">{{WhoNamedIt|synd|1811}}</ref> and colloquially as '''kissing disease'''—from its oral transmission—or as '''mono''' in [[North America]] and as '''glandular fever''' in other English-speaking countries) is an infectious, very widespread [[viral disease]] caused by the [[Epstein-Barr virus]] (EBV), one type of [[herpesviridae|herpes virus]], to which more than 90% of adults have been exposed.<ref>http://www.kenyon.edu/x26163.xml</ref> Most people are exposed to the virus as children, when the disease produces no noticeable symptoms or only flu-like symptoms. In underdeveloped countries, people are exposed to the virus in early childhood more often than in developed countries, which is why the disease in its observable form is more common in developed countries. It is most common among adolescents and young adults.  <ref>{{cite web|url=http://www.health.state.ny.us/diseases/communicable/mononucleosis/fact_sheet.htm |title=Infectious Mononucleosis (mono, EBV mononucleosis) |publisher=Health.state.ny.us |date= |accessdate=2009-11-27}}</ref>

Especially in [[adolescent]]s and young adults, the disease is characterized by [[fever]], sore throat and [[fatigue (medical)|fatigue]], along with several other possible signs and symptoms. It is primarily diagnosed by observation of symptoms, but suspicion can be confirmed by several diagnostic tests.

The syndrome was described as an infectious process by [[Nil Filatov]]<ref>Н. Филатов: Лекции об острых инфекционных болезнях у детей (N. Filatov: Lektsii ob ostrikh infeksionnîkh boleznyakh u dietei). 2 volumes. Moscow, A. Lang, 1887.</ref> in 1887 and independently by [[Emil Pfeiffer]]<ref>E. Pfeiffer: Drüsenfieber. Jahrbuch für Kinderheilkunde und physische Erziehung, Wien, 1889, 29: 257-264.</ref> in 1889.<ref name="wni1811"></ref>

Retrieved on 7 Mars, 2009</ref><ref name=webMD>[http://www.webmd.com/a-to-z-guides/infectious-mononucleosis-symptoms WebMD > Infectious Mononucleosis] Last Updated: September 19, 2007. Retrieved on 7 Mars, 2009</ref><ref>[http://emedicine.medscape.com/article/222040-overview (History section of) eMedicine Specialties > Infectious Diseases > Infectious Mononucleosis.] Author: Burke A Cunha, MD, Professor of Medicine</ref>]]
The classical symptoms of mononucleosis are a sore throat, [[fever]], [[fatigue (medical)|fatigue]], [[anorexia (symptom)|weight loss]], [[malaise]], [[Human pharynx|pharyngeal]] inflammation, [[petechia]]e and loss of appetite. Common signs include [[lymphadenopathy]] (enlarged [[lymph nodes]]), [[splenomegaly]] (enlarged [[spleen]]), [[hepatitis]] (refers to inflammation of hepatocytes - cells in the liver) and [[hemolysis]] (the bursting of [[red blood cells]]). Older adults are less likely to have a sore throat or lymphadenopathy, but are instead more likely to present with [[hepatomegaly]] (enlargement of the liver) and [[jaundice]]. Rarer signs and symptoms include [[thrombocytopenia]] (lower levels of [[platelet]]s), with or without [[pancytopenia]] (lower levels of all types of blood cells), [[splenic rupture]], splenic hemorrhage, upper airway obstruction, [[pericarditis]] and [[pneumonitis]]. Another rare manifestation of mononucleosis is [[erythema multiforme]].<ref name="OHCM">{{cite book | last=Longmore | first=Murray | coauthors=Ian Wilkinson, Tom Turmezei, Chee Kay Cheung | title=Oxford Handbook of Clinical Medicine, 7th edition | publisher=Oxford University Press | date=2007 | page=389 | isbn=0-19-856837-1 }}</ref><ref name="AFP">{{cite journal | author = Ebell MH | title = Epstein-Barr virus infectious mononucleosis | journal = American Family Physician | volume = 70 | issue = 7 | pages = 1279–87 | year = 2004 | month = November| pmid = 15508538}}</ref>

=== Ebola hemorrhagic fever ===
{{main|Ebola hemorrhagic fever}}
*[[Ebola hemorrhagic fever]]<ref>{{cite web|url=http://www.who.int/csr/disease/ebola/en/index.html |title=WHO &#124; Ebola haemorrhagic fever |publisher=Who.int |date= |accessdate=2010-03-09}}</ref>
'''Ebola''' is the virus '''Ebolavirus''' (EBOV), a viral [[genus]], and the disease '''Ebola hemorrhagic fever''' (EHF), a [[viral hemorrhagic fever]] (VHF). The virus is named after the [[Ebola River]] Valley in the [[Democratic Republic of the Congo]] (formerly [[Zaire]]), which is near the site of the first recognized outbreak, a mission hospital run by [[Flemish people|Flemish]] [[nun]]s, in 1976.<ref>{{Cite journal|last=Bardi|first=Jason Socrates|year=2002|title=Death Called a River|journal=Scripps Research Institute|volume=2|issue=1|url=http://www.scripps.edu/newsandviews/e_20020114/ebola1.html|accessdate=2006-12-08}}</ref> There are four recognized species within the ebolavirus genus, which have a number of specific [[strains]].<ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_filov.htm|title=Filoviridae|accessdate=2009-10-04|last1=Netesov|first1=SV|last2=Feldmann|first2=H|last3=Jahrling|first3=PB|last4=Kiley|first4=MP|last5=Klenk|first5=H-D|last6=Sanchez|first6=A|date=2004-04-24|publisher=International Committee on Taxonomy of Viruses}}</ref> The ''Zaire virus'' is the [[type species]], which is also the first discovered and the most lethal. Electron micrographs show long filaments, characteristic of the [[Filoviridae]] viral family. The virus interferes with the [[endothelial cells]] lining the interior surface of blood vessels and with coagulation. As the blood vessel walls become damaged and the platelets are unable to coagulate, patients succumb to [[Hypovolemia|hypovolemic shock]]. Ebola is transmitted through bodily fluids, while [[conjunctiva]] exposure may also lead to transmission. Ebola first emerged in 1976 in Zaire. However, it remained largely obscure until 1989 when several widely publicized outbreaks among monkeys in the United States occurred.

Classification:

The genera ''Ebolavirus'' and ''[[Marburgvirus]]'' was originally classified as the species of the now-obsolete ''Filovirus'' genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the [[International Committee on Taxonomy of Viruses]] (ICTV) to change the ''Filovirus'' genus to the ''[[Filoviridae]]'' family with two specific genera: ''Ebola-like viruses'' and ''Marburg-like viruses''. This proposal was implemented in Washington, D.C. as of April ,2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington, D.C. to change the "-like viruses" to "-virus" resulting in today's ''Ebolavirus'' and ''Marburgvirus''.<ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/01.025.0.02.htm|title=ICTVdB Virus Description - 01.025.0.02. Ebolavirus|accessdate=2009-06-02|last=Büchen-Osmond|first=Cornelia|date=2006-04-25|publisher=International Committee on Taxonomy of Viruses}}</ref>


Rates of genetic change are one hundred times slower than [[Influenza A]] in humans, but on the same magnitude of that of [[Hepatitis B]]. Using these rates, the Ebolavirus and Marburgvirus are estimated to have diverged several thousand years ago.<ref>{{Cite pmid|9254917}}</ref>

; Zaire virus (ZEBOV) : The ''Zaire virus'', formerly named ''Zaire Ebola Virus'', has the highest case-fatality rate, up to 90% in some epidemics, with an average case fatality rate of approximately 83% over 27 years. There have been more outbreaks of ''Zaire ebolavirus'' than any other species. The first outbreak took place on 26 August 1976 in [[Yambuku]]. Mabalo Lokela, a 44-year-old schoolteacher, became the first recorded case. The symptoms resembled [[malaria]], and subsequent patients received [[quinine]]. The initial transmission was believed to be due to reuse of the needle for Lokela's injection without sterilization. Subsequent transmission was also due to lack of [[Universal precautions|barrier nursing]] and the traditional burial preparation method, which involves washing and [[gastrointestinal tract]] cleansing.<ref>{{Cite journal|author=Isaacson, M; Sureau, P; Courteille, G; Pattyn, SR;|title=Clinical Aspects of Ebola Virus Disease at the Ngaliema Hospital, Kinshasa, Zaire, 1976|url=http://www.itg.be/ebola/ebola-12.htm|accessdate=2009-07-08}}</ref>
; Sudan ebolavirus (SEBOV) : The virus was the second species of Ebola emerging simultaneous with the ''Zaire virus''. It was believed to have originated amongst cotton factory workers in Nzara, [[Sudan]], with the first case reported as a worker exposed to a potential natural reservoir. Scientists tested all animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The lack of barrier nursing facilitated the spread of the disease. The most recent outbreak occurred in May 2004. 20 confirmed cases were reported in Yambio County, Sudan, with five deaths resulting. The average fatality rates for were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001.
; [[Reston ebolavirus]] (REBOV) : Discovered during an outbreak of [[Simian hemorrhagic fever virus]] (SHFV) in [[Crab-eating Macaque|crab-eating macaques]] from [[Covance|Hazleton Laboratories]] (now Covance) in 1989. Since the initial outbreak in [[Reston, Virginia]], it has emerged in the Philippines, Siena Italy, Texas,<ref name="KnownCasesCDC">{{Cite web|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/ebolatable.htm|title=Known Cases and Outbreaks of Ebola Hemorrhagic Fever|accessdate=2008-08-02|author=Special Pathogens Branch CDC|date=2008-01-14|publisher=Center for Disease Control and Prevention}}</ref> and among pigs in the Philippines.<ref>{{Cite web|url=http://www.nytimes.com/2009/01/24/health/24ebola.html|title=Pig-to-Human Ebola Case Suspected in Philippines|accessdate=2009-01-26|date=2009-01-24|publisher=New York Times}}</ref> Despite its status as a [[Biosafety level#Biosafety Level 4|Level-4]] organism, it is non-[[pathogen]]ic to humans however hazardous in monkeys.<ref>{{harvnb|McCormick|Fisher-Hoch|1999|p=300}}</ref>
; Cote d'Ivoire ebolavirus (CIEBOV) : Also referred to as ''Ivory Coast ebolavirus'' and ''Tai ebolavirus'', it was first discovered among [[chimpanzee]]s from the Tai Forest in [[Côte d'Ivoire]], [[Africa]] on 1 November 1994. [[Necropsies]] showed blood within the heart to be brown, no obvious marks were seen on the organs, and one necropsy displayed lungs filled with blood. Studies of tissues taken from the chimpanzees showed results similar to human cases during the 1976 Ebola outbreaks in Zaire and Sudan. As more dead chimpanzees were discovered, with many testing positive to Ebola using molecular techniques. The source of contamination was believed to be the meat of infected [[Western Red Colobus]] monkeys, upon which the chimpanzees preyed. One of the scientists performing the necropsies on the infected chimpanzees contracted Ebola. She developed symptoms similar to those of [[dengue fever]] approximately a week after the necropsy, and was transported to Switzerland for treatment. She was discharged from hospital after two weeks and had fully recovered six weeks after the infection.<ref>{{Cite book|last=Waterman|first=Tara|title=Ebola Cote D'Ivoire Outbreaks|url=http://virus.stanford.edu/filo/eboci.html|accessdate=2009-05-30|year=1999|publisher=Stanford University}}</ref>
; Bundibugyo ebolavirus : On November 24, 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the [[Bundibugyo District]]. After confirmation of samples tested by the United States National Reference Laboratories and the [[Centers for Disease Control and Prevention|CDC]], the [[World Health Organization]] confirmed the presence of the new species. On 20 February 2008, the Uganda Ministry officially announced the end of the epidemic in Bundibugyo with the last infected person discharged on 8 January 2008.<ref>{{Cite press release|title=End of Ebola outbreak in Uganda|publisher=World Health Organization|date=2008-02-20|url=http://www.who.int/csr/don/2007_02_20b/en/index.html}}</ref> Ugandan officials confirmed a total of 149 cases of this new Ebola species, with 37 deaths attributed to the strain (24.83%).<ref>{{Cite news|first=Tim|last=Cocks|title=Uganda confirms 113 suspected Ebola cases|url=http://africa.reuters.com/top/news/usnBAN126612.html|publisher=Reuters|date=2007-12-11|accessdate=2008-02-25}}</ref>

Virology, Structure, and Genome

Each virion contains one molecule of linear, single-stranded, [[Sense (molecular biology)|negative-sense]] RNA, 18,959 to 18,961 nucleotides in length. The 3′ terminus is not polyadenylated and the 5′ end is not capped. It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are sufficient for replication.<ref>{{harvnb|Klenk|Feldmann|2004|p=9}}</ref> It codes for seven structural proteins and one non-structural protein. The gene order is 3′ - leader - NP - VP35 - VP40 - GP/sGP - VP30 - VP24 - L - trailer - 5′; with the leader and trailer being non-transcribed regions, which carry important signals to control transcription, replication, and packaging of the viral genomes into new virions. The genomic material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA polymerase, are necessary to transcribe the viral genome into mRNAs, as well as for replication of the viral genome.

Replication:

Being acellular, viruses do not grow through cell division; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves, and they assemble in the cell.<ref name="BiomarkerDatabase" />

* The virus attaches to host receptors through the [[glycoprotein]] (GP) surface [[peplomer]] and is endocytosed into vesicles in the host cell
* Viral membrane fuses with [[Vesicle (biology)|vesicle]] membrane, [[nucleocapsid]] is released into the [[cytoplasm]]
* Encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3' - 5') of polyadenylated, monocistronic mRNAs
* Using the host cell's machinery translation of the mRNA into viral proteins occurs
* Viral proteins are processed, glycoprotein precursor (GP0) is cleaved to GP1 and GP2, which are heavily glycosylated. These two molecules assemble, first into heterodimers, and then into trimers to give the surface peplomers. Secreted glycoprotein (sGP) precursor is cleaved to sGP and delta peptide, both of which are released from the cell.
* As viral protein levels rise, a switch occurs from translation to replication. Using the negative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly encapsidated.
* The newly-formed nucleocapsides and envelope proteins associate at the host cell's plasma membrane; [[Viral shedding|budding]] occurs.

Pathogenesis of ebola hemorrhagic fever:

[[Endothelial cells]], mononuclear [[phagocytes]], and [[hepatocytes]] are the main targets of infection. After infection, in a secreted glycoprotein (sGP) the Ebola virus glycoprotein (GP) is synthesized. Ebola replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a [[Trimer (biochemistry)|trimeric complex]], which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a [[Dimer|dimeric protein]] which interferes with [[neutrophils]], which are a type of [[white blood cell]], signaling which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. The presence of viral particles and cell damage resulting from [[Viral shedding|budding]] causes the release of [[cytokines]] (specifically [[Tumor necrosis factor-alpha|TNF-α]], [[Interleukin 6|IL-6]], [[Interleukin 8|IL-8]], etc), which are the signaling molecules for fever and inflammation. The [[cytopathic effect]], from infection in the endothelial cells, results in a loss of vascular integrity. This loss in vascular integrity is furthered with synthesis of GP, which reduces specific integrins responsible for cell adhesion to the inter-cellular structure, and damage to the liver, which leads to [[coagulopathy]]. Without vascular integrity and effective [[coagulation]], blood quickly leaks through the blood vessel leading to [[hypovolemic shock]].<ref name="doi10.1128/JVI.77.18.9733-9737.2003">{{Cite doi|10.1128/JVI.77.18.9733-9737.2003}}</ref>

Epidemiology of ebola hemorrhagic fever:
Natural reservoirs of Ebola virus:

Between 1976 and 1998, from 30,000 mammals, birds, reptiles, amphibians, and [[arthropod]]s sampled from outbreak regions, no ''Ebolavirus'' was detected apart from some genetic material found in six rodents (''[[Mus setulosus]]'' and ''[[Praomys]]'') and one [[shrew]] (''[[Sylvisorex ollula]]'') collected from the [[Central African Republic]].<ref name="Pourrut2005">{{Cite doi|10.1016/j.micinf.2005.04.006}}</ref><ref name="Morvan1999">{{Cite doi|10.1016/S1286-4579(99)00242-7}}</ref> The virus was detected in the carcasses of [[gorilla]]s, [[chimpanzee]]s, and [[duiker]]s during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high mortality from infection in these species makes them unlikely as a natural reservoir.<ref name="Pourrut2005" />

{{Double image stack|right|Ecologic and Geographic Distribution of Filovirus Disease in Africa.jpg|Ecologic and Geographic Distribution of Filovirus Disease in Asia and the Philippines.jpg|180|Distribution of Ebola and [[Marburg virus|Marburg]] in Africa. (A) Known points of filovirus hemorrhagic fevers. Projected distribution of ecological niche of: (B) all filoviruses, (C) Ebola, (D) Marburg.|Distribution of ecological niche of Reston ebolavirus in southeastern Asia and the Philippines. (A) Areas of research determining whether similar ecological conditions exist. (B) Projected distribution. Insert, detailed view of [[Mindanao]], Philippines}}

[[Plant]]s, [[arthropods]], and birds have also been considered as possible reservoirs, however, [[bat]]s are considered the most likely candidate.<ref>{{Cite news|title=Fruit bats may carry Ebola virus |url=http://news.bbc.co.uk/2/hi/health/4484494.stm|work=BBC News|date=2005-12-11|accessdate=2008-02-25}}</ref> Bats were known to reside in the cotton factory in which the index cases for the 1976 and 1979 outbreaks were employed, and they have also been implicated in Marburg infections in 1975 and 1980.<ref name="Pourrut2005" /> Of 24 plant species and 19 vertebrate species experimentally inoculated with ''Ebolavirus'', only bats became infected.<ref>{{Cite pmid|8969248}}</ref> The absence of clinical signs in these bats is characteristic of a reservoir species. In a 2002–2003 survey of 1,030 animals which included 679 bats from [[Gabon]] and the [[Republic of the Congo]], 13 fruit bats were found to contain ''Ebolavirus'' RNA.<ref>{{Cite doi|10.1038/438575a}}</ref> As of 2005, three [[fruit bat]] species (''[[Hypsignathus monstrosus]]'', ''[[Epomops franqueti]]'', and ''[[Myonycteris torquata]]'') have been identified as carrying the virus while remaining asymptomatic. They are believed to be a natural host species, or reservoir, of the virus.<ref>{{Cite pmid|17940947}}</ref>

Reston ebolavirus—unlike its African counterparts—is non-pathogenic in humans. The high mortality among monkeys and its recent emergence in swine, makes them an unlikely natural reservoirs.<ref>{{Cite web|first=Juan|last=Lubroth|title=Ebola-Reston Virus in Pigs: Disease situation in swine in the Philippines|url=http://www.fao.org/Ag/againfo/programmes/en/empres/ebola_111208.html|publisher=Food and Agriculture Organization of the United Nations|accessdate=2009-09-27}}</ref>

Transmission of ebola hemorrhagic fever:

Bats drop partially eaten fruits and pulp, terrestrial mammals such as gorillas and duikers feed on these fallen fruits. This chain of events forms a possible indirect means of transmission from the natural host to animal populations, which have led to research towards viral shedding in the saliva of bats. Fruit production, animal behavior, and other factors vary at different times and places which may trigger outbreaks among animal populations.<ref>{{Cite pmid|17848072}}</ref> Transmission between natural reservoirs and humans are rare, and outbreaks are usually traceable to a single index case where an individual has handled the carcass of gorilla, chimpanzee, or duiker.<ref>{{Cite pmid|15078595}}</ref> The virus then spreads person-to-person, especially within families, hospitals, and during some [[mortuary]] rituals where contact among individuals becomes more likely.<ref>{{Cite book|title=Questions and Answers about Ebola Hemorrhagic Fever|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm|accessdate=2009-05-31|date=2009-03-25|publisher=Centers for Disease Control and Prevention}}</ref>

The virus has been confirmed to be transmitted through [[body fluid]]s. Transmission through oral exposure and through [[conjunctiva]] exposure is likely,<ref>{{Cite pmid|8551825}}</ref> which have been confirmed in non-human primates.<ref>{{Cite pmid|8712894}}</ref> Filoviruses are not naturally transmitted by aerosol. They are, however, highly infectious as breathable 0.8-1.2 micron droplets in laboratory conditions;<ref>{{Cite pmid|7547435}}</ref> because of this potential route of infection, these viruses have been classified as Category A biological weapons.<ref>{{Cite pmid|15588056}}</ref>

All epidemics of Ebola have occurred in sub-optimal hospital conditions, where practices of basic hygiene and sanitation are often either luxuries or unknown to caretakers and where disposable needles and [[autoclave]]s are unavailable or too expensive. In modern hospitals with disposable needles and knowledge of basic hygiene and [[Universal precautions|barrier nursing]] techniques, Ebola has never spread on a large scale. In isolated settings such as a quarantined hospital or a remote village, most victims are infected shortly after the first case of infection is present. The quick onset of symptoms from the time the disease becomes contagious in an individual makes it easy to identify sick individuals and limits an individual's ability to spread the disease by traveling. Because bodies of the deceased are still infectious, some doctors had to take measures to properly dispose dead bodies in a safe manner despite local traditional burial rituals.<ref name="nyt">{{Cite news|first=Blaine|last=Harden|title=Dr. Matthew's Passion|url=http://www.nytimes.com/library/magazine/home/20010218mag%2debola.html|work=[[New York Times]] Magazine|date=2001-02-18|accessdate=2008-02-25}}</ref>

Prevalence of Ebola hemorrhagic fever:

{{For|more about specific outbreaks and their descriptions|List of Ebola outbreaks}}

Outbreaks of Ebola, with the exception of Reston ebolavirus, have mainly been restricted to Africa. The virus often consumes the population, governments and individuals quickly respond to quarantine the area, and the lack of roads and transportation—helps to contain the outbreak.<ref name="KnownCasesCDC" />

* '''Zaire virus''' first emerged in an outbreak among human populations in 1976 in [[Zaire]] (now Democratic Republic of the Congo) with no further recognized cases until 1994. Since then it has occurred again in the [[Democratic Republic of the Congo]], [[Republic of the Congo]], and [[Gabon]]. There have been two contained cases in [[South Africa]].
* '''Sudan ebolavirus''' emerged in a simultaneous outbreak with the Zaire virus in 1976 in [[Sudan]]. It appeared again in another outbreak in 1979. No further cases were recognized until a 2000 outbreak in [[Uganda]] and 2004 outbreak in Sudan. There has been one confirmed accidental incidence in 1976 in [[England]].
* '''Reston ebolavirus''' was first recognized among monkeys in 1989 in the [[Reston, Virginia]] and again in [[Alice, Texas]] in the [[United States]], both were traced to the [[Philippines]]. In 1994 it was recognized in cases among monkeys in an import facility in [[Italy]]. In 2008 cases of infection among pigs were recognized in the Philippines.
* '''Ivory Coast ebolavirus''' was first recognized in 1994 after a scientist became ill after conducting an autopsy on a wild chimpanzee in the [[Tai Forest]], [[Côte d'Ivoire]].
* '''Bundibugyo ebolavirus''' was first recognized in 2007 in an outbreak in [[Bundibugyo District]], [[Uganda]].

Clinical aspects of Ebola hemorrhagic fever:
Prevention of Ebola hemorrhagic fever:
In the early stages, Ebola may not be highly contagious. Contact with someone in early stages may not even transmit the disease. As the illness progresses, bodily fluids from diarrhea, vomiting, and bleeding represent a hazard. Due to lack of proper equipment and hygienic practices, large-scale epidemics occur mostly in poor, isolated areas without modern hospitals or well-educated medical staff. Many areas where the infectious reservoir exists have just these characteristics. In such environments, all that can be done is to immediately cease all needle-sharing or use without adequate [[Sterilization (microbiology)|sterilization]] procedures, isolate patients, and observe strict [[Universal precautions|barrier nursing]] procedures with the use of a medical rated disposable face mask, gloves, goggles, and a gown at all times. This should be strictly enforced for all medical personnel and visitors.<ref>{{Cite book|last=Centers for Disease Control and Prevention and World Health Organization|title=Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual/entire.pdf|format=PDF|accessdate=2009-05-31|year=1998|publisher=Centers for Disease Control and Prevention|location=Atlanta, Georgia, USA|ref=CITEREFCDCWHO1998}}</ref>

Vaccines have successfully protected non-human primates, however the six months needed to complete immunization made it impractical in an epidemic. To resolve this, in 2003 a vaccine using an [[Adenoviridae|adenoviral]] (ADV) vector carrying the Ebola spike protein was tested on crab-eating macaques. The monkeys were challenged with the virus twenty-eight days later, and remained resistant.<ref name="Sullivan2003">{{Cite doi|10.1038/nature01876}}</ref> In 2005 a vaccine based on attenuated recombinant [[vesicular stomatitis virus]] (VSV) vector carrying either the Ebola glycoprotein or Marburg glycoprotein successfully protected non-human primates,<ref name="Jones2005">{{Cite doi|10.1038/nm1258}}</ref> opening clinical trials in humans.<ref>{{Cite book|last=Oplinger|first=Anne A.|date=2003-11-18|title=NIAID Ebola vaccine enters human trial|url=http://news.bio-medicine.org/medicine-news-2/NIAID-Ebola-vaccine-enters-human-trial-4881-1/|publisher=Bio-Medicine}}</ref> By October the study completed the first human trial giving three vaccinations over three months showing capability of safely inducing an immune response. Individuals were followed for a year, and in 2006 a study testing a faster-acting, single shot vaccine began. This study was completed in 2008.<ref name="NIAIDVaccineDevelopment">{{Cite press release|title=Ebola/Marburg Vaccine Development|publisher=National Institute of Allergy and Infectious Diseases|date=2008-09-15|url=http://www3.niaid.nih.gov/topics/ebolaMarburg/default.htm}}</ref>

Symptoms of Ebola hemorrhagic fever:

The [[incubation period]] ranges from 2–21&nbsp;days, although it is generally 5–18&nbsp;days,<ref>{{Cite pmid|14718087}}</ref> although Bundibugyo ebolavirus may be more than twice as long at 42 days.<ref name="WHO-PR20080220">{{Cite press release|title=End of Ebola outbreak in Uganda|publisher=World Health Organization|date=2008-02-20|url=http://www.who.int/csr/don/2007_02_20b/en/index.html|accessdate=2009-11-29}}</ref> Illness is characterized by the rapid onset of fever, malaise, muscle pain, headache, and the inflammation of the [[pharynx]]. Six days following vomiting and bloody diarrhea, individuals may develop maculopapular rash with bleeding at needle sites and bodily orifices.<ref name="10.1371/journal.pmed.0010059" />

Reston ebolavirus is non-pathogenic to humans and individuals often do not show any symptoms, although it is fatal in monkeys. There is only one known case of Ivory Coast ebolavirus. There has been only one outbreak of Bundibugyo ebolavirus. Zaire virus, then Sudan ebolavirus, are the most common. Symptoms include: [[abdominal pain]] (60-80%), [[fever]] (90%-100%), [[headache]] (40%-90%), [[Hematemesis|bloody vomit]] (10%-40%), [[Maculopapular rash]] (5%-20%), [[malaise]] (75%-85%), [[Arthralgia|joint]] and [[Myalgia|muscle]] pain (40%-80%), [[Pharyngitis|inflammation of the pharynx]] (20%-40%),<ref>{{Cite pmid|9893380}}</ref> blood fails to clot (71%-78%), [[chest pain]] (SEBOV only 83%), [[Central nervous system|CNS]] involvement (rare), dry and [[sore throat]] (63%), [[hemorrhagic diathesis]] (71%-78%), [[hiccups]] (15%), non-bloody [[diarrhea]] (81%), [[vomiting]] (59%).<ref>{{Cite book|last1=Zaki|first1=S. R.|last2=Kilmarx|first2=P.|title=Pathology of Emerging Infections|year=1997|publisher=American Society for Microbiology|location=Washington, DC|chapter=Ebola Virus Hemorrhagic Fever}}</ref> [[Purpura]], [[petechia]], [[Sclerosis (medicine)|sclerotic arterioles]], and low [[Hypotension|blood-pressure]] are characteristic as the disease progresses.

=== Marburg hemorrhagic fever ===
{{main|Marburg hemorrhagic fever}}
*[[Marburg hemorrhagic fever]]<ref>{{cite web|url=http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg/qa.htm |title=Marburg Hemorrhagic Fever: Q & A &#124; CDC Special Pathogens Branch |publisher=Cdc.gov |date= |accessdate=2010-03-09}}</ref>



'''''Marburg virus''''' or simply '''Marburg''' is the common name for the the genus of viruses '''''Marburgvirus''''', which contains one species, ''Lake Victoria marburgvirus''. The virus causes the disease '''Marburg [[Viral hemorrhagic fever|Hemorrhagic Fever]]''' (MHF), also referred to as ''Marburg Virus Disease'', and previously also known as ''green monkey disease'' due to its primate origin. Marburg originated in Central and East Africa, and infects both human and nonhuman primates. The Marburg Virus is in the same taxonomic family as [[Ebola]], and both are identical structurally although they elicit different [[antibodies]].

Etymology:

The genera ''Marburgvirus'' and ''[[Ebolavirus]]'' were originally classified as the species of the now nonexistent ''Filovirus'' genus. In March 1998, the Vertebrate Virus Subcommittee proposed to the [[International Committee on Taxonomy of Viruses]] (ICTV) to change the ''Filovirus'' genus to ''[[Filovirus]]'' family with two specific genera: ''Ebola-like viruses'' and ''Marburg-like viruses''. This proposal was implemented in Washington DC as of April 2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington DC to change the "-like viruses" to "-virus" (e.g. ''Ebolavirus'', ''Marburgvirus'') in addition to renaming the only species in the ''Marburgvirus'' genus from ''Marburg virus'' to ''Lake Victoria Marburgvirus''.<ref>{{cite web | url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/01.025.0.01.htm | title=ICTVdB Virus Description - 01.025.0.01. Marburgvirus | accessdate=2009-02-09 | author= | last=Büchen-Osmond | first=Cornelia | authorlink= | coauthors= | date=2006-04-25 | year= | month= | work= | publisher=International Committee on Taxonomy of Viruses | location= | pages= | language= | doi= | archiveurl= | archivedate= | dateformat= | quote=}}</ref>

The item "Marburg" was named after the location of the first outbreak in 1967 in [[Marburg, Germany]].

Virology and Structure:

The viral structure is typical of [[filovirus]]es, with long threadlike particles which have a consistent diameter but vary greatly in length from an average of 800 to 14,000 [[nanometer]]s (nm), with peak infectious activity at about 790&nbsp;nm. [[Virion]]s (viral particles) contain seven known structural [[protein]]s. While nearly identical to [[Ebola]] virus in structure, Marburg virus is [[antigen]]ically distinct from Ebola virus; in other words, it triggers different [[antibodies]] in infected organisms. It was the first [[filovirus]] to be identified.

Genome:

Marburg contains a single molecule of linear negative-sense, 19100 nucleotides long, single-stranded RNA.<ref>[http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/01.025.0.01.htm]</ref>

Natural reservoir:

In September 2007, ''[[New Scientist]]'' magazine reported that the virus has been found in cave-dwelling African fruit bats in [[Gabon]], the first time the virus has been found outside primates. The virus has now also been confirmed in bats in a Uganda mine[http://www.newsdaily.com/stories/tre56u65n-us-bats-virus/] after two miners contracted Marburg in August 2007. [[Ebola]] antibodies (a close relative to Marburg) were found in three species of fruit bats in 2005. Marburg antibodies have been found in healthy bats, suggesting that the bats had been previously infected. Although no one has yet found complete live viruses from a bat, the team suggest that "[I] think we can be sure that these fruit bats are the reservoir of Marburg virus".<ref>{{Citation |last=Mackenzie |first=Debora |publication-date=2007-09-01 |title=Marburg virus found in fruit bats. |periodical=[[New Scientist]] |issue= 2619 |pages= 14 |url=http://www.newscientist.com/channel/health/mg19526193.200-fruit-bats-carry-deadly-marburg-virus.html |accessdate= 2007-09-26}}</ref>

The same techniques used to identify those genes were also used to identify Marburg genes found in Egyptian fruit bats, ''[[Rousettus aegyptiacus]]''.<ref>{{cite journal |author=Towner JS, Pourrut X, Albariño CG, ''et al.'' |title=Marburg virus infection detected in a common African bat |journal=PLoS ONE |volume=2 |issue=1 |pages=e764 |year=2007 |pmid=17712412 |pmc=1942080 |doi=10.1371/journal.pone.0000764 |url=http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000764}}</ref>

Epidemiology and Prevalence:

Outbreaks of Marburg are centered in Africa, where the natural reservoir is believed to be located.

Transmission of marburg hemorrhagic fever:

The disease is spread through [[bodily fluid]]s, including [[blood]], [[excrement]], [[saliva]], and [[vomit]]. Early symptoms are often non-specific, and usually include fever, headache and [[myalgia]] after an incubation period of three to nine days. After five days, a maculopapular<!-- ?[[maculopapular]] --> [[rash]] is often present on the trunk. Later-stage Marburg infection is acute and can include [[jaundice]], [[pancreatitis]], weight loss, [[delirium]] and neuropsychiatric symptoms, [[Hemorrhage|haemorrhaging]], [[Hypovolemia|hypovolemic shock]] and multi-organ dysfunction, with liver failure most common. Accounts of external haemorrhaging from [[Body orifice|bodily orifices]] are pervasive in popular references to the disease but are in fact rare. Time course varies but symptoms usually last for one to three weeks until the disease either resolves or kills the infected host. The fatality rate is from 23% to over 90%.<ref>
{{cite web
| url = http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm
| title = CDC special pathogins branch- Marburg page
| language =
| accessdate = 2007-05-03
}}</ref><ref>
{{cite web
| url = http://www.who.int/csr/don/2005_08_24/en/index.html
| title = World Health Organization - Report after final death 2004-2005 outbreak
| language =
| accessdate = 2007-05-03
}}</ref>

Medical aspects of marburg hemorrhagic fever:

Caregivers require barrier infection control measures including double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings.

Marburg is a biosafety level-four agent, and thus requiring the highest level of precautions.<ref>{{cite web
| url = http://www.phac-aspc.gc.ca/msds-ftss/msds98e-eng.php
| title = Marburg virus - Material Safety Data Sheets (MSDS)
| accessdate = 2008-10-12
| author =
| last =
| first =
| authorlink =
| coauthors =
| date = 1997-10-11
| year =
| month =
| format =
| work =
| publisher = Public Health Agency of Canada
| location =
| pages =
| language =
| doi =
| archiveurl =
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}}</ref>

A few [[research]] groups are working on [[medication|drug]]s and vaccines to fight the virus. In 1998, a group at the [[United States Army Medical Research Institute of Infectious Diseases]] (USAMRIID) published the first peer reviewed article detailing the development of the first experimental Marburg virus vaccine demonstrated to completely protect animals from lethal Marburg virus infection<ref name="Hevey1998">{{Cite doi|10.1006/viro.1998.9367}}</ref> Following, in 2002, [[Genphar]], a company doing research for the [[United States Army]]'s [[biodefense]] program, announced that an experimental vaccine protected animals from a high dose of Marburg virus. The tests were conducted by the United States Army Medical Research Institute of Infectious Diseases ([[USAMRIID]]). According to the company, all animals in the control group died within days whereas all animals that received the regular dosage of the vaccine were fully protected.

In June 2005 scientists at [[Canada]]'s [[National Microbiology Laboratory]] announced that they had also developed vaccines for both Marburg and Ebola that showed significant promise in primate testing. Studies on mice also suggested that the vaccine might be an effective treatment for the disease if it is administered shortly after a patient is infected. To make the vaccines the scientists fused a surface protein from the viruses they hope to protect against onto an animal virus - [[vesicular stomatitis virus|vesicular stomatitis]] - which is thought to be of no threat to humans.<ref name="Jones2006">{{cite journal | author=Jones SM, Feldmann H, Stroher U ''et al.'' | title=Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses | journal=Nature Med | year=2005 | volume=11 | issue=7 | pages=786–90 | pmid=15937495 | doi=10.1038/nm1258 }}</ref> In the rhesus macaque monkey model of the disease, the vaccine is effective even when given after infection with the virus.<ref name="Daddario-DiCaprio2006">{{cite journal |author=Daddario-DiCaprio KM, Geisbert TW, Ströher U, ''et al.'' |title=Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment |journal=Lancet |volume=367 |issue=9520 |pages=1399–404 |year=2006 |pmid=16650649 |doi=10.1016/S0140-6736(06)68546-2 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(06)68546-2}}</ref>

Symptoms of marburg hemorrhagic fever:

Many of the symptoms of Marburg haemorrhagic fever are similar to those of other infectious diseases, such as [[malaria]] or [[typhoid]], but are most similar to those of [[Ebola]] strains.

Diagnosing marburg hemorrhagic fever:

Diagnosis of Marburg is similar to Ebola using the [[Enzyme-Linked ImmunoSorbent Assay]] (ELISA) test.<ref>[http://www.mayoclinic.com/health/ebola-virus/DS00996/DSECTION=tests-and-diagnosis]</ref>

Prognosis of marburg hemorrhagic fever:

If a patient survives, recovery is usually prompt and complete, though it may be prolonged in some cases, with inflammation or secondary infection of various organs, including: [[orchitis]] ([[testicle]]s), [[hepatitis]] ([[liver]]), [[transverse myelitis]] ([[spinal cord]]), [[uveitis]] ([[eye]]s), and [[parotitis]] ([[Parotid gland|salivary glands]]){{Citation needed|date=July 2008}}. Recovered patients often have little or no memory of being sick, though only 10-40% survive.

Treatment:

There is no specific antiviral therapy indicated for treating Marburg, and hospital care is usually supportive in nature. [[Hypotension]] and shock may require early administration of vasopressors and haemodynamic monitoring with attention to fluid and electrolyte balance, circulatory volume, and blood pressure. [[Viral haemorrhagic fever]] (VHF) patients tend to respond poorly to fluid infusions and may develop [[pulmonary edema]].

=== Streptococcal pharyngitis ===
{{main|Streptococcal pharyngitis}}
*[[Streptococcal pharyngitis]]<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/000639.htm |title=Strep throat: MedlinePlus Medical Encyclopedia |publisher=Nlm.nih.gov |date=2010-02-23 |accessdate=2010-03-09}}</ref>
'''Streptococcal pharyngitis''' or '''streptococcal sore throat''' (known colloquially as '''strep throat''' in [[American English]]) is a form of [[group A streptococcal infection]]<ref>{{DorlandsDict|nine/100014400|streptococcal pharyngitis}}</ref> that affects the [[pharynx]] and possibly the [[larynx]] and [[tonsils]].  It is a very contagious infection, spread by close contact with an infected individual, which can lead to various other complications if not swiftly treated.  [[Antibiotics]] can help reduce contagiousness.

Signs and symptoms of streptococcal pharyngitis:
Streptococcal pharyngitis usually appears suddenly with severe sore throat pain that may make talking or swallowing painful.

Signs and symptoms may include
* Inflamed [[tonsils]]
* [[Tonsillar Exudate|White spots on the tonsils]]<ref>{{cite journal |author=Xu J, Schwartz K, Monsur J, Northrup J, Neale AV |title=Patient-clinician agreement on signs and symptoms of 'strep throat': a MetroNet study |journal=Fam Pract |volume=21 |issue=6 |pages=599–604 |year=2004 |month=December |pmid=15528291 |doi=10.1093/fampra/cmh604 |url=http://fampra.oxfordjournals.org/cgi/content/full/21/6/599}}</ref>
* Difficulty swallowing ([[dysphagia]])
* Tender [[Cervical lymph nodes|cervical]] [[lymphadenopathy]]
* Bumps, bruises, inflamation, or swelling; ('''goose eggs'''), on the right, or uncommonly left side of neck.
* [[Fever]]
* [[Headache]] (often prior to other symptoms)
* [[Malaise]], general discomfort, feeling ill or uneasy
* [[Halitosis]]
* Abdominal pain, nausea and vomiting<ref>Know the Tell-Tale Signs of Strep, http://www.myfamilywellness.org/MainMenuCategories/FamilyHealthCenter/ChildrensHealth/Strep.aspx</ref>
* [[Rash]]<ref>[http://www.kidshealth.org/parent/infections/lung/strep_throat.html Kids Health]</ref>
* [[Urticaria|Hives]]
* Chills
* Loss of appetite
* Ear pain
* Peeling of skin on hands and feet
* Ears locking up

Additional symptoms such as [[sinusitis]], [[vaginitis]], or [[impetigo]] may be present if the strep bacteria infects both the throat and a secondary location.  For additional information on non-pharynx symptoms, see [[Group A streptococcal infection|Group A Streptococcal (GAS) Infection]].

Diagnosis of streptococcal pharyngitis:
There are several causes for [[pharyngitis]], not just streptococcus bacteria.  Productive coughing, nasal discharge, and red, irritated eyes in addition to fever and sore throat are more indicative of a viral sore throat than of strep throat, though a co-infection with a virus is possible and may explain the presence of these additional symptoms. A [[rapid strep test]] (also called rapid antigen detection testing or RADT) or a throat culture may be undertaken to clarify diagnosis. The rapid strep test is quicker but less sensitive and specific than a throat culture developed on a blood [[agar plate]].<ref name=IDSAGuideline2002>{{cite journal |author=Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH |title=Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. [[Infectious Diseases Society of America]] |journal=Clin. Infect. Dis. |volume=35 |issue=2 |pages=113–25 |year=2002 |month=July |pmid=12087516 |doi=10.1086/340949 |url=http://www.journals.uchicago.edu/doi/abs/10.1086/340949}}</ref> Positive tests in association with symptoms establish a positive diagnosis, which can be treated with antibiotics.<ref name=IDSAGuideline2002/> Asymptomatic patients should not be routinely tested with a throat culture because a certain percentage of the population persistently "carries" strep throat.<ref name=IDSAGuideline2002/>

=== Pneumonia ===
{{main|Pneumonia}}
*[[Pneumonia]]<ref>https://health.google.com/health/ref/Pneumonia</ref>
'''Pneumonia''' is an abnormal [[Inflammation|inflammatory]] condition of the [[lung]].<ref>{{EMedicineDictionary|pneumonia}}</ref> It is often characterized as including inflammation of the [[parenchyma]] of the lung (that is, the [[alveolus|alveoli]]) ''and'' abnormal alveolar filling with fluid ([[consolidation (medicine)|consolidation]] and [[exudation]]).<ref>{{DorlandsDict|six/000084139|pneumonia}}</ref>

The alveoli are microscopic air-filled sacs in the lungs responsible for gas exchange.  Pneumonia can result from a variety of causes, including [[infection]] with [[bacteria]], [[virus]]es, [[fungus|fungi]], or [[parasite]]s, and chemical or physical injury to the lungs. Its cause may also be officially described as ''[[Idiopathic interstitial pneumonia|idiopathic]]''—that is, unknown—when infectious causes have been excluded.

Typical symptoms associated with pneumonia include [[cough]], [[chest pain]], [[fever]], and [[shortness of breath|difficulty in breathing]]. [[medical diagnosis|Diagnostic]] tools include x-rays and examination of the [[sputum]]. Treatment depends on the cause of pneumonia; bacterial pneumonia is treated with [[antibiotic]]s. 

Pneumonia is a common illness which occurs in all age groups, and is a leading cause of death among the elderly and people who are [[chronic illness|chronically]] and [[terminal illness|terminally]] ill. Additionally, it is the leading cause of death in children under five years old worldwide.<ref>World Health Organization. Global causes of under 5 mortality. http://www.who.int/entity/child_adolescent_health/media/causes_death_u5_neonates_2004.pdf.</ref> [[Vaccine]]s to prevent certain types of pneumonia are available. The [[prognosis]] depends on the type of pneumonia, the appropriate treatment, any complications, and the person's underlying health.

Classification of [[Pneumonia]]:
Pneumonias can be classified in several ways. Pathologists originally classified them according to the [[anatomy|anatomic]] changes that were found in the lungs during [[autopsy|autopsies]]. As more became known about the microorganisms causing pneumonia, a [[microbiology|microbiologic]] classification arose, and with the advent of [[x-ray]]s, a [[radiology|radiological]] classification. Another important system of classification is the combined clinical classification, which combines factors such as age, risk factors for certain microorganisms, the presence of underlying lung disease and underlying systemic disease, and whether the person has recently been hospitalized. 

Early classification schemes:
Initial descriptions of pneumonia focused on the [[anatomic]] or [[pathology|pathologic]] appearance of the lung, either by direct inspection at [[autopsy]] or by its appearance under a [[microscope]]. 
* A [[Lobar pneumonia|''lobar'' pneumonia]] is an infection that only involves a single lobe, or section, of a [[lung]]. Lobar pneumonia is often due to ''[[Streptococcus pneumoniae]]'' (though ''[[Klebsiella pneumoniae]]'' is also possible.)<ref name="pmid1792415">{{cite journal |author=Feldman C, Kallenbach JM, Levy H, Thorburn JR, Hurwitz MD, Koornhof HJ |title=Comparison of bacteraemic community-acquired lobar pneumonia due to Streptococcus pneumoniae and Klebsiella pneumoniae in an intensive care unit |journal=Respiration |volume=58 |issue=5-6 |pages=265–70 |year=1991 |pmid=1792415 |doi=10.1159/000195943}}</ref>
* ''Multilobar'' pneumonia involves more than one lobe, and it often causes a more severe illness.
* [[Bronchial pneumonia]] affects the lungs in patches around the tubes (bronchi or bronchioles).
* [[Usual interstitial pneumonia|''Interstitial'' pneumonia]] involves the areas in between the alveoli, and it may be called "interstitial pneumonitis." It is more likely to be caused by viruses or by atypical bacteria. 

The discovery of x-rays made it possible to determine the anatomic type of pneumonia without direct examination of the lungs at autopsy and led to the development of a [[radiology|radiological]] classification. Early investigators distinguished between typical lobar pneumonia and atypical (e.g. Chlamydophila) or viral pneumonia using the location, distribution, and appearance of the opacities they saw on chest x-rays. Certain x-ray findings can be used to help predict the course of illness, although it is not possible to clearly determine the microbiologic cause of a pneumonia with x-rays alone. 

With the advent of modern microbiology, classification based upon the causative microorganism became possible. Determining which microorganism is causing an individual's pneumonia is an important step in deciding treatment type and length. Sputum cultures, blood cultures, tests on respiratory secretions, and specific blood tests are used to determine the microbiologic classification. Because such laboratory testing typically takes several days, microbiologic classification is usually not possible at the time of initial diagnosis.

Combined clinical classification:
Traditionally, clinicians have classified pneumonia by clinical characteristics, dividing them into "acute" (less than three weeks duration) and "chronic" pneumonias. This is useful because chronic pneumonias tend to be either non-infectious, or mycobacterial, fungal, or mixed bacterial infections caused by airway obstruction. Acute pneumonias are further divided into the classic bacterial bronchopneumonias (such as ''[[Streptococcus pneumoniae]]''), the atypical pneumonias (such as the interstitial pneumonitis of ''[[Mycoplasma pneumoniae]]'' or ''[[Chlamydia pneumoniae]]''), and the aspiration pneumonia syndromes.

Chronic pneumonias, on the other hand, mainly include those of ''[[Nocardia]]'', ''[[Actinomyces]]'' and ''[[Blastomyces dermatitidis]]'', as well as the granulomatous pneumonias (''[[Mycobacterium tuberculosis]]'' and [[atypical mycobacteria]], ''[[Histoplasma capsulatum]]'' and ''[[Coccidioides immitis]]'').<ref name=Kumar13-7> Table 13-7 in: {{cite book |author=Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson |title=Robbins Basic Pathology |publisher=Saunders |location=Philadelphia |year=2007 |isbn=1-4160-2973-7 |edition=8th}}</ref>

The combined clinical classification, now the most commonly used classification scheme, attempts to identify a person's risk factors when he or she first comes to medical attention. The advantage of this classification scheme over previous systems is that it can help guide the selection of appropriate initial treatments even before the microbiologic cause of the pneumonia is known. There are two broad categories of pneumonia in this scheme: community-acquired pneumonia and hospital-acquired pneumonia. A recently introduced type of [[healthcare-associated pneumonia]] (in patients living outside the hospital who have recently been in close contact with the health care system) lies between these two categories.

Community-acquired [[Pneumonia]]:
{{Main|Community-acquired pneumonia}}
[[Community-acquired pneumonia]] (CAP) is infectious pneumonia in a person who has not recently been hospitalized. CAP is the most common type of pneumonia. The most common causes of CAP vary depending on a person's age, but they include ''[[Streptococcus pneumoniae]]'', viruses, the atypical bacteria, and ''[[Haemophilus influenzae]]''. Overall, ''Streptococcus pneumoniae'' is the most common cause of community-acquired pneumonia worldwide. [[Gram-negative bacteria]] cause CAP in certain at-risk populations. CAP is the fourth most common cause of death in the [[United Kingdom]] and the sixth in the [[United States]]. The term "walking pneumonia" has been used to describe a type of community-acquired pneumonia of less severity (because the sufferer can continue to "walk" rather than require hospitalization).<ref>{{cite web |url=http://www.uptodate.com/online/content/topic.do?topicKey=pedi_id/18313&selectedTitle=1~1&source=search_result |title=UpToDate Inc. |format= |work= |accessdate=~~~~~}}</ref> Walking pneumonia is usually caused by the atypical bacterium, ''[[Mycoplasma pneumoniae]]''.<ref>{{cite journal |author=Krause DC, Balish MF |title=Cellular engineering in a minimal microbe: structure and assembly of the terminal organelle of Mycoplasma pneumoniae |journal=Mol. Microbiol. |volume=51 |issue=4 |pages=917–24 |year=2004 |month=February |pmid=14763969 |doi= 10.1046/j.1365-2958.2003.03899.x|url=}}</ref>

=== Septicemia ===
{{main|Septicemia}}
*[[Septicemia]]<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/001355.htm |title=Septicemia: MedlinePlus Medical Encyclopedia |publisher=Nlm.nih.gov |date= |accessdate=2010-03-09}}</ref>

'''Sepsis''' is a serious [[medicine|medical]] condition that is characterized by a whole-body [[Inflammation|inflammatory]] state (called a [[systemic inflammatory response syndrome]] or SIRS)  and the presence of a known or suspected [[infection]].<ref
 name="pmid12682500">{{cite journal 
|author=Levy MM, Fink MP, Marshall JC, ''et al.'' 
|title=2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 
|journal=Crit. Care Med. |volume=31 |issue=4 |pages=1250–6 |year=2003 |month=April |pmid=12682500 |doi=10.1097/01.CCM.0000050454.01978.3B 
|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0090-3493&volume=31&issue=4&spage=1250}}</ref><ref
 name="1992consensus">{{cite journal 
|author=Bone RC, Balk RA, Cerra FB, ''et al.'' 
|title=Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine 
|journal=Chest |volume=101 |issue=6 |pages=1644–55 |year=1992 
|month=Jun |pmid=1303622 |doi= 10.1378/chest.101.6.1644 |url=http://www.chestjournal.org/content/101/6/1644}}</ref> The body may develop this inflammatory response to [[microbes]] in the blood, urine, lungs, skin, or other tissues. A lay term for sepsis is '''blood poisoning''', more aptly applied to septicemia, below.

'''Septicemia''' (also '''septicaemia''' or '''septicæmia'''&nbsp;[sep⋅ti⋅cæ⋅mi⋅a]<ref>[http://dictionary.reference.com/search?q=Septicemia Dictionary]</ref>, or erroneously '''septasemia'''<!-- redirects to here, synonym--> and '''septisema''') is a related but deprecated (formerly sanctioned) medical term referring to the presence of pathogenic organisms in the bloodstream, leading to sepsis.<ref>{{EMedicineDictionary|septicemia}}</ref> The term has not been sharply defined. It has been inconsistently used in the past by medical professionals, for example as a synonym of [[bacteremia]], causing some confusion. The present medical consensus is therefore that the term "septicemia" is problematic and should be avoided.<ref name="1992consensus"/> 

Sepsis is usually treated in the [[intensive care unit]] with [[intravenous fluids]] and [[antibiotics]]. If fluid replacement is insufficient to maintain blood pressure, specific [[vasopressor]] medications can be used. [[Artificial ventilation]] and [[dialysis]] may be needed to support the function of the lungs and kidneys, respectively. To guide therapy, a [[central venous catheter]] and an [[arterial catheter]] may be placed. Sepsis patients require preventive measures for [[deep vein thrombosis]], [[stress ulcer]]s and [[pressure ulcer]]s, unless other conditions prevent this. Some patients might benefit from tight control of [[glycemia|blood sugar levels]] with [[insulin]] (targeting [[stress hyperglycemia]]), low-dose [[corticosteroids]] or [[activated drotrecogin alfa]] ([[Recombinant DNA|recombinant]] [[protein C]]).<ref name="campaign">{{cite journal |author=Dellinger RP, Levy MM, Carlet JM, et al., for the International Surviving Sepsis Campaign Guidelines Committee. |title=Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008 |journal=Crit Care Med |year=2008 |volume=36 |issue=1 |pages=296–327 |pmid=18158437 |url=http://www.ccmjournal.com/pt/re/ccm/searchresults.htm |doi=10.1097/01.CCM.0000298158.12101.41 |format=Subscription required}}</ref>

Terminology:
'''Severe sepsis''' occurs when sepsis leads to organ dysfunction, low blood pressure ([[hypotension]]), or insufficient blood flow ([[hypoperfusion]]) to one or more organs (causing, for example, [[lactic acidosis]], [[oliguria|decreased urine production]], or [[altered mental status]]). Sepsis can lead to [[septic shock]], [[multiple organ dysfunction syndrome]] (formerly known as multiple organ failure), and death. Organ dysfunction results from '''sepsis-induced hypotension''' (< 90 mmHg or a reduction of ≥ 40 mmHg from baseline) and [[diffuse intravascular coagulation]], among other things.

[[Bacteremia]] is the presence of viable [[bacteria]] in the bloodstream. Likewise, the terms [[viremia]] and [[fungemia]] simply refer to [[virus]]es and [[fungus|fungi]] in the bloodstream. These terms say nothing about the consequences this has on the body. For example, bacteria can be introduced into the bloodstream during [[toothbrushing]].<ref name="pmid18541739">{{cite journal |author=Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK |title=Bacteremia associated with toothbrushing and dental extraction |journal=Circulation |volume=117 |issue=24 |pages=3118–25 |year=2008 |month=Jun |pmid=18541739 |doi=10.1161/CIRCULATIONAHA.107.758524 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18541739}}</ref> This form of bacteremia almost never causes problems in normal individuals. However, bacteremia associated with certain dental procedures can cause bacterial infection of the [[heart valves]] (known as [[endocarditis]]) in high-risk patients.<ref name="pmid17446442">{{cite journal |author=Wilson W, Taubert KA, Gewitz M, ''et al.'' |title=Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group |journal=Circulation |volume=116 |issue=15 |pages=1736–54 |year=2007 |month=Oct |pmid=17446442 |doi=10.1161/CIRCULATIONAHA.106.183095 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=17446442}}</ref> Conversely, a systemic inflammatory response syndrome can occur in patients without the presence of infection, for example in those with [[burns]], [[polytrauma]], or the initial state in [[pancreatitis]] and [[chemical pneumonitis]].<ref name="1992consensus"/>

Signs and symptoms of septicemia:
In addition to symptoms related to the provoking infection, sepsis is characterized by evidence of acute [[inflammation]] present throughout the entire body, and is, therefore, frequently associated with [[fever]] and elevated [[white blood cell]] count ([[leukocytosis]]) or low white blood cell count and lower-than-average temperature, and vomiting {{Citation needed|date=November 2009}}. The modern concept of sepsis is that the host's immune response to the infection causes most of the symptoms of sepsis, resulting in hemodynamic consequences and damage to organs. This host response has been termed [[systemic inflammatory response syndrome]] (SIRS) and is characterized by hemodynamic compromise and resultant metabolic derangement.  Outward physical symptoms of this response frequently include a high heart rate (above 100 beats per minute), high respiratory rate (above 20 breaths per minute), elevated WBC count (above 12,000) and elevated or lowered body temperature (under 36&nbsp;°C or over 38&nbsp;°C). Sepsis is differentiated from SIRS by the presence of a known pathogen. For example SIRS and a positive blood culture for a pathogen indicates the presence of sepsis. Without a known infection, it's not possible to classify the above symptoms as sepsis, only SIRS.

This immunological response causes widespread activation of [[acute-phase proteins]], affecting the [[complement system]] and the [[coagulation]] pathways, which then cause damage to the vasculature as well as to the organs. Various neuroendocrine counter-regulatory systems are then activated as well, often compounding the problem. Even with immediate and aggressive treatment, this may progress to [[multiple organ dysfunction syndrome]] and eventually [[death]].

=== Malaria ===
{{main|Malaria}}
*[[Malaria]]<ref>{{cite web|url=http://www.mayoclinic.com/health/malaria/DS00475/DSECTION=symptoms |title=Malaria: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>

'''Malaria''' is a [[mosquito]]-borne [[infectious disease]] caused by a [[eukaryotic]] [[protist]] of the genus ''[[Plasmodium]]''. It is widespread in [[Tropics|tropical]] and subtropical regions, including parts of the [[Americas]], [[Asia]], and [[Africa]]. Each year, there are approximately 350–500 million cases of malaria,<ref>[http://www.cdc.gov/malaria/facts.htm Malaria Facts]. ''Centers for Disease Control and Prevention.''</ref> killing between one and three million people, the majority of whom are young children in [[sub-Saharan Africa]].<ref>{{cite journal | author = Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI| title = The global distribution of clinical episodes of Plasmodium falciparum malaria | journal = Nature | volume = 434 | issue = 7030 | pages = 214–7 | year = 2005 | pmid = 15759000  | doi = 10.1038/nature03342}}</ref> Ninety percent of malaria-related deaths occur in sub-Saharan Africa. Malaria is commonly associated with poverty, but is also a cause of poverty<ref>{{Cite web|url=http://ftp.iza.org/dp2997.pdf|format=PDF|title=Malaria: Disease Impacts and Long-Run Income Differences|publisher=[[Institute for the Study of Labor]]|accessdate=2008-12-10}}</ref> and a major hindrance to [[economic development]].

Five species of the plasmodium parasite can infect humans; the most serious forms of the disease are caused by ''[[Plasmodium falciparum]]''. Malaria caused by ''[[Plasmodium vivax]]'', ''[[Plasmodium ovale]]'' and ''[[Plasmodium malariae]]'' causes milder disease in humans that is not generally fatal. A fifth species, ''[[Plasmodium knowlesi]]'', is a [[zoonosis]] that causes malaria in [[macaques]] but can also infect humans.<ref>{{cite journal |author=Fong YL, Cadigan FC, Coatney GR |title=A presumptive case of naturally occurring Plasmodium knowlesi malaria in man in Malaysia |journal=Trans. R. Soc. Trop. Med. Hyg. |volume=65 |issue=6 |pages=839–40 |year=1971 |pmid=5003320 |doi= 10.1016/0035-9203(71)90103-9|url=}}</ref><ref>{{cite journal |author=Singh B, Kim Sung L, Matusop A, ''et al.'' |title=A large focus of naturally acquired Plasmodium knowlesi infections in human beings |journal=Lancet |volume=363 |issue=9414 |pages=1017–24 |year=2004 |month=March |pmid=15051281 |doi=10.1016/S0140-6736(04)15836-4 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673604158364}}</ref>

Malaria is naturally transmitted by the bite of a female [[Anopheles|''Anopheles'' mosquito]]. When a mosquito bites an infected person, a small amount of blood is taken, which contains malaria parasites.  These develop within the mosquito, and about one week later, when the mosquito takes its next blood meal, the parasites are injected with the mosquito's saliva into the person being bitten.  After a period of between two weeks and several months (occasionally years) spent in the liver, the malaria parasites start to multiply within [[red blood cell]]s, causing symptoms that include [[fever]] and [[headache]].  In severe cases, the disease worsens, leading to [[coma]] and death.

A wide variety of [[antimalarial drugs]] are available to treat malaria. In the last 5 years, treatment of P. falciparum infections in [[Endemism|endemic]] countries has been transformed by the use of combinations of drugs containing an [[artemisinin]] derivative.  Severe malaria is treated with intravenous or intramuscular quinine or, increasingly, the [[artemisinin]] derivative artesunate<ref>{{cite journal |author=Dondorp AM, Day NP |title=The treatment of severe malaria. |journal=Trans. R. Soc. Trop. Med. Hyg. |volume=101 |issue=7 |pages=633–4 |year=2007 |month=July |pmid=17434195 |doi=10.1016/j.trstmh.2007.03.011 |url=http://linkinghub.elsevier.com/retrieve/pii/S0035-9203(07)00093-4}}</ref>.  Several drugs are also available to prevent malaria in travellers to malaria-[[Endemic (epidemiology)|endemic]] countries ([[malaria prophylaxis|prophylaxis]]).  Resistance has developed to several antimalarial drugs, most notably [[chloroquine]]<ref>{{cite journal |author=Wellems TE |title=Plasmodium chloroquine resistance and the search for a replacement antimalarial drug |journal=Science |volume=298 |issue=5591 |pages=124–6 |year=2002 |month=October |pmid=12364789 |doi=10.1126/science.1078167 |url=http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=12364789}}</ref>.

Malaria transmission can be reduced by preventing mosquito bites by distribution of inexpensive [[mosquito net]]s and [[insect repellent]]s, or by mosquito-control measures such as spraying [[insecticide]]s inside houses and draining standing water where mosquitoes lay their eggs.  

Although many are under development, the challenge of producing a widely available [[vaccine]] that provides a high level of protection for a sustained period is still to be met<ref>{{cite journal |author=Kilama W, Ntoumi F |title=Malaria: a research agenda for the eradication era |journal=Lancet |volume=374 |issue=9700 |pages=1480–2 |year=2009 |month=October |pmid=19880004 |doi=10.1016/S0140-6736(09)61884-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)61884-5}}</ref>.

=== Dengue fever ===
{{main|Dengue fever}}
*[[Dengue fever]]{{citation needed}}


'''Dengue fever''' (pronounced {{IPA-en|ˈdɛŋɡeɪ|UK}}, {{IPA-en|ˈdɛŋɡiː|US}}) and '''dengue hemorrhagic fever''' (DHF) are acute [[fever|febrile]] [[tropical disease|disease]]s which occur in the [[tropics]], can be life-threatening, and are caused by four closely related [[virus]] [[serotype]]s of the genus ''[[Flavivirus]]'', family [[Flaviviridae]].<ref>{{cite web |url= http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=dengue.htm|title=Chapter 4, Prevention of Specific Infectious Diseases|publisher=CDC Traveler's Health:  Yellow Book|accessdate=2007-05-20}}</ref>  It is also known as '''breakbone fever'''. It occurs widely in the tropics, including northern [[Argentina]], northern [[Australia]], the entirety of [[Bangladesh]], [[Barbados]], [[Bolivia]]<ref name="Dengue fever outbreak in Bolivia">{{cite web|url=http://news.bbc.co.uk/2/hi/americas/7866908.stm|title=Dengue fever outbreak in Bolivia |date=2009-02-03|accessdate=2009-02-26|publisher=[[BBC]]}}</ref>, [[Belize]], [[Brazil]], [[Cambodia]], [[Costa Rica]], [[Dominican Republic]], [[El Salvador]], [[Guatemala]], [[Guyana]], [[Honduras]], [[India]], [[Indonesia]], [[Jamaica]], [[Laos]], [[Malaysia]], [[Mexico]], [[Micronesia]], [[Panama]], [[Paraguay]]<ref>[http://www.nytimes.com/2007/03/04/world/americas/04paraguay.html  Reuters, "Dengue Fever Hits Paraguay", ''New York Times" (March 4, 2007)]</ref>, [[Philippines]], [[Puerto Rico]], [[Samoa]]<ref>http://www.samoalivenews.com/Health/Dengue-Fever-Outbreak-Confirmed-In-Samoa.html</ref>, [[Singapore]], [[Sri Lanka]], [[Suriname]], [[Taiwan]], [[Thailand]], [[Trinidad]], [[Venezuela]] and [[Vietnam]], and increasingly in southern [[China]]<ref name="Zhuhai reports outbreak of dengue fever">{{cite web|url=http://www.chinadaily.com.cn/china/2007-09/06/content_6087035.htm|title=Zhuhai reports outbreak of dengue fever|date=200-09-06|accessdate=2009-11-18|publisher=[[China Daily]]}}</ref>. Unlike [[malaria]], dengue is just as prevalent in the urban districts of its range as in rural areas. Each [[serotype]] is sufficiently different that there is no cross-protection and [[epidemic]]s caused by multiple serotypes (hyperendemicity) can occur. Dengue is transmitted to humans by the ''[[Aedes aegypti]]'' or more rarely the ''[[Aedes albopictus]]'' [[mosquito]], which feed during the day.<ref>[http://www.searo.who.int/en/Section10/Section332_12647.htm Dengue Fever – Information Sheet.] [[World Health Organization]], October 9, 2006.  Retrieved on 2007-11-30.</ref>

The [[WHO]] says some 2.5 billion people, two fifths of the world's population, are now at risk from dengue and estimates that there may be 50 million cases of dengue infection worldwide every year. The disease is now endemic in more than 100 countries.<ref>[http://www.news-medical.net/?id=20348 Dengue epidemic threatens India's capital]</ref>

Signs and symptoms of Dengue fever:
The disease manifests as a sudden onset of severe headache, muscle and joint pains ([[myalgia]]s and [[arthralgia]]s—severe pain that gives it the nickname break-bone fever or bonecrusher disease), [[fever]], and [[rash]].<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th | pages=592| publisher = McGraw Hill | year = 2004 | isbn = 0838585299}}</ref> The dengue rash is characteristically bright red [[petechiae]] and usually appears first on the lower limbs and the chest; in some patients, it spreads to cover most of the body. There may also be [[gastritis]] with some combination of associated  [[abdominal pain]], [[nausea]], [[vomiting]], or [[diarrhea]].

Some cases develop much milder symptoms which can be misdiagnosed as [[influenza]] or other viral infection when no rash is present. Thus travelers from tropical areas may pass on dengue inadvertently, having not been properly diagnosed at the height of their illness. Patients with dengue can pass on the infection only through mosquitoes or blood products and only while they are still [[fever|febrile]]. The classic dengue fever lasts about two to seven days, with a smaller peak of fever at the trailing end of the disease (the so-called "biphasic pattern"). Clinically, the [[platelet]] count will drop until the patient's temperature is normal. Cases of DHF also show higher fever, variable hemorrhagic phenomena, [[thrombocytopenia]], and [[hemoconcentration]]. A small proportion of cases lead to [[dengue shock syndrome]] (DSS) which has a high mortality rate. 

Diagnosis of dengue fever:

The diagnosis of dengue is usually made clinically. The classic picture is high fever with no localising source of infection, a [[petechia]]l rash with [[thrombocytopenia]] and relative [[leukopenia]] - low [[platelet]] and [[white blood cell]] count.
Care has to be taken as diagnosis of DHF can mask end stage liver disease and vice versa.

# Fever, bladder problem, constant headaches, eye pain, severe dizziness and loss of appetite.
# [[Bleeding|Hemorrhagic]] tendency (positive [[tourniquet test]], spontaneous bruising, bleeding from [[mucosa]], [[gingiva]], injection sites, etc.; vomiting blood, or bloody [[diarrhea]])
# [[Thrombocytopenia]] (&lt;100,000 platelets per mm³ or estimated as less than 3 platelets per high power field)
# Evidence of plasma leakage ([[hematocrit]] more than 20% higher than expected, or drop in hematocrit of 20% or more from baseline following IV fluid, [[pleural effusion]], [[ascites]], hypoproteinemia)
# Encephalitic occurrences.

''Dengue shock syndrome'' is defined as dengue hemorrhagic fever plus:

* Weak rapid pulse,
* Narrow pulse pressure (less than 20&nbsp;mm Hg)
* Cold, clammy skin and restlessness.

Dependable, immediate diagnosis of dengue can be performed in rural areas by the use of Rapid Diagnostic Test kits, which also differentiate between primary and secondary dengue infections.<ref>Such a diagnostic kit may consist of a "test cassette" or other device. One type is described as follows: "Dengue fever rapid test devices, also known as one-step dengue tests, are a solid phase immuno-chromatographic assay for the rapid, qualitative and differential detection of dengue IgG and IgM antibodies to dengue fever virus in human serum, plasma or whole blood." Atlas Link Biotech co. Ltd (2008)''Dengue Fever Rapid Test Kits''. Accessed: 27/06/09. Available at:  http://www.ivdpretest.com/Dengue-Rapid-Tests.html</ref>
[[Serology]] and [[polymerase chain reaction]] (PCR) studies are available to confirm the diagnosis of dengue if clinically indicated. Dengue can be a life threatening fever.

Cause of Dengue fever:
Dengue fever is caused by [http://microbewiki.kenyon.edu/index.php/Dengue_virus Dengue virus (DENV)], a mosquito-borne flavivirus. DENV is an ssRNA positive-strand virus of the family ''Flaviviridae''; genus ''Flavivirus''. There are four serotypes of DENV. The virus has a genome of about 11000 bases that codes for three structural proteins, C, prM, E; seven nonstructural proteins, NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5; and short non-coding regions on both the 5' and 3' ends.<ref name= HanleyKA>{{cite book |author= Hanley, K.A. and Weaver, S.C. (editors)| year=2010 |title=Frontiers in Dengue Virus Research | publisher=Caister Academic Press | isbn= 978-1-904455-50-9}}</ref>

The potential factors causing hemorrhagic fever are varied. The most suspected factors are human's cross-serotypic immune response and membrane fusion process.

=== Meningococcal disease ===
{{main|Meningococcal disease}}
*[[Meningococcal disease]], including meningococcal meningitis.<ref>{{cite web|url=http://www.who.int/mediacentre/factsheets/fs141/en/index.html |title=WHO &#124; Meningococcal meningitis |publisher=Who.int |date=2010-02-15 |accessdate=2010-03-09}}</ref>

'''Meningococcal disease''' describes infections caused by the bacterium ''[[Neisseria meningitidis]]'' (also termed meningococcus). It carries a high mortality rate if untreated. Whilst best known as a cause of [[meningitis]], wide spread blood infection ([[sepsis]]) is more damaging and dangerous. Meningitis and [[Meningococcemia]] are major causes of illness, death and disability in both developed and under developed countries worldwide. 

The disease's host/pathogen interaction is not fully understood. The pathogen originates harmlessly in a large number of the general population, but thereafter can invade the blood stream and the brain, causing serious illness. Over the past few years, experts have made an intensive effort to understand specific aspects of meningococcal biology and host interactions, however the development of improved treatments and effective vaccines will depend on novel efforts by workers in many different fields.<ref>Meningococcal Disease (2001) Humana Press, Andrew J. Pollard and Martin C.J. Maiden</ref> 

The incidence of endemic meningococcal disease during the last 13 years ranges from 1 to 5 per 100,000 in developed countries, and from 10 to 25 per 100,000 in developing countries. During epidemics the incidence of meningococcal disease approaches 1000 per 1,000,000. There are approximately 2,600 cases of bacterial meningitis per year in the United States, and on average 333,000 cases in developing countries. The case fatality rate ranges between 10 and 20 per cent.<ref>Reido, F.S. et al. 1995. Ped. Infect. Dis. J. 14, PP. 643–657</ref>. 

While Meningococcal disease is not as contagious as the [[common cold]] (which is spread through casual contact), it can be transmitted through [[saliva]] and occasionally through close, prolonged general contact with an infected person. 

Pathogenesis of meningococcal disease:
Meningococcal disease causes life-threatening meningitis and sepsis conditions. In the case of meningitis, bacteria attack the lining between the brain and skull called the [[meninges]]. Infected fluid from the meninges then passes into the [[spinal cord]], causing symptoms including stiff neck, [[fever]] and [[rash]]es. The meninges (and sometimes the brain itself) begin to swell, which affects the [[central nervous system]]. 

Even with antibiotics, approximately 1 in 10 victims of meningococcal meningitis will die; However, about as many survivors of the disease lose a limb or [[deaf|their hearing]], or suffer permanent [[brain damage]].<ref>Centers for Disease Control and Prevention. Meningococcal disease among college students: ACIP modifies recommendations for meningitis vaccination. Press release. 1999 Oct 20</ref> The sepsis type of infection is much more deadly, and results in a severe [[blood poisoning]] called meningococcal sepsis that affects the entire body. In this case, bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Within hours, patient's health can change from seemingly good to mortally ill.<ref>Jeeri R. Reddy and Thiombiano S. Rigobert. Infections à méningocoques Maladies infectieuses et Africa. West Africa. Med. Bull. 2007</ref>. 

The ''N. meningitidis'' bacterium is surrounded by a slimy outer coat that contains disease-causing endotoxin. While many bacteria produce endotoxin, the levels produced by meningococcal bacteria are 100 to 1,000 times greater (and accordingly more lethal) than normal. As the bacteria multiply and move through the bloodstream, it sheds concentrated amounts of toxin. The endotoxin directly affects the heart, reducing its ability to circulate blood, and also causes pressure on blood vessels throughout the body. As some blood vessels start to [[hemorrhage]], major organs like the lungs and kidneys are damaged. 

Patients suffering from meningococcal disease are treated with a large dose of [[antibiotic]]. The systemic antibiotic flowing through the bloodstream rapidly kills the bacteria but, as the bacteria are killed, even more toxin is released. It takes up to several days for the toxin to be neutralized from the body by using continuous liquid treatment and antibiotic therapy<ref>Jeeri R Reddy and Thiombiano S. Rigobert. Infections à méningocoques Maladies infectieuses et  Africa. West Africa. Med. Bull. 2008</ref>.
Signs and symptoms of [[meningococcal disease]]
Meningitis:
The patient with meningigococcal meningitis typically presents with high fever, [[meningism]] (stiff neck), [[Kernig's sign]], severe headache, vomiting, [[purpura]], photophobia, and sometimes chills, altered mental status, or seizures. Diarrhea or respiratory symptoms are less common. Petechiae is often also present, but does not always occur, so its absence should not be used against the diagnosis  of meningococcal disease. Anyone with symptoms of meningococcal meningitis should receive intravenus antibiotics pending results of [[lumbar puncture]], as delay in treatment worsens the prognosis.
[[Meningococcemia]]:
Symptoms of [[meningococcemia]] are, at least initially, similar to those of [[influenza]]. Typically, the first symptoms include [[fever]], [[nausea]], myalgia, headache, [[arthralgia]], [[chills]], diarrhea, and malaise. Later symptoms include [[septic shock]], [[purpura]], hypotension, cyanosis, [[petechiae]], seizures, anxiety, and [[multiple organ dysfunction syndrome]]. [[Acute respiratory distress syndrome]] and altered mental status may also occur. Meningococcal sepsis has a higher mortality rate then meningococcal meningitis, but the risk of neurologic sequalae is much lower.{{Citation needed|date=February 2010}}

Types of infection:
[[Meningococcemia]]:
[[Meningococcemia]], like many [[gram-negative]] blood infections, can cause [[disseminated intravascular coagulation]] (DIC), a condition where blood starts to clot throughout the body, sometimes causing [[ischemic]] tissue damage. DIC also causes bleeding, when the [[clotting factors]] are used up, causing the characteristic [[purpuric]] rash.

Meningitis:
Meningococcal meningitis is a consequence of bacteria entering the [[cerebrospinal fluid]] (CSF) and irritating the [[meninges]] - the membranes that line the brain and spinal cord. Sub-Saharan Africa, Americas, Western Europe, UK and Ireland face multifarious challenges, 200 years after the discovery of bacterial meningitis<ref>[http://www.emro.who.int/sudan/media/pdf/Control%20of%20epidemic%20meningococcal%20disease.pdf WHO/EMC/BAC/98.3]</ref>. 

Other types of infection:
As with any gram negative bacterium, ''N. meningitidis'' can infect a variety of sites. 

Meningococcal [[pneumonia]] can appear during influenza pandemics and in military camps. This is a multilobar, rapidly evolving pneumonia, sometimes associated with septic shock. With prompt treatment with penicillin or chloramphenicol, the prognosis is excellent. [[Pericarditis]] can appear, either as a septic pericarditis with grave prognosis or as a rective pericarditis in the wake of meningitis or septicaemia. [[Myocarditis]] can be a complication of meningococcemia and can be contributive to shock seen in this form of disease. [[Pharyngitis]] and [[conjunctivitis]] can also appear and can constitute the portal of entry for the bacterium. Septic [[arthritis]] due to ''N. meningitidis'' can be seen, usually accompanying disseminated infection. Other forms of disease can rarely be seen, like [[osteomyelitis]], [[endophthalmitis]] and [[urethritis]].
=== Hantavirus ===
{{main|Hantavirus}}
*[[Hantavirus]]<ref>{{cite web|url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5850a3.htm |title=Hantavirus Pulmonary Syndrome in Five Pediatric Patients - Four States, 2009 |publisher=Cdc.gov |date= |accessdate=2010-03-09}}</ref>

'''Hantaviruses''' belong to the ''[[Bunyaviridae]]'' family of [[virus]]es. The ''Bunyaviridae'' family is divided into 5 genera: ''[[Orthobunyavirus]]'', ''[[Nairovirus]]'', ''[[Phlebovirus]]'', ''[[Tospovirus]]'', and ''Hantavirus''. Like all members of this family, hantaviruses have [[genomes]] comprising three [[negative-sense]], single-stranded RNA segments, and so are classified as negative sense [[RNA virus]]es. Viruses in the genus ''Hantavirus'' are unique in that they are transmitted by aerosolized [[rodent]] excreta or rodent bites, whereas all other genera in the ''Bunyaviridae'' family are [[arthropod]]-borne viruses.

The name ''hantavirus'' is derived from the [[Hantan River]], where the Hantaan virus (the etiologic agent of Korean [[hemorrhagic fever]]) was first isolated by Dr. [[Ho-Wang Lee]] and colleagues. The disease associated with Hantaan virus is called '''hemorrhagic fever with renal syndrome''' (HFRS), a term that is accepted by the [[World Health Organization]]. It was formerly called '''Korean hemorrhagic fever''' (a term that is no longer in use).

History of hantavirus infection:
The hantaviruses constitute a relatively newly discovered genus of viruses; the disease entity HFRS was first recognized by Korean Dr.Lee Ho Wang who worked for Western medicine during the [[Korean War]] in the early 1950s. 

In 1993, a newly-recognized species of hantavirus was found to be behind the '''Hantavirus cardiopulmonary syndrome''' (HCPS, also called HPS) caused by the [[Sin Nombre virus]] (in [[Spanish language|Spanish]], "Virus sin nombre", for "nameless virus") in [[New Mexico]] and other [[Four Corners (United States)|Four Corners]] states. It was first identified by [[Terry Yates]], a professor at the [[University of New Mexico]].<ref name=bg> {{cite news |first=Matt |last=Schudel |title=Terry Yates, 57; biologist found source of hantavirus |url=http://www.boston.com/bostonglobe/obituaries/articles/2007/12/24/terry_yates_57_biologist_found_source_of_hantavirus/ |work= [[Washington Post]] |publisher=[[Boston Globe]] |date=2007-12-24 |accessdate=2007-01-04}}</ref> In addition to Hantaan virus and Sin Nombre virus, several other hantaviruses have been implicated as etiologic agents for either HFRS or HCPS.
Virology and Genome:
Like other members of the bunyavirus family, hantaviruses are enveloped viruses with a genome that consists of three single-stranded, negative sense RNA segments designated S (small), M (medium), and L (large). The S RNA encodes the [[nucleocapsid]] (N) protein. The M RNA encodes a [[polyprotein]] that is cotranslationally cleaved to yield the envelope [[glycoprotein]]s G1 and G2. The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. Within [[virion]]s, the genomic RNAs of hantaviruses are thought to complex with the N protein to form helical nucleocapsids, the RNA component of which circularizes due to sequence complementarity between the 5' and 3' terminal sequences of genomic segments.

Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent [[endocytosis]]. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the [[endosomal membrane]]. Subsequent to release of the nucleocapsids into cytoplasm, the complexes are targeted to the ER-Golgi Intermediate compartments (ERGIC) through microtubular associated movement resulting in the formation of viral factories at ERGIC. These factories then facilitate transcription and subsequent translation of the viral proteins. Transcription of viral genes must be initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this "cap snatching," the mRNAs of hantaviruses are capped and contain nontemplated 5' terminal extensions. The G1 (aka Gn) and G2 (Gc) glycoproteins form [[hetero-oligomers]] and are then transported from the [[endoplasmic reticulum]] to the [[Golgi complex]], where [[glycosylation]] is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirus virions are believed to assemble by association of nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the [[Golgi cisternae]]. Nascent virions are then transported in secretory [[Vesicle (biology)|vesicles]] to the [[plasma membrane]] and released by [[exocytosis]].

Pathogenesis of hantavirus infection:
The pathogenesis of Hantavirus infections is unclear as there is a lack of animal models (rats and mice do not seem to acquire severe disease). While the primary replication site is not clear, in both HFRS and HPS, the main effect is in the blood vessels. There is increased vascular permeability and decreased blood pressure due to endothelial dysfunction. In HFRS, the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs, spleen, and gall bladder are most affected.

===[[Scarlet fever]]===
<ref>{{cite web|url=http://kidshealth.org/parent/infections/bacterial_viral/scarlet_fever.html |title=Scarlet Fever |publisher=Kidshealth.org |date= |accessdate=2010-03-09}}</ref> 
===[[West Nile Virus]]===
{{main|West nile virus}}
<ref>{{cite web|url=http://emedicine.medscape.com/article/234009-overview |title=West Nile Encephalitis: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-08-01 |accessdate=2010-03-09}}</ref>
WNV has three different effects on humans. The first is an asymptomatic infection; the second is a mild febrile syndrome termed West Nile Fever;[1] the third is a neuroinvasive disease termed West Nile meningitis or encephalitis.[2] In many infected individuals the ratio between the three states is roughly 110:30:1.[3]
The second, febrile stage has an incubation period of 2 to 8 days followed by fever, headache, chills, diaphoresis (excessive sweating), weakness, lymphadenopathy (swollen lymph nodes), drowsiness, pain in the joints and symptoms like those of influenza or the flu. Occasionally there is a short-lived truncal rash and some patients experience gastrointestinal symptoms including nausea, vomiting, loss of appetite, or diarrhea. All symptoms are resolved within 7 to 10 days, although fatigue can last for some weeks and lymphadenopathy can take up to two months to resolve.
The more dangerous encephalitis is characterized by similar early symptoms but also a decreased level of consciousness, sometimes approaching near-coma. Deep tendon reflexes are hyperactive at first, later diminished. There are also extrapyramidal disorders. Recovery is marked by a long convalescence with fatigue. An atypical case of West Nile encephalitis presenting as jaw pain has been described.
More recent outbreaks have resulted in a deeper study of the disease and other, rarer, outcomes have been identified. The spinal cord may be infected, marked by anterior myelitis with or without encephalitis.[4] WNV-associated Guillain-Barré syndrome has been identified[5] and other rare effects include multifocal chorioretinitis (which has 100% specificity for identifying WNV infection in patients with possible WNV encephalitis),[6] hepatitis, myocarditis, nephritis, pancreatitis, and splenomegaly.[7][8][9]

===Acute HIV infection===
*[[Acute HIV infection]]
'''Acute HIV infection''' or '''primary HIV infection''' (also known as "Acute seroconversion syndrome"<ref name="Andrews">{{cite book |author=James, William D.; Berger, Timothy G.; et al. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |location= |year=2006 |pages= |isbn=0-7216-2921-0 |oclc= |doi= |accessdate=}}</ref>{{rp|416}}) is the first stage of [[HIV]] infection. It occurs before the latency stage and the potential [[AIDS]] succeeding the latency stage.

Symptoms of [[Acute HIV infection]]:
During this period (usually 2–4 weeks post-exposure) most individuals (80 to 90%) develop influenza or mononucleosis-like symptoms, most commonly [[fever]], [[lymphadenopathy]], [[pharyngitis]], generalized [[rash]] of [[maculopapular]]<ref>[http://wrongdiagnosis.com/s/skin_rash/causes.htm wrongdiagnosis.com] skin rash causes</ref> type, [[myalgia]], [[malaise]], mouth and esophagal sores, and may also include, but less commonly, [[headache]], [[nausea]] and [[vomiting]], enlarged liver/spleen, [[weight loss]], [[Candidiasis|thrush]], and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. The acute illness can last between a few days and 10 weeks, though usually less than 14 days.<ref name=Kahn>

{{cite journal
| author=Kahn, J. O. and Walker, B. D. | title=Acute Human Immunodeficiency Virus type 1 infection | journal=N. Engl. J. Med. | year=1998 | pages=33–39 | volume=331 | issue=1 | pmid=9647878 | doi=10.1056/NEJM199807023390107

}}</ref> 
In some very rare cases, about 10 patients from 1989 to date<ref>http://www.journals.uchicago.edu/doi/abs/10.1086/511876</ref>, a bilateral [[Bell's palsy|facial palsy]] has been associated with acute HIV-1 infection. <!-- This info was added to the Bell's palsy page - if you delete it here, please also delete it at that page, (plus justification) -->

Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. Consequently, these primary symptoms are not used to diagnose HIV infection as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.
<ref name="pmid11187417">{{cite journal |author=Daar ES, Little S, Pitt J, ''et al.'' |title=Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network |journal=Ann. Intern. Med. |volume=134 |issue=1 |pages=25–9 |year=2001 |pmid=11187417 |doi=}}</ref>

These [[nonspecific symptoms]] can also be symptoms of other infections; consequently, having these symptoms does not reliably indicate the presence of HIV.

===[[Lyme disease]]===
'''Lyme disease''', or '''lyme borreliosis''',<ref name="Bolognia">{{cite book |author=Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |pages= |isbn=1-4160-2999-0 |oclc= |doi= |accessdate=}}</ref> is an [[emerging infectious disease]] caused by at least three [[species]] of [[bacteria]] belonging to the [[genus]] ''[[Borrelia]]''.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th | pages = 434–437 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299}}</ref>  ''[[Borrelia burgdorferi]] [[sensu stricto|sensu lato]]''<ref name=Hu>{{cite book | author = Hu MD, Linden | chapter = Clinical Manifestations of Lyme Disease in Adults | title = UpToDate | publisher = UpToDate | year = 2009 }}</ref> is the main cause of Lyme disease in the [[United States]], whereas ''[[Borrelia afzelii]]'' and ''[[Borrelia garinii]]'' cause most [[Europe]]an cases. The disease is named after the village of [[Lyme, Connecticut|Lyme]], [[Connecticut]], USA, where a number of cases were identified in 1975. Although [[Allen Steere]] realized in 1978 that Lyme disease was a [[tick-borne disease]], the cause of the disease remained a mystery until 1982, when ''B. burgdorferi'' was identified by [[Willy Burgdorfer]].

Lyme disease is the most common tick-borne disease in the [[Northern Hemisphere]]. ''Borrelia'' is transmitted to humans by the bite of infected ticks belonging to a few species of the genus ''[[Ixodes]]'' ("hard ticks").<ref name=Baron>{{cite book | author = Johnson RC | chapter = Borrelia | title = Baron's Medical Microbiology ''(Baron S ''et al.'', eds.)| edition = 4th | publisher = Univ of Texas Medical Branch | year = 1996 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?&rid=mmed.section.1965 | isbn = 0-9631172-1-1 }}</ref> Early symptoms may include [[fever]], [[headache]], [[fatigue (medical)|fatigue]], [[Depression (mood)|depression]], and a characteristic circular skin rash called [[Erythema chronicum migrans|erythema migrans]]. Left untreated, later symptoms may involve the joints, heart, and [[central nervous system]]. In most cases, the infection and its symptoms are eliminated by [[antibiotics]], especially if the illness is treated early.{{Citation needed|date=December 2009}} Late, delayed, or inadequate treatment can lead to the more serious symptoms, which can be disabling and difficult to treat.<ref name="Cairns">{{cite journal | author = Cairns V, Godwin J | title = Post-Lyme borreliosis syndrome: a meta-analysis of reported symptoms | journal = Int J Epidemiol | volume = 34 | issue = 6 | pages = 1340–1345 |url = http://ije.oxfordjournals.org/cgi/content/full/34/6/1340 | year = 2005 | pmid = 16040645 | doi = 10.1093/ije/dyi129}}</ref> Occasionally, symptoms such as [[arthritis]] persist after the infection has been eliminated by antibiotics, prompting suggestions that ''Borrelia'' causes [[autoimmunity]].<ref name=Singh/>
[[Lyme disease]], is an increasingly common tick-borne spirochetal infection.<ref>{{cite web|url=http://www.webmd.com/rheumatoid-arthritis/arthritis-lyme-disease |title=Learn More About Lyme Disease |publisher=Webmd.com |date= |accessdate=2010-03-09}}</ref>
===[[Varicella]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/969773-overview |title=Varicella: eMedicine Pediatrics: General Medicine |publisher=Emedicine.medscape.com |date=2009-07-31 |accessdate=2010-03-09}}</ref>'''Chickenpox''' or '''chicken pox''' is a highly [[Infectious disease|contagious]] illness caused by primary [[infection]] with [[varicella zoster virus]] (VZV).<ref> {{cite journal |author=Wood MJ |title=History of Varicella Zoster Virus |journal=Herpes |volume=7 |issue=3 |pages=60–65 |year=2000 |month=October |pmid=11867004 |doi= |url=http://www.ncbi.nlm.nih.gov/pubmed/11867004}}</ref> It usually starts with  [[Vesicle (dermatology)|vesicular]] skin [[rash]] mainly on the body and head rather than at the periphery and become itchy raw [[pockmarks]] which mostly heal without scarring.

Chicken pox is spread easily through coughs or sneezes of ill individuals, or through direct contact with secretions from the rash. Following primary infection there is usually lifelong protective immunity from further episodes of chickenpox. 

Chickenpox is rarely fatal, although it is generally more severe in adult males than in adult females or children. Pregnant women and those with a suppressed immune system are at highest risk of serious complications. Chicken pox is now believed to be the cause of one third of stroke cases in children.<ref>http://stroke.ahajournals.org/cgi/content/abstract/32/6/1257</ref> The most common late complication of chicken pox is [[herpes zoster|shingles]], caused by reactivation of the varicella zoster virus decades after the initial episode of chickenpox.
===[[Measles]]===
<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/measles.html |title=Measles: MedlinePlus |publisher=Nlm.nih.gov |date= |accessdate=2010-03-09}}</ref>

'''Measles''' is an infection of the respiratory system caused by a [[virus]], specifically a [[paramyxovirus]] of the genus ''[[Morbillivirus]]''.  Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses.  Symptoms include  [[fever]], [[cough]], [[coryza|runny nose]], [[conjunctivitis|red eyes]] and a generalized, [[maculopapular rash|maculopapular]], [[erythema]]tous rash.

Measles is spread through respiration (contact with [[fluid]]s from an [[infection|infected]] person's nose and mouth, either directly or through [[Particulate|aerosol]] transmission), and is highly contagious&mdash;90% of people without [[immune system|immunity]] sharing a house with an infected person will catch it. The infection has an average incubation period of 14 days (range 6–19 days) and infectivity lasts from 2–4 days prior, until 2–5 days following the onset of the rash (i.e. 4–9 days infectivity in total).<ref>{{cite web |url=http://www.patient.co.uk/showdoc/40000391/ |title=Measles |format= |work= |accessdate=}}</ref>

An alternative name for measles in English-speaking countries is ''rubeola'', which is sometimes confused with ''[[rubella]]'' (German measles); the diseases are unrelated.<ref>[http://www.merriam-webster.com/dictionary/rubeola Merriam-webster:Rubeola] Accessed 2009-09-20.</ref><ref>T. E. C. Jr. [http://pediatrics.aappublications.org/cgi/content/abstract/49/1/150-a Letters to the editor] ''Pediatrics'' Vol. 49 No. 1 January 1972, pp. 150-151.</ref> In some other European languages, ''rubella'' and ''rubeola'' are synonyms, and ''rubeola'' is not an alternative name for measles.<ref>[http://www.websters-online-dictionary.org/Ge/German_measles.html Webster's Online Dictionary: German measles] Accessed 2009-09-20</ref>

===[[Mumps]]===
<ref>{{cite web|url=http://www.medicinenet.com/mumps/article.htm |title=Mumps Causes, Symptoms, Treatment, MMR Vaccine and Prevention Facts on |publisher=Medicinenet.com |date= |accessdate=2010-03-09}}</ref>
Mumps and epidemic parotitis is a viral disease of the human species, caused by the mumps virus. Prior to the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide, and is still a significant threat to health in the third world.[1]
Painful swelling of the salivary glands (classically the parotid gland) is the most typical presentation.[2] Painful testicular swelling (orchitis) and rash may also occur. The symptoms are generally not severe in children. In teenage males and men, complications such as infertility or subfertility are more common, although still rare in absolute terms.[3][4][5] The disease is generally self-limited, running its course before receding, with no specific treatment apart from controlling the symptoms with painkillers.
===[[Rubella]]===
May sometimes cause fever, particulary in adults.<ref>https://health.google.com/health/ref/Rubella</ref>
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is often mild and attacks often pass unnoticed. The disease can last one to three days. Children recover more quickly than adults. Infection of the mother by Rubella virus during pregnancy can be serious; if the mother is infected within the first 20 weeks of pregnancy, the child may be born with congenital rubella syndrome (CRS), which entails a range of serious incurable illnesses. Spontaneous abortion occurs in up to 20% of cases.[1]
Rubella is a common childhood infection usually with minimal systemic upset although transient arthropathy may occur in adults. Serious complications are very rare. Apart from the effects of transplacental infection on the developing fetus, rubella is a relatively trivial infection.
Acquired (i.e. not congenital) rubella is transmitted via airborne droplet emission from the upper respiratory tract of active cases. The virus may also be present in the urine, feces and on the skin. There is no carrier state: the reservoir exists entirely in active human cases. The disease has an incubation period of 2 to 3 weeks.[2]
In most people the virus is rapidly eliminated. However, it may persist for some months post partum in infants surviving the CRS. These children are a significant source of infection to other infants and, more importantly, to pregnant female contacts.
The name rubella is sometimes confused with rubeola, an alternative name for measles in English-speaking countries; the diseases are unrelated.[3][4] In some other European languages, rubella and rubeola are synonyms, and rubeola is not an alternative name for measles.[5]
*[[Common cold]] <ref>{{cite web|url=http://kidshealth.org/parent/infections/common/cold.html |title=Common Cold |publisher=Kidshealth.org |date= |accessdate=2010-03-09}}</ref>
*[[Eastern equine encephalitis virus]]<ref>http://www.cdc.gov/EasternEquineEncephalitis/index.html</ref>
*[[Viral gastroenteritis]]<ref>http://mayoclinic.com/health/viral-gastroenteritis/DS00085/DSECTION=symptoms</ref>
*[[Rocky mountain spotted fever]]<ref>http://www.mayoclinic.com/health/rocky-mountain-spotted-fever/DS00600/DSECTION=symptoms</ref>
*[[Appendicitis]]<ref>http://mayoclinic.com/health/appendicitis/DS00274/DSECTION=symptoms,</ref>
*[[Schistosomiasis]]<ref>{{cite web|url=http://www.webmd.com/a-to-z-guides/schistosomiasis |title=Schistosomiasis |publisher=Webmd.com |date= |accessdate=2010-03-09}}</ref>
*[[Meningitis]]<ref>{{cite web|url=http://children.webmd.com/vaccines/tc/meningitis-topic-overview |title=Meningitis- What is Meningitis? - Meningitis Overview |publisher=Children.webmd.com |date=2008-12-24 |accessdate=2010-03-09}}</ref>
*[[Babesiosis]]{{citation needed}}
*[[Tularemia]]<ref>{{cite web|url=http://www.bt.cdc.gov/agent/tularemia/facts.asp |title=CDC Tularemia &#124; Key Facts About Tularemia |publisher=Bt.cdc.gov |date=2003-10-07 |accessdate=2010-03-09}}</ref>
*[[Typhus]]<ref>{{cite web|url=http://emedicine.medscape.com/article/231374-overview |title=Typhus: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-09-18 |accessdate=2010-03-09}}</ref>
*[[Relapsing fever]]<ref>{{cite web|url=http://www.cdc.gov/ncidod/dvbid/RelapsingFever/ |title=Home - CDC Tick Borne Relapsing Fever |publisher=Cdc.gov |date= |accessdate=2010-03-09}}</ref>
===[[Typhoid fever]]===
<ref>{{cite web|url=http://www.mayoclinic.com/health/typhoid-fever/DS00538/DSECTION=symptoms |title=Typhoid fever: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>

'''Typhoid fever''', also known as '''''Salmonella'' Typhi''' or commonly just '''typhoid''',<ref>{{MedlinePlus|001332|Typhoid fever}}</ref> is a common worldwide illness, transmitted by the ingestion of food or water contaminated with the [[feces]] of an infected person.<ref name="Baron">{{cite book |author=Giannella RA |chapter=Salmonella |title=Baron's Medical Microbiology ''(Baron S ''et al.'', eds.) |edition=4th |publisher=Univ of Texas Medical Branch |year=1996 |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.1221 |isbn=0-9631172-1-1}}</ref> The bacteria then perforate through the intestinal wall and are [[Phagocytosis|phagocytosed]] by [[macrophages]]. 
The organism is a [[Gram-negative bacteria|Gram-negative]] short bacillus that is motile due to its peritrichous [[Flagellum|flagella]]. The bacterium grows best at {{convert|37|°C|°F|abbr=on|lk=on|disp=s}} – human body temperature.

This fever received various names, such as '''gastric fever''', '''the bends''', '''abdominal typhus''', '''infantile remittent fever''', '''slow fever''', '''nervous fever''', '''pythogenic fever''', etc. The name of " typhoid " was given by Louis in 1829, as a derivative from typhus.

The impact of this disease falls sharply with the application of modern sanitation techniques.

Typhoid fever is characterized by  a slowly progressive [[fever]] as high as {{convert|40|°C|°F|abbr=on|lk=off}}, profuse sweating,  [[gastroenteritis]], and nonbloody [[diarrhea]]. Less commonly a [[rash]] of flat, rose-colored spots may appear.<ref>{{CDCDiseaseInfo|typhoidfever_g}}</ref>

Classically, the    course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, there is a slowly rising temperature with relative [[bradycardia]], [[malaise]], headache and cough. A bloody nose ([[epistaxis]]) is seen in a quarter of cases and abdominal pain is also possible. There is [[leukopenia]], a decrease in the number of circulating white blood cells, with [[eosinopenia]] and relative [[lymphocytosis]], a positive diazo reaction and blood cultures are positive for ''[[Salmonella]] typhi'' or ''paratyphi''. The classic [[Widal test]] is negative in the first week.

In the second week of the infection, the patient lies prostrated with high fever in plateau around {{convert|40|°C|°F|abbr=on|lk=off}} and [[bradycardia]] (Sphygmo-thermic dissociation), classically with a [[dicrotic pulse]] wave. Delirium is frequent, frequently calm, but sometimes agitated.  This [[delirium]] gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around 1/3 patients. There are [[rhonchi]] in lung bases. The abdomen is distended and painful in the right lower quadrant where [[borborygmi]] can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea-soup. However, constipation is also frequent. The spleen and liver  are enlarged ([[hepatosplenomegaly]]) and tender and there is elevation of liver [[transaminases]]. The Widal reaction is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.
(The major symptom of this fever is the [[fever]]  usually rises in the afternoon up to the first and second week.)

In the third week of typhoid fever a number of complications can occur:
* Intestinal hemorrhage due to bleeding in congested [[Peyer's patches]]; this can be very serious but is usually non-fatal.
===[[Peritonitis]]===
Fever typically coincides with severe abdominal pain<ref>{{cite web|url=http://www.umm.edu/altmed/articles/peritonitis-000127.htm |title=Peritonitis |publisher=Umm.edu |date=2008-09-16 |accessdate=2010-03-09}}</ref>


'''Peritonitis''' is an [[inflammation]] of the [[peritoneum]], the [[serous membrane]] which lines part of the [[abdomen|abdominal cavity]] and [[viscera]]. Peritonitis may be localized or generalized, and may result from [[infection]] (often due to [[gastrointestinal perforation|rupture of a hollow organ]] as may occur in [[abdominal trauma]] or [[appendicitis]]) or from a non-infectious process.

The main manifestations of peritonitis are acute '''[[abdominal pain]]''', '''[[abdominal tenderness]]''', and '''[[abdominal guarding]]''', which are exacerbated by moving the peritoneum, e.g. coughing (forced cough may be used as a test), flexing one's hips, or eliciting the [[Blumberg sign]] (a.k.a. [[rebound tenderness]], meaning that pressing a hand on the abdomen elicits less pain than releasing the hand abruptly, which will aggravate the pain, as the peritoneum snaps back into place). The presence of these signs in a patient is sometimes referred to as peritonism.<ref name="titleBiology Online's definition of peritonism">{{cite web |url=http://www.biology-online.org/dictionary/Peritonism |title=Biology Online's definition of peritonism |accessdate=2008-08-14 |format= |work=}}</ref> The localization of these manifestations depends on whether peritonitis is localized (e.g. [[appendicitis]] or [[diverticulitis]] before perforation), or generalized to the whole [[abdomen]]. In either case pain typically starts as a generalized abdominal pain (with involvement of poorly localizing innervation of the visceral [[Peritoneum#Layers|peritoneal layer]]), and may become localized later (with the involvement of the somatically innervated parietal peritoneal layer). Peritonitis is an example of an [[acute abdomen]].

* Diffuse abdominal rigidity ("[[washboard abdomen]]") is often present, especially in generalized peritonitis
* [[Fever]]
* [[Sinus tachycardia]]
* Development of [[ileus|ileus paralyticus]] (i.e. intestinal paralysis), which also causes [[nausea]] and [[vomiting]]

Complications of peritonitis 
* Sequestration of [[fluid]] and [[electrolyte]]s, as revealed by decreased [[central venous pressure]], may cause [[electrolyte disturbance]]s, as well as significant [[hypovolemia]], possibly leading to [[Shock (circulatory)|shock]] and [[acute renal failure]].
* A [[peritoneal abscess]] may form (e.g. above or below the [[liver]], or in the lesser sac
* [[Sepsis]] may develop, so [[blood cultures]] should be obtained.
* The fluid may push on the diaphragm causing splinting and subsequent breathing difficulties.

===[[Necrotizing fasciitis]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/784690-overview |title=Necrotizing Fasciitis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-03-25 |accessdate=2010-03-09}}</ref>
'''Necrotizing fasciitis''' ('''NF'''), commonly known as '''flesh-eating disease''' or '''flesh-eating [[bacteria]]''', is a [[Rare disease|rare]] [[infection]] of the deeper layers of [[skin]] and [[Subcutis|subcutaneous tissues]], easily spreading across the [[fascia]]l plane within the subcutaneous tissue.

Type I describes a polymicrobial infection, whereas Type II describes a monomicrobial infection. Many types of bacteria can cause necrotizing fasciitis (e.g., [[Group A streptococcal infection|Group A streptococcus (''Streptococcus pyogenes'')]], ''[[Staphylococcus aureus]]'', ''[[Vibrio vulnificus]]'', ''[[Clostridium perfringens]]'', ''[[Bacteroides fragilis]]''). Such infections are more likely to occur in people with compromised [[immune systems]].<ref>[http://www.ncbi.nlm.nih.gov/pubmed/8623695 K.S. Kotrappa, R.S. Bansal, N.M. Amin, "Necrotizing fasciitis", ''Am Fam Physician'', 1996 Apr;53(5):1691-7.]</ref>

Historically, Group A streptococcus made up most cases of Type II infections. However, since at least 2001, another serious form of monomicrobial necrotizing fasciitis has been observed with increasing frequency.<ref>{{cite journal |author=Lee TC, Carrick MM, Scott BG, et al. |title=Incidence and clinical characteristics of methicillin-resistant fasciitis in a large urban hospital |journal=Am J Surg |volume=194 |pages=809–13 |year=2007|pmid=18005776 |doi=10.1016/j.amjsurg.2007.08.047 |issue=6}}</ref> In these cases, the bacterium causing it is [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'' (MRSA)]], a strain of ''S. aureus'' that is [[Antibiotic resistance|resistant]] to [[methicillin]], the [[antibiotic]] used in the laboratory that determines the bacterium's sensitivity to [[flucloxacillin]] or [[nafcillin]] that would be used for treatment clinically.

Symptoms of necrotizing fasciitis:
The infection begins locally, at a site of [[Physical trauma|trauma]], which may be severe (such as the result of [[surgery]]), minor, or even non-apparent. Patients usually complain of intense pain that may seem in excess given the external appearance of the skin. With progression of the disease, tissue becomes swollen, often within hours. Diarrhea and vomiting are also common symptoms. 

In the early stages, signs of inflammation may not be apparent if the bacteria are deep within the tissue. If they are ''not'' deep, signs of inflammation, such as redness and swollen or hot skin, show very quickly. [[Skin color]] may progress to violet, and blisters may form, with subsequent [[necrosis]] (death) of the [[subcutaneous tissue]]s. 

Patients with necrotizing fasciitis typically have a [[fever]] and appear very ill. Mortality rates have been noted as high as 73 percent if left untreated.<ref>http://www.medscape.com/viewarticle/444061</ref> Without surgery and medical assistance, such as [[antibiotic]]s, the infection will rapidly progress and will eventually lead to death.<ref>[http://www.webmd.com/a-to-z-guides/Necrotizing-Fasciitis-Flesh-Eating-Bacteria-Topic-Overview Necrotizing Fasciitis (Flesh-Eating Bacteria)]</ref>

===[[Cellulitis]]===
'''Cellulitis''' is a diffuse [[inflammation]]<ref>{{DorlandsDict|two/000019077|cellulitis}}</ref> of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal [[skin flora]] or by [[exogenous bacteria]], and often occurs where the skin has previously been broken: cracks in the skin, cuts, [[blister]]s, [[burn (injury)|burns]], [[insect bite]]s, surgical wounds, or sites of [[intravenous]] [[catheter]] insertion.  Skin on the face or lower legs is most commonly affected by this infection, though cellulitis can occur on any part of the body.  The mainstay of therapy remains treatment with appropriate [[antibiotic]]s. 

[[Erysipelas]] is the term used for a more superficial infection of the dermis and upper subcutaneous layer that presents clinically with a well defined edge. Erysipelas and cellulitis often coexist, so it is often difficult to make a distinction between the two.

Cellulitis is unrelated (except etymologically) to [[cellulite]], a cosmetic condition featuring dimpling of the skin.


Cellulitis is caused by a type of [[bacterium|bacteria]] entering the skin, usually by way of a cut, abrasion, or break in the skin. This break does not need to be visible. [[Group A streptococcal infection|Group A]] ''[[Streptococcus]]'' and ''[[Staphylococcus]]'' are the most common of these bacteria, which are part of the normal flora of the skin but cause no actual infection while on the skin's outer surface. Predisposing conditions for cellulitis include insect bites, [[blister]]ing, animal bite, [[tattoos]], pruritic skin rash, recent [[surgery]], [[athlete's foot]], [[xeroderma|dry skin]], [[eczema]], injecting drugs (especially subcutaneous or intramuscular injection or where an attempted IV injection "misses" or blows the vein), pregnancy, diabetes and obesity, which can affect circulation, as well as burns and [[boil]]s, though there is debate as to whether minor foot lesions contribute.

There is a very rare [[dermatological]] condition called [[Hidradenitis Suppurativa]] (HS). HS is a non-contagious skin disease that includes numerous and chronic manifestaions of symptoms, including [[abscesses]], several types of [[cysts]] (epidermoid, sebaceous, pilonidal), just to name a few. These [[infections]] of the [[skin]] usually occurs in clusters, leading to multilocalized infections that are extremely sensitive and often cause debilitating pain. Persistent and reoccuring [[lesions]] can cause scarring and may cause the formation of sinus tracts depending on the extent of the [[wounds]]. These lesions can also cause the formation of tunnels connecting the abscesses or infections underneath the skin. Most patients with HS require multiple surgeries in order to be able to live somewhat comfortably. [[Wound dehiscence]] is a premature bursting open of the wounds along surgical sutures, which only further complicates the resistant healing process. [[Wound dehiscence]] can be considered a surgical complication, although it occurs very frequently in patients with [[Hidradenitis Suppurativa]] who have undergone surgery specifically for their skin wounds. Occurrences of [[bacterial infections]] and [[cellulitis]] (deep tissue inflammation) often occur at these sites. [[Hidradenitis Suppurativa]] pain and depression can be extremely difficult to manage <ref>HS-USA :: What is Hidradenitis Suppurativa?". http://www.hs-usa.org/hidradenitis_suppurativa.htm. Retrieved 2007-07-08</ref>. HS has been linked with other [[auto-immune]] conditions<ref>ClinicalTrials.gov NCT00329823 Etanercept in Hidradenitis Suppurativa</ref>, androgen dysfunction, plugged or dysfunctional [[apocrine]] (sweat) glands<ref>DermNet acne/hidradenitis-suppurativa</ref> and/or [[hair follicles]]<ref>"HSF - What is Hidradenitis Suppurativa? What is HS?". http://www.hs-foundation.org/abouths/what.htm. Retrieved 2007-07-08.</ref> (creates [[inflammation]], pain, and swollen lesions; and there may be an [[autoimmune]] component implied)), bacterial infections (which are infections that are [[secondary infections]] and therefore not contagious), [[Crohn's Disease]], [[Rheumatoid Arthiritis]], [[Squamous Cell Carcinoma]], [[Hashimoto's Thyroiditis]], [[obesity]], [[anemia]], [[amyloidosis]], [[arthropathy]]. Stage III [[Hidradenitis Suppurative]] complications are extremely painful and can lead to death in some cases.

The photos shown here of Cellulitis are more severe cases than what can be spotted normally at earlier stages. Usually the itch and/or rash appears a little after it vanishes leaving only a small mark which is commonly ignored.

The appearance of the skin will help a doctor make a diagnosis. The doctor may also suggest blood tests, a wound culture or other tests to help rule out a blood clot deep in the veins of the legs. Cellulitis in the lower leg is characterized by signs and symptoms that may be similar to those of a clot occurring deep in the veins, such as warmth, pain and swelling (inflammation).

This reddened skin or rash may signal a deeper, more serious infection of the inner layers of skin. Once below the skin, the bacteria can spread rapidly, entering the lymph nodes and the bloodstream and spreading throughout the body.

In rare cases, the infection can spread to the deep layer of tissue called the fascial lining. [[Necrotizing fasciitis]], also called by the media "flesh-eating bacteria," is an example of a deep-layer infection. It represents an extreme [[medical emergency]].

Risk factors for cellulitis:
The elderly and those with immunodeficiency (a weakened immune system) are especially vulnerable to contracting cellulitis. [[diabetes mellitus|Diabetics]] are more susceptible to cellulitis than the general population because of impairment of the immune system; they are especially prone to cellulitis in the feet because the disease causes impairment of blood circulation in the legs leading to diabetic foot/foot ulcers. Poor control of blood glucose levels allows bacteria to grow more rapidly in the affected tissue and facilitates rapid progression if the infection enters the bloodstream. Neural degeneration in diabetes means these ulcers may not be painful and thus often become infected.

Immunosuppressive drugs, and other illnesses or infections that weaken the immune system are also factors that make infection more likely. Chickenpox and shingles often result in blisters that break open, providing a gap in the skin through which bacteria can enter. Lymphedema, which causes swelling on the arms and/or legs, can also put an individual at risk.

Diseases that affect blood circulation in the legs and feet, such as chronic venous insufficiency and varicose veins, are also risk factors for cellulitis.

Cellulitis is also extremely prevalent among dense populations sharing hygiene facilities and common living quarters, such as military installations, college dormitories, and homeless shelters.

Diagnosing cellulitis:
Cellulitis is most often a clinical diagnosis, and local cultures do not always identify the causative organism. [[Blood culture]]s usually are positive only if the patient develops generalized [[sepsis]]. Conditions that may resemble cellulitis include [[deep vein thrombosis]], which can be diagnosed with a compression leg [[medical ultrasonography|ultrasound]], and [[stasis dermatitis]], which is inflammation of the skin from poor blood flow.
===Yellow fever===
{{Main|Yellow fever}}
<ref>{{cite web|url=http://emedicine.medscape.com/article/232244-overview |title=Yellow Fever: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
'''Yellow fever''' is an [[acute]] [[Virus|viral]] hemorrhagic disease.<ref name="Baron">{{cite book |author=Schmaljohn AL, McClain D. |chapter=Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae) |editor=Baron S |title=Medical Microbiology |edition=4th |publisher=Univ of Texas Medical Branch |year=1996 |isbn=0-9631172-1-1 }}</ref> The virus is a 40 to 50&nbsp;[[nanometer|nm]] enveloped [[RNA virus]] with positive [[Sense (molecular biology)|sense]] of the [[Flaviviridae]] family.

The yellow fever virus is [[Vector (biology)|transmitted]] by the bite of female [[mosquito]]s (the yellow fever mosquito, ''[[Aedes aegypti]]'', and other species) and is found in [[Tropics|tropic]]al and [[Subtropics|subtropic]]al areas in [[South America]] and [[Africa]], and [[Asia]].<ref name="urlCDC Yellow Fever">{{cite web
|url=http://www.cdc.gov/ncidod/dvbid/yellowfever/
|title=CDC Yellow Fever
|format=
|work=
|accessdate=2010-03-13
}}</ref> The only known hosts of the virus are [[primates]] and several species of [[mosquito]]. The origin of the disease is most likely to be Africa, from where it was introduced to South America through the [[slave trade]] in the 16th century. Since the 17th century, several major [[List of epidemics|epidemic]]s of the disease have been recorded in the Americas, Africa and Europe. In the 19th century, yellow fever was deemed one of the most dangerous [[infectious disease]]s.<ref>{{cite book |last = Oldstone |first = Michael B. A. |title = Viruses, Plagues, and History |publisher = Oxford University Press |edition = 1st  |year = 2000 |isbn = 0195134222 |pages= 45}}</ref>

Clinically, yellow fever presents in most cases with [[fever]], [[nausea]], and pain and it generally subsides after several days. In some patients, a toxic phase follows, in which liver damage with [[jaundice]] (giving the name of the disease) can occur and lead to death. Because of the increased bleeding tendency ([[bleeding diathesis]]), yellow fever belongs to the group of [[Viral hemorrhagic fever|hemorrhagic fevers]]. The [[World Health Organization|WHO]] estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations;<ref name="WHO_2001">{{cite web |title=Yellow fever fact sheet |work=WHO&mdash;Yellow fever |url=http://www.who.int/mediacentre/factsheets/fs100/en/ |accessdate=2006-04-18}}</ref> around 90% of the infections occur in Africa.<ref name="pmid19327647"/>

A  safe and effective [[vaccine]] against yellow fever has existed since the middle of the 20th century and some countries require vaccinations for travelers.<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 0-8385-8529-9 }}</ref> Since no therapy is known, vaccination programs are, along with measures to reduce the population of the transmitting mosquito, of great importance in affected areas. Since the 1980s, the number of cases of yellow fever has been increasing, making it a ''reemerging disease''.<ref name="pmid16913829">{{cite journal |author=Barrett AD, Higgs S |title=Yellow fever: a disease that has yet to be conquered |journal=Annu. Rev. Entomol. |volume=52 |issue= |pages=209–29 |year=2007 |pmid=16913829 |doi=10.1146/annurev.ento.52.110405.091454 |url=}}</ref>

Signs and symptoms of Yellow fever:
Yellow fever begins suddenly after an incubation period of three to six days. Most cases only cause a mild infection with fever, headache, chills, back pain, loss of appetite, nausea and vomiting.<ref name="urlWHO | Yellow fever">{{cite web |url=http://www.who.int/mediacentre/factsheets/fs100/en/ |title=WHO &#124; Yellow fever |format= |work= |accessdate=2009-08-13}}</ref> In these cases the infection lasts only three to four days. 15% of cases enter a second, toxic phase of the disease with recurring fever, this time accompanied by [[jaundice]] due to [[hepatitis|liver damage]], as well as abdominal pain. Bleeding in the mouth, the eyes and in the [[gastrointestinal tract]] can cause [[hematemesis|vomitus containing blood]] (giving the name "vómito negro").<ref name="pmid14582304">{{cite journal |author=Chastel C |title=[Centenary of the discovery of yellow fever virus and its transmission by a mosquito (Cuba 1900–1901)] |language=French |journal=Bull Soc Pathol Exot |volume=96 |issue=3 |pages=250–6 |year=2003 |month=August |pmid=14582304 |doi= |url=}}</ref> The toxic phase is fatal in approximately 20% of cases.<ref name="pmid18061688">{{cite journal |author=Monath TP |title=Treatment of yellow fever |journal=Antiviral Res. |volume=78 |issue=1 |pages=116–24 |year=2008 |month=April |pmid=18061688 |doi=10.1016/j.antiviral.2007.10.009 |url=}}</ref>

===Smallpox===
{{main|Smallpox}}
<ref>{{cite web|url=http://www.bt.cdc.gov/agent/smallpox/faq/smallpox_disease.asp |title=CDC Smallpox Q & A |publisher=Bt.cdc.gov |date=2009-03-13 |accessdate=2010-03-09}}</ref>
'''Smallpox''' is an [[infectious disease]] unique to humans, caused by either of two [[virus (biology)|virus]] variants, ''Variola major'' and ''Variola minor''.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th | pages = 525&ndash;8 | publisher = McGraw Hill | year = 2004 |isbn = 0838585299 }}</ref> The disease is also known by the [[Latin]] names ''Variola'' or ''Variola vera'', which is a derivative of the Latin ''varius'', meaning spotted, or ''varus'', meaning "pimple". The term "smallpox" was first used in Europe in the 15th century to distinguish variola from the "great pox" ([[syphilis]]).<ref name=Barquet>{{cite journal |author=Barquet N, Domingo P |title=Smallpox: the triumph over the most terrible of the ministers of death |url= http://www.annals.org/cgi/content/full/127/8_Part_1/635|journal=Ann. Intern. Med. |volume=127 |issue=8 Pt 1 |pages=635–42 |date=15 October 1997|pmid=9341063 |doi=10.1059/0003-4819-127-8_Part_1-199710150-00010 |doi_brokendate=2010-03-07 }}</ref>

Smallpox localizes in small [[blood vessel]]s of the skin and in the mouth and throat. In the skin, this results in a characteristic [[maculopapular]] rash, and later, raised fluid-filled [[blister]]s. ''V. major'' produces a more serious disease and has an overall [[mortality rate]] of 30–35%. ''V. minor'' causes a milder form of disease (also known as [[alastrim]], cottonpox, milkpox, whitepox, and Cuban itch) which kills about 1% of its victims.<ref name=Behbehani_1983>{{cite journal |author=Behbehani AM |title=The smallpox story: life and death of an old disease |journal=Microbiol Rev |volume=47 |issue=4 |pages=455–509 |date=1 December 1983|pmid=6319980 |pmc=281588 |url=http://mmbr.asm.org/cgi/pmidlookup?view=long&pmid=6319980 }}</ref><ref name=AFIP/> Long-term complications of ''V. major'' infection include characteristic scars, commonly on the face, which occur in 65–85% of survivors.<ref>{{cite journal |author=Jezek Z, Hardjotanojo W, Rangaraj AG |title=Facial scarring after varicella. A comparison with variola major and variola minor |journal=Am. J. Epidemiol. |volume=114 |issue=6 |pages=798–803 |year=1981 |pmid=7315828 }}</ref> [[Blindness]] resulting from [[corneal ulcer]]ation and scarring, and limb deformities due to arthritis and [[osteomyelitis]] are less common complications, seen in about 2–5% of cases.

Smallpox is believed to have emerged in [[human population]]s about 10,000 BC.<ref name=Barquet/> The disease killed an estimated 400,000 Europeans per year during the closing years of the 18th century (including five [[monarch]]s),<ref>"''[http://books.google.com/books?id=GyE8Qt-kS1kC&pg=PA151&dq=&lr=&hl=en&cd=23#v=onepage&q=false Epidemics and pandemics: their impacts on human history]''". J. N. Hays (2005). p.151. ISBN 1851096582</ref> and was responsible for a third of all blindness.<ref name=Behbehani_1983/><ref>"[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3 Smallpox and Vaccinia]". ''National Center for Biotechnology Information.''</ref> Of all those infected, 20–60%—and over 80% of infected children—died from the disease.<ref>{{cite journal |author=Riedel S |title=Edward Jenner and the history of smallpox and vaccination |pmc=1200696 |journal=Proc (Bayl Univ Med Cent) |volume=18 |issue=1 |pages=21–5 |year=2005 |pmid=16200144 }}</ref>

During the 20th century, it is estimated that smallpox was responsible for 300–500 million deaths.<ref>{{cite book |author=Koplow, David A. |title=Smallpox: the fight to eradicate a global scourge |url=http://books.google.com/books/ucpress?vid=ISBN9780520242203|publisher=University of California Press |location=Berkeley |year=2003 |pages= |isbn=0-520-24220-3 }}</ref><ref>{{cite web |url=http://ucdavismagazine.ucdavis.edu/issues/su06/feature_1b.html |title=UC Davis Magazine, Summer 2006: Epidemics on the Horizon |accessdate=2008-01-03 |work=}}</ref><ref>[http://www.sciencedaily.com/releases/2008/01/080131122956.htm How Poxviruses Such As Smallpox Evade The Immune System], ScienceDaily, February 1, 2008</ref> In the early 1950s an estimated 50 million cases of smallpox occurred in the world each year.<ref name=WHO_Factsheet/> As recently as 1967, the [[World Health Organization]] (WHO) estimated that 15 million people contracted the disease and that two million died in that year.<ref name=WHO_Factsheet>{{cite web | title=Smallpox | work=WHO Factsheet | url=http://www.who.int/mediacentre/factsheets/smallpox/en/ | accessdate=2007-09-22}}</ref> After successful [[vaccination]] campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in December 1979.<ref name=WHO_Factsheet /> To this day, smallpox is the only human infectious disease to have been eradicated.<ref>{{cite journal | author = De Cock KM | title = (Book Review) The Eradication of Smallpox: Edward Jenner and The First and Only Eradication of a Human Infectious Disease | url = http://www.nature.com/nm/journal/v7/n1/full/nm0101_15b.html| journal = Nature Medicine | year = 2001 | volume = 7 | pages = 15–6 | doi = 10.1038/83283 | pmid = 83283 | last1 = Kanda | first1 = N | issue = 1}}</ref>

Cause:
Smallpox is caused by infection with variola virus, which belongs to the genus [[Orthopoxvirus]], the family [[Poxviridae]], and subfamily chordopoxvirinae. Variola is a large brick-shaped virus measuring approximately 302 to 350 [[nanometer]]s by 244 to 270&nbsp;nm,<ref>{{cite journal |author=Dubochet J, Adrian M, Richter K, Garces J, Wittek R |title=Structure of intracellular mature vaccinia virus observed by cryoelectron microscopy |journal=J. Virol. |volume=68 |issue=3 |pages=1935–41 |year=1994 |pmid=8107253 |pmc=236655 }}</ref> with a single linear [[dsDNA|double stranded DNA]] [[genome]] 186 [[kilobase pair]]s (kbp) in size and containing a [[hairpin loop]] at each end.<ref name=Moss>{{cite book | author= Moss B| chapter=Poxviridae: the viruses and their replication | editors= Fields BN, Knipe DM, Howley PM, ''et al.'' (eds)| title=Fields Virology | volume=Vol 2 | edition=5th |location=Philadelphia, PA | publisher=Lippincott-Raven | year=2006 |isbn=0781760607 | pages=2905–46}}</ref><ref name=Damon>{{cite book | author= Damon I| chapter=Poxviruses | editors= Fields BN, Knipe DM, Howley PM, ''et al.'' (eds)| title=Fields Virology | volume=Vol 2 | edition=5th |location=Philadelphia, PA | publisher=Lippincott-Raven | year=2006 |isbn=0781760607 | pages=2947–76}}</ref> The two classic varieties of smallpox are variola major and variola minor. The closest viral relative is [[molluscum contagiosum]], which, like smallpox, infects only humans. However, unlike variola species, molluscum infection is benign.

Four orthopoxviruses cause infection in humans: variola, [[vaccinia]], [[cowpox]], and [[monkeypox]]. Variola virus infects only humans in nature, although primates and other animals have been infected in a laboratory setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature.<ref name = PinkBook>{{cite book | author = Atkinson W, Hamborsky J, McIntyre L, Wolfe S (eds.) | chapter = Smallpox | title = Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book) | edition = 9th | pages = 281–306 | publisher = Public Health Foundation | location =Washington DC |year = 2005 | url = http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/smallpox.pdf | format = PDF}}</ref>

The lifecycle of poxviruses is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among DNA viruses in that they replicate in the [[cytoplasm]] of the cell rather than in the [[Cell nucleus|nucleus]]. In order to replicate, poxviruses produce a variety of specialized proteins not produced by other [[DNA viruses]], the most important of which is a viral-associated [[DNA-dependent RNA polymerase]].
Both [[viral envelope|enveloped]] and unenveloped virions are infectious. The viral envelope is made of modified [[Golgi]] membranes containing viral-specific polypeptides, including [[hemagglutinin]].<ref name=Moss/> Infection with either variola major or variola minor confers immunity against the other.<ref name=AFIP>{{cite web |url=http://web.archive.org/web/20071009141639/http://www.afip.org/Departments/infectious/sp/text/1_1.htm |title=Smallpox |accessdate=2008-10-28 |work=Armed Forces Institute of Pathology: Department of Infectious and Parasitic Diseases}}</ref>

Transmission of Smallpox
Transmission of smallpox occurs through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or [[pharynx|pharyngeal]] [[mucosa]] of an infected person. It is transmitted from one person to another primarily through prolonged face-to-face contact with an infected person, usually within a distance of 6 feet, but can also be spread through direct contact with infected [[bodily fluid]]s or contaminated objects ([[fomite]]s) such as bedding or clothing. Rarely, smallpox has been spread by virus carried in the air in enclosed settings such as buildings, buses, and trains.<ref name= FactSheet/> The virus can cross the [[placenta]], but the incidence of [[congenital]] smallpox is relatively low.<ref name=AFIP/>
Smallpox is not notably infectious in the [[prodrome|prodromal]] period and viral shedding is usually delayed until the appearance of the rash, which is often accompanied by [[lesion]]s in the mouth and pharynx. The virus can be transmitted throughout the course of the illness, but is most frequent during the first week of the rash, when most of the skin lesions are intact.<ref name= PinkBook/> Infectivity wanes in 7 to 10 days when scabs form over the lesions, but the infected person is contagious until the last smallpox scab falls off.<ref>{{cite journal |author=Henderson DA, Inglesby TV, Bartlett JG, ''et al.'' |title=Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense |journal=JAMA |volume=281 |issue=22 |pages=2127–37 |year=1999 |pmid=10367824 |doi=10.1001/jama.281.22.2127 |last12=Parker |first12=G |last13=Perl |first13=T |last14=Russell |first14=PK |last15=Tonat |first15=K }}</ref>

Smallpox is highly contagious, but generally spreads more slowly and less widely than some other viral diseases, perhaps because transmission requires close contact and occurs after the onset of the rash. The overall rate of infection is also affected by the short duration of the infectious stage. In [[temperate]] areas, the number of smallpox infections were highest during the winter and spring. In tropical areas, seasonal variation was less evident and the disease was present throughout the year.<ref name= PinkBook/> Age distribution of smallpox infections depends on [[acquired immunity]]. [[Vaccination]] [[immunity (medical)|immunity]] declines over time and is probably lost in all but the most recently vaccinated populations.<ref name=AFIP/> Smallpox is not known to be transmitted by insects or animals and there is no [[asymptomatic carrier]] state.<ref name= PinkBook/>

Signs and symptoms of smallpox:
There are two clinical forms of smallpox. Variola major is the severe and most common form of smallpox, with a more extensive rash and higher fever. There are four types of variola major smallpox based on the Rao classification:<ref>Rao, A. R. (1972). Smallpox. Bombay: Kothari Book Depot. {{Oclc|723806}}</ref> ordinary, modified, flat, and hemorrhagic. Historically, variola major has an overall [[fatality rate]] of about 30%; however, flat and hemorrhagic smallpox are usually fatal.<ref name=eMedicine_Smallpox>{{cite web | author = Hogan CJ, Harchelroad F | title=CBRNE - Smallpox | work=eMedicine | url=http://www.emedicine.com/emerg/topic885.htm | accessdate=2006-09-23}}</ref> In addition, a form called ''variola sine eruptione'' (smallpox without rash) is seen generally in vaccinated persons. This form is marked by a fever that occurs after the usual incubation period and can be confirmed only by antibody studies or, rarely, by virus isolation.<ref name= PinkBook/>

Variola minor is a less common presentation of smallpox, and a much less severe disease, with historical death rates of 1% or less.<ref name=FactSheet>{{cite web |url=http://www.bt.cdc.gov/agent/smallpox/overview/disease-facts.asp |title=CDC Smallpox |accessdate= 2007-12-26 |format= |work=Smallpox Overview }}</ref> Subclinical ([[asymptomatic]]) infections with variola virus have also been noted, but are not believed to be common.<ref name= PinkBook/>
The [[incubation period]] between contraction and the first obvious symptoms of the disease is around 12 days. Once inhaled, variola virus invades the oropharyngeal (mouth and throat) or the [[respiratory]] mucosa, migrates to regional [[lymph nodes]], and begins to multiply. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, [[lysis]] of many infected cells occurs and the virus is found in the [[blood]]stream in large numbers (this is called ''[[viremia]]''), and a second wave of multiplication occurs in the spleen, [[bone marrow]], and lymph nodes. The initial or prodromal symptoms are similar to other viral diseases such as [[influenza]] and the [[common cold]]: [[fever]] (at least {{convert|38.5|°C|°F|0}}), [[myalgia|muscle pain]], malaise, headache, [[prostration]], and as the [[Gastrointestinal tract|digestive tract]] is commonly involved, nausea and vomiting and backache often occur. The prodrome, or preeruptive stage, usually lasts 2–4 days. By days 12–15 the first visible lesions—small reddish spots called ''enanthem''—appear on mucous membranes of the mouth, tongue, [[palate]], and throat, and temperature falls to near normal. These lesions rapidly enlarge and rupture, releasing large amounts of virus into the [[saliva]].<ref name= AFIP/>

Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called [[macule]]s) associated with the disease. A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically the macules first appear on the forehead, then rapidly spread to the whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear.<ref name= AFIP/> At this point Variola major infection can take several very different courses.

*[[Q fever]]<ref>{{cite web|url=http://emedicine.medscape.com/article/227156-overview |title=Q Fever: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-11-18 |accessdate=2010-03-09}}</ref>
*[[Leptospirosis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/220563-overview |title=Leptospirosis: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-08-11 |accessdate=2010-03-09}}</ref>
*[[Bubonic plague]]<ref name="medscape1">{{cite web|url=http://emedicine.medscape.com/article/235627-overview |title=Plague: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
*[[Meningeal plague]]<ref name="medscape1"/>
*Pharyngeal plague<ref name="medscape1"/>
*[[Pneumonic plague]]<ref name="medscape1"/>
*[[Septicemic plague]]<ref name="medscape1"/>
===[[Endocarditis]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/782264-overview |title=Endocarditis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-11-23 |accessdate=2010-03-09}}</ref>

'''Endocarditis''' is an [[inflammation]] of the inner layer of the [[heart]], the [[endocardium]]. It usually involves the [[heart valve]]s (native or prosthetic valves). Other structures which may be involved include the [[interventricular septum]], the [[chordae tendineae]], the mural endocardium, or even on intracardiac devices. Endocarditis is characterized by a prototypic lesion, the ''[[Vegetation (pathology)|vegetation]]'', which is a mass of [[platelets]], [[fibrin]], microcolonies of microorganisms, and scant inﬂammatory cells.<ref name=Harrison>{{cite book | author= Kasper DL, Brunwald E, [[Anthony Fauci|Fauci AS]], Hauser S, Longo DL, Jameson JL| title = [[Harrison's Principles of Internal Medicine]] | publisher = [[McGraw-Hill]] | year = 2005 | pages = 731–40 | month = May | isbn = 0-07-139140-1 | oclc = 54501403 56437106 56801936 56967424 }}</ref>  In the [[subacute]] form of infective endocarditis, the vegetation may also include a center of [[granuloma|granulomatous tissue]], which may fibrose or calcify.<ref name=Robbins>{{cite book |author=Mitchell RS, Kumar V, Robbins SL, Abbas AK, Fausto N |title=Robbins Basic Pathology |publisher=Saunders/Elsevier |edition= 8th |year=2007 |pages=406–8 |isbn=1-4160-2973-7}}</ref>

There are multiple ways to classify endocarditis. The simplest classification is based on [[etiology]]: either ''infective'' or ''non-infective'', depending on whether a [[microorganism]] is the source of the inflammation. Regardless, diagnosis of endocarditis is based on the clinical features, investigations such as [[echocardiogram]], as well as any [[blood culture]]s demonstrating the presence of endocarditis-causing microorganisms. 

Infective endocarditis:
{{main|Infective endocarditis}}
Since the valves of the heart do not receive any dedicated blood supply, defensive immune mechanisms (such as [[white blood cell]]s) cannot directly reach the valves via the bloodstream. If an organism (such as [[bacterium|bacteria]]) attaches to a valve surface and forms a vegetation, the host immune response is blunted. The lack of blood supply to the valves also has implications on treatment,since drugs also have difficulty reaching the infected valve.

Normally, blood flows smoothly through these valves. If they have been damaged (from [[rheumatic fever]], for example) the risk of bacteria attachment is increased.<ref name=Robbins/>

Non-infective endocarditis:
Nonbacterial thrombic endocarditis (NBTE) or [[marantic endocarditis]] is most commonly found on previously undamaged valves<ref name=Robbins/>.  As opposed to infective endocarditis, the vegetations in NBTE are small, sterile, and tend to aggregate along the edges of the valve or the cusps<ref name=Robbins/>.  Also unlike infective endocarditis, NBTE does not cause an inflammation response from the body<ref name=Robbins/>.  NBTE usually occurs during a hypercoagulable state such as system wide bacterial infection, or pregnancy, though it is also sometimes seen in patients with venous catheters<ref name=Robbins/>.  NBTE may also occur in patients with cancers, particularly mucinous adenocarcinoma<ref name=Robbins/> where [[Trousseau syndrome]] can be encountered. Typically NBTE does not cause many problems on its own, but parts of the vegetations may break off and embolize to the heart or brain, or they may serve as a focus where bacteria can lodge, thus causing infective endocarditis<ref name=Robbins/>.

Another form of sterile endocarditis, is termed [[Libman-Sacks endocarditis]]; this form occurs more often in patients with [[lupus erythematosus]] and is thought to be due to the deposition of immune complexes<ref name=Robbins/>.  Like NBTE, Libman-Sacks endocarditis involves small vegetations, while infective endocarditis is composed of large vegetations<ref name=Robbins/>.  These immune complexes precipitate an inflammation reaction, which helps to differentiate it from NBTE.  Also unlike NBTE, Libman-Sacks endocarditis does not seem to have a preferred location of deposition and may form on the undersurfaces of the valves or even on the endocardium<ref name=Robbins/>.

Prognosis:
Features suggestive of a worse prognosis are Acute endocarditis (Staphylococcus aureus), heart failure, IV drug abuse (often left and right sided disease), prosthetic valve infection, infection of the aortic rather than mitral valve, associated rhythm disturbance. Subacute bacterial endocarditis (Streptococcus viridans) has a better prognosis.


*[[Pericarditis]]<ref>{{cite web|url=http://www.mayoclinic.com/health/pericarditis/DS00505/DSECTION=symptoms |title=Pericarditis: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Myocarditis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/759212-overview |title=Myocarditis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-12-01 |accessdate=2010-03-09}}</ref>
===[[Tuberculosis]]===
<ref>{{cite web|url=http://www.webmd.com/lung/tc/tuberculosis-tb-topic-overview |title=Tuberculosis (Pulmonary Tuberculosis)-Symptoms, How It's Spread, Types |publisher=Webmd.com |date=2009-04-23 |accessdate=2010-03-09}}</ref>


'''Tuberculosis''' or '''TB''' (short for Tubercles [[Bacillus (shape)|Bacillus]]) is a common and often deadly [[infectious disease]] caused by [[mycobacterium|mycobacteria]], usually ''[[Mycobacterium tuberculosis]]'' in humans.<ref name=Robbins>{{cite book |author=Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. |year=2007 |title=Robbins Basic Pathology |edition=8th |publisher=Saunders Elsevier |pages=516–522 |isbn=978-1-4160-2973-1}}</ref> Tuberculosis usually attacks the [[lung]]s but can also affect other parts of the body. It is spread through the air, when people who have the disease cough, sneeze, or spit<ref name=AP>Konstantinos, A (2010). "Testing for tuberculosis". ''Australian Prescriber'', 33:12-18.  http://www.australianprescriber.com/magazine/33/1/12/18/</ref>. Most infections in humans result in an [[asymptomatic]], latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of its victims.

The classic symptoms are a [[cough|chronic cough]] with [[hemoptysis|blood-tinged]] [[sputum]], [[fever]], [[night sweats]], and [[weight loss]]. Infection of other organs causes a wide range of symptoms. [[Medical diagnosis|Diagnosis]] relies on [[tuberculosis radiology|radiology]] (commonly [[chest X-ray]]s), a [[Mantoux test|tuberculin skin test]], blood tests, as well as microscopic examination and [[microbiological culture]] of bodily fluids. [[Tuberculosis treatment|Treatment]] is difficult and requires long courses of multiple antibiotics. Contacts are also screened and treated if necessary. [[Antibiotic resistance]] is a growing problem in ([[Extensively drug-resistant tuberculosis|extensively]]) [[multi-drug-resistant tuberculosis]]. Prevention relies on screening programs and [[vaccination]], usually with [[Bacillus Calmette-Guérin]] vaccine.

A third of the world's population are thought to be infected with ''M. tuberculosis'',<ref>{{cite journal |author=Jasmer RM, Nahid P, Hopewell PC |title=Clinical practice. Latent tuberculosis infection |journal=N. Engl. J. Med. |volume=347 |issue=23 |pages=1860–6 |year=2002 |month=December |pmid=12466511 |doi=10.1056/NEJMcp021045 |url=http://jasoncartermd.com/resources/pdf/Latent%20TB%20Infection.pdf}}</ref> and new infections occur at a rate of about one per second.<ref name=WHO2004data/> The proportion of people who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing.<ref name=WHO2004data/> In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in [[Developing nation|developing countries]].<ref name=WHO2009-Epidemiology/> In addition, more people in the [[Developed country|developed world]] are contracting tuberculosis because their [[immune system]]s are compromised by [[immunosuppressive drug]]s, [[substance abuse]], or [[AIDS]].  The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5-10% of the US population test positive.<ref name=Robbins/>

Classification of [[Tuberculosis]]
{{Main|Tuberculosis classification}}

The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.{{Citation needed|date=June 2009}}

{| class="wikitable" style="font-size: 90%; text-align: left; "
|+ Classification System for TB
|- align="center"|
!Class || Type  || Description
|-
| 0 || No TB exposure<br/>Not infected || No history of exposure<br/>Negative reaction to [[tuberculin]] skin test
|-
| 1 || TB exposure<br/>No evidence of infection|| History of exposure<br/>Negative reaction to tuberculin skin test
|-
| 2 || TB infection <br/>No disease || Positive reaction to tuberculin skin test<br/>Negative bacteriologic studies (if done)<br/>No clinical, bacteriologic, or radiographic evidence of TB
|-
| 3 || TB, clinically active || ''M. tuberculosis'' cultured (if done)<br/> Clinical, bacteriologic, or radiographic evidence of current disease
|-
|4 ||TB <br/> Not clinically active || History of episode(s) of TB <br/> '''or''' <br/>Abnormal but stable radiographic findings <br/>Positive reaction to the tuberculin skin test<br/> Negative bacteriologic studies (if done) <br/> '''and'''<br/> No clinical or radiographic evidence of current disease
|-
|5||TB suspect ||Diagnosis pending<br/>TB disease should be ruled in or out within 3 months
|}

Signs and symptoms of [[Tuberculosis]]:
[[File:Tuberculosis symptoms.svg|thumb|Main symptoms of variants and stages of tuberculosis,<ref>[http://www.emedicinehealth.com/tuberculosis/page3_em.htm Tuberculosis Symptoms] From [[:en:eMedicine|eMedicine]]Health. Author: George Schiffman, MD, FCCP. Last Editorial Review: 1/15/2009</ref><ref>Additional symptoms for primary/early pulmonary infection: [http://www.wrongdiagnosis.com/t/tuberculosis/symptoms.htm wrongdiagnosis.com --> Diseases » Tuberculosis » Symptoms] Retrieved on 1 June 2009</ref> with many symptoms overlapping with other variants, while others are more (but not entirely) specifc for certain variants. Multiple variants may be present simultaneously.]]
[[Image:Mycobacterium tuberculosis.jpg|right|thumb|Scanning electron micrograph of ''[[Mycobacterium tuberculosis]]'']]
[[Image:Mycobacterium phylogenetic tree.png|thumb|right|[[Phylogenetic tree]] of the genus ''[[Mycobacterium]]''.]]

When the disease becomes active, 75% of the cases are [[pulmonary]] TB, that is, TB in the lungs. Symptoms include [[chest pain]], [[hemoptysis|coughing up blood]], and a productive, prolonged cough for more than three weeks. Systemic symptoms include [[fever]], [[rigor (medicine)|chills]], [[night sweats]], [[appetite loss]], [[weight loss]], [[pallor]], and often a tendency to [[fatigue (medical)|fatigue]] very easily.<ref name="WHO2004data"/>

In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extrapulmonary tuberculosis.<ref>[http://www.aafp.org/afp/20051101/1761.html Extrapulmonary Tuberculosis: An Overview] MARJORIE P. GOLDEN, M.D., Yale University School of Medicine and Hospital of Saint Raphael, New Haven, Connecticut. HOLENARASIPUR R. VIKRAM, M.D., Mayo Clinic, Scottsdale, Arizona.</ref> This occurs more commonly in [[immunosuppressed]] persons and young children. Extrapulmonary infection sites include the [[pleura]] in tuberculosis pleurisy, the [[central nervous system]] in [[meningitis]], the [[lymphatic system]] in [[scrofula]] of the neck, the [[genitourinary system]] in [[urogenital tuberculosis]], and bones and joints in [[Pott's disease]] of the spine. An especially serious form is disseminated TB, more commonly known as [[miliary tuberculosis]]. Extrapulmonary TB may co-exist with pulmonary TB as well.<ref name=CDCcourse>[[Centers for Disease Control and Prevention]] (CDC), Division of Tuberculosis Elimination. [http://www.cdc.gov/tb/pubs/corecurr/default.htm Core Curriculum on Tuberculosis: What the Clinician Should Know.] 4th edition (2000). Updated August 2003.</ref>

Causes of [[Tuberculosis]]:
{{Main|Mycobacterium tuberculosis}}

The primary cause of TB, ''[[Mycobacterium tuberculosis]]'', is a small [[aerobic organism|aerobic]] non-motile [[bacillus]]. High [[lipid]] content of this pathogen accounts for many of its unique clinical characteristics.<ref>{{cite book |last=Southwick |first=Frederick |title=Infectious Diseases: A Clinical Short Course, 2nd ed. |publisher=McGraw-Hill Medical Publishing Division |date=10 December 2007 |pages=313–314 |chapter=Chapter 4: Pulmonary Infections |page=104 |url=http://pharma-books.blogspot.com/2009/01/infectious-disease-clinical-short.html |isbn=0071477225}}</ref> It [[cell division|divides]] every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.<ref name=Cox_2004>{{cite journal |author=Cox R |title=Quantitative relationships for specific growth rates and macromolecular compositions of ''Mycobacterium tuberculosis'', ''Streptomyces coelicolor'' A3(2) and ''Escherichia coli'' B/r: an integrative theoretical approach |journal=Microbiology |volume=150 |issue=Pt 5 |pages=1413–26 |year=2004 |url=http://mic.sgmjournals.org/cgi/content/full/150/5/1413?view=long&pmid=15133103#R35 | pmid = 15133103 | doi = 10.1099/mic.0.26560-0}}</ref> (For example, one of the fastest-growing bacteria is a strain of ''[[E. coli]]'' that can divide roughly every 20 minutes.) Since MTB has a cell wall but lacks a [[phospholipid]] [[Bacterial cell structure|outer membrane]], it is [[Tuberculosis classification|classified]] as a [[Gram-positive]] bacterium. However, if a [[Gram stain]] is performed, MTB either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall.<ref name=Madison_2001>{{cite journal |author=Madison B |title=Application of stains in clinical microbiology |journal=Biotech Histochem |volume=76 |issue=3 |pages=119–25 |year=2001 |pmid=11475314 |doi=10.1080/714028138}}</ref> MTB can withstand weak [[disinfectant]]s and survive in a [[Endospore|dry state]] for weeks. In nature, the bacterium can grow only within the cells of a [[host (biology)|host]] organism, but ''M. tuberculosis'' can be cultured ''[[in vitro]]''.<ref name=Parish_1999>{{cite journal |author=Parish T, Stoker N |title=Mycobacteria: bugs and bugbears (two steps forward and one step back) |journal=Mol Biotechnol |volume=13 |issue=3 |pages=191–200 |year=1999 | pmid = 10934532 | doi = 10.1385/MB:13:3:191}}</ref>

Using [[histology|histological]] stains on expectorate samples from [[phlegm]] (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an [[acid-fast bacillus]] (AFB).<ref name=Robbins/><ref name=Madison_2001>{{cite journal |author=Madison B |title=Application of stains in clinical microbiology |journal=Biotech Histochem |volume=76 |issue=3 |pages=119–25 |year=2001 | pmid = 11475314 |doi=10.1080/714028138}}</ref> The most common acid-fast staining technique, the [[Ziehl-Neelsen stain]], dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an [[auramine-rhodamine stain]] and [[Fluorescence microscope|fluorescent microscopy]].

The ''M. tuberculosis'' complex includes four other TB-causing[[mycobacterium|mycobacteria]]: ''[[Mycobacterium bovis|M. bovis]]'', ''[[Mycobacterium africanum|M. africanum]]'', ''[[Mycobacterium canetti|M. canetti]]'' and ''[[Mycobacterium microti|M. microti]]''.<ref>{{cite journal |author=van Soolingen D, Hoogenboezem T, de Haas PE, ''et al.'' |title=A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa |journal=Int. J. Syst. Bacteriol. |volume=47 |issue=4 |pages=1236–45 |year=1997 |month=October |pmid=9336935 |doi=10.1099/00207713-47-4-1236 |url=http://ijs.sgmjournals.org/cgi/reprint/47/4/1236}}</ref> ''[[Mycobacterium africanum|M. africanum]]'' is not widespread, but in parts of Africa it is a significant cause of tuberculosis.<ref>{{cite journal |author=Niemann S, Rüsch-Gerdes S, Joloba ML, ''et al.'' |title=''Mycobacterium africanum'' subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda |journal=J. Clin. Microbiol. |volume=40 |issue=9 |pages=3398–405 |year=2002 |month=September |pmid=12202584 |pmc=130701 |url=http://jcm.asm.org/cgi/pmidlookup?view=long&pmid=12202584 |doi=10.1128/JCM.40.9.3398-3405.2002 |last12=Okwera |first12=A |last13=Schwander |first13=SK}}</ref><ref>{{cite journal |author=Niobe-Eyangoh SN, Kuaban C, Sorlin P, ''et al.'' |title=Genetic biodiversity of ''Mycobacterium tuberculosis'' complex strains from patients with pulmonary tuberculosis in Cameroon |journal=J. Clin. Microbiol. |volume=41 |issue=6 |pages=2547–53 |year=2003 |month=June |pmid=12791879 |pmc=156567 |url=http://jcm.asm.org/cgi/pmidlookup?view=long&pmid=12791879 |doi=10.1128/JCM.41.6.2547-2553.2003}}</ref> ''[[Mycobacterium bovis|M. bovis]]'' was once a common cause of tuberculosis, but the introduction of [[pasteurisation|pasteurized milk]] has largely eliminated this as a public health problem in developed countries.<ref name=Robbins/><ref>{{cite journal |author=Thoen C, Lobue P, de Kantor I |title=The importance of ''Mycobacterium bovis'' as a zoonosis |journal=Vet. Microbiol. |volume=112 |issue=2-4 |pages=339–45 |year=2006 |month=February |pmid=16387455 |doi=10.1016/j.vetmic.2005.11.047}}</ref> ''M. canetti'' is rare and seems to be limited to Africa, although a few cases have been seen in African emigrants.<ref>{{cite journal |author=Pfyffer GE, Auckenthaler R, van Embden JD, van Soolingen D |title=Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa |journal=Emerging Infect. Dis. |volume=4 |issue=4 |pages=631–4 |year=1998 |pmid=9866740 |pmc=2640258 |doi=10.3201/eid0404.980414}}</ref> ''M. microti'' is mostly seen in immunodeficient people, although it is possible that the [[prevalence]] of this pathogen has been underestimated.<ref name=Niemann_2000>{{cite journal |author=Niemann S, Richter E, Dalügge-Tamm H, Schlesinger H, Graupner D, Königstein B, Gurath G, Greinert U, Rüsch-Gerdes S |title=Two cases of ''Mycobacterium microti'' derived tuberculosis in HIV-negative immunocompetent patients |journal=Emerg Infect Dis |volume=6 |issue=5 |pages=539–42 |year=2000 |pmid = 10998387 |doi=10.3201/eid0605.000516 |pmc=2627952}}</ref>

Other known pathogenic [[Mycobacterium|mycobacteria]] include ''[[Mycobacterium leprae]]'', ''[[Mycobacterium avium complex|Mycobacterium avium]]'' and ''M. kansasii''. The last two are part of the [[nontuberculous mycobacteria]] (NTM) group. Nontuberculous mycobacteria cause neither TB nor [[leprosy]], but they ''do'' cause pulmonary diseases resembling TB.<ref name=ALA_1997>{{cite journal |author= |title=Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association |journal=Am J Respir Crit Care Med |volume=156 |issue=2 Pt 2 |pages=S1–25 |year=1997 |pmid = 9279284}}</ref>

*[[Histoplasmosis]],also known as darling's disease.<ref>{{cite web|url=http://www.mayoclinic.com/health/histoplasmosis/DS00517/DSECTION=symptoms |title=Histoplasmosis: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Septic arthritis]]<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/000430.htm |title=Septic arthritis: MedlinePlus Medical Encyclopedia |publisher=Nlm.nih.gov |date= |accessdate=2010-03-09}}</ref>
*[[Fifth disease]]<ref>{{cite web|url=http://www.mayoclinic.com/health/parvovirus-infection/DS00437/DSECTION=symptoms |title=Parvovirus infection: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Roseola]]<ref>{{cite web|url=http://kidshealth.org/parent/infections/skin/roseola.html |title=Roseola |publisher=Kidshealth.org |date= |accessdate=2010-03-09}}</ref>
*[[Toxic shock syndrome]]<ref>{{cite web|url=http://www.emedicinehealth.com/toxic_shock_syndrome/article_em.htm |title=Toxic Shock Syndrome |publisher=Emedicinehealth.com |date= |accessdate=2010-03-09}}</ref>
*[[Paratyphoid fever]]<ref>{{cite web|url=http://www.who.int/water_sanitation_health/diseases/typhoid/en/ |title=WHO &#124; Water-related Diseases |publisher=Who.int |date=2009-02-21 |accessdate=2010-03-09}}</ref>
*[[Hepatitis A]]<ref>{{cite web|url=http://www.mayoclinic.com/health/hepatitis-a/DS00397/DSECTION=symptoms |title=Hepatitis A: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Cat scratch disease]]<ref>{{cite web|url=http://www.webmd.com/a-to-z-guides/cat-scratch-disease |title=Cat Scratch Disease |publisher=Webmd.com |date=2009-04-08 |accessdate=2010-03-09}}</ref>
*[[Respiratory syncytial virus]]<ref>{{cite web|url=http://www.cdc.gov/RSV/clinical/description.html |title=CDC - RSV: Clinical Description and Diagnosis |publisher=Cdc.gov |date= |accessdate=2010-03-09}}</ref>
*[[Echovirus]]<ref>{{cite web|url=http://emedicine.medscape.com/article/216564-overview |title=Echoviruses: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-11-25 |accessdate=2010-03-09}}</ref>
*[[Coxsackie virus]]<ref>{{cite web|url=http://kidshealth.org/parent/infections/bacterial_viral/coxsackie.html |title=Coxsackievirus Infections |publisher=Kidshealth.org |date= |accessdate=2010-03-09}}</ref>
*[[Poliomyelitis]]<ref>{{cite web|url=http://www.health.state.ny.us/diseases/communicable/poliomyelitis/fact_sheet.htm |title=Poliomyelitis (infantile paralysis, polio) |publisher=Health.state.ny.us |date= |accessdate=2010-03-09}}</ref>
*[[Rickettsialpox]]<ref>{{cite web|url=http://emedicine.medscape.com/article/227956-overview |title=Rickettsialpox: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-04-11 |accessdate=2010-03-09}}</ref>
*[[Trench fever]]<ref>{{cite web|url=http://emedicine.medscape.com/article/230294-overview |title=Trench Fever: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-02-20 |accessdate=2010-03-09}}</ref>
*[[Human Anaplasmosis]]<ref>{{cite web|url=http://www.health.state.mn.us/divs/idepc/diseases/anaplasmosis/hcp.html |title=Human Anaplasmosis Information for Health Professionals - Minnesota Dept. of Health |publisher=Health.state.mn.us |date=2009-11-30 |accessdate=2010-03-09}}</ref>
*[[Chagas disease]], often along with hepatosplenomegaly<ref>{{cite web|url=http://emedicine.medscape.com/article/214581-overview |title=Chagas Disease (American Trypanosomiasis): eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-12-17 |accessdate=2010-03-09}}</ref><ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/chagasdisease.html |title=Chagas Disease: MedlinePlus |publisher=Nlm.nih.gov |date= |accessdate=2010-03-09}}</ref>
*[[Anthrax]]<ref>{{cite web|url=http://www.bt.cdc.gov/agent/anthrax/faq/signs.asp |title=CDC Anthrax Q & A: Signs and Symptoms |publisher=Bt.cdc.gov |date=2003-06-02 |accessdate=2010-03-09}}</ref>
*[[Legionellosis]]<ref>{{cite web|url=http://www.health.state.ny.us/diseases/communicable/legionellosis/fact_sheet.htm |title=Legionellosis (Legionnaires' disease) |publisher=Health.state.ny.us |date= |accessdate=2010-03-09}}</ref>
*[[Listeria]] infection<ref>{{cite web|url=http://www.webmd.com/a-to-z-guides/listeriosis-topic-overview |title=Listeriosis-Topic Overview |publisher=Webmd.com |date=2009-02-23 |accessdate=2010-03-09}}</ref>
*[[Primary amebic meningoencephalitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/996227-overview |title=Amebic Meningoencephalitis: eMedicine Pediatrics: General Medicine |publisher=Emedicine.medscape.com |date=2009-01-21 |accessdate=2010-03-09}}</ref>
*[[Rift valley fever]]<ref>{{cite web|url=http://www.who.int/mediacentre/factsheets/fs207/en/ |title=WHO &#124; Rift Valley fever |publisher=Who.int |date=2008-12-29 |accessdate=2010-03-09}}</ref>
*[[Hantavirus pulmonary syndrome]]<ref>https://health.google.com/health/ref/Hantavirus></ref>
*[[Lymphocytic choriomeningitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/220796-overview |title=Lymphocytic Choriomeningitis: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-02-06 |accessdate=2010-03-09}}</ref>
*[[Rat-bite fever]]<ref>{{cite web|url=http://www.cdc.gov/nczved/dfbmd/disease_listing/ratbitefever_gi.html |title=CDC - Division of Foodborne, Bacterial and Mycotic Diseases (DFBMD) - NCZVED |publisher=Cdc.gov |date= |accessdate=2010-03-09}}</ref>
*[[Rotavirus|Rotavirus disease]]<ref>{{cite web|url=http://www.medicinenet.com/rotavirus/article.htm |title=Rotavirus Symptoms, Causes, Treatment, Vaccine and Diagnosis on |publisher=Medicinenet.com |date= |accessdate=2010-03-09}}</ref>
*[[Severe Acute Respiratory Syndrome]]<ref>{{cite web|url=http://health.nytimes.com/health/guides/disease/severe-acute-respiratory-syndrome-sars/overview.html |title=Severe Acute Respiratory Syndrome SARS - Symptoms, Diagnosis, Treatment of Severe Acute Respiratory Syndrome SARS - NY Times Health Information |publisher=Health.nytimes.com |date=2009-02-03 |accessdate=2010-03-09}}</ref>
*[[Toxoplasmosis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/229969-overview |title=Toxoplasmosis: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-01-27 |accessdate=2010-03-09}}</ref>
*[[Leishmaniasis]]<ref>https://health.google.com/health/ref/Leishmaniasis</ref>
*[[Staphylococcal scalded skin syndrome]]<ref>{{cite web|url=http://emedicine.medscape.com/article/788199-overview |title=Staphylococcal Scalded Skin Syndrome: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-06-18 |accessdate=2010-03-09}}</ref>
*[[Otitis media]]<ref>{{cite web|url=http://emedicine.medscape.com/article/764006-overview |title=Otitis Media: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
*[[Malignant otitis externa]]<ref>https://health.google.com/health/ref/Malignant+otitis+externa</ref>
*[[Bacterial sinusitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/764534-overview |title=Sinusitis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
*[[Retropharyngeal abscess]]<ref>{{cite web|url=http://emedicine.medscape.com/article/764421-overview |title=Retropharyngeal Abscess: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-09-16 |accessdate=2010-03-09}}</ref>
*[[Peritonsillar abscess]]<ref>{{cite web|url=http://emedicine.medscape.com/article/764188-overview |title=Peritonsillar Abscess: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-03-11 |accessdate=2010-03-09}}</ref>
*[[Epiglottitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/801369-overview |title=Pediatrics, Epiglottitis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-01-29 |accessdate=2010-03-09}}</ref>
*[[Rabies]]<ref>{{cite web|url=http://emedicine.medscape.com/article/785543-overview |title=Rabies: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-05-11 |accessdate=2010-03-09}}</ref>
*[[Venezuelan equine encephalitis virus]]<ref>{{cite web|url=http://emedicine.medscape.com/article/233913-overview |title=Venezuelan Encephalitis: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-10-10 |accessdate=2010-03-09}}</ref>
*[[Herpes simplex encephalitis]]
*[[Dental abscess]]<ref>https://health.google.com/health/ref/Tooth+abscess</ref>
*[[Brain abscess]]<ref>{{cite web|url=http://emedicine.medscape.com/article/212946-overview |title=Brain Abscess: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2008-06-26 |accessdate=2010-03-09}}</ref>
*[[Croup]]<ref>{{cite web|url=http://emedicine.medscape.com/article/962972-overview |title=Croup: eMedicine Pediatrics: General Medicine |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
*[[Pyelonephritis]]<ref>{{cite web|url=http://www.mayoclinic.com/health/kidney-infection/DS00593/DSECTION=symptoms |title=Kidney infection: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Cystitis]]<ref>{{cite web|url=http://www.mayoclinic.com/health/cystitis/DS00285/DSECTION=symptoms |title=Cystitis: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Cholangitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/774245-overview |title=Cholangitis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-09-29 |accessdate=2010-03-09}}</ref>
*[[Hepatic abscess]]<ref>{{cite web|url=http://emedicine.medscape.com/article/193182-overview |title=Pyogenic Hepatic Abscesses: eMedicine General Surgery |publisher=Emedicine.medscape.com |date=2009-01-23 |accessdate=2010-03-09}}</ref>
*[[Orbital cellulitis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/1217858-overview |title=Cellulitis, Orbital: eMedicine Ophthalmology |publisher=Emedicine.medscape.com |date=2009-12-23 |accessdate=2010-03-09}}</ref>

==Rheumatic/autoimmune==
===[[Rheumatic fever]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/808945-overview |title=Rheumatic Fever: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>
'''Rheumatic fever''' is an [[inflammatory disease|inflammatory]] [[disease]] that occurs following a [[Group A streptococcal infection]], (such as [[strep throat]] or [[scarlet fever]]). Believed to be caused by [[antibody]] [[cross-reactivity]] that can involve the [[heart]], [[joint]]s, [[skin]], and [[brain]],<ref name=Robbins> Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; & Mitchell, Richard N. (2007). ''Robbins Basic Pathology'' (8th ed.). Saunders Elsevier. pp. 403-406 ISBN 978-1-4160-2973-1</ref> the illness typically develops two to three weeks after a streptococcal infection. Acute rheumatic fever commonly appears in children between the ages of 5 and 15, with only 20% of first-time attacks occurring in adults.<ref name=Robbins/> The illness is so named because of its similarity in presentation to [[rheumatism]].<ref>{{DorlandsDict|nine/000956569|rheumatic fever}}</ref>

'''Diagnosis of Rheumatic fever:'''
 [[Image:Rheumatic heart disease, gross pathology 20G0013 lores.jpg|thumb|right|'''Rheumatic heart disease''' at [[autopsy]] with characteristic findings (thickened [[mitral valve]], thickened [[chordae tendineae]], hypertrophied left ventricular [[myocardium]]).]]
Modified Jones criteria were first published in 1944 by T. Duckett Jones, MD.<ref>{{cite journal |author=Jones TD |title=The diagnosis of rheumatic fever. |journal=[[Journal of the American Medical Association|JAMA]] |volume=126 |issue= |pages=481–4 |year=1944 |pmid= |doi= |url=}}</ref> They have been periodically revised by the [[American Heart Association]] in collaboration with other groups.<ref>{{cite journal |author=Ferrieri P |title=Proceedings of the Jones Criteria workshop |journal=Circulation |volume=106 |issue=19 |pages=2521–3 |year=2002 |pmid=12417554 |doi= 10.1161/01.CIR.0000037745.65929.FA|url=http://circ.ahajournals.org/cgi/content/full/106/19/2521?ck=nck |last2=Jones Criteria Working |first2=Group}}</ref> According to revised Jones criteria, the diagnosis of rheumatic fever can be made when two of the major criteria, or one major criterion plus two minor criteria, are present along with evidence of streptococcal infection.  Exceptions are [[chorea (disease)|chorea]] and [[indolent carditis]], each of which by itself can indicate rheumatic fever.  <ref>{{cite web |url=http://www.emedicine.com/emerg/topic509.htm |title=eMedicine — Rheumatic Fever | author = Steven J Parrillo, DO, FACOEP, FACEP |accessdate=2007-07-14 |work=}}</ref><ref>{{cite journal |author= |title=Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association |journal=JAMA |volume=268 |issue=15 |pages=2069–73 |year=1992 |pmid=1404745 |doi=}}</ref><ref>{{cite journal|first=Anita|last=Saxena|title=Diagnosis of rheumatic fever: Current status of Jones criteria and role of echocardiography|journal=Indian Journal of Pediatrics|volume=67|issue=4|pages=283–6|year=2000|pmid=11129913|doi=10.1007/BF02758174}}</ref>
	 
'''Major criteria:'''
*[[Arthritis|Migratory polyarthritis]]: a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards. 	
*[[Carditis]]: inflammation of the heart muscle which can manifest as [[congestive heart failure]] with shortness of breath, [[pericarditis]] with a rub, or a new [[heart murmur]].  
*Subcutaneous nodules: painless, firm collections of collagen fibers over bones or [[tendons]]. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees. 
*[[Erythema marginatum]]: a long lasting [[rash]] that begins on the trunk or arms as [[macule]]s and spreads outward to form a snake like ring while clearing in the middle. This rash never starts on the face and it is made worse with heat.  
*[[Sydenham's chorea]] (St. Vitus' dance): a characteristic series of rapid movements without purpose of the face and arms. This can occur very late in the disease.

'''Minor criteria:''' 	 
*[[Fever]] 
*[[Arthralgia]]: Joint pain without swelling 
*Raised [[Erythrocyte sedimentation rate]] or [[C reactive protein]]
*[[Leukocytosis]] 
*[[Electrocardiogram|ECG]] showing features of [[heart block]], such as a prolonged [[PR interval]]<ref>http://www.utmb.edu/Pedi_Ed/CoreConceptsOfPediatrics/Cardiology/page_40.htm</ref>
*Supporting evidence of Streptococcal infection: elevated or rising [[Antistreptolysin O titre]] or DNAase.<ref name=Robbins/>.
*Previous episode of rheumatic fever or inactive heart disease

*[[Henoch-Schonlein purpura]]<ref>{{cite web|url=http://familydoctor.org/online/famdocen/home/children/parents/special/birth/312.html |title=Henoch-Schönlein Purpura |publisher=familydoctor.org |date=1998-08-01 |accessdate=2010-03-09}}</ref>
*[[Kawasaki disease]]<ref>https://health.google.com/health/ref/Kawasaki+disease</ref>
*[[Systemic lupus erythematosus]]<ref>{{cite web|url=http://emedicine.medscape.com/article/332244-overview |title=Systemic Lupus Erythematosus: eMedicine Rheumatology |publisher=Emedicine.medscape.com |date=2009-01-22 |accessdate=2010-03-09}}</ref>
*[[Polyarteritis nodosa]]<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/001438.htm |title=Polyarteritis nodosa: MedlinePlus Medical Encyclopedia |publisher=Nlm.nih.gov |date= |accessdate=2010-03-09}}</ref>
*[[Temporal arteritis]]<ref>{{cite web|url=http://emedicine.medscape.com/article/809492-overview |title=Temporal Arteritis: eMedicine Emergency Medicine |publisher=Emedicine.medscape.com |date=2009-09-08 |accessdate=2010-03-09}}</ref>
*[[Polymyalgia rheumatica]]<ref>https://www.vasculitisfoundation.org/polymyalgiarheumatica</ref>
*[[Wegener's Granulomatosis]]<ref>https://www.vasculitisfoundation.org/wegenersgranulomatosis</ref>
*[[Sarcoidosis]]<ref>{{cite web|author=Foundation for Sarcoidosis Research |url=http://www.stopsarcoidosis.org/sarcoidosis/symptoms.htm |title=FSR - Symptoms of Sarcoidosis |publisher=Stopsarcoidosis.org |date= |accessdate=2010-03-09}}</ref><ref>{{cite web|url=http://emedicine.medscape.com/article/1123970-overview |title=Sarcoidosis: eMedicine Dermatology |publisher=Emedicine.medscape.com |date=2009-09-08 |accessdate=2010-03-09}}</ref>

==Malignant==
===[[Lymphoma]]===
'''Lymphoma''' is a [[cancer]] that begins in the [[lymphocyte]]s of the [[immune system]] and presents as a solid [[tumor]] of lymphoid cells. It is treatable with chemotherapy, and in some cases radiotherapy and/or [[bone marrow transplantation]], and can be curable, depending on the histology, type, and stage of the disease.<ref name="isbn0-8153-4093-1">{{cite book |author=Parham, Peter |title=The immune system |publisher=Garland Science |location=New York |year=2005 |page=414 |isbn=0-8153-4093-1 }}</ref> These malignant cells often originate in [[lymph node]]s, presenting as an enlargement of the node (a tumor). Lymphomas are closely related to [[lymphoid leukemia]]s, which also originate in lymphocytes but typically involve only circulating blood and the [[bone marrow]] (where blood cells are generated in a process termed [[haematopoesis]]) and do not usually form static tumors.<ref name="isbn0-8153-4093-1">{{cite book |author=Parham, Peter |title=The immune system |publisher=Garland Science |location=New York |year=2005 |page=414 |isbn=0-8153-4093-1 }}</ref> There are many types of lymphomas, and in turn, lymphomas are a part of the broad group of diseases called [[Hematological malignancy|hematological neoplasms]].

[[Thomas Hodgkin]] published the first description of lymphoma in 1832, specifically of the form named after him, [[Hodgkin's lymphoma]].<ref name="Mauch1999">{{cite book | last = Hellman | first = Samuel | authorlink =  | coauthors = Mauch, P.M. Ed. | title = Hodgkin's Disease | publisher = Lippincott Williams & Wilkins | date = 1999 | location = Chapter 1 | page = 5 | url = | doi =  | id = | isbn = 0-7817-1502-4}}</ref> Since then, many other forms of lymphoma have been described, grouped under several proposed classifications. The 1982 [[Working formulation]] classification became very popular. It introduced the category [[non-Hodgkin lymphoma]] (NHL), divided into 16 different diseases. However, because these different lymphomas have little in common with each other, the NHL label is of limited usefulness for doctors or patients and is slowly being abandoned. The latest classification by the [[World Health Organization|WHO]] (2001) lists 43 different forms of lymphoma divided in four broad groups.

Some forms of lymphoma are categorized as indolent (e.g. [[small lymphocytic lymphoma]]), compatible with a long life even without treatment, whereas other forms are aggressive (e.g. [[Burkitt's lymphoma]]), causing rapid deterioration and death.  However, most of the aggressive lymphomas respond well to treatment and are curable. The [[prognosis]] therefore depends on the correct classification of the disease, established by a [[pathology|pathologist]] after examination of a [[biopsy]].<ref>Wagman LD. [http://www.cancernetwork.com/cancer-management-11/chapter01/article/10165/1399286 "Principles of Surgical Oncology"] in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) [http://www.cancernetwork.com/cancer-management-11/ Cancer Management: A Multidisciplinary Approach]. 11 ed. 2008.</ref>

Although older classifications referred to histiocytic lymphomas, these are recognized in newer classifications as of [[B cell|B]], [[T cell|T]] or [[NK cell]] lineage. True [[histiocyte|histiocytic]] malignancies are rare and are classified as [[sarcoma]]s.<ref name = "isbn92-832-2411-6"/>

Classification of lymphoma:
A number of different classification systems exist for lymphoma.
As an alternative to the American Lukes-Butler classification, in the early 1970s, Karl Lennert of [[Kiel]], Germany, proposed a new system of classifying lymphomas based on cellular [[morphology (biology)|morphology]] and their relationship to cells of the normal peripheral lymphoid system.<ref name="isbn3-540-63801-6">{{cite book |author=Lennert, Karl; Feller, Alfred C.; Jacques Diebold; M. Paulli; A. Le Tourneau |title=Histopathology of Non-Hodgkin's Lymphomas (Based on the Updated Kiel Classification) |publisher=Springer |location=Berlin |year=2002 |pages=2 |isbn=3-540-63801-6 |oclc= |doi= |accessdate=}}</ref>

REAL:
In the mid 1990s, the '''Revised European-American Lymphoma (REAL) Classification''' attempted to apply immunophenotypic and genetic features in identifying distinct clinicopathologic entities among all the lymphomas except [[Hodgkin's lymphoma]].<ref>www.emedicine.com on Lymphoma, Non-Hodgkin</ref>  REAL has been superseded by the WHO classification.

WHO:

The '''WHO Classification''', published in 2001 and updated in 2008,<ref name="isbn92-832-2411-6">{{cite book |author= ed. by Elaine S. Jaffe ....|title=Pathology and Genetics of Haemo (World Health Organization Classification of tumors S.) |publisher=Oxford Univ Pr |location= |year= 2001|pages= |isbn=92-832-2411-6 |oclc= |doi=}}</ref> is the latest classification of lymphoma and is based upon the foundations laid within the "Revised European-American Lymphoma classification" (REAL). This system attempts to group lymphomas by cell type (i.e. the normal cell type that most resembles the tumor) and defining [[phenotypic]], [[molecular]] or [[cytogenetic]] characteristics. There are three large groups: the [[B cell]], [[T cell]], and [[natural killer cell]] tumors. Other less common groups, are also recognized. Hodgkin's lymphoma, although considered separately within the [[WHO]] (and preceding) classifications, is now recognized as being a tumor of, albeit markedly abnormal, lymphocytes of mature B cell lineage.

Mature [[B cell]] neoplasms:
[[Image:lymphoma microarray.jpg|thumb|right|DNA-microarray analysis of Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in lymphoma cells (as compared to normal cells), whereas red indicates genes that are overexpressed in lymphoma cells.]]

*[[Chronic lymphocytic leukemia]]/[[Small lymphocytic lymphoma]]
*[[B-cell prolymphocytic leukemia]]
*[[Lymphoplasmacytic lymphoma]] (such as [[Waldenström macroglobulinemia]])
*[[Splenic marginal zone lymphoma]]
*[[Plasma cell]] neoplasms:
**[[Plasma cell myeloma]]
**[[Plasmacytoma]]
**[[Monoclonal immunoglobulin deposition diseases]]
**[[Heavy chain diseases]]
*[[Extranodal marginal zone B cell lymphoma]], also called [[MALT lymphoma]]
*[[Nodal marginal zone B cell lymphoma]] (NMZL)
*[[Follicular lymphoma]]
*[[Mantle cell lymphoma]]
*[[Diffuse large B cell lymphoma]]
*[[Mediastinal tumor|Mediastinal]] (thymic) large B cell lymphoma
*[[Intravascular large B cell lymphoma]]
*[[Primary effusion lymphoma]]
*[[Burkitt's lymphoma|Burkitt lymphoma/leukemia]]
<ref>{{cite web|url=http://www.leukemia-lymphoma.org/all_mat_toc.adp?item_id=59546 |title=Leukemia & Lymphoma Society |publisher=Leukemia-lymphoma.org |date=2001-01-08 |accessdate=2010-03-09}}</ref><ref>{{cite web|url=http://www.leukemia-lymphoma.org/all_page?item_id=8312 |title=Leukemia & Lymphoma Society - Hodgkin Lymphoma Facts & Statistics |publisher=Leukemia-lymphoma.org |date= |accessdate=2010-03-09}}</ref>
<ref>{{cite web|url=http://www.leukemia-lymphoma.org/all_page?item_id=8965 |title=Leukemia & Lymphoma Society - Non-Hodgkin Lymphoma Facts & Statistics |publisher=Leukemia-lymphoma.org |date= |accessdate=2010-03-09}}</ref> <ref>{{cite web|url=http://www.merck.com/mmpe/sec11/ch142/ch142b.html |title=Acute Leukemia: Leukemias: Merck Manual Professional |publisher=Merck.com |date= |accessdate=2010-03-09}}</ref>
===[[Acute lymphoblastic leukemia]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/207631-overview |title=Acute Lymphoblastic Leukemia: eMedicine Hematology |publisher=Emedicine.medscape.com |date=2009-02-03 |accessdate=2010-03-09}}</ref>
'''Acute lymphoblastic leukemia''' ('''ALL'''), also known as is a form of [[leukemia]], or [[hematological malignancy|cancer of the white blood cells]] characterized by excess [[lymphoblast]]s.

[[Malignant]], immature [[lymphoblasts|white blood cells]] continuously multiply and are overproduced in the [[bone marrow]]. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading ([[metastasis|metastasizing]]) to other organs. ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age. The overall cure rate in children is 85%, and about 50% of adults have long-term disease-free survival.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th Edition,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref> 

''Acute'' refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of [[Chronic Lymphocytic Leukemia]] which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic (although lymphoblastic is becoming the preferred term). This refers to the cells that are involved, which if they were normal would be referred to as [[lymphocytes]] but are seen in this disease in a relatively immature (also termed 'blast') state.

Symptoms of ALL:

Initial symptoms are not specific to ALL, but worsen to the point that medical help is sought. The signs and symptoms of ALL are variable but follow from bone marrow replacement and/or organ infiltration. 
* Generalized weakness and [[Fatigue (physical)|fatigue]]
* [[Anemia]]
* Frequent or unexplained [[fever]] and [[infection]]s
* Weight loss and/or loss of appetite
* Excessive and unexplained bruising
* [[Bone pain]], [[joint pain]]s (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
* [[Breathlessness]]
* Enlarged [[lymph nodes]], [[liver]] and/or [[spleen]]
* Pitting edema (swelling) in the lower limbs and/or abdomen
* [[Petechia]]e, which are tiny red spots or lines in the skin due to low [[platelet]] levels

The signs and [[symptoms]] of ALL result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature [[leukocytes]] (white blood cells). Therefore, people with ALL experience symptoms from malfunctioning of their [[erythrocytes]] (red blood cells), leukocytes, and platelets. Laboratory tests which might show abnormalities include [[blood count]] tests, [[renal function]] tests, [[electrolyte]] tests and [[liver enzyme]] tests.

Diagnosis of ALL:

[[medical diagnosis|Diagnosing]] ALL begins with a medical history and [[physical examination]], [[Full blood count|complete blood count]], and blood smears. Because the symptoms are so general, many other diseases with similar symptoms must be excluded. Typically, the higher the white blood cell count, the worse the prognosis.<ref>{{cite book
  | last = Collier
  | first = J.A.B
  | title = Oxford Handbook of Clinical Specialties, Third Edition
  | publisher = Oxford
  | date = 1991
  | pages = 810
  | isbn = 0-19-262116-5}}</ref> Blast cells are seen on [[blood smear]] in 90% of cases. A [[bone marrow biopsy]] is conclusive proof of ALL.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th EditioN,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref> A [[lumbar puncture]] (also known as a spinal tap) will tell if the spinal column and [[central nervous system|brain]] has been invaded. 

[[Histopathology|Pathological]] examination, [[cytogenetics]] (particularly the presence of [[Philadelphia chromosome]]) and [[immunophenotyping]], establish whether the "blast" cells began from the [[B lymphocyte]]s or [[T lymphocyte]]s. DNA testing can establish how aggressive the disease is; different mutations have been associated with shorter or longer survival. 

[[Medical imaging]] (such as [[medical ultrasonography|ultrasound]] or [[CT scan]]ning) can find invasion of other [[Organ (anatomy)|organs]] commonly the [[lung]], liver, spleen, lymph nodes, brain, kidneys and reproductive organs.<ref>[http://www.merck.com Merck Manual] {{Fact|date=September 2007}}</ref>

Pathophysiology of ALL:

The cause of most ALL is not known. In general, cancer is caused by damage to [[Deoxyribonucleic Acid|DNA]] that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth, or interrupting chemical signals that control growth. Damage can be caused through the formation of [[fusion genes]], as well as the dysregulation of a  [[proto-oncogene]] via juxtaposition of it to the promotor of another gene, e.g. the [[T-cell receptor]] gene. This damage may be caused by environmental factors such as chemicals, drugs or radiation. 

ALL is associated with exposure to [[ionizing radiation|radiation]] and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the [[Chernobyl]] nuclear reactor and [[atom bombs]] in [[Hiroshima]] and [[Nagasaki, Nagasaki|Nagasaki]]. In animals, exposure to [[benzene]] and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Some evidence suggests that secondary leukemia can develop in individuals who are treated for other cancers with radiation and chemotherapy as a result of that treatment.<ref name=smith>{{cite journal
 | first = Malcolm A.
 | last = Smith
 | authorlink = 
 | author = 
 | coauthors = et al.
 | curly = Secondary Leukemia or Myelodysplastic Syndrome After Treatment With Epipodophyllotoxins
 | issue = 2
 | volume = 17
 | url = http://jco.ascopubs.org/cgi/reprint/17/2/569
 | format = PDF
 | journal = Journal of Clinical Oncology
 | publisher = American Society for Clinical Oncology 
 | pages = 569–77
 | page = 
 | year = 1999
 | month = Feb
 | title = Secondary Leukemia or Myelodysplastic Syndrome After Treatment With Epipodophyllotoxins
 | pmid = 10080601
 }}
</ref>

Cytogenetics:

Cytogenetic [[translocations]] associated with specific molecular genetic abnormalities in ALL
{| class="wikitable"
!Cytogenetic translocation         
!Molecular genetic abnormality
!%
|-
|cryptic t(12;21)                    
| [[ETV6|TEL]]-[[AML1]] fusion<ref name="pmid15837750">{{cite journal |author=Stams WA, den Boer ML, Beverloo HB, ''et al.'' |title=Expression levels of TEL, AML1, and the fusion products TEL-AML1 and AML1-TEL versus drug sensitivity and clinical outcome in t(12;21)-positive pediatric acute lymphoblastic leukemia |journal=Clin. Cancer Res. |volume=11 |issue=8 |pages=2974–80 |year=2005 |month=April |pmid=15837750 |doi=10.1158/1078-0432.CCR-04-1829 |url=http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15837750}}</ref>
| 25.4%<ref name="pmid18665825">{{cite journal |author=Pakakasama S, Kajanachumpol S, Kanjanapongkul S, ''et al.'' |title=Simple multiplex RT-PCR for identifying common fusion transcripts in childhood acute leukemia |journal=Int J Lab Hematol |volume=30 |issue=4 |pages=286–91 |year=2008 |month=August |pmid=18665825 |doi=10.1111/j.1751-553X.2007.00954.x |url=http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1751-5521&date=2008&volume=30&issue=4&spage=286}}</ref>
|-
|t(1;19)(q23;p13)                   
|[[E2A]]-[[Pre-B-cell leukemia homeobox|PBX]] ([[PBX1]]) fusion<ref name="pmid10500199">{{cite journal |author=McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR, Murre C |title=Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=20 |pages=11464–9 |year=1999 |month=September |pmid=10500199 |pmc=18056 |doi= 10.1073/pnas.96.20.11464|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10500199}}</ref>
| 4.8%<ref name="pmid18665825"/>
|-
|t(9;22)(q34;q11)
|[[BCR-ABL]] fusion(P185)<ref name="pmid16080957">{{cite journal |author=Rudolph C, Hegazy AN, von Neuhoff N, ''et al.'' |title=Cytogenetic characterization of a BCR-ABL transduced mouse cell line |journal=Cancer Genet. Cytogenet. |volume=161 |issue=1 |pages=51–6 |year=2005 |month=August |pmid=16080957 |doi=10.1016/j.cancergencyto.2004.12.021 |url=http://linkinghub.elsevier.com/retrieve/pii/S0165-4608(05)00019-1}}</ref>
| 1.6%<ref name="pmid18665825"/>
|-
|t(4;11)(q21;q23)                  
|[[MLL (gene)|MLL]]-[[AF4]] fusion<ref name="pmid14990976">{{cite journal |author=Caslini C, Serna A, Rossi V, Introna M, Biondi A |title=Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein |journal=Leukemia |volume=18 |issue=6 |pages=1064–71 |year=2004 |month=June |pmid=14990976 |doi=10.1038/sj.leu.2403321}}</ref>
| 1.6%<ref name="pmid18665825"/>
|-
|t(8;14)(q24;q32)                    
|[[IGH]]-[[MYC]] fusion<ref name="pmid15852472">{{cite journal |author=Martín-Subero JI, Odero MD, Hernandez R, ''et al.'' |title=Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas |journal=Genes Chromosomes Cancer |volume=43 |issue=4 |pages=414–23 |year=2005 |month=August |pmid=15852472 |doi=10.1002/gcc.20187}}</ref>
|-
|t(11;14)(p13;q11)                   
|[[TCR]]-[[RBTN2]] fusion <ref name="pmid7497440">{{cite journal |author=Zalcberg IQ, Silva ML, Abdelhay E, ''et al.'' |title=Translocation 11;14 in three children with acute lymphoblastic leukemia of T-cell origin |journal=Cancer Genet. Cytogenet. |volume=84 |issue=1 |pages=32–8 |year=1995 |month=October |pmid=7497440 |doi= 10.1016/0165-4608(95)00062-3|url=http://linkinghub.elsevier.com/retrieve/pii/0165460895000623}}</ref>
|}

Prognosis of ALL:

The survival rate has improved from zero four decades ago, to 20-75 percent currently, largely due to [[clinical trial]]s on new chemotherapeutic agents and improvements in [[stem cell transplantation]] (SCT) technology.

Five-year survival rates evaluate older, not current, treatments. New drugs, and matching treatment to the genetic characteristics of the blast cells, may improve those rates. The prognosis for ALL differs between individuals depending on a variety of factors:

* Sex: females tend to fare better than males.
* Ethnicity: [[Whites|Caucasians]] are more likely to develop acute leukemia than [[African American|African-Americans]], [[Asian American|Asians]] and [[Hispanics in the United States|Hispanics]] and tend to have a better prognosis than non-Caucasians.
* Age at diagnosis: children between 1–10 years of age are most likely to develop ALL and to be cured of it.  Cases in older patients are more likely to result from chromosomal abnormalities (e.g. the Philadelphia chromosome) that make treatment more difficult and prognoses poorer.
* White blood cell count at diagnosis of less than 50,000/µl
* Cancer spread into the [[Central nervous system]] ([[brain]] or [[spinal cord]]) has worse outcomes.
* Morphological, immunological, and genetic subtypes
* Patient's response to initial treatment
* [[Genetic disorder]]s such as [[Down syndrome|Down's Syndrome]]

*[[Acute myeloid leukemia]]<ref>https://health.google.com/health/ref/Acute+myeloid+leukemia</ref>
*[[Chronic myeloid leukemia]]<ref>{{cite web|url=http://www.mayoclinic.com/health/chronic-myelogenous-leukemia/DS00564/DSECTION=symptoms |title=Chronic myelogenous leukemia: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Chronic lymphocytic leukemia]]<ref>{{cite web|url=http://www.mayoclinic.com/health/chronic-lymphocytic-leukemia/DS00565/DSECTION=symptoms |title=Chronic lymphocytic leukemia: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Juvenile myelomonocytic leukemia]]<ref>{{cite web|url=http://www.jmmlfoundation.org/modules.php?name=Content&pa=showpage&pid=7/ |title=Content |publisher=JMML Foundation |date=2005-05-13 |accessdate=2010-03-09}}</ref>
===[[Renal cell carcinoma]]===
{{main|Renal cell carcinoma}}
<ref>{{cite web|url=http://emedicine.medscape.com/article/281340-overview |title=Renal Cell Carcinoma: eMedicine Oncology |publisher=Emedicine.medscape.com |date=2009-06-25 |accessdate=2010-03-09}}</ref>

'''Renal cell carcinoma''' ('''RCC''', also known as '''hypernephroma''') is a [[kidney cancer]] that originates in the lining of the [[Proximal tubule|proximal convoluted tubule]], the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases<ref name="m">{{cite journal |author=Mulders PF, Brouwers AH, Hulsbergen-van der Kaa CA, van Lin EN, Osanto S, de Mulder PH |title=[Guideline 'Renal cell carcinoma'] |language=Dutch; Flemish |journal=Ned Tijdschr Geneeskd |volume=152 |issue=7 |pages=376–80 |year=2008 |month=February |pmid=18380384 |doi=}}</ref>. It is also known to be the most lethal of all the genitourinary tumors. Initial treatment is most commonly a radical or partial [[nephrectomy]] and remains the mainstay of curative treatment.<ref name="r">{{cite journal |author=Rini BI, Rathmell WK, Godley P |title=Renal cell carcinoma |journal=Curr Opin Oncol |volume=20 |issue=3 |pages=300–6 |year=2008 |month=May |pmid=18391630 |doi=10.1097/CCO.0b013e3282f9782b |doi_brokendate=2009-06-26}}</ref> Where the tumour is confined to the renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where [[metastases]] have spread.  It is resistant to [[radiation therapy]] and [[chemotherapy]], although some cases respond to [[immunotherapy]]. Targeted cancer therapies such as [[sunitinib]], [[temsirolimus]], [[bevacizumab]], interferon-alpha, and possibly [[sorafenib]] have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.

Signs and symptoms of [[renal cell carcinoma]]:

A wide range of symptoms can be present with renal carcinoma depending on which areas of the body have been affected. <ref name="Renal">{{cite web|url=http://www.renalcarcinoma.net/|title=Renal Carcinoma or hypernephroma |accessdate=2010-03-31}}</ref> The classic triad is [[hematuria]] (blood in the urine), flank pain and an abdominal mass. This triad only occurs in 10-15% of cases, and is generally indicative of more advanced disease. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Signs may include:
*Abnormal urine color (dark, rusty, or brown) due to [[blood in the urine]] (found in 60% of cases)
*Loin pain (found in 40% of cases)
*Abdominal mass (25% of cases)
*Malaise, weight loss or anorexia (30% of cases)
*[[Polycythemia]] (5% of cases)
*[[Anaemia]] resulting from depression of [[erythropoietin]] (5% of cases)
*The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to the bone
*[[Varicocele]], the enlargement of one testicle, usually on the left (2% of cases<ref name="pmid8778606">{{cite journal |author=Motzer RJ, Bander NH, Nanus DM |title=Renal-cell carcinoma |journal=N. Engl. J. Med. |volume=335 |issue=12 |pages=865–75 |year=1996 |month=September |pmid=8778606 |doi= 10.1056/NEJM199609193351207|url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=8778606&promo=ONFLNS19}}</ref>). This is due to blockage of the left [[testicular vein]] by tumor invasion of the left [[renal vein]]; this typically does not occur on the right as the right gonadal vein drains directly into the [[inferior vena cava]].
*Vision abnormalities 
*Pallor or plethora
*[[Hirsutism]] - Excessive hair growth (females) 
*Constipation
*[[Hypertension]] (high blood pressure) resulting from secretion of [[renin]] by the tumour (30% of cases)
*Elevated calcium levels ([[Hypercalcemia]])
*[[Stauffer syndrome]] - [[paraneoplastic disease|paraneoplastic]], non-metastatic [[liver]] disease
*Night Sweats
*Severe Weight Loss

Patients may also experience the following symptoms:
* Recurrent [[Fever|fevers]] <ref name="Renal Cell">{{cite web|url=http://www.cancercompass.com/renal-cell-cancer-information/symptoms.htm/ |title=Renal Cell Cancer |accessdate=2010-03-31}}</ref> which occur in 9% of the patients <ref name="Omnimedi">{{cite web|url=http://www.omnimedicalsearch.com/conditions-diseases/renal-cell-carcinoma-symptoms.html|title=Renal Cell Carcinoma |accessdate=2010-03-31}}</ref>
* Cold [[Intolerance|intolerance]] <ref name="Medline">{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/000516.htm|title=Causes |accessdate=2010-03-31}}</ref>
* Back pain
* Chronic fatigue <ref name="About">{{cite web|url=http://cancer.about.com/od/kidneycancerrenalcell/a/kidneysymptoms.htm|title=Kidney Cancer Symptoms (Renal Cell)|accessdate=2010-03-31}}</ref> 
* Leg and ankle swelling
* Loss of appetite 

Classification of [[renal cell carcinoma]]:
[[Image:Renal clear cell ca (1) Nephrectomy.jpg|thumb|right|Micrograph of clear cell renal cell carcinoma. Nephrectomy specimen. H&E stain.]]
[[Image:Papillary renal cell carcinoma 1.jpg|right|thumb|[[Micrograph]] of papillary '''renal cell carcinoma''', showing vascular [[papillae]] with [[foam cell]]s. [[H&E stain]].]]
[[Image:Oncocytic chromophobe rcc high mag.jpg|right|thumb|Micrograph of [[chromophobe]] renal cell carcinoma [[oncocyte|oncocytic]] variant. [[H&E stain]].]]
Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:<ref name="pmid10768592">{{cite journal |author=Reuter VE, Presti JC |title=Contemporary approach to the classification of renal epithelial tumors |journal=Semin. Oncol. |volume=27 |issue=2 |pages=124–37 |year=2000 |month=April |pmid=10768592 |doi= |url=}}</ref><ref name="pmid12351585">{{cite journal |author=Bodmer D, van den Hurk W, van Groningen JJ, ''et al.'' |title=Understanding familial and non-familial renal cell cancer |journal=Hum. Mol. Genet. |volume=11 |issue=20 |pages=2489–98 |year=2002 |month=October |pmid=12351585 |doi= 10.1093/hmg/11.20.2489|url=http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12351585}}</ref><ref name="isbn0-7216-0187-1">{{cite book |author=Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2005 |pages=1016 |isbn=0-7216-0187-1 |oclc= |doi= |accessdate=}}</ref>

* [[Clear cell carcinoma]] ([[Von Hippel-Lindau tumor suppressor|VHL]] and others on [[chromosome 3]])
* [[Papillary]] carcinoma ([[C-Met|MET]], [[PRCC (gene)|PRCC]])
* [[Chromophobe]] renal carcinoma
* [[Collecting duct]] carcinoma

Renal epithelial neoplasms have characteristic cytogenetic aberrations that can aid in classification<ref>van den Berg E, Storkel S . Kidney: Renal cell carcinoma. Atlas Genet Cytogenet Oncol Haematol. June 2003.</ref>. See also [http://atlasgeneticsoncology.org//Tumors/RenalCellCarcinID5021.html Atlas of Genetics and Cytogenetics in Oncology and Haematology]. 
*Clear cell carcinoma: loss of 3p
*Papillary carcinoma: trisomy 7, 16, 17
*Chromophobe carcinoma: hypodiploid with loss of chromosomes 1, 2, 6, 10, 13, 17, 21

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.<ref>{{cite journal |author=Hagenkord JM, Parwani AV, Lyons-Weiler MA, ''et al.'' |title=Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors |journal=Diagn Pathol |volume=3 |issue= |pages=44 |year=2008 |pmid=18990225 |pmc=2588560 |doi=10.1186/1746-1596-3-44}}</ref><ref>{{cite journal |author=Monzon FA, Hagenkord JM, Lyons-Weiler MA, ''et al.'' |title=Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors |journal=Mod. Pathol. |volume=21 |issue=5 |pages=599–608 |year=2008 |month=May |pmid=18246049 |doi=10.1038/modpathol.2008.20}}</ref> Array-based karyotyping performs well on paraffin embedded tumors<ref>{{cite journal |author=Lyons-Weiler M, Hagenkord J, Sciulli C, Dhir R, Monzon FA |title=Optimization of the Affymetrix GeneChip Mapping 10K 2.0 Assay for routine clinical use on formalin-fixed paraffin-embedded tissues |journal=Diagn. Mol. Pathol. |volume=17 |issue=1 |pages=3–13 |year=2008 |month=March |pmid=18303412 |doi=10.1097/PDM.0b013e31815aca30}}</ref> and is amenable to routine clinical use. See also [[Virtual Karyotype]] for CLIA certified laboratories offering array-based karyotyping of solid tumors.

Other associated genes include [[TRC8]], [[OGG1]], [[HNF1A]], [[HNF1B]], [[TFE3]], [[RCCP3]], and [[RCC17]].

[[Epidemiology]] of [[renal cell carcinoma]]:
The incidence of renal cell cancer has been rising steadily. Nearly 51190 new diagnoses and 12890 deaths reported in the United States in 2007. It is more common in men than women: the male-to-female ratio is 1.6:1 and has been decreasing over the last decade. Blacks have a slightly higher rate of renal cell cancer than whites. The reasons for this are not clear.<ref> American Cancer Society. Cancer facts & figures 2007. American Cancer Society; 2007.</ref> Note: in epidemiology, RCC is registered together with renal pelvis carcinoma, which is predominantly transitional cell type.

In Europe the incidence of RCC has doubled in the period from 1975 to 2005.<ref>{{cite journal |author=Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P |title=Estimates of the cancer incidence and mortality in Europe in 2006 |journal=Ann. Oncol. |volume=18 |issue=3 |pages=581–92 |year=2007 |month=March |pmid=17287242 |doi=10.1093/annonc/mdl498}}</ref>  RCC accounted for 3777 deaths in the UK in 2006; male 2372, female 1820.<ref>Office for National Statistics, Mortality Statistics: Cause England & Wales, 2006. Vol. DH2 No.32. 2006: TSO.</ref><ref>GRO for Scotland Registrar General's Annual Report, 2006.</ref><ref>Northern Ireland Cancer Registry, Cancer Mortality in Northern Ireland, 2006. 2006.</ref>

Risk factors for [[renal cell carcinoma]]:
Cigarette smoking and obesity are the strongest risk factors. [[Hypertension]] and a family history of the disease are also risk factors.<ref>{{cite journal |author=Lipworth L, Tarone RE, McLaughlin JK |title=The epidemiology of renal cell carcinoma |journal=J. Urol. |volume=176 |issue=6 Pt 1 |pages=2353–8 |year=2006 |month=December |pmid=17085101 |doi=10.1016/j.juro.2006.07.130}}</ref>

[[Dialysis]] patients with acquired cystic disease of the kidney showed a 30 times greater risk than in the general population for developing RCC.<ref>{{cite journal |author=Brennan JF, Stilmant MM, Babayan RK, Siroky MB |title=Acquired renal cystic disease: implications for the urologist |journal=Br J Urol |volume=67 |issue=4 |pages=342–8 |year=1991 |month=April |pmid=2032071 |doi=10.1111/j.1464-410X.1991.tb15158.x}}</ref>

Exposure to asbestos, polycyclic aromatic hydrocarbons, gasoline has not been shown to be consistently associated with RCC risk.<ref>McLaughlin JK, Kidney Cancer, Oxford University Press, Oxford, 2006, pp. 1087–1100.</ref>

Patients with certain inherited disorders such as [[von Hippel-Lindau disease]], hereditary papillary renal cancer, a hereditary leiomyoma RCC syndrome and Birt-Hogg-Dubé syndrome, show an enhanced risk of RCC.<ref>{{cite journal |author=Lamiell JM, Salazar FG, Hsia YE |title=von Hippel-Lindau disease affecting 43 members of a single kindred |journal=Medicine (Baltimore) |volume=68 |issue=1 |pages=1–29 |year=1989 |month=January |pmid=2642584 |doi=}}</ref><ref>{{cite journal |author=Pavlovich CP, Schmidt LS |title=Searching for the hereditary causes of renal-cell carcinoma |journal=Nat. Rev. Cancer |volume=4 |issue=5 |pages=381–93 |year=2004 |month=May |pmid=15122209 |doi=10.1038/nrc1364}}</ref><ref>{{cite journal |author=Washecka R, Hanna M |title=Malignant renal tumors in tuberous sclerosis |journal=Urology |volume=37 |issue=4 |pages=340–3 |year=1991 |month=April |pmid=2014599 |doi=10.1016/0090-4295(91)80261-5}}</ref>

[[Hysterectomy]] is associated with an approximately doubled risk. Hormonal factors or injury of the ureter during surgery were considered as possible causes. <ref>{{Cite pmid|10566555 }}</ref> <ref>{{Cite pmid|18711701 }}</ref>

Diagnosing [[renal cell carcinoma]]:
{{Copypaste|date=November 2009}}
An accurate diagnose may be difficult to establish given that the early stages of renal cancer are asymptomatic. However, the first steps taken in order to diagnose this condition are observing the signs and symptoms and an anamnesis (the detailed medical review of past health state).

'''By Signs and symptoms'''   But unfortunately, early kidney cancers do not usually cause any signs or symptoms, but larger ones may. {{Citation needed|date=November 2009}}

'''Anamnesis'''    (detailed medical review of past health state)

'''Physical examination'''   The physical examination may be useful in providing information about the signs of kidney cancer. During a physical exam, the doctor checks the general signs of health and tests for fever and high blood pressure. The palpitation of the abdomen may reveal the presence of a mass or an organ enlargement. <ref name="MedlinePlus">{{cite web|url=http://www.nlm.nih.gov/medlineplus/ency/article/000516.htm/ |title=Renal cell carcinoma |accessdate=2010-03-31}}</ref> The doctor also checks general signs of health and tests for fever and high blood pressure.

If a patient has symptoms that suggest kidney cancer, the doctor may perform one or more of the following procedures:

'''Lab tests'''   Lab tests are not usually used to diagnose kidney cancer, but they can sometimes give the first hint that there may be a kidney problem. They are also done to get a sense of a person’s overall health and to help tell if cancer may have spread to other areas.They can help tell if a person is healthy enough to have an operation. The laboratory tests may provide information whether there are signs of cancer or, if its presence is confirmed, they can show if cancer has spread. Urine tests such as the urine cytology and the urinalysis and blood tests complete blood count and serum calcium) may reveal abnormalities in the kidneys functioning. <ref name="Mednet">{{cite web|url=http://www.medicinenet.com/kidney_cancer/page3.htm#symptoms/ |title=Symptoms of kidney cancer |accessdate=2010-03-31}}</ref>

''Urinalysis(Urine tests)''    These set of tests check for several indicators of the cancer such as blood, sugar, proteins, and bacteria.{{Citation needed|date=November 2009}}

''Complete blood count''    A complete blood count can detect findings sometimes seen with renal cell cancer.

''Blood chemistry tests''     Blood chemistry tests are usually done in people who may have kidney cancer, as it can affect the levels of certain chemicals in the blood.

'''Imaging tests'''   Imaging tests use x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. imaging tests can give doctors a reasonable amount of certainty that a kidney mass is (or is not) cancerous. Unlike most other cancers, doctors can often diagnose a kidney cancer fairly certainly without the need for a biopsy.{{Citation needed|date=November 2009}} In some patients, however, a biopsy may be needed to be sure.{{Citation needed|date=November 2009}}  The imaging tests are a reliable source of information for doctors because they provide clear pictures of the organs and tissues of the body. The main imaging tests performed in order to establish a renal carcinoma are the abdominal CT scan, ultrasound test of the abdomen and kidneys, renal angiography, MRI scan or an intravenous pyelogram (IVP).



Computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, intravenous pyelograms, and ultrasound can be very helpful in diagnosing most kinds of kidney tumors, although patients rarely need all of these tests.{{Citation needed|date=November 2009}}

''Computed tomography(CT)''   This imaging test is similar with an x-ray test, and creates a detailed cross-sectional image of the body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. The pictures of the patient's kidneys show if there is a kidney tumor or not. It is a test similar to the x-rays in which is used a contrast agent and the diagnosis is made based on the pictures taken before the contrast agent is injected compared to the pictures taken after the contrast agent was administrated.

The abdominal CT scan consists in taking clear pictures of the patient's kidneys, showing if there is a kidney tumor or not.CT scanning is one of the most useful tests for finding and looking at a mass inside your kidney.{{Citation needed|date=November 2009}} It is also useful in checking whether or not a cancer has spread to organs and tissues beyond the kidney. The CT scan will provide precise information about the size, shape, and position of a tumor, and can help find enlarged lymph nodes that might contain cancer.

''Magnetic resonance imaging(MRI)''   Like CT scans, magnetic resonance imaging (MRI) scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the tissues and then revealed into a recognizable pattern on a special monitor.

They may be done in cases where CT scans aren’t practical, such as if a person is allergic to the CT contrast dye. MRI scans may also be done if there’s a chance that the cancer involves a major vein in the abdomen (the inferior vena cava), because they provide a better picture of blood vessels than CT scans.

But MRI scans are a little more uncomfortable than CT scans. First, they take longer — often up to an hour. Second, you have to lie inside a narrow tube, which is confining and can upset people with claustrophobia (a fear of enclosed spaces). 

Ultrasound or ultrasonography   Ultrasound imaging is a safe, noninvasive and brief test that can detect tumors. Ultrasound imaging is a medical technique that uses high-frequency sound waves to create an interior image of the body on a special computer screen. For this test, a small, microphone-like instrument called a transducer is placed on the skin near the kidney. Ultrasound can be helpful in determining if a kidney mass is solid or filled with fluid.{{Citation needed|date=November 2009}} The echo patterns produced by most kidney tumors look different from those of normal kidney tissue. If a renal carcinoma is suspected, the doctor will examine the kidneys, ureters and the bladder. The image created by an ultrasound is actually formed by echoes of the sound waves on the surface of the organs but the abnormal tissue masses and organs reflect sound waves differently and this is why the ultrasound may be useful in diagnosing renal carcinoma. <ref name="OmniMedS">{{cite web|url=http://www.omnimedicalsearch.com/conditions-diseases/renal-cell-carcinoma-tests-diagnosis.html |title=Renal Cell Carcinoma |accessdate=2010-03-31}}</ref> 

If a kidney biopsy is needed, this test can be used to guide a biopsy needle into the mass to obtain a sample.

If cancer was already diagnosed, the evolution of the disease must be closely observed. The tests that can provide information on the evolution of the condition are the PET scan, chest x-rays, biopsy and the bone scan.

''Positron emission tomography''(PET scan)   This is a very specialized imaging technique that provides useful information about the tumor location and how far the cancer has spread. The Pet scan uses radioactive glucose (known as fluorodeoxyglucose or FDG) to locate the cancer, because the cancerous cells absorb a higher amount of this substance than normal tissues.

This test can be useful to see if the cancer may have spread to lymph nodes near the kidney. PET scans can also be useful if your doctor thinks the cancer may have spread but doesn’t know where. {{Citation needed|date=November 2009}}

''Intravenous pyelogram(IVP)''   The doctor injects dye into a vein in the arm. The dye travels from the bloodstream into the kidneys and then passes into the ureters and bladder. The dye makes them show up on x-rays. An IVP can be useful in finding abnormalities of the urinary tract, such as cancer, but you might not need an IVP if you have already had a CT or MRI.

''Angiography''   Like the IVP, this type of x-ray also uses a contrast dye. The renal angiography may be required in order to examine the blood vessels in the kidneys. The test implies using a contrast agent which is injected into the renal artery and which is absorbed by the cancerous cells.This contrast agent is absorbed by the cancerous cells and displayed on an angiogram. Because angiography can outline the blood vessels that supply a kidney tumor, it can help a surgeon plan surgery in some patients who need blood vessels mapped before the operation. Angiography can also help diagnose renal cancers since the blood vessels usually have a special appearance with this test.{{Citation needed|date=November 2009}} .An intravenous pyelogram (IPV) can reveal the presence of an abnormal mass which can develop within the kidneys. In order to get clear images of the urinary tract, a dye substance is administrated into the patient's arm vein.

Other tests described here, such as chest x-rays and bone scans, are more often used to help determine if the cancer has spread (metastasized) to other parts of the body{{Citation needed|date=November 2009}}

'''Chest x-ray'''The chest x-rays may determine if the cancer has spread to the other organs by using high energy electromagnetic radiation. A bone scan can show whether the cancer has spread to the bone tissues or not.

'''Bone scan'''

'''Biopsy'''    Biopsies are not often used to diagnose kidney tumors. Imaging studies usually provide enough information. But, biopsy is sometimes used to get a small sample of cells from a suspicious area if imaging test results are not conclusive enough to warrant removing a kidney. Biopsy may also be done to confirm the diagnosis of cancer if a person’s health is too poor for surgery and other local treatments (such as radiofrequency ablation, arterial embolization or cryotherapy) are being considered. (10 questions to ask your doctor before a Biopsy) In many cases, the biopsy is the most accurate procedure that can confirm if the tumor or abnormal growth is a malignant tissue or not. This procedure consists in the removal of a sample of tissue from the abnormal tumor of mass. It can be performed in two different ways, either by a fine needle aspiration either by a core needle biopsy.

''Fine needle aspiration''    This procedure involves taking a sample of tissue from the tumor by using a thin needle attached to a syringe. Fine needle aspiration is performed only if the tumor can be easy reached. In kidney cancer patients, fine needle aspiration is the most used procedure of removing a sample of tissue.{{Citation needed|date=November 2009}}

''Core needle biopsy''    This procedure is performed under local anesthesia and involves removing a small cylinder of tumor tissue.

'''Fuhrman grade'''   The Fuhrman grade is determined by looking at kidney cancer cells (taken during a biopsy or during surgery) under a microscope. It is used by many doctors as a way to describe how aggressive the cancer is likely to be. The grade is based on how closely the cancer cells’ nuclei (part of a cell in which DNA is stored) look like those of normal kidney cells.{{Citation needed|date=November 2009}}

Renal cell cancers are usually graded on a scale of 1 through 4. Grade 1 renal cell cancers have cell nuclei that differ very little from normal kidney cell nuclei. These cancers usually grow and spread slowly and tend to have a good outlook (prognosis). At the other extreme, grade 4 renal cell cancer nuclei look quite different from normal kidney cell nuclei and have a worse prognosis.{{Citation needed|date=November 2009}}

Although the cell type and grade are sometimes helpful in predicting a prognosis, the cancer’s stage is by far the best predictor of survival.{{Citation needed|date=November 2009}} Staging is explained in Kidney cancer staging.[http://www.beatrcc.com/2009/07/renal-cell-carcinoma-diagnose]

Pathology:

[[Image:Renal cell carcinoma.jpg|thumb|Renal cell carcinoma]]
[[Image:Kidney cancer.jpg|thumb|Renal cell carcinoma]]

The gross and microscopic appearance of renal cell carcinomas is highly variable. The following describes a typical clear cell carcinoma, which is the most common type.

The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids. <ref name="Brit">{{cite web|url=http://www.britannica.com/EBchecked/topic/497921/renal-carcinoma |title=Clear-cell Carcinoma, Hypernephroid Tumour, or Hypernephroma |accessdate=2010-03-31}}</ref> The body of the tumor shows large blood vessels that have walls composed of cancerous cells.

[[Gross examination]] often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring. 

Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Also, the cells that make up a renal carcinoma may be clear, granular, mixed clear and granular or sarcomatoid or spindle type. Recent studies have brought to attention that the type of cancerous cells and the aggressiveness of the condition are closely related.Because these cells accumulate [[glycogen]] and [[lipid]]s, their cytoplasm appear "clear", the nuclei remain in the middle of the cells, and the cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor compresses the surrounding parenchyma, producing a pseudocapsule.<ref name="title">{{cite web |url=http://www.pathologyatlas.ro/renal-cell-carcinoma-grawitz-tumor-kidney-pathology.php |title=pathologyatlas.ro |accessdate=2007-12-29 |format= |work=}}</ref>

The clear cells are thought to be the least likely to spread and usually respond more favorably to treatment. <ref name="Patho">{{cite web|url=http://www.urologychannel.com/kidneycancer/pathology.shtml |title=PathologyPathology |accessdate=2010-03-31}}</ref> However, most of the tumors contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumor is mixed, containing both clear and granular cells.

Secretion of vasoactive substances (e.g. [[renin]]) may cause [[arterial hypertension]], and release of [[erythropoietin]] may cause [[erythrocytosis]] (increased production of [[red blood cell]]s).

Radiology:


The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour.  It will frequently have an irregular or lobulated margin.  Traditionally 85 to 90%% of solid renal masses will turn out to be RCC but this number may be decreasing as renal masses are being found at smaller and smaller sizes with larger numbers of benign lesions.  10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion  and encasement of the perirenal fat).  Following intravenous contrast administration ([[computed tomography]] or [[magnetic resonance imaging]]), enhancement will be noted, and will highlight the tumor relative to normal renal parenchyma.{{Citation needed|date=October 2008}}

In particular, reliably distinguishing renal cell carcinoma from an [[oncocytoma]] (a benign lesion) is not possible using current medical imaging or percutaneous biopsy.{{Citation needed|date=October 2008}}

Renal cell carcinoma may also be cystic.  As there are several benign cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the [[radiologist]] to differentiate a benign cystic lesion from a malignant one.  A classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available<ref>{{cite journal |author=Israel GM, Bosniak MA |title=How I do it: evaluating renal masses |journal=Radiology |volume=236 |issue=2 |pages=441–50 |year=2005 |month=August |pmid=16040900 |doi=10.1148/radiol.2362040218 |url=}}</ref>.

At diagnosis, 30% of renal cell carcinoma has spread to that kidney's renal vein, and 5-10% has continued on into the inferior vena cava<ref>{{cite journal |author=Oto A, Herts BR, Remer EM, Novick AC |title=Inferior vena cava tumor thrombus in renal cell carcinoma: staging by MR imaging and impact on surgical treatment |journal=AJR Am J Roentgenol. |volume=171 |issue=6 |pages=1619–24 |year=1998 |month=December |pmid=9843299 |doi= |url=http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=9843299}}</ref>.

Percutaneous biopsy can be performed by a [[radiologist]] using [[medical ultrasonography|ultrasound]] or [[computed tomography]] to guide sampling of the tumor for the purpose of diagnosis.  However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective. This is not completely accurate, there are new experimental treatments.

Treatment of renal cell carcinoma:
If it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with [[surgery]]. If it has spread outside of the kidneys, often into the [[lymph nodes]] or the main vein of the kidney, then it must be treated with adjunctive therapy, including cytoreductive surgery. RCC is resistant to chemotherapy and radiotherapy in most cases, but does respond well to immunotherapy with interleukin-2 or interferon-alpha, biologic, or targeted therapy. In early stage cases, cryotherapy and surgery are the preferred options.

Watchful waiting:
Small renal tumors (< 4&nbsp;cm) are treated increasingly by way of partial [[nephrectomy]] when possible.<ref>{{cite journal |author=Novick AC |title=Nephron-sparing surgery for renal cell carcinoma |journal=Br J Urol |volume=82 |issue=3 |pages=321–4 |year=1998 |month=September |pmid=9772865 |doi=}}</ref><ref>{{cite journal |author=Herr HW |title=Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10-year followup |journal=J. Urol. |volume=161 |issue=1 |pages=33–4; discussion 34–5 |year=1999 |month=January |pmid=10037361 |doi=10.1016/S0022-5347(01)62052-4}}</ref><ref>{{cite journal |author=Van Poppel H, Bamelis B, Oyen R, Baert L |title=Partial nephrectomy for renal cell carcinoma can achieve long-term tumor control |journal=J. Urol. |volume=160 |issue=3 Pt 1 |pages=674–8 |year=1998 |month=September |pmid=9720519 |doi=10.1016/S0022-5347(01)62751-4}}</ref> Most of these small renal masses manifest indolent biological behavior with excellent prognosis.<ref>{{cite journal |author=Mattar K, Jewett MA |title=Watchful waiting for small renal masses |journal=Curr Urol Rep |volume=9 |issue=1 |pages=22–5 |year=2008 |month=January |pmid=18366970 |doi=10.1007/s11934-008-0006-3}}</ref> More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation.  In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3–5&nbsp;cm, beyond which the risk of distant spread (metastases) is about 5%.

Surgery for [[renal cell carcinoma]]
[[Image:Embolization kidney.jpg|thumb|right|200px|[[Micrograph]] of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.]]
Surgical removal of all or part of the kidney ([[nephrectomy]]) is recommended.<ref name="r"/> This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues.  In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium, this portion of the tumor can be surgically removed, as well. In cases of known metastases, surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival<ref>{{cite journal |author=Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED |title=Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis |journal=J Urol. |volume=171 |issue=3 |pages=1071–6 |year=2004 |month=March |pmid=14767273 |doi=10.1097/01.ju.0000110610.61545.ae |url=}}</ref>, as well as resection of a solitary metastatic lesion.  Kidneys are sometimes [[embolization|embolized]] prior to surgery to minimize blood loss<ref name="m"/> (see image).

Surgery is increasingly performed via [[laparoscopy|laparoscopic]] techniques. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery.<ref name="r"/>  For small exophytic lesions that do not extensively involve the major vessels or urinary collecting system, a partial nephrectomy (also referred to as "nephron sparing surgery") can be performed.  This may involve temporarily stopping blood flow to the kidney while the mass is removed as well as renal cooling with an ice slush. [[Mannitol]] can also be administered to help limit damage to the kidney.  This is usually done through an open incision although smaller lesions can be done laparoscopically with or without robotic assistance.

Laparoscopic [[cryotherapy]] can also be done on smaller lesions.  Typically a biopsy is taken at the time of treatment.  Intraoperative ultrasound may be used to help guide placement of the freezing probes. Two freeze/thaw cycles are then performed to kill the tumor cells.  As the tumor is not removed followup is more complicated (see below) and overall disease free rates are not as good as those obtained with surgical removal.

Percutaneous therapies for renal cell carcinoma:
[[Percutaneous]], image-guided therapies, usually managed by [[radiologists]], are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure.  This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by [[computed tomography]], [[ultrasound]], or even [[magnetic resonance imaging]] guidance, and then destroying the tumor with heat ([[radiofrequency ablation]]) or cold ([[cryotherapy]]). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.<ref>{{cite journal |author=Mogami T, Harada J, Kishimoto K, Sumida S |title=Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell carcinoma |journal=Int. J. Clin. Oncol. |volume=12 |issue=2 |pages=79–84 |year=2007 |month=April |pmid=17443274 |doi=10.1007/s10147-006-0654-6}}</ref><ref>{{cite journal |author=Boss A, Clasen S, Kuczyk M, Schick F, Pereira PL |title=Image-guided radiofrequency ablation of renal cell carcinoma |journal=Eur Radiol |volume=17 |issue=3 |pages=725–33 |year=2007 |month=March |pmid=17021704 |doi=10.1007/s00330-006-0415-y}}</ref>

Medications used in the treatment of [[renal cell carcinoma]]:
RCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions." This has encouraged a strategy of using immunomodulating therapies, such as [[cancer vaccines]] and [[interleukin-2]] (IL-2), to reproduce this response. IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. [[Bevacizumab]], an antibody to [[Vascular endothelial growth factor|VEGF]], has significantly prolonged time to progression, but phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.<ref>{{cite journal |author=Michaelson MD, Iliopoulos O, McDermott DF, McGovern FJ, Harisinghani MG, Oliva E |title=Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma |journal=N Engl J Med. |volume=358 |issue=22 |pages=2389–96 |year=2008 |month=May |pmid=18509125 |doi=10.1056/NEJMcpc0802449 |url=http://content.nejm.org/cgi/content/full/358/22/2389}}</ref>

Treatment with [[tyrosine kinase inhibitor]]s including [[nexavar]], [[pazopanib]], and [[rapamycin]] have shown promise in improving the prognosis for advanced RCC since 2004.

[[Sorafenib]], a protein kinase inhibitor, was FDA approved in December 2005 for treatment of advanced renal cell cancer.

A month later, [[Sunitinib]]  was approved as well.  Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting [[angiogenesis]] as well as tumor cell proliferation. Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib. However, these agents have not been directly compared against one another in a single trial. [http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sunitinib][http://www.cancer.gov/Templates/drugdictionary.aspx?searchTxt=sorafenib]

Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the ''[[New England Journal of Medicine]]''. This study showed that [[Sunitinib]] offered superior efficacy compared with [[interferon-α]]. Progression-free survival (primary endpoint) was more than doubled. The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α. Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa.<ref name=motzer>{{cite journal | author = Motzer RJ ''et al.'' | title = Sunitinib versus interferon alfa in metastatic renal-cell carcinoma | journal = [[New England Journal of Medicine|N Engl J Med]] | volume = 356 | issue = 2 | pages = 115–124 | year = 2007 | pmid = 17215529 | doi = 10.1056/NEJMoa065044}}</ref> 

Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mammalian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features. The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www.ASCO.org).

Date of Approval: March 30, 2009
Company: Novartis AG
Treatment for: Renal Cell Carcinoma
Afinitor (everolimus) is an oral once-daily inhibitor of mTOR indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.
Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib - March 30, 2009

Chemotherapy in the treatment of [[renal cell carcinoma]]:
Most of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC,as response rates are very low,often just 5-15%,and most responses are short lived.<ref name="m"/> The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section

Vaccine:
[[Cancer vaccines]], such as [[TroVax]], have shown promising results in phase 2 trials for treatment of renal cell carcinoma.<ref>[http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770 Vaccine for kidney and bowel cancers 'within three years' | Mail Online<!-- Bot generated title -->]</ref> However, issues of tumor [[immunosuppression]] and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.<ref>{{cite journal |author=Amato RJ |title=Vaccine therapy for renal cancer |journal=Expert Rev Vaccines |volume=7 |issue=7 |pages=925–35 |year=2008 |month=September |pmid=18767943 |doi=10.1586/14760584.7.7.925}}</ref>

Prognosis of [[renal cell carcinoma]]: 
The [[five year survival rate]] is around 90-95% for tumors less than 4&nbsp;cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%.{{Citation needed|date=October 2008}} For tumors that extend through the renal capsule and out of the local [[fascial]] investments, the survivability reduces to near 60%.{{Citation needed|date=October 2008}} If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.{{Citation needed|date=October 2008}}

For those that have tumor recurrence after surgery, the prognosis is generally poor.  Renal cell carcinoma does not generally respond to chemotherapy or radiation.  Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise.  Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series. Most recently, treatment with [[tyrosine kinase inhibitor]]s including [[nexavar]], [[pazopanib]], and [[rapamycin]] have shown promise in improving the prognosis for advanced RCC since 2004.

History of [[Renal cell carcinoma]]:
Historically, RCC was also known as '''nephrocellular carcinoma'''.<ref name="pmid1225265">{{cite journal
| author = Vasil'eva NN
| title = [Patho-anatomical characteristics of renal cell cancer]
| language = Russian
| journal = Arkh. Patol.
| volume = 37
| issue = 10
| pages = 11–8
| year = 1975
| pmid = 1225265
| doi = 
| url = 
| issn = 
}}</ref>
[[Paul Grawitz]] first described renal cell carcinoma in 1883.

Metastatic renal cell carcinoma:
The metastatic stage of the renal cell carcinoma occurs when the disease invades and spreads to other organs. It is most likely to spread to neighboring lymph nodes, the lungs, the liver, the bones, or the brain. <ref name="eMedhealth">{{cite web|url=http://www.emedicinehealth.com/renal_cell_cancer/article_em.htm/ |title=Renal Cell Cancer |accessdate=2010-03-31}}</ref>
Metastatic renal cell carcinoma presents a special challenge to oncologists, as about 70% of patients with renal cell carcinoma develop metastases during the course of their disease, and 5 year survival for patients with metastatic renal cell carcinoma is between 5-15%,though it is much improved if metastatectomy and [[nephrectomy]] to remove all visible disease is performed. even if [[metastases]] are not removed,cytoreductive [[nephrectomy]] is sometimes used in the treatment of metastatic renal cell carcinoma,and at least 1 study has supported the use of cytoreductive nephrectomy in "some cases" of metastatic renal cell carcinoma,citing improved response rates to [[interleukin-2]] [[immunotherapy]] and modestly prolonged survival. [[Radiotherapy]] and [[chemotherapy]] have less of a role in therapy of renal cell carcinoma then in other malignancies; but they are still sometimes used in treatment of metastatic renal cell carcinoma. Radiotherapy is used in bone metastases from renal cell carcinoma to reduce pain and lower the risk of [[pathologic fracture]], in patients with brain metastases, and to palliate symptoms of metastatic disease to the liver, [[adrenals]], or [[lungs]] from renal cell carcinoma. Interleukin-2, has been the standard of care since the 1990s in metastatic renal cell carcinoma, as although response rates are low [7-16%], about half of patients that respond have long term disease free survival, and some of these patients may be cured of their disease. However,the side effects of [[interleukin-2]] are very severe side effects, including decreased [[neutrophil]] function, resulting in a increased risk of dissemenated infection, including [[central venus catheter]] infections, [[septicaemia]], and [[bacterial endocarditis]], capilary leak syndrome, which can result in [[myocardial infarction]], [[renal failure]], [[angina]], [[hypotension]], reduced organ perfusion, [[altered mental status]], [[pulmonary failure]] requiring [[intubation]], [[cardiac arrythmias]], [[edema]], and gastrointestinal bleeding. Proleukin also can result in lethargy and somnolence; if interleukin-2 therapy is not discontinued lethargy may progress to coma. Interleukin-2 can also worsen pre-existing autoimmune diseases.exacerbation of [[scleroderma]], [[diabetes mellitus]], [[thyroiditis]], [[inflammotory bowel disease]], myesthinisa gravis, [[nephritis]], and other autoimmune diseases have been reported. Neurological side effects can also occur, and include [[ataxia]], cortical blindness, [[hallucinations]], [[psychosis]], [[speech problems]], and coma. Other side effects include [[abdominal pain]], [[rigors]], [[fever]], [[malaise]], [[asthenia]], [[acidosis]], [[tachycardia]], [[vasodialation]], [[diarrhea]], [[vomiting]], mouth sores, loss of appetite, [[dermatitis]], [[dyspnea]], [[thrombocytopenia]], and anaemia. Also, patients must be in good health with normal cardiovascular, hepatic, pulmanary,and neurological function to be treated with interleukin-2. Recently, targeted therapys including [[torisel]], [[nexavar]], [[sutent]], and [[bevacizumab]] have been developed, and all are now approved for the treatment of metastatic renal cell carcinoma. Also, [[votrient]] [pazopanib] was approved for the treatment of metastatic renal cell carcinoma in October 2009. This is the sixth drug to be approved for metastatic renal cell carcinoma since 2005. The last 3–5 years have seen dramatic improvements in treatment for those with metastatic renal cell carcinoma, Richard Pazdur, MD, director of the office of oncology drugs at the the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA). However, despite these improvements in therapy, overall survival in metastatic renal cell carcinoma remains quite poor. Currently, tumor vaccines and chemotheraputic, biologic, and immunologic agents are being researched in the treatment of metastatic renal cell carcinoma, and some appear promising. It is not known whether or not detecting metastatic renal cell carcinoma earliar improves survival or response to treatment. Symptoms of metastatic renal cell carcinoma are often mistaken for other, less severe illness,and include: for bone metastases, pain, stiffness, [[bruit]], and pathologic fracture,for liver metastases, [[abdominal pain]], [[jaundice]], elevations in AST and [[ALT]], and [[vomiting]], for [[lung]] metastases, [[cough]], [[dyspnea]], and abnormal [[chest radiograph]]. [[Brain metastases]] produce [[diplopia]], personality changes, [[headache]], [[ataxia]], [[Vertigo (medical)|vertigo]], and [[seizures]]. Systemic symptoms occur in some people with metastatic renal cell carcinoma, and include [[anorexia]], [[fatigue]], [[fever of unknown origin]], [[weight loss]], and [[malaise]]. Given that many diseases can cause these symptoms, extensive testing is typically required to diagnose metastatic renal cell carcinoma. Differential diagnoses include [[leukaemia]], [[arthritis]], any other [[neoplastic]] disease, [[locomotor ataxia]], [[Lyme disease]] [in the case of unexplained malaise, [[fatigue]], and bone pain], and other chronic infections.{{Citation needed|date=December 2009}}
*[[Hepatocellular carcinoma]]<ref>{{cite web|url=http://www.childrenshospital.org/az/Site1015/mainpageS1015P0.html |title=Hepatocellular Carcinoma - My Child Has - Children's Hospital Boston |publisher=Childrenshospital.org |date= |accessdate=2010-03-09}}</ref>
*[[Breast cancer]]<ref name="medscape2">{{cite web|url=http://emedicine.medscape.com/article/217675-overview |title=Fever of Unknown Origin: eMedicine Infectious Diseases |publisher=Emedicine.medscape.com |date=2009-12-17 |accessdate=2010-03-09}}</ref>
*[[Pancreatic cancer]]<ref name="medscape2"/>
*[[Colon cancer]]<ref name="medscape2"/>
*[[Histiocytosis|Malignant histiocytosis]]<ref name="medscape2"/>
*[[Neuroblastoma]]<ref>{{cite web|url=http://www.mayoclinic.com/health/neuroblastoma/DS00780/DSECTION=symptoms |title=Neuroblastoma: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Wilm's tumor]]<ref>https://health.google.com/health/ref/Wilms+tumor</ref>
*[[Ewing sarcoma]], a malignancy affecting adolescences, other symptoms include severe bone pain and weight loss. It can be treated using surgery, [[Radiotherapy|radiation]], and/or [[chemotherapy]].<ref>http://www.ucsfchildrenshospital.org/conditions/ewings_sarcoma/</ref>

==Other==
===[[Krabbe's disease]]===
<ref>{{cite web|url=http://www.mayoclinic.com/health/krabbe-disease/DS00937/DSECTION=symptoms |title=Krabbe disease: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
Symptoms of Krabbes disease:
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, [[fever]]s, limb stiffness, [[seizure]]s, feeding difficulties, [[vomit]]ing, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of [[cerebral palsy]]. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy and blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression.

Diagnosing krabbes disease:
The disease may be diagnosed by its characteristic grouping of certain cells ([[multinucleated globoid cells]]), nerve demyelination and degeneration, and destruction of brain cells. Special stains for [[myelin]] (e.g; [[luxol fast blue]]) may be used to aid diagnosis.

*[[Thyrotoxosis]]<ref>https://health.google.com/health/ref/Thyroid+storm</ref>
*[[Familial Mediterranean fever]]<ref>https://health.google.com/health/ref/Familial+Mediterranean+fever</ref> 
*[[Sickle cell anemia]]<ref>https://health.google.com/health/ref/Sickle+cell+anemia</ref>
*[[Drug fever]]<ref name="medscape2"/>
*[[Adrenal insufficiency]]<ref name="medscape2"/> 
*[[Thrombophlebitis]]<ref name="medscape2"/>
*[[Granulomatous hepatitis]]<ref name="medscape2"/>
*[[Neuroleptic malignant syndrome]]<ref>{{cite web|url=http://emedicine.medscape.com/article/288482-overview |title=Neuroleptic Malignant Syndrome: eMedicine Psychiatry |publisher=Emedicine.medscape.com |date=2009-05-07 |accessdate=2010-03-09}}</ref>
*[[Erythema multiforme]]<ref>https://health.google.com/health/ref/Erythema+multiforme</ref>
*[[Stevens-johnson syndrome]]<ref>{{cite web|url=http://www.mayoclinic.com/health/stevens-johnson-syndrome/DS00940/DSECTION=symptoms |title=Stevens-Johnson syndrome: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
*[[Encephalitis lethargica]]<ref>{{cite web|url=http://www.bbc.co.uk/health/conditions/encephalitislethargica1.shtml#what_are_the_symptoms |title=Health - Conditions - Encephalitis lethargica |publisher=BBC |date= |accessdate=2010-03-09}}</ref>
*[[Acute disseminated encephalomyelitis]]<ref>{{cite web|url=http://www.ninds.nih.gov/disorders/acute_encephalomyelitis/acute_encephalomyelitis.htm |title=Acute Disseminated Encephalomyelitis Information Page: National Institute of Neurological Disorders and Stroke (NINDS) |publisher=Ninds.nih.gov |date=2007-08-16 |accessdate=2010-03-09}}</ref>
*[[Dressler's syndrome]]<ref>{{cite web|url=http://www.mayoclinic.com/health/dresslers-syndrome/DS00666/DSECTION=symptoms |title=Dressler's syndrome: Symptoms |publisher=MayoClinic.com |date= |accessdate=2010-03-09}}</ref>
===[[Myocardial infarction]]===
<ref>{{cite web|url=http://emedicine.medscape.com/article/155919-overview |title=Myocardial Infarction: eMedicine Cardiology |publisher=Emedicine.medscape.com |date= |accessdate=2010-03-09}}</ref>

'''Myocardial infarction''' ('''MI''') or '''acute myocardial infarction''' ('''AMI'''), commonly known as a '''heart attack''', is the interruption of [[Blood flow|blood supply]] to part of the [[heart]], causing some heart cells to die. This is most commonly due to occlusion (blockage) of a [[coronary artery]] following the rupture of a [[Vulnerable plaque|vulnerable atherosclerotic plaque]], which is an unstable collection of [[lipids]] (fatty acids) and [[white blood cell]]s (especially [[macrophage]]s) in the wall of an [[artery]]. The resulting [[ischemia]] (restriction in blood supply) and [[Hypoxia (medical)|oxygen shortage]], if left untreated for a sufficient period of time, can cause damage or death (''[[infarction]]'') of heart muscle tissue (''[[myocardium]]'').

Classical symptoms of acute myocardial infarction include sudden [[chest pain]] (typically radiating to the left arm or left side of the neck), [[dyspnea|shortness of breath]], [[nausea]], [[vomiting]], [[palpitation]]s, [[sweating]], and [[anxiety]] (often described as a sense of impending doom). Women may experience fewer typical symptoms than men, most commonly shortness of breath, weakness, a feeling of indigestion, and [[fatigue (physical)|fatigue]].<ref name="Kosuge">{{cite journal | last=Kosuge | first=M | coauthors= Kimura K, Ishikawa T et al. | title=Differences between men and women in terms of clinical features of ST-segment elevation acute myocardial infarction | journal=Circulation Journal | volume=70 | issue=3 | pages=222–226 | date=March 2006 | pmid=16501283 | url=http://www.jstage.jst.go.jp/article/circj/70/3/222/_pdf | accessdate=2008-05-31 | doi=10.1253/circj.70.222 }}</ref> Approximately one quarter of all myocardial infarctions are silent, without chest pain or other symptoms. 

People will receive a number of diagnostic tests, such as an [[electrocardiogram]], a chest [[X-ray]] and [[blood test]]s to detect heart muscle damage. The most often used markers are the [[creatine kinase]]-MB (CK-MB) fraction and the [[troponin]] levels. On the basis of the ECG, a distinction is made between ST elevation MI (STEMI) or non-ST elevation MI (non-STEMI). Immediate treatment for suspected acute myocardial infarction includes [[oxygen therapy|oxygen]], [[aspirin]], and sublingual [[nitroglycerin]]. If further [[Analgesia|pain relief]] is needed [[morphine sulfate]] is typically used.<ref>{{cite journal |author=Erhardt L, Herlitz J, Bossaert L, ''et al.'' |title=Task force on the management of chest pain |journal=Eur. Heart J. |volume=23 |issue=15 |pages=1153–76 |year=2002 |pmid=12206127 |doi=10.1053/euhj.2002.3194| url=http://eurheartj.oxfordjournals.org/cgi/reprint/23/15/1153|format=PDF |author10=Task Force on the management of chest pain}}</ref>  A 2009 review about the use of high flow oxygen for treating myocardial infarction found high flow oxygen administration increased mortality and infarct size, calling into question the recommendation for its routine use.<ref name="heart.bmj.com">{{cite web |url=http://heart.bmj.com/cgi/content/full/95/3/198 |title=Routine use of oxygen in the treatment of myocardial infarction: systematic review -- Wijesinghe et al. 95 (3): 198 -- Heart |format= |work= |accessdate=}}</ref>  Most cases of STEMI are treated with [[thrombolysis]] or  [[percutaneous coronary intervention]] (PCI). NSTEMI is managed with medication, although PCI is often performed during hospital admission. In people who have multiple blockages and who are relatively stable, or in a few emergency cases, [[Coronary artery bypass surgery|bypass surgery]] maybe an option.

Heart attacks are the leading cause of death for both men and women worldwide.<ref name="WHO-2002">{{cite book | title=The World Health Report 2004 - Changing History | publisher=[[World Health Organization]] | date=2004 | pages=120–4 | format=PDF | url=http://www.who.int/entity/whr/2004/en/report04_en.pdf | isbn= 92-4-156265-X | author=Robert Beaglehole, ''et al.''}}</ref> Important [[risk factor]]s are previous [[cardiovascular disease]], older age, [[tobacco smoking]], high blood levels of certain lipids ([[triglyceride]]s, [[low-density lipoprotein]]) and low levels of [[high density lipoprotein]] (HDL), [[Diabetes mellitus|diabetes]], [[Hypertension|high blood pressure]], [[obesity]], [[chronic kidney disease]], [[heart failure]], [[Alcohol and cardiovascular disease|excessive alcohol consumption]], the abuse of certain drugs (such as [[cocaine]] and [[methamphetamine]]), and chronic high stress levels.<ref name="pmid18241872">{{cite journal |author=Bax L, Algra A, Mali WP, Edlinger M, Beutler JJ, van der Graaf Y |title=Renal function as a risk indicator for cardiovascular events in 3216 patients with manifest arterial disease |journal=Atherosclerosis |volume= 200|issue= 1|pages= 184|year=2008 |pmid=18241872 |doi=10.1016/j.atherosclerosis.2007.12.006 |url=http://linkinghub.elsevier.com/retrieve/pii/S0021-9150(07)00768-X}}</ref><ref name="pmid16651468">{{cite journal |author=Pearte CA, Furberg CD, O'Meara ES, ''et al.'' |title=Characteristics and baseline clinical predictors of future fatal versus nonfatal coronary heart disease events in older adults: the Cardiovascular Health Study |journal=Circulation |volume=113 |issue=18 |pages=2177–85 |year=2006 |pmid=16651468 |doi=10.1161/CIRCULATIONAHA.105.610352 |url=http://circ.ahajournals.org/cgi/content/full/113/18/2177}}</ref>

Classification:


There are two basic types of acute myocardial infarction:
*Transmural: associated with atherosclerosis involving major coronary artery. It can be subclassified into anterior, posterior, or inferior. Transmural infarcts extend through the whole thickness of the heart muscle and are usually a result of complete occlusion of the area's blood supply.
*Subendocardial: involves small area in the subendocardial wall of the left ventricle, ventricular septum, or papillary muscles. Subendocardial infarcts are thought to be a result of locally decreased blood supply, possibly from a narrowing of the coronary arteries. The subendocardial area is farthest from the heart's blood supply and is more susceptible to this type of pathology.

Clinically, myocardial infarction is further subclassified into ST elevation MI versus non ST elevation MI based on ECG changes.

The phrase "heart attack" is sometimes used incorrectly to describe [[sudden cardiac death]], which may or may not be the result of acute myocardial infarction.  A heart attack is different from, but can be the cause of [[cardiac arrest]], which is the stopping of the heartbeat, and [[cardiac arrhythmia]], an abnormal heartbeat. It is also distinct from [[heart failure]], in which the pumping action of the heart is impaired; severe myocardial infarction may lead to heart failure, but not necessarily.

Signs and symptoms of [[Myocardial infarction]]:
[[Image:AMI pain front.png|right|thumb|Rough diagram of pain zones in myocardial infarction (dark red = most typical area, light red = other possible areas, view of the chest).]]
[[Image:AMI pain back.png|right|thumb|Back view.]]

The onset of symptoms in myocardial infarction (MI) is usually gradual, over several minutes, and rarely instantaneous.<ref name=warningsigns>[[National Heart, Lung and Blood Institute]]. [http://www.nhlbi.nih.gov/actintime/haws/haws.htm Heart Attack Warning Signs]. Retrieved November 22, 2006.</ref> [[Chest pain]] is the most common symptom of acute myocardial infarction and is often described as a sensation of tightness, pressure, or squeezing. Chest pain due to [[ischemia]] (a lack of blood and hence oxygen supply) of the heart muscle is termed [[angina pectoris]]. Pain radiates most often to the left [[arm]], but may also radiate to the lower [[jaw]], [[neck]], right arm, [[Human back|back]], and [[epigastrium]], where it may mimic [[heartburn]]. [[Levine's sign]], in which the patient localizes the chest pain by clenching their fist over the [[sternum]], has classically been thought to be predictive of cardiac chest pain, although a prospective observational study showed that it had a poor positive predictive value.<ref name="pmid17208083">{{cite journal |author=Marcus GM, Cohen J, Varosy PD, ''et al.'' |title=The utility of gestures in patients with chest discomfort |journal=[[Am. J. Med.]] |volume=120 |issue=1 |pages=83–9 |year=2007 |pmid=17208083 |doi=10.1016/j.amjmed.2006.05.045 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9343(06)00668-1}}</ref>

Shortness of breath ([[dyspnea]]) occurs when the damage to the heart limits the [[Cardiac output|output]] of the [[left ventricle]], causing [[left ventricular failure]] and consequent [[pulmonary edema]].  Other symptoms include [[diaphoresis]] (an excessive form of [[sweating]]), weakness, [[light-headedness]], [[nausea]], [[vomiting]], and [[palpitation]]s. These symptoms are likely induced by a massive surge of [[catecholamines]] from the [[sympathetic nervous system]]<ref name="pmid3524599">{{cite journal |author=Little RA, Frayn KN, Randall PE, ''et al.'' |title=Plasma catecholamines in the acute phase of the response to myocardial infarction |journal=[[Arch Emerg Med]] |volume=3 |issue=1 |pages=20–7 |year=1986 |pmid=3524599 |doi= |pmc=1285314}}</ref> which occurs in response to pain and the hemodynamic abnormalities that result from cardiac dysfunction. [[Unconsciousness|Loss of consciousness]] (due to inadequate cerebral perfusion and cardiogenic shock) and even [[sudden cardiac death|sudden death]] (frequently due to the development of ventricular fibrillation) can occur in myocardial infarctions.

Women and older patients experience atypical symptoms more frequently than their male and younger counterparts.<ref name="ACSwomen">{{cite journal |author=Canto JG, Goldberg RJ, Hand MM, ''et al.'' |title=Symptom presentation of women with acute coronary syndromes: myth vs reality |journal=Arch. Intern. Med. |volume=167 |issue=22 |pages=2405–13 |year=2007 |month=December |pmid=18071161 |doi=10.1001/archinte.167.22.2405 |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=18071161}}</ref> Women also have more symptoms compared to men (2.6 on average vs 1.8 symptoms in men).<ref name="ACSwomen"/> The most common symptoms of MI in women include [[dyspnea]], weakness, and [[fatigue (physical)|fatigue]]. Fatigue, sleep disturbances, and dyspnea have been reported as frequently occurring symptoms which may manifest as long as one month before the actual clinically manifested ischemic event. In women, [[chest pain]] may be less predictive of coronary [[ischemia]] than in men.<ref name=McSweeney>{{cite journal | author=McSweeney JC, Cody M, O'Sullivan P, Elberson K, Moser DK, Garvin BJ | title=Women's early warning symptoms of acute myocardial infarction | journal=Circulation | year=2003 | pages=2619–23 | volume=108 | issue=21 | pmid=14597589 | doi = 10.1161/01.CIR.0000097116.29625.7C}}</ref>

Approximately half of all MI patients have experienced warning symptoms such as chest pain prior to the infarction.<ref name=MedicineNet>D Lee, D Kulick, J Marks. [http://www.medicinenet.com/heart_attack/article.htm Heart Attack (Myocardial Infarction)] by MedicineNet.com . Retrieved November 28, 2006.</ref>

Approximately one fourth of all myocardial infarctions are silent, without chest pain or other symptoms.<ref name="Kannel-1986">{{cite journal | author=Kannel WB. | title=Silent myocardial ischemia and infarction: insights from the Framingham Study | journal=Cardiol Clin | year=1986 | volume=4 | issue=4| pages=583–91 | pmid=3779719}}</ref>  These cases can be discovered later on electrocardiograms, using blood enzyme tests or at autopsy without a prior history of related complaints. A silent course is more common in the [[elderly]], in  patients with [[diabetes mellitus]]<ref name="Diabetologica2004-David">{{cite journal | author=Davis TM, Fortun P, Mulder J, Davis WA, Bruce DG | title=Silent myocardial infarction and its prognosis in a community-based cohort of Type 2 diabetic patients: the Fremantle Diabetes Study | journal=Diabetologia | year=2004 | pages=395–9 | volume=47 | issue=3 | pmid=14963648 | doi = 10.1007/s00125-004-1344-4}}</ref> and after [[heart transplantation]], probably because the [[Organ donation|donor]] heart is not connected to nerves of the host.<ref name=rubin>{{cite book | coauthors = Emanuel Rubin, Fred Gorstein, Raphael Rubin, Roland Schwarting, David Strayer | title = Rubin's Pathology - Clinicopathological Foundations of Medicine | publisher = Lippincott Williams & Wilkins | date = 2001 | location = Maryland | pages = 549 | isbn = 0-7817-4733-3 }}</ref> In diabetics, differences in [[pain threshold]], [[autonomic neuropathy]], and [[psychology|psychological]] factors have been cited as possible explanations for the lack of symptoms.<ref name="Diabetologica2004-David"/>

Any group of symptoms compatible with a sudden interruption of the blood flow to the heart are called an [[acute coronary syndrome]].<ref name=ACS>[http://www.americanheart.org/presenter.jhtml?identifier=3010002 Acute Coronary Syndrome]. [[American Heart Association]]. Retrieved November 25, 2006.</ref>

The [[differential diagnosis]] includes other catastrophic causes of chest pain, such as [[pulmonary embolism]], [[aortic dissection]], [[pericardial effusion]] causing [[cardiac tamponade]], [[tension pneumothorax]], and [[esophageal rupture]]. Other non-catastrophic differentials include [[Gastroesophageal reflux disease|gastroesophageal reflux]] and [[Tietze's syndrome]].<ref name="pmid16199332">{{cite journal |author=Boie ET |title=Initial evaluation of chest pain |journal=[[Emerg. Med. Clin. North Am.]] |volume=23 |issue=4 |pages=937–57 |year=2005 |pmid=16199332 |doi=10.1016/j.emc.2005.07.007 |url=http://linkinghub.elsevier.com/retrieve/pii/S0733-8627(05)00059-3}}</ref>

Causes of [[Myocardial infarction]]:
Heart attack rates are higher in association with intense exertion, be it [[stress (psychology)|psychological stress]] or [[physical]] exertion, especially if the exertion is more intense than the individual usually performs.<ref name="Framingham1998">Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. "[http://circ.ahajournals.org/cgi/content/full/97/18/1837 Prediction of coronary heart disease using risk factor categories]". ''Circulation'' 1998; '''97'''(18): 1837-47. PMID 9603539</ref> Quantitatively, the period of intense exercise and subsequent recovery is associated with about a 6-fold higher myocardial infarction rate (compared with other more relaxed time frames) for people who are physically very fit.<ref name="Framingham1998"/> For those in poor physical condition, the rate differential is over 35-fold higher.<ref name="Framingham1998"/> One observed mechanism for this phenomenon is the increased arterial pulse pressure stretching and relaxation of arteries with each heart beat which, as has been observed with [[intravascular ultrasound]], increases mechanical "shear stress" on [[atheroma]]s and the likelihood of plaque rupture.<ref name="Framingham1998"/>

Acute severe infection, such as [[pneumonia]], can trigger myocardial infarction. A more controversial link is that between ''[[Chlamydophila pneumoniae]]'' infection and atherosclerosis.<ref name="Saikku-1992">{{cite journal | author=Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Manttari M, Frick MH, Huttunen JK. | title=Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study | journal=Ann Intern Med | year=1992 | volume=116 | issue=4 | pages=273–8 | pmid=1733381}}</ref> While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor.<ref name="Saikku-1992"/> Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.<ref name="Andraws-2005">{{cite journal | author=Andraws R, Berger JS, Brown DL. | title=Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials | journal=JAMA | year=2005 | volume=293 | issue=21 | pages=2641–7 | pmid=15928286 | doi = 10.1001/jama.293.21.2641}}</ref>

There is an association of an increased incidence of a heart attack in the morning hours, more specifically around 9 a.m.<ref name="pmid2865677">{{cite journal |author=Muller JE, Stone PH, Turi ZG, ''et al.'' |title=Circadian variation in the frequency of onset of acute myocardial infarction |journal=[[N. Engl. J. Med.]] |volume=313 |issue=21 |pages=1315–22 |year=1985 |pmid=2865677 |doi=}}</ref><ref name="pmid3673917">{{cite journal |author=Beamer AD, Lee TH, Cook EF, ''et al.'' |title=Diagnostic implications for myocardial ischemia of the circadian variation of the onset of chest pain |journal=[[Am. J. Cardiol.]] |volume=60 |issue=13 |pages=998–1002 |year=1987 |pmid=3673917 |doi=10.1016/0002-9149(87)90340-7}}</ref><ref name="pmid9036740">{{cite journal |author=Cannon CP, McCabe CH, Stone PH, ''et al.'' |title=Circadian variation in the onset of unstable angina and non-Q-wave acute myocardial infarction (the TIMI III Registry and TIMI IIIB) |journal=[[Am. J. Cardiol.]] |volume=79 |issue=3 |pages=253–8 |year=1997 |pmid=9036740 |doi= 10.1016/S0002-9149(97)00743-1|url=http://linkinghub.elsevier.com/retrieve/pii/S0002914997007431}}</ref>. Some investigators have noticed that the ability of platelets to aggregate varies according to a circadian rhythm, although they have not proven causation.<ref name="pmid3587281">{{cite journal |author=Tofler GH, Brezinski D, Schafer AI, ''et al.'' |title=Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death |journal=[[N. Engl. J. Med.]] |volume=316 |issue=24 |pages=1514–8 |year=1987 |pmid=3587281 |doi=}}</ref> Some investigators theorize that this increased incidence may be related to the circadian variation in cortisol production affecting the concentrations of various cytokines and other mediators of inflammation.<ref name="pmid12027868">{{cite journal |author=Fantidis P, Perez De Prada T, Fernandez-Ortiz A, ''et al.'' |title=Morning cortisol production in coronary heart disease patients |journal=[[Eur. J. Clin. Invest.]] |volume=32 |issue=5 |pages=304–8 |year=2002 |pmid=12027868 |doi= 10.1046/j.1365-2362.2002.00988.x|url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0014-2972&date=2002&volume=32&issue=5&spage=304}}</ref>

Risk factors for [[Myocardial infarction]]

Risk factors for [[atherosclerosis]] are generally risk factors for myocardial infarction:
*[[Diabetes mellitus|Diabetes]] (with or without [[insulin resistance]]) - the single most important risk factor for [[ischaemic heart disease]] (IHD)
*[[Tobacco smoking]]
*[[Hypercholesterolemia]] (more accurately [[hyperlipoproteinemia]], especially high [[low density lipoprotein]] and low [[high density lipoprotein]])
*[[Hypertension|High blood pressure]]
*Family history of [[ischaemic heart disease]] (IHD)
*[[Obesity]]<ref name="Yusuf-2005">{{cite journal | author=Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai P Jr, Razak F, Sharma AM, Anand SS; INTERHEART Study Investigators. | title=Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study | journal=Lancet | year=2005 | volume=366 | issue=9497 | pages=1640–9 | pmid=16271645 | doi = 10.1016/S0140-6736(05)67663-5}}</ref> (defined by a [[body mass index]] of more than 30&nbsp;kg/m², or alternatively by waist circumference or [[waist-hip ratio]]).
*[[Ageing|Age]]: Men acquire an independent risk factor at age 45, Women acquire an independent risk factor at age 55; in addition individuals acquire another independent risk factor if they have a first-degree male relative (brother, father) who suffered a coronary vascular event at or before age 55. Another independent risk factor is acquired if one has a first-degree female relative (mother, sister) who suffered a coronary vascular event at age 65 or younger. 
*[[Hyperhomocysteinemia]] (high [[homocysteine]], a toxic blood [[amino acid]] that is elevated when intakes of [[vitamins]] B2, B6, B12 and [[folic acid]] are insufficient)
*[[Workplace stress|Stress]] (occupations with high stress index are known to have susceptibility for [[atherosclerosis]])
*[[Alcohol]]  Studies show that prolonged exposure to high quantities of alcohol can increase the risk of heart attack
* Males are more at risk than females.<ref name="Framingham1998">{{cite journal | author=Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. | title=Prediction of coronary heart disease using risk factor categories | journal=Circulation | year=1998 | volume=97 | issue=18 | pages=1837–47 | format=[[PDF]] | url=http://circ.ahajournals.org/cgi/reprint/97/18/1837.pdf | pmid=9603539}}</ref>

===Myelofibrosis===
*[[Myelofibrosis]]<ref>http://www.mayoclinic.com/health/myelofibrosis/DS00886/DSECTION=symptoms</ref>
Myelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, and primary myelofibrosis,[1] is a disorder of the bone marrow. It is currently classified as a myeloproliferative disease in which the proliferation of an abnormal type of bone marrow stem cell results in fibrosis, or the replacement of the marrow with collagenous connective tissue fibers.[2]
Myelofibrosis was first described in 1879.

==See also==
*[[Fever]]
*[[Hyperthermia]]

==References==
{{reflist|2}}
==External links==
*http://www.mayoclinic.com/health/fever/DS00077

[[Category:Medical signs]]
[[Category:2Fix]]