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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
| | #Redirect[[Pneumocystis jirovecii pneumonia]] |
| {{DiseaseDisorder infobox |
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| Name = Pneumocystis jirovecii pneumonia |
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| ICD10 = {{ICD10|B|20|6|b|20}} |
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| ICD9 = {{ICD9|136.3}} |
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| ICDO = |
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| Image = Pneumocystis.jpg |
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| Caption = '''''Pneumocystis jirovecii''''' cysts from bronchoalveolar lavage, stained with [[Toluidin blue O stain]] |
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| OMIM = |
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| OMIM_mult = |
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| MedlinePlus = 000671 |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| DiseasesDB = 10160 |
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| MeshID = D011020 |
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| }}
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| {{Search infobox}}
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| {{CMG}}
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| ==Overview==
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| '''''Pneumocystis'' pneumonia''' ('''PCP''') is a form of [[pneumonia]] caused by the yeast-like [[fungus|fungal]] ''Pneumocystis jirovecii'' (Jirovecii is pronounced "yee row vet zee eye"). The causal agent was originally described as a protozoan and spelled ''P. jiroveci'' and prior to then was classified as a form of ''Pneumocystis carinii'', a name still in common usage.<ref name=Stringer_2002>{{cite journal | author=Stringer JR, Beard CB, Miller RF, Wakefield AE | title=A new name (''Pneumocystis jiroveci'') for ''Pneumocystis'' from humans | journal=Emerg Infect Dis | year=2002 | pages=891-6 | volume=8 | issue=9 | id=PMID 12194762}}</ref><ref name=Redhead_2006>{{cite journal | author=Redhead SA, Cushion MT, Frenkel JK, Stringer JR | title=''Pneumocystis'' and ''Trypanosoma cruzi'': nomenclature and typifications | journal=J Eukaryot Microbiol | year=2006 | pages=2–11 | volume=53 | issue=1 | id=PMID 16441572}}</ref> These names are discussed below. As a result, '''Pneumocystis pneumonia (PCP)''' has also been known as '''Pneumocystis jiroveci[i] pneumonia''' and as '''Pneumocystis carinii pneumonia''', as is also explained below.<ref name=Cushion_1998>{{cite journal | author=Cushion MT .| title = Chapter 34. ''Pneumocystis carinii''. In: Collier, L., Balows, A. & Sussman, M. (ed.), Topley and Wilson's Microbiology and Microbial Infections 9th ed. Arnold and Oxford Press, New York. | year = 1998 | pages = 645–683}}</ref><ref name=Cushion_1998b>{{cite journal | author=Cushion MT | title = Taxonomy, genetic organization, and life cycle of ''Pneumocystis carinii'' | | journal = Semin. Respir. Infect | year = 1998 | volume = 13 | issue =4 | pages = 304–312}}</ref><ref name=Cushion_2004>{{cite journal | author=Cushion MT | title = ''Pneumocystis'': unraveling the cloak of obscurity | | journal = Trends Microbiol | year = 2004 | volume = 12 | issue =5 | pages = 243–249}}</ref>
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| It is relatively rare in people with normal immune systems but common among people with
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| weakened [[immune system]]s, such as premature or severely malnourished children, the elderly, and especially [[AIDS]] patients, in whom it is most commonly observed today.<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0838585299 }}</ref> PCP can also develop in patients who are taking [[Immunosuppressive drug|immunosuppressant medications]] (e.g. patients who have undergone [[Organ transplant|solid organ transplantation]]) and in patients who have undergone [[bone marrow transplantation]].
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| The organism is distributed worldwide<ref name=Morris_2004>{{cite journal | author=Morris A et al | title= Current Epidemiology of Pneumocystis Pneumonia | journal=Emerg Infect Dis | year=2004 | pages=1713-1720 | volume=10 | issue=10 | id=PMID 15504255}}</ref>[http://www.cdc.gov/ncidod/eid/vol10no10/03-0985.htm].
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| ==Epidemiology==
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| Pneumocystis pneumonia has been described in all continents except Antarctica.<ref name=Morris_2004/> It was originally described as a rare cause of [[pneumonia]] in [[neonate]]s. It is believed to be an environmental organism, and human-to-human transmission is thought not to occur (although in one outbreak of 12 cases among transplant patients in Leiden it was postulated, but not proven, that human-to-human spread may have occurred).<ref>{{cite journal | author=de Boer M, Bruijnesteijn van Coppenraet L, Gaasbeek A, ''et al.'' | title=An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant [[genotype]]
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| among renal transplant recipients: interhuman transmission or a common environmental source? | journal=Clin Infect Dis |year=2007 | volume=44 | issue=9 | pages=1143–49 | id=PMID 17407029 }}</ref> Greater than 75% of children are seropositive by the age of 4, which suggest a high background exposure to the organism.
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| Since the start of the [[HIV]] pandemic, PCP has been closely associated with AIDS. Because it only occurs in an immunocompromised host, it may be the first clue to a new AIDS diagnosis if the patient has no other reason to be immunocompromised (e.g. taking immunosuppressive drugs for [[organ transplant]]). An unusual rise in the number of PCP cases in North America, noticed when physicians began requesting large quantities of the rarely used antibiotic [[pentamidine]], was the first clue to the existence of AIDS in the early 1980s.<ref>{{cite journal | title=A Cluster of Kaposi's Sarcoma and ''Pneumocystis carinii'' pneumonia among homosexual male residents of Los Angeles and Range Counties, California | author=Fannin S, Gottlieb MS, Weisman JD, ''et al.'' | year=1982 | journal=MMWR Weekly | volume=31 | issue=32 | pages=305–7 }}</ref><ref>{{cite journal | author=Masur H, Michelis MA, Greene JB, ''et al.'' |title=An outbreak of community-acquired Pneumocystis carinii pneumonia |journal=N Engl J Med |year=1981 |volume=305 |pages=1431–8 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/00001114.htm }}</ref>
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| Prior to the development of more effective treatments, PCP was a common and rapid cause of death in persons living with AIDS. Much of the incidence of PCP has been reduced by instituting a standard practice of using oral [[co-trimoxazole]] to prevent the disease in people with [[CD4]] counts less than 200/mm³. In populations that do not have access to preventative treatment, PCP continues to be a major cause of death in AIDS.
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| In [[immunocompromised]] patients (e.g. cancer patients on [[chemotherapy]], or persons living with [[AIDS]] with a [[T helper cell|CD4+ T-cell]] count below 200/μl), [[prophylaxis]] with regular [[pentamidine]] inhalations or [[sulfamethoxazole]]/[[trimethoprim]] ([[co-trimoxazole]] or [[TMP-SMX]]) may be necessary to prevent PCP.
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| ==Symptoms==
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| Symptoms of PCP include fever, non-productive cough, shortness of breath (especially on exertion), weight loss and night sweats. There is usually not a large amount of [[sputum]] with PCP unless the patient has an additional bacterial infection. The fungus can invade other visceral organs, such as the [[liver]], [[spleen]] and [[kidney]], but only in a minority of cases.
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| ==Pathophysiology==
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| The risk of pneumonia due to Pneumocystis jirovecii increases when [[CD4]] levels are less than 200 cells/μl. In these [[Immunosuppression|immunosuppressed]] individuals the manifestations of the infection are highly variable.<ref>{{cite book | author = Hughes WT | title = Pneumocystis Carinii. ''In:'' Barron's Medical Microbiology ''(Barron S ''et al'', eds.)| edition = 4th ed. | publisher = Univ of Texas Medical Branch | year = 1996 | id = [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.4516 (via NCBI Bookshelf)] ISBN 0-9631172-1-1 }}</ref> The disease attacks the interstitial, fibrous tissue of the lungs, with marked thickening of the alveolar septa and [[alveoli]] and leading to significant [[Hypoxia (medical)|hypoxia]] which can be fatal if not treated aggressively; ergo, [[LDH]] levels increase and gas exchange is compromised. Oxygen is less able to diffuse into the blood, leading to [[hypoxia (medical)|hypoxia]]. Hypoxia, along with high arterial [[carbon dioxide]] (CO<sub>2</sub>) levels, stimulates [[ventilation (physiology)|ventilation]], thereby causing [[dyspnea]].
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| ==Diagnosis==
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| The diagnosis can be confirmed by the characteristic appearance of the [[chest x-ray]] which shows widespread pulmonary infiltrates, and an [[arterial blood gas|arterial oxygen level]] (pO<sub>2</sub>) strikingly lower than would be expected from symptoms. The diagnosis can be definitively confirmed by pathologic identification of the causative organism in induced [[sputum]] or [[bronchia]]l washings obtained by [[bronchoscopy]] with coloration by [[toluidine blue]] or [[immunofluorescence assay]], which will show characteristic [[cyst]]s [http://www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu8/std/pcp.html].
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| ''Pneumocystis'' infection can also be diagnosed by [[immunofluorescent]] or [[histochemical staining]] of the specimen, and more recently by molecular analysis of [[PCR]] products comparing [[DNA]] samples. Notably, simple molecular detection of ''Pneumocystis jirovecii'' in lung fluids does not mean that a person has Pneumocystis pneumonia or infection by [[HIV]]. The fungus appears to be present in healthy individuals also in the general population.<ref name=Medrano_2005>{{cite journal | author=Medrano FJ et al | title= ''Pneumocystis jiroveci''i in General Population | journal=Emerg Infect Dis | year=2005 | pages=245–250 | volume=11 | issue=2 | id=PMID 15752442 }}</ref>
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| [[Image:PCPxray.jpg|thumb|left|250px|'''X-ray of Pneumocystis jirovecii pneumonia''' There is increased white (opacity) in the lower lungs on both sides, characteristic of ''Pneumocystis'' pneumonia]]
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| ==Life-cycle==
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| The complete life-cycles of any of the species of ''Pneumocystis'' are not known, but presumably all resemble the others in the genus. The terminology follows zoological terms, rather than mycological terms, reflecting the initial misdetermination as a protozoan parasite. All stages are found in lungs and because they cannot be cultured, direct observation of living ''Pneumocystis'' is difficult. The trophozoite stage is the vegetative state. It is single-celled and appears amoeboid (multilobed) and closely associated with host cells. Globular cysts eventually form that have a thicker wall. Within these [[ascus]]-like cysts, eight spores form which are released through rupture of the cyst wall. The cysts often collapse forming crescent-shaped bodies visible in stained tissue. It is not known for certain if [[meiosis]] takes place within the cysts, or what the genetic status is of the various cell types [http://www.dpd.cdc.gov/dpdx/HTML/Pneumocystis.htm - see DPDx life-cycle diagram].
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| ==Treatment==
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| Antipneumocystic medication is used with concomitant [[steroids]] in order to avoid inflammation, which causes an exacerbation of symptoms about four days after treatment begins if steroids are not used. By far the most commonly used medication is a combination of [[trimethoprim]] and [[sulfamethoxazole]] ([[co-trimoxazole]], with the tradenames Bactrim, Septrin, or Septra), but some patients are unable to tolerate this treatment due to allergies. Other medications that are used, alone or in combination, include [[pentamidine]], [[trimetrexate]], [[dapsone]], [[atovaquone]], [[primaquine]], and [[clindamycin]]. Treatment is usually for a period of about 21 days.
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| [[Pentamidine]] is less often used as its major limitation is the high frequency of [[side effect]]s. These include acute [[pancreatitis]], [[renal failure]], [[hepatotoxicity]], [[leukopenia]], [[rash]], [[fever]] and [[hypoglycaemia]].
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| ==Guidelines==
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| To read about guidelines for prevention and treatment of Pneumocystis pneumonia Infections in HIV-Infected Adults and Adolescents, click [[HIV opportunistic infection pneumocystis pneumonia: prevention and treatment guidelines|'''here''']].
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| ==Nomenclature==
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| The name ''P. jirovecii'', to distinguish the organism found in humans from physiological variants of ''Pneumocystis'' found in other animals, was first proposed in 1976, in honor of Otto Jirovec, who described ''Pneumocystis'' pneumonia in humans in 1952. After DNA analysis showed significant differences in the human variant, the proposal was made again in 1999 and has come into common use; ''P. carinii'' still describes the species found in rats<ref name=Stringer_2002 /> and that name is typified by an isolate from rats.<ref name=Redhead_2006 /> The International Code of Botanical Nomenclature (ICBN) requires that the name to be spelled ''jirovecii'' rather than ''jiroveci''. The latter spelling originated when ''Pneumocystis'' was believed to be a protozoan, rather than a fungus, and therefore was spelled using the International Code of Zoological Nomenclature; both spellings are commonly used. A change in the ICBN in 2005 now recognizes the validity of the 1976 publication, making the 1999 proposal redundant, and cites ''Pneumocystis'' and ''P. jirovecii'' as examples of the change in ICBN Article 45, Ex 8. The name ''P. jirovecii'' is typified (both lectotypified and epitypified) by samples from human autopsies dating from the 1960s.<ref name=Redhead_2006 />
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| The term PCP, which was widely used by practitioners and patients, has been retained for convenience, with the rationale that it now stands for the more general '''P'''neumo'''c'''ystis '''p'''neumonia rather than '''P'''neumocystis '''c'''arinii '''p'''neumonia.
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| ==History==
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| The earliest report of this genus appears to have been that of Carlos Chagas in 1909<ref name=Chagas_1909>{{cite journal | author = Chagas C| title = Neue Trypanosomen | journal = Vorläufige Mitteilung. Arch. Schiff. Tropenhyg. | year = 1909 | volume = 13 | issue = | pages = 120–122 }}</ref> who discovered it in experimental animals but confused it with part of the life-cycle of ''[[Trypanosoma cruzi]]'' (causal agent of [[Chagas Disease]]) and later called both organisms '' 'Schizotrypanum cruzi' '' a form of [[trypanosome]] infecting humans.<ref name=Chagas_1909b>{{cite journal | author = Chagas C| title = Nova tripanozomiase humana: Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem | journal = Mem Inst Oswaldo Cruz | year = 1909 | volume = 1 | issue =2 | pages = 159–218}}</ref> The rediscovery of ''Pneumocystis'' cysts was reported by Antonio Carini in 1910 also in Brazil.<ref name=Carini_1910>{{cite journal | author = Carini A. | title = Formas des eschizogonia do ''Trypanosoma lewisi''. | journal = Soc Med Cir São Paulo | year = 1910 | volume = 38 | issue = 8| pages = – | url= }}</ref> The genus was again discovered in 1912 by Delanoë and Delanoë this time at the Pasteur Institute in Paris, France who found it in rats and who proposed the genus and species name ''Pneumocystis carinii'' after Carini.<ref name=Delanoë_1912>{{cite journal | author = Delanoë P, Delanoë M.| title = Sur les rapports des kystes de Carini du poumon des rats avec le ''Trypanosoma lewisi''. | journal = Comptes rendus de l’Academie des sciences. | year = 1912 | volume = 155 | issue = | pages = 658–61 | url= }}</ref>
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| ''Pneumocystis'' was redescribed as a human pathogen in 1942 by two Dutch investigators, van der Meer and Brug who found it in three new cases: a 3-month-old infant with [[congenital heart disease]] and in 2 of 104 [[autopsy]] cases - a 4-month-old infant and a 21-year-old adult.<ref name=Meer_1942>{{cite journal | author = van der Meer MG, Brug SL. | title = Infection à ''Pneumocystis'' chez l’homme et chez les animaux. | journal = Amer Soc Belge Méd Trop | year = 1942 | volume = 22| issue = | pages = 301–9 | url= }}</ref> There being only one described [[species]] in the [[genus]], they considered the human parasite to be ''P. carinii''. Nine years later (1951) Dr. Josef Vanek at Charles University in Prague in Prague, Czechoslovakia showed in a study of lung sections from sixteen children that the organism labelled "''P. carinii''" was the causative agent of pneumonia in these children.<ref name=Vanek_1951>{{cite journal | author = Vanek J. | title = Atypicka (interstitiálni) pneumonie detí vyvolaná ''Pneumocystis carinii'' (Atypical interstitial pneumonia of infants produced by ''Pneumocystis carinii''). | journal = Casop lék cesk | year = 1951 | volume = 90 | issue = | pages = 1121–4 | url= }}</ref> The following year (1952) Jírovec reported "''P. carinii''" as the cause of [[interstitial pneumonia]] in [[neonate]]s.<ref name=Jírovec_1952>{{cite journal | author = Jírovec O. | title = ''Pneumocystis carinii'' puvodce t. zv intertitialnich plasmocelularnich pneumonii kojencw (''Pneumocystis carinii'', the cause of interstitial plasmacellular pneumonia in neonates) | journal = P Csl. Hyg epid mikrob | year = 1952 | volume = 1 | issue = | pages = 141 | url= }}</ref><ref name=Vanek_1953>{{cite journal | author = Vanek J, Jírovec O, Lukes J.| title = Interstitial plasma cell pneumonia in infants. | journal = Ann Paediatrici | year = 1953 | volume = 180 | issue = | pages = 1–21 | url= }}</ref><ref name=Gajdusek_1957>{{cite journal | author = Gajdusek DC| title = ''Pneumocystis carinii''; etiologic agent of interstitial plasma cell pneumonia of premature and young infants. | journal = Pediatrics | year = 1957 | volume = 19 | issue = | pages = 543–65 | url= }}</ref> Following the realization that ''Pneumocystis'' from humans could not infect experimental animals such as rats, and that the rat form of ''Pneumocystis'' differed physiologically and had different [[antigen]]ic properties, Frenkel<ref name=Frenkel_1976>{{cite journal | author=Frenkel JK | title=''Pneumocystis jiroveci'' n. sp. from man: morphology, physiology, and immunology in relation to pathology | journal=Natl Cancer Inst Monogr | year=1976 | pages=13–27 | volume=43 | id=PMID 828240}}</ref> was the first to recognize the human pathogen as a distinct species. He named it ''Pneumocystis jirovecii'' (see nomenclature above). There has been controversy over the relabeling of ''P. carinii'' in humans as ''P. jirovecii'',<ref name=Gigliotti_2005>{{cite journal |author=Gigliotti F |title=''Pneumocystis carinii'': has the name really been changed? |journal=Clin Infect Dis |volume=41 |issue=12 |pages=1752–5 |year=2005 |id=PMID 16288399}}</ref><ref name=Redhead_2006/> which is why both names still appear in publications. However, only the name ''P. jirovecii'' is used exclusively for the human pathogen, whereas the name ''P. carinii'' has had a broader application to many species.<ref name=Hawksworth_2007>{{cite journal | author=Hawksworth DL | title=Responsibility in naming pathogens: the case of Pneumocystis jirovecii, the causal agent of pneumocystis pneumonia | journal=Lancet Infect. Dis. | year=2007 | pages=3–5 | volume=7(1) | id=PMID 17182335}}</ref> Frenkel and those before him, believed that all ''Pneumocystis'' were [[protozoa]]ns, but soon afterwards evidence began accumulating that ''Pneumocystis'' was a [[fungal]] genus. Recent studies show it to be an unusual, in some ways a primitive genus of [[Ascomycota]], related to a group of [[yeast]]s.<ref name=James_2006>{{cite journal | author=James TY et al | title=Reconstructing the early evolution of Fungi using a six-gene phylogeny | journal=Nature | year=2006 | pages=818–822 | volume=443 }}</ref> Every tested primate, including humans, appears to have their own type of ''Pneumocystis'' that is incapable of cross-infecting other host species and has co-evolved with each [[mammal]] species.<ref name=Hugot_2003>{{cite journal | author=Hugot J, Demanche C, Barriel V, Dei-Cas E, Guillot J | title=Phylogenetic systematics and evolution of primate-derived ''Pneumocystis'' based on mitochondrial or nuclear DNA sequence comparison | journal=Syst Biol | year=2003 | pages=735–744 | volume=52 }}</ref> Currently only 5 species have been formally named: ''P. jirovecii'' from humans, ''P. carinii'' as originally named from rats, ''P. murina'' from mice,<ref name=Keely_2004>{{cite journal |author=Keely S, Fischer J, Cushion M, Stringer J |title=Phylogenetic identification of ''Pneumocystis murina'' sp. nov., a new species in laboratory mice |journal=Microbiology |volume=150 |issue=Pt 5 |pages=1153–65 |year=2004 |id=PMID 15133075}}</ref> ''P. wakefieldiae''<ref name=Cushion_2004b>{{cite journal | author=Cushion MT, Keely SP, Stringer JR | title=Molecular and phenotypic description of Pneumocystis wakefieldiae sp. nov., a new species in rats | journal=Mycologia | year=2004 | pages=429–438 | volume=96 }}</ref><ref name=Cushion_2005>{{cite journal | author=Cushion MT, Keely SP, Stringer JR | title=Validation of the name Pneumocystis wakefieldiae | journal=Mycologia | year=2005 | pages=268 – 268 | volume=97 }}</ref> also from rats, and ''P. oryctolagi'' from rabbits.<ref name=Dei-Cas_2006>{{cite journal | author=Dei-Cas E et al | title=Pneumocystis oryctolagi sp. nov., an uncultured fungus causing pneumonia in rabbits at weaning: review of current knowledge, and description of a new taxon on genotypic, phylogenetic and phenotypic bases | journal=FEMS Micriobiol. Rev. | year=2006 | pages=853–871| volume=30(6) | id=PMID 17064284}}</ref>
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| Historical and even recent reports of ''P. carinii'' from humans are based upon older classifications (still used by many, or those still debating the recognition of distinct species in the genus ''Pneumocystis'') which does not mean that the true ''P. carinii'' from rats actually infects humans. In an intermediate classification system, the various [[taxa]] in different mammals have been called formae speciales or forms. For example the human "form" was called ''Pneumocystis carinii'' f. [or f. sp.] ''hominis'', while the original rat infecting form was called ''Pneumocystis carinii'' f. [or f. sp.] ''carinii''. This terminology is still used by some researchers. The species of ''Pneumocystis'' species originally seen by Chagas have not yet been named as distinct species.<ref name=Redhead_2006/> Many other undescribed species presumably exist and those that have been detected in many mammals are only known from molecular sample detection from lung tissue or fluids, rather than by direct physical observation.<ref name=Demanche_2001>{{cite journal | author=Demanche C et al | title=Phylogeny of ‘’Pneumocystis carinii’’ from 18 [[primate]] species confirms [[host specificity]] and suggests [[coevolution]] | journal=J. Clinical Microbiol. | year=2001 | pages=2126–2133 | volume=39 | issue=6 | id=PMID 11376046 }}</ref> As of yet, they are cryptic taxa.
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| ==Pneumocystis Genome Project==
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| ''Pneumocystis'' species cannot be grown in culture. Therefore, there is a limitation to the availability of the human disease causing agent, ''P. jirovecii''. Hence, investigation of the whole genome of a ''Pneumocystis'' is largely based upon true ''P. carinii'' available from experimental rats which can be maintained with infections. The project is described in the site linked here. Genetic material of other species, such as ''P. jirovecii'' can be compared to the genome of ''P. carinii''.
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| [http://pgp.cchmc.org/ Pneumocystis Genome Project]
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| ==References==
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| {{Reflist|2}}
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| {{Mycoses}}
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| [[de:Pneumocystis jiroveci]]
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| [[es:Pneumocystis jiroveci]]
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| [[fr:Pneumocystose]]
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| [[fr:Pneumocystis jiroveci]]
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| [[ja:ニューモシスチス肺炎]]
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| [[pt:Pneumocistose]]
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| [[pl:Pneumocystis jiroveci]]
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| [[Category:Fungal diseases]]
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| [[Category:Ascomycota]]
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| [[Category:Infectious disease]]
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| [[Category:Overview complete]]
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