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| | '''For the patient information, click [[Microsporidiosis (patient information)|here]]''' |
| | {{Microsporidiosis}} |
| | {{CMG}}; {{AE}}{{AY}} |
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| ==Overview==
| | {{SK}} Microsporidial infection, Infection by microsporidia |
| {{Infobox_Disease | | | == [[Microsporidiosis overview|Overview]] == |
| Name = {{PAGENAME}} |
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| Image = |
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| Caption = |
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| DiseasesDB = 31870 |
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| ICD10 = {{ICD10|B|60|8|b|50}} |
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| ICD9 = {{ICD9|136.8}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| MeshID = D016881 |
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| }}
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| '''Microspridiosis''' is an opportunistic intestinal infection that causes [[diarrhea]] and wasting in [[immunocompromised]] individuals ([[HIV]], for example). It results from different species of [[microsporidia]], a group of [[protozoa]]l parasites.
| | == [[Microsporidiosis historical perspective|Historical perspective]] == |
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| In [[HIV]] infected individuals, microsporidiosis generally occurs when [[CD4]]+ [[T cell]] counts fall below 100.
| | == [[Microsporidiosis classification|Classification]] == |
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| ==Causative agents== | | == [[Microsporidiosis pathophysiology|Pathophysiology]] == |
| At least 14 microsporidian species have been recognized as human [[pathogen]]s, spread across eight genera:
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| * ''Brachiola''
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| ** ''B. algerae'', ''B. connori'', ''B. vesicularum''
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| * ''Encephalitozoon''
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| ** ''E. cuniculi'', ''E. hellem'', ''E. intestinalis''
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| * Enterocytozoon
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| ** ''E. bieneusi''
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| * ''[[Microsporidium]]''
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| ** ''M. ceylonensis'', ''M. africanum''
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| * ''[[Nosema]]''
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| ** ''N. ocularum''
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| * ''Pleistophora sp.''
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| * ''Trachipleistophora''
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| ** ''T. hominis'', ''T. anthropophthera''
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| * ''Vittaforma''
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| ** ''V. corneae.''
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| ==Life cycle== | | == [[Microsporidiosis causes|Causes]] == |
| [[Image:Microsporidiosis 01.jpg|thumb|right|Life cycle of the various organisms that cause microsporidiosis.]] | |
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| ''(Coded to [[:Image:Microsporidiosis 01.jpg|image]] at right).''
| | == [[Microsporidiosis differential diagnosis|Differentiating Microsporidiosis from other Diseases]] == |
| # The infective form of microsporidia is the resistant [[spore]] and it can survive for an exteneded period of time in the environment.
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| # The spore extrudes its polar tubule and infects the host cell.
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| # The spore injects the infective sporoplasm into the [[eukaryotic]] host cell through the polar tubule.
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| # Inside the cell, the sporoplasm undergoes extensive multiplication either by [[merogony]] (binary fission) or [[schizogony]] (multiple fission).
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| # This development can occur either in direct contact with the host cell [[cytoplasm]] (''E. bieneusi'') or inside a [[vacuole]] called a parasitophorous vacuole (''E. intestinalis''). Either free in the cytoplasm or inside a parasitophorous vacuole, microsporidia develop by [[sporogony]] to mature spores.
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| # During sporogony, a thick wall is formed around the spore, which provides resistance to adverse environmental conditions. When the spores increase in number and completely fill the host cell cytoplasm, the cell membrane is disrupted and releases the spores to the surroundings.
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| # These free mature spores can infect new cells thus continuing the cycle.
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| | == [[Microsporidiosis epidemiology and demographics|Epidemiology and Demographics]] == |
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| ==CDC Guidelines for Prevention and Treatment of Microsporidiosis Infections in HIV-Infected Adults and Adolescents== | | == [[Microsporidiosis risk factors|Risk Factors]] == |
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| ===Treatment Recommendations=== | | == [[Microsporidiosis natural history, complications and prognosis|Natural History, Complications and Prognosis]] == |
| ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with resolution of symptoms of enteric microsporidiosis, including that caused by E. bieneusi.<ref name="pmid10795595">{{cite journal |author=Maggi P, Larocca AM, Quarto M, Serio G, Brandonisio O, Angarano G, Pastore G |title=Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1 |journal=Eur. J. Clin. Microbiol. Infect. Dis. |volume=19 |issue=3 |pages=213–7 |year=2000 |month=March |pmid=10795595 |doi= |url=http://link.springer.de/link/service/journals/10096/bibs/0019003/00190213.htm |accessdate=2012-04-19}}</ref><ref name="pmid9365777">{{cite journal |author=Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM |title=Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy |journal=AIDS |volume=11 |issue=13 |pages=1658–9 |year=1997 |month=November |pmid=9365777 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=11&issue=13&spage=1658 |accessdate=2012-04-19}}</ref><ref name="pmid9598440">{{cite journal |author=Conteas CN, Berlin OG, Speck CE, Pandhumas SS, Lariviere MJ, Fu C |title=Modification of the clinical course of intestinal microsporidiosis in acquired immunodeficiency syndrome patients by immune status and anti-human immunodeficiency virus therapy |journal=Am. J. Trop. Med. Hyg. |volume=58 |issue=5 |pages=555–8 |year=1998 |month=May |pmid=9598440 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=9598440 |accessdate=2012-04-19}}</ref> All patients should be offered ART as part of the initial management of their infection ('''AII'''). Nevertheless, data indicate that microsporidia are suppressed but not eliminated.<ref name="pmid9365777">{{cite journal |author=Goguel J, Katlama C, Sarfati C, Maslo C, Leport C, Molina JM |title=Remission of AIDS-associated intestinal microsporidiosis with highly active antiretroviral therapy |journal=AIDS |volume=11 |issue=13 |pages=1658–9 |year=1997 |month=November |pmid=9365777 |doi=|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=11&issue=13&spage=1658 |accessdate=2012-04-19}}</ref>
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| No specific therapeutic agent is active against E. bieneusi infection. A controlled clinical trial suggests that E. bieneusi might respond to oral fumagillin (60 mg/day), a water insoluble antibiotic made by Aspergillus fumigatus ('''BII''').<ref name="pmid10930148">{{cite journal |author=Molina JM, Goguel J, Sarfati C, Michiels JF, Desportes-Livage I, Balkan S, Chastang C, Cotte L, Maslo C, Struxiano A, Derouin F, Decazes JM |title=Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA |journal=AIDS |volume=14 |issue=10 |pages=1341–8 |year=2000 |month=July |pmid=10930148 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=14&issue=10&spage=1341 |accessdate=2012-04-19}}</ref><ref name="pmid12075057">{{cite journal |author=Molina JM, Tourneur M, Sarfati C, Chevret S, de Gouvello A, Gobert JG, Balkan S, Derouin F |title=Fumagillin treatment of intestinal microsporidiosis |journal=N. Engl. J. Med. |volume=346 |issue=25 |pages=1963–9 |year=2002 |month=June |pmid=12075057 |doi=10.1056/NEJMoa012924 |url=http://dx.doi.org/10.1056/NEJMoa012924 |accessdate=2012-04-19}}</ref> However, fumagillin is not available for systemic use in the United States. One report indicates that 60 days of nitazoxanide might resolve chronic diarrhea caused by E. bieneusi in the absence of ART.<ref name="pmid10602740">{{cite journal |author=Bicart-Sée A, Massip P, Linas MD, Datry A |title=Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS |journal=Antimicrob. Agents Chemother. |volume=44 |issue=1 |pages=167–8 |year=2000 |month=January |pmid=10602740 |pmc=89645 |doi= |url= |accessdate=2012-04-19}}</ref> However, the effect might be minimal among patients with low CD4+ T cell counts. Nitazoxanide is approved for use among children and is expected to be approved by the FDA for use among adults.
| | == Diagnosis == |
| | [[Microsporidiosis history and symptoms|History and Symptoms]] | [[Microsporidiosis physical examination|Physical Examination]] | [[Microsporidiosis laboratory findings|Laboratory Findings]] | [[Microsporidiosis x ray|X ray]] | [[Microsporidiosis CT|CT]] | [[Microsporidiosis MRI|MRI]] | [[Microsporidiosis other imaging studies|Other imaging studies]] | [[Microsporidiosis other diagnostic studies|Other Diagnostic Studies]] |
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| Albendazole and fumagillin have demonstrated consistent activity against other microsporidia in vitro and in vivo.<ref name="pmid9210681">{{cite journal |author=Didier ES |title=Effects of albendazole, fumagillin, and TNP-470 on microsporidial replication in vitro |journal=Antimicrob. Agents Chemother. |volume=41 |issue=7 |pages=1541–6 |year=1997 |month=July |pmid=9210681 |pmc=163955 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9210681 |accessdate=2012-04-19}}</ref><ref name="pmid9420047">{{cite journal |author=Katiyar SK, Edlind TD |title=In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives |journal=Antimicrob. Agents Chemother. |volume=41 |issue=12 |pages=2729–32 |year=1997 |month=December |pmid=9420047 |pmc=164197 |doi= |url=http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9420047 |accessdate=2012-04-19}}</ref><ref name="pmid9593027">{{cite journal |author=Molina JM, Chastang C, Goguel J, Michiels JF, Sarfati C, Desportes-Livage I, Horton J, Derouin F, Modaï J |title=Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial |journal=J. Infect. Dis. |volume=177 |issue=5 |pages=1373–7 |year=1998 |month=May |pmid=9593027 |doi= |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9593027 |accessdate=2012-04-19}}</ref><ref name="pmid9262551">{{cite journal |author=Gritz DC, Holsclaw DS, Neger RE, Whitcher JP, Margolis TP |title=Ocular and sinus microsporidial infection cured with systemic albendazole |journal=Am. J. Ophthalmol. |volume=124 |issue=2 |pages=241–3 |year=1997 |month=August |pmid=9262551 |doi= |url= |accessdate=2012-04-19}}</ref><ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref>
| | == Treatment == |
| Albendazole, a benzimidazole that binds to b-tubulin, has activity against many species of microsporidia, but it is not effective for Enterocytozoon infections, although fumagillin has activity in vitro and in vivo.
| | [[Microsporidiosis medical therapy|Medical Therapy]] | [[Microsporidiosis surgery|Surgery]] | [[Microsporidiosis primary prevention|Primary Prevention]] | [[Microsporidiosis secondary prevention|Secondary Prevention]] | [[Microsporidiosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Microsporidiosis future or investigational therapies|Future or Investigational Therapies]] |
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| Albendazole is recommended for initial therapy of intestinal and disseminated (not ocular) microsporidiosis caused by microsporidia other than E. bieneusi ('''AII'''). Itraconazole also might be useful in disseminated disease when combined with albendazole especially in infections caused by Trachipleistophora or Brachiola ('''CIII''').
| | ==Case Studies== |
| | [[Microsporidiosis case study one|Case #1]] |
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| Ocular infections caused by [[microsporidia]] should be treated with [[topical]] Fumidil B (fumagillin bicylohexylammonium) in [[saline]] (to achieve a concentration of 70 mg/mL of fumagillin)('''BII''').<ref name="pmid8117342">{{cite journal |author=Diesenhouse MC, Wilson LA, Corrent GF, Visvesvara GS, Grossniklaus HE, Bryan RT |title=Treatment of microsporidial keratoconjunctivitis with topical fumagillin |journal=Am. J. Ophthalmol. |volume=115 |issue=3 |pages=293–8 |year=1993 |month=March |pmid=8117342 |doi= |url= |accessdate=2012-04-19}}</ref> Topical fumagillin is the only formulation available for treatment in the United States and is investigational. Although clearance of microsporidia from the eye can be demonstrated, the organism often is still present systemically and can be detected in the urine or in nasal smears. In such cases, the use of albendazole as a companion systemic agent is recommended ('''BIII''').
| | ==Related Chapters== |
| | *[[Opportunistic infections]] |
| | *[[HIV opportunistic infections]] |
| | *[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines]] |
| | *[[HIV opportunistic infection pneumocystis pneumonia: prevention and treatment guidelines]] |
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| Metronidazole and atovaquone are not active in vitro or in animal models and should not be used to treat microsporidiosis ('''DII'''). Fluid support should be offered if diarrhea has resulted in dehydration ('''AIII'''). Malnutrition and wasting should be treated with nutritional supplementation ('''AIII''').
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| ===Monitoring and Adverse Events===
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| Albendazole side effects are rare but hypersensitivity (rash, pruritis, fever), neutropenia (reversible), CNS effects (dizziness, headache), gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting), hair loss (reversible), and elevated hepatic enzymes (reversible) have been reported. Albendazole is not carcinogenic or mutagenic. Topical fumagillin has not been associated with substantial side effects. Oral fumagillin has been associated with thrombocytopenia, which is reversible on stopping the drug.
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| ===Management of Treatment Failure===
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| Supportive treatment and optimizing ART to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure ('''CIII''').
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| ===Prevention of Recurrence===
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| Treatment for ocular microsporidiosis should be continued indefinitely because recurrence or relapse might follow treatment discontinuation ('''BIII'''). Whether treatment can be safely discontinued after immune restoration with ART is unknown, although it is reasonable, on the basis of the experience with discontinuation of secondary prophylaxis (chronic maintenance therapy) for other opportunistic infections during advanced HIV-1 disease, to discontinue chronic maintenance therapy if patients remain asymptomatic with regard to signs and symptoms of microsporidiosis and have a sustained (e.g. >6 months) increase in their CD4+ T lymphocyte counts to levels >200 cells/µL after ART ('''CIII''').
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| ===Special Considerations During Pregnancy===
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| Among animals (i.e., rats and rabbits), albendazole is embryotoxic and teratogenic at dosages of 30 mg/kg body weight. Therefore, albendazole is not recommended for use among pregnant women ('''DIII'''). However, well-controlled studies in human pregnancy have not been performed. Systemic fumagillin has been associated with increased resorption and growth retardation in rats. No data on use in human pregnancy are available. However, because of the antiangiogenic effect of fumagillin, this drug should not be used among pregnant women ('''EIII'''). Topical fumagillin has not been associated with [[embryotoxic]] or [[teratogenic]] effects among [[pregnant]] women and might be considered when therapy with this agent is appropriate ('''CIII''').
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| ==Source==
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| ==External links== | | ==External links== |
| * CDC's [http://www.dpd.cdc.gov/dpdx/HTML/Microsporidiosis.htm microsporidiosis] info page. | | * CDC's [http://www.dpd.cdc.gov/dpdx/HTML/Microsporidiosis.htm microsporidiosis] info page. |
| | * '''Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents''', ''Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/Infectious Diseases Society of America'' CDC's [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5315a1.htm] |
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