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>
ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with complete resolution of cryptosporidiosis, and all patients with cryptosporidiosis should be offered ART as part of the initial management of their infection (AII). No consistently effective pharmacologic or immunologic therapy directed specifically against C. parvum exists. Approximately 95 interventional agents have been tried for the treatment of cryptosporidiosis with no consistent success.
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.
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>
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.
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''').
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''').
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''').
Cryptosporidiosis is caused by Cryptosporidium species, a group of protozoan parasites that infect the small bowel mucosa, and in immunosuppressed persons, the large bowel and extraintestinal sites. Those at greatest risk for disease are patients with advanced immunosuppression (i.e., CD4+ T lymphocyte counts generally <100 cells/µL)[1] The three most common species infecting humans are C. hominis (formerly C. parvum genotype 1 or human genotype), C. parvum (formerly C. parvum genotype 2 or bovine genotype), and C. meleagridis. In addition, infections with C. canis, C. felis, C. muris, and Cryptosporidium pig genotype have been reported in immunocompromised patients. Preliminary analyses indicate that some zoonotic species might have a stronger association with chronic diarrhea than C. hominis. However, whether the different Cryptosporidium species are associated with differences in severity of disease or response to therapy is unknown.
Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents
ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with complete resolution of cryptosporidiosis, and all patients with cryptosporidiosis should be offered ART as part of the initial management of their infection (AII). No consistently effective pharmacologic or immunologic therapy directed specifically against C. parvum exists. Approximately 95 interventional agents have been tried for the treatment of cryptosporidiosis with no consistent success.
Monitoring and Adverse Events
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.
Management of Treatment Failure
Supportive treatment and optimizing ART to attempt to achieve full virologic suppression are the only feasible approaches to the management of treatment failure (CIII).
Prevention of Recurrence
No drug regimens are proven to be effective in preventing the recurrence of cryptosporidiosis.
Special Considerations During Pregnancy
As with nonpregnant woman, initial treatment efforts should rely on rehydration and initiation of ART. Pregnancy should not preclude the use of ART.
Source
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[2]