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==Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents== | ==Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents== | ||
Outline of the Guideline: | Outline of the Guideline: | ||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Treatment Recommendations|Treatment Recommendations]] | |||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Monitoring and Adverse Events|Monitoring and Adverse Events]] | |||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Treatment | |||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Monitoring and Adverse Events | |||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Management of Treatment Failure|Management of Treatment Failure]] | *[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Management of Treatment Failure|Management of Treatment Failure]] | ||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines # | *[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Prevention of Recurrence|Preventing Recurrence]] | ||
*[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Special Considerations During Pregnancy|Special Considerations During Pregnancy]] | *[[HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines #Special Considerations During Pregnancy|Special Considerations During Pregnancy]] | ||
==Treatment Recommendations== | ==Treatment Recommendations== | ||
ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with resolution of | ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with complete resolution of cryptosporidiosis<ref name="pmid11103042">{{cite journal |author=Miao YM, Awad-El-Kariem FM, Franzen C, Ellis DS, Müller A, Counihan HM, Hayes PJ, Gazzard BG |title=Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy |journal=J. Acquir. Immune Defic. Syndr. |volume=25 |issue=2 |pages=124–9 |year=2000 |month=October |pmid=11103042 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1525-4135&volume=25&issue=2&spage=124 |accessdate=2012-04-20}}</ref><ref name="pmid9457096">{{cite journal |author=Carr A, Marriott D, Field A, Vasak E, Cooper DA |title=Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy |journal=Lancet |volume=351 |issue=9098 |pages=256–61 |year=1998 |month=January |pmid=9457096 |doi=10.1016/S0140-6736(97)07529-6 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(97)07529-6 |accessdate=2012-04-20}}</ref>, 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. | ||
Paromomycin, a nonabsorbable aminoglycoside that is indicated for the treatment of intestinal amebiasis, is effective in high doses for the treatment of cryptosporidiosis in animal models.<ref name="pmid8556484">{{cite journal |author=Tzipori S, Rand W, Griffiths J, Widmer G, Crabb J |title=Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy of paromomycin and hyperimmune bovine colostrum-immunoglobulin |journal=Clin. Diagn. Lab. Immunol. |volume=1 |issue=4 |pages=450–63 |year=1994 |month=July |pmid=8556484 |pmc=368287 |doi= |url=http://cvi.asm.org/cgi/pmidlookup?view=long&pmid=8556484 |accessdate=2012-04-20}}</ref> A meta-analysis of 11 published paromomycin studies in humans reported a response rate of 67%. However, relapse was common in certain studies, with long-term success rates of only 33%. Two randomized controlled trials have compared paromomycin with placebo among patients with AIDS and cryptosporidiosis; modest, but statistically significant improvement in symptoms and oocyst shedding was demonstrated in one, but no difference from placebo was observed in the other.<ref name="pmid11049793">{{cite journal |author=Hewitt RG, Yiannoutsos CT, Higgs ES, Carey JT, Geiseler PJ, Soave R, Rosenberg R, Vazquez GJ, Wheat LJ, Fass RJ, Antoninievic Z, Walawander AL, Flanigan TP, Bender JF |title=Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group |journal=Clin. Infect. Dis. |volume=31 |issue=4 |pages=1084–92 |year=2000 |month=October |pmid=11049793 |doi=10.1086/318155 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11049793 |accessdate=2012-04-20}}</ref><ref name="pmid8035029">{{cite journal |author=White AC, Chappell CL, Hayat CS, Kimball KT, Flanigan TP, Goodgame RW |title=Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial |journal=J. Infect. Dis. |volume=170 |issue=2 |pages=419–24 |year=1994 |month=August |pmid=8035029 |doi= |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8035029 |accessdate=2012-04-20}}</ref> A small open-label study suggested a substantial benefit of paromomycin when used in combination with azithromycin, but few cures were noted.<ref name="pmid9728569">{{cite journal |author=Smith NH, Cron S, Valdez LM, Chappell CL, White AC |title=Combination drug therapy for cryptosporidiosis in AIDS |journal=J. Infect. Dis. |volume=178 |issue=3 |pages=900–3 |year=1998 |month=September |pmid=9728569 |doi= |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9728569 |accessdate=2012-04-20}}</ref> Therefore, efficacy data do not support a recommendation for the use of paromomycin for therapy, although the drug appears to be safe ('''CIII'''). | |||
Nitazoxanide, an orally administered nitrothiazole benzamide, has in vivo activity against a broad range of helminths, bacteria, and protozoa, including cryptosporidia.<ref name="pmid11398117">{{cite journal |author=Rossignol JF, Ayoub A, Ayers MS |title=Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide |journal=J. Infect. Dis. |volume=184 |issue=1 |pages=103–6 |year=2001 |month=July |pmid=11398117 |doi=10.1086/321008 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11398117 |accessdate=2012-04-20}}</ref><ref name="pmid10326116">{{cite journal |author=Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Romero JL, Padierna J, Geyne A, Ayers MS |title=A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico |journal=Trans. R. Soc. Trop. Med. Hyg. |volume=92 |issue=6 |pages=663–6 |year=1998 |pmid=10326116 |doi= |url= |accessdate=2012-04-20}}</ref><ref name="pmid7768380">{{cite journal |author=Simon DM, Cello JP, Valenzuela J, Levy R, Dickerson G, Goodgame R, Brown M, Lyche K, Fessel WJ, Grendell J |title=Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea |journal=Gastroenterology |volume=108 |issue=6 |pages=1753–60 |year=1995 |month=June |pmid=7768380 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0016508595001879 |accessdate=2012-04-20}}</ref> A short-term study among patients with HIV-1 infection documented increased cure rates compared with controls (based on clearance of organisms from stool and reduced rates of diarrhea) among patients with CD4+ T lymphocyte counts >50 cells/µL, but not in those with CD4+ T lymphocyte counts <50 cells/µL.<ref name="pmid10326116">{{cite journal |author=Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Romero JL, Padierna J, Geyne A, Ayers MS |title=A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico |journal=Trans. R. Soc. Trop. Med. Hyg. |volume=92 |issue=6 |pages=663–6 |year=1998 |pmid=10326116 |doi= |url= |accessdate=2012-04-20}}</ref> Available data do not warrant a definite recommendation for use of this agent in this setting, but the drug has been approved by the U.S. Food and Drug Administration (FDA) for use in children and is expected to be approved for use in adults ('''CIII'''). | |||
Treatment of persons with cryptosporidiosis should include symptomatic treatment of diarrhea ('''AIII'''). Rehydration and repletion of electrolyte losses by either the oral or intravenous route is important. Severe diarrhea, which might be >10 L/day among patients with AIDS, often requires intensive support. Aggressive efforts at oral rehydration should be made with oral rehydration solutions that contain glucose, sodium bicarbonate, potassium, magnesium, and phosphorus ('''AIII'''). | |||
Treatment with antimotility agents can play an important adjunctive role in therapy, but these agents are not consistently effective ('''BIII'''). Loperamide or tincture of opium will often palliate symptoms. Octreotide, a synthetic octapeptide analog of naturally occurring somatostatin that is approved for the treatment of secreting tumor induced diarrhea, is no more effective than other oral antidiarrheal agents, and is generally not recommended ('''DII''').<ref name="pmid7768380">{{cite journal |author=Simon DM, Cello JP, Valenzuela J, Levy R, Dickerson G, Goodgame R, Brown M, Lyche K, Fessel WJ, Grendell J |title=Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea |journal=Gastroenterology |volume=108 |issue=6 |pages=1753–60 |year=1995 |month=June |pmid=7768380 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0016508595001879 |accessdate=2012-04-20}}</ref> | |||
==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 [[Liver function tests|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''<ref name="pmid15841069">{{cite journal |author=Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK |title=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 |journal=MMWR Recomm Rep |volume=53 |issue=RR-15 |pages=1–112 |year=2004 |month=December |pmid=15841069 |doi= |url=http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5315a1.htm |accessdate=2012-04-19}}</ref> | |||
==Related Chapters== | |||
*[[Cryptosporidiosis]] | |||
*[[Opportunistic infections]] | |||
*[[HIV opportunistic infections]] | |||
*[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines]] | |||
*[[HIV opportunistic infection pneumocystis pneumonia: prevention and treatment guidelines]] | |||
==Reference== | ==Reference== | ||
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[[Category:Sexually transmitted diseases]] | [[Category:Sexually transmitted diseases]] | ||
[[Category:Immunodeficiency]] | [[Category:Immunodeficiency]] | ||
[[Category:Immunology]] | [[Category:Immunology]] | ||
[[Category:Immune system disorders]] | [[Category:Immune system disorders]] | ||
Latest revision as of 18:02, 18 September 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief:, Ujjwal Rastogi, MBBS [2]
Overview
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
Outline of the Guideline:
- Treatment Recommendations
- Monitoring and Adverse Events
- Management of Treatment Failure
- Preventing Recurrence
- Special Considerations During Pregnancy
Treatment Recommendations
ART with immune restoration (an increase of CD4+ T lymphocyte count to >100 cells/µL) is associated with complete resolution of cryptosporidiosis[2][3], 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.
Paromomycin, a nonabsorbable aminoglycoside that is indicated for the treatment of intestinal amebiasis, is effective in high doses for the treatment of cryptosporidiosis in animal models.[4] A meta-analysis of 11 published paromomycin studies in humans reported a response rate of 67%. However, relapse was common in certain studies, with long-term success rates of only 33%. Two randomized controlled trials have compared paromomycin with placebo among patients with AIDS and cryptosporidiosis; modest, but statistically significant improvement in symptoms and oocyst shedding was demonstrated in one, but no difference from placebo was observed in the other.[5][6] A small open-label study suggested a substantial benefit of paromomycin when used in combination with azithromycin, but few cures were noted.[7] Therefore, efficacy data do not support a recommendation for the use of paromomycin for therapy, although the drug appears to be safe (CIII).
Nitazoxanide, an orally administered nitrothiazole benzamide, has in vivo activity against a broad range of helminths, bacteria, and protozoa, including cryptosporidia.[8][9][10] A short-term study among patients with HIV-1 infection documented increased cure rates compared with controls (based on clearance of organisms from stool and reduced rates of diarrhea) among patients with CD4+ T lymphocyte counts >50 cells/µL, but not in those with CD4+ T lymphocyte counts <50 cells/µL.[9] Available data do not warrant a definite recommendation for use of this agent in this setting, but the drug has been approved by the U.S. Food and Drug Administration (FDA) for use in children and is expected to be approved for use in adults (CIII).
Treatment of persons with cryptosporidiosis should include symptomatic treatment of diarrhea (AIII). Rehydration and repletion of electrolyte losses by either the oral or intravenous route is important. Severe diarrhea, which might be >10 L/day among patients with AIDS, often requires intensive support. Aggressive efforts at oral rehydration should be made with oral rehydration solutions that contain glucose, sodium bicarbonate, potassium, magnesium, and phosphorus (AIII).
Treatment with antimotility agents can play an important adjunctive role in therapy, but these agents are not consistently effective (BIII). Loperamide or tincture of opium will often palliate symptoms. Octreotide, a synthetic octapeptide analog of naturally occurring somatostatin that is approved for the treatment of secreting tumor induced diarrhea, is no more effective than other oral antidiarrheal agents, and is generally not recommended (DII).[10]
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[11]
Related Chapters
- Cryptosporidiosis
- Opportunistic infections
- HIV opportunistic infections
- HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines
- HIV opportunistic infection pneumocystis pneumonia: prevention and treatment guidelines
Reference
- ↑ Flanigan T, Whalen C, Turner J, Soave R, Toerner J, Havlir D, Kotler D (1992). "Cryptosporidium infection and CD4 counts". Ann. Intern. Med. 116 (10): 840–2. PMID 1348918. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Miao YM, Awad-El-Kariem FM, Franzen C, Ellis DS, Müller A, Counihan HM, Hayes PJ, Gazzard BG (2000). "Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy". J. Acquir. Immune Defic. Syndr. 25 (2): 124–9. PMID 11103042. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Carr A, Marriott D, Field A, Vasak E, Cooper DA (1998). "Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy". Lancet. 351 (9098): 256–61. doi:10.1016/S0140-6736(97)07529-6. PMID 9457096. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Tzipori S, Rand W, Griffiths J, Widmer G, Crabb J (1994). "Evaluation of an animal model system for cryptosporidiosis: therapeutic efficacy of paromomycin and hyperimmune bovine colostrum-immunoglobulin". Clin. Diagn. Lab. Immunol. 1 (4): 450–63. PMC 368287. PMID 8556484. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Hewitt RG, Yiannoutsos CT, Higgs ES, Carey JT, Geiseler PJ, Soave R, Rosenberg R, Vazquez GJ, Wheat LJ, Fass RJ, Antoninievic Z, Walawander AL, Flanigan TP, Bender JF (2000). "Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group". Clin. Infect. Dis. 31 (4): 1084–92. doi:10.1086/318155. PMID 11049793. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ White AC, Chappell CL, Hayat CS, Kimball KT, Flanigan TP, Goodgame RW (1994). "Paromomycin for cryptosporidiosis in AIDS: a prospective, double-blind trial". J. Infect. Dis. 170 (2): 419–24. PMID 8035029. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Smith NH, Cron S, Valdez LM, Chappell CL, White AC (1998). "Combination drug therapy for cryptosporidiosis in AIDS". J. Infect. Dis. 178 (3): 900–3. PMID 9728569. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Rossignol JF, Ayoub A, Ayers MS (2001). "Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide". J. Infect. Dis. 184 (1): 103–6. doi:10.1086/321008. PMID 11398117. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ 9.0 9.1 Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Romero JL, Padierna J, Geyne A, Ayers MS (1998). "A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico". Trans. R. Soc. Trop. Med. Hyg. 92 (6): 663–6. PMID 10326116.
|access-date=requires|url=(help) - ↑ 10.0 10.1 Simon DM, Cello JP, Valenzuela J, Levy R, Dickerson G, Goodgame R, Brown M, Lyche K, Fessel WJ, Grendell J (1995). "Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea". Gastroenterology. 108 (6): 1753–60. PMID 7768380. Retrieved 2012-04-20. Unknown parameter
|month=ignored (help) - ↑ Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK (2004). "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". MMWR Recomm Rep. 53 (RR-15): 1–112. PMID 15841069. Retrieved 2012-04-19. Unknown parameter
|month=ignored (help)