HIV opportunistic infection cryptosporidiosis: prevention and treatment guidelines

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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

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

Reference

  1. ↑ 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)
  2. ↑ 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)
  3. ↑ 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)
  4. ↑ 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)
  5. ↑ 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)
  6. ↑ 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)
  7. ↑ 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)
  8. ↑ 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. ↑ 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. ↑ 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)
  11. ↑ 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)


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