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Meta-Analysis
. 2007 Jan 24;2007(1):CD004932.
doi: 10.1002/14651858.CD004932.pub2.

Prevention and treatment of cryptosporidiosis in immunocompromised patients

Affiliations
Meta-Analysis

Prevention and treatment of cryptosporidiosis in immunocompromised patients

I Abubakar et al. Cochrane Database Syst Rev. .

Abstract

Background: Cryptosporidiosis is a disease that causes diarrhoea lasting about one to two weeks, sometimes extending up to 2.5 months among the immunocompetent and becoming a more severe life-threatening illness among immunocompromised individuals. Cryptosporidium is a common cause of gastroenteritis. Cryptosporidiosis is common in HIV-infected individuals.

Objectives: The objective of the review was to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised individuals.

Search strategy: We searched the following databases for randomised controlled trials up to August 2005: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, Geobase, and the Environmental Sciences and Pollution Management.

Selection criteria: Randomised controlled trials that compared the use of any intervention to treat or prevent cryptosporidiosis in immunocompromised persons were included. The outcome measures for treatment studies included symptomatic diarrhoea and oocyst clearance.

Data collection and analysis: Two reviewers independently assessed the trials for quality of randomisation, blinding, withdrawals, and adequacy of allocation concealment. The relative risk for each intervention was calculated using a random effects model.

Main results: Seven trials involving 169 participants were included. There were 130 adults with AIDS enrolled in five studies. Evidence of significant heterogeneity was present. There was no evidence for a reduction in the duration or frequency of diarrhoea by nitazoxanide (RR 0.83 (95% CI 0.36-1.94)) and paramomycin (RR 0.74 (95% CI 0.42-1.31)) compared with placebo. Nitazoxanide led to a significant evidence of oocyst clearance compared with placebo among all children with a relative risk of 0.52 (95% CI 0.30-0.91). The effect was not significant for HIV-seropositive participants (RR 0.71 (95% CI 0.36-1.37)). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09-0.80) based on a single study. The single study comparing spiramycin with placebo found no significant difference in reduction of the duration of hospitalisation (mean difference -0.40 days (95% CI -6.62-5.82)) or in mortality between the two arms of the trial (RR 0.43 (95% CI 0.04-4.35)). One study assessed the role of bovine dialyzable leukocyte extract, reporting a relative risk for decreased stool frequency of 0.19 (95% CI 0.03-1.19), while another compared bovine hyperimmune colostrum with placebo and found no evidence for improvement of stool volume (RR 3.00 (95% CI 0.61-14.86)) or in oocyst concentration per ml of stool (RR 0.27 (95% CI 0.02-3.74)). No studies were found that assessed prevention.

Authors' conclusions: This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces the load of parasites and may be useful in immunocompetent individuals. Due to the seriousness of the potential outcomes of cryptosporidiosis, the use of nitaxozanide should be considered in immunocompromised patients. The absence of effective therapy highlights the need to ensure that infection is avoided. Unfortunately, evidence for the effectiveness and cost-effectiveness of preventive interventions is also lacking.

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Conflict of interest statement

None

Figures

1.1
1.1. Analysis
Comparison 1 Treatment with Nitazoxamide versus Placebo, Outcome 1 Comparison of resolution of diarrhoea with Nitazoxanide versus Placebo.
1.2
1.2. Analysis
Comparison 1 Treatment with Nitazoxamide versus Placebo, Outcome 2 Comparison of number of individuals acheiving oocyst clearance with Nitazoxanide versus Placebo.
1.3
1.3. Analysis
Comparison 1 Treatment with Nitazoxamide versus Placebo, Outcome 3 Comparison of mortality with Nitazoxanide versus Placebo.
2.1
2.1. Analysis
Comparison 2 Treatment with Paramomycin or placebo, Outcome 1 Comparison of the number of individuals with decreased stool frequency ‐ Paramomycin and placebo.
2.2
2.2. Analysis
Comparison 2 Treatment with Paramomycin or placebo, Outcome 2 Comparison of the number of individuals with oocyst clearance ‐ Paramomycin versus placebo.
3.1
3.1. Analysis
Comparison 3 Treatment with Spiramycin and Placebo, Outcome 1 Comparison of the number of individuals with oocyst clearance ‐ Spiramycin versus placebo.
3.2
3.2. Analysis
Comparison 3 Treatment with Spiramycin and Placebo, Outcome 2 Comparison of mortality ‐ Spiramycin versus placebo.
3.3
3.3. Analysis
Comparison 3 Treatment with Spiramycin and Placebo, Outcome 3 Comparison of duration of hospital stay in days ‐ Spiramycin and placebo.
4.1
4.1. Analysis
Comparison 4 Treatment with Bovine dialyzable leukocyte extract, Outcome 1 Comparison of the number of individuals with decreased stool frequency.
4.2
4.2. Analysis
Comparison 4 Treatment with Bovine dialyzable leukocyte extract, Outcome 2 Comparison of the change in stool volume ‐ Bovine DLE versus Non immune DLE.
4.3
4.3. Analysis
Comparison 4 Treatment with Bovine dialyzable leukocyte extract, Outcome 3 Comparison of the number of individuals with oocyst clearance.
6.1
6.1. Analysis
Comparison 6 Treatment using Bovine Hyperimmune Colostrum, Outcome 1 Comparison bovine hyperimmune colostrum with placebo on the number of subjects with a decreased stool volume.
6.2
6.2. Analysis
Comparison 6 Treatment using Bovine Hyperimmune Colostrum, Outcome 2 Comparison of the number of individuals with oocyst clearance ‐ bovine hyperimmune colostrum versus placebo.

Update of

  • doi: 10.1002/14651858.CD004932

References

References to studies included in this review

Amadi 2002 {published data only}
    1. Amadi, B, Mwiya, M, Musuku, J, Watuka, A, Sianongo, S, Ayoub, A, & Kelly, P. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. Lancet 2002;360(9343):1375‐1380. - PubMed
Hewitt 2000 {published data only}
    1. Hewitt, R. G, Yiannoutsos, C. T, Higgs, E. S, Carey, J. T, Geiseler, P. J, Soave, R, Rosenberg, R, Vazquez, G. J, Wheat, L. J, Fass, R. J, Antoninievic, Z, Walawander, A. L, Flanigan, T. P, & Bender, J. F. 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. 2000;31(4):1084‐1092. - PubMed
McMeeking 1990 {published data only}
    1. McMeeking, A, Borkowsky, W, Klesius, P. H, Bonk, S, Holzman, R. S, & Lawrence, H. S. A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS. J. Infect. Dis 1990;161(1):108‐112. - PubMed
Nord 1990 {published data only}
    1. Nord, J, Ma, P, DiJohn, D, Tzipori, S, & Tacket, C. O. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS 1990;4(6):581‐584. - PubMed
Rossignol 1998 {published data only}
    1. Rossignol, J. F, Hidalgo, H, Feregrino, M, Higuera, F, Gomez, W. H, Romero, J. L, Padierna, J, Geyne, A, & Ayers, M. S. 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 1998;92(6):663‐666. - PubMed
White 1994 {published data only}
    1. White, A. C, Jr, Chappell, C. L, Hayat, C. S, Kimball, K. T, Flanigan, T. P, & Goodgame, R. W. Paromomycin for cryptosporidiosis in AIDS: a prospective, double‐blind trial. J. Infect. Dis 1994;179(2):419‐424. - PubMed
Wittenberg 1989 {published data only}
    1. Wittenberg, D. F, Miller, N. M, & van den, E. J. Spiramycin is not effective in treating cryptosporidium diarrhea in infants: results of a double‐blind randomized trial. J. Infect. Dis 1989;159(1):131‐132. - PubMed

References to studies excluded from this review

Amenta 1999 {published data only}
    1. Amenta, M, Dalle Nogare, E. R, Colomba, C, Prestileo, T. S, Di Lorenzo, F, Fundaro, S, Colomba, A, & Ferrieri, A. Intestinal protozoa in HIV‐infected patients: effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections. J. Chemother. 1999;11(5):391‐395. - PubMed
Dionisio 1998 {published data only}
    1. Dionisio, D, Orsi, A, Sterrantino, G, Meli, M, Di Lollo, S, Ibba, M. L, Trotta, M, Pozzi, M, Sani, L, & Leoncini, F. Chronic cryptosporidiosis in patients with AIDS: stable remission and possible eradication after long‐term, low dose azithromycin. J. Clin. Pathol. 1998;51(2):138‐142. - PMC - PubMed
Fichtenbaum 2000 {published data only}
    1. Fichtenbaum, C. J, Zackin, R, Feinberg, J, Benson, C, & Griffiths, J. K. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS 2000;14(18):2889‐2893. - PubMed
Flanigan 1996 {published data only}
    1. Flanigan, T. P, Ramratnam, B, Graeber, C, Hellinger, J, Smith, D, Wheeler, D, Hawley, P, Heath‐Chiozzi, M, Ward, D. J, Brummitt, C, & Turner, J. Prospective trial of paromomycin for cryptosporidiosis in AIDS. Am J Med 1996;100(3):370‐372. - PubMed
Greenberg 1996 {published data only}
    1. Greenberg, P. D, Cello. J. P. Treatment of severe diarrhea caused by Cryptosporidium parvum with oral bovine immunoglobulin concentrate in patients with AIDS. J Acquir.Immune.Defic.Syndr.Hum.Retrovirol 1996;13(4):348‐354. - PubMed
Hellard 2001 {published data only}
    1. Hellard, M. E, Sinclair, M. I, Forbes, A. B, & Fairley, C. K. A randomized, blinded, controlled trial investigating the gastrointestinal health effects of drinking water quality. Environ.Health Perspect 2001;109(8):773‐778. - PMC - PubMed
Kadappu 2002 {published data only}
    1. Kadappu, K. K, Nagaraja, M. V, Rao, P. V, & Shastry, B. A. Azithromycin as treatment for cryptosporidiosis in human immunodeficiency virus disease. J. Postgrad. Med 2002;48(3):179‐181. - PubMed
Okhuysen 1997 {published data only}
    1. Okhuysen, P. C, Chappell, C. L, Crabb, J, Valdez, L. M, Douglass, E. T, & DuPont, H. L. Prophylactic effect of bovine anti‐Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum. Clin. Infect. Dis. 1998;26(6):1324‐1329. - PubMed
Rossignol 2001 {published data only}
    1. Rossignol, J. F, Ayoub, A, & Ayers, M. S. Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double‐blind, placebo‐controlled study of Nitazoxanide. J. Infect. Dis. 2001;104(1):103‐106. - PubMed
Saez‐Llorens 1989 {published data only}
    1. Saez‐Llorens, X, Odio, C. M, Umana, M. A, & Morales, M. V. Spiramycin vs. placebo for treatment of acute diarrhea caused by Cryptosporidium. Pediatr.Infect.Dis J 1989;8(3):136‐140. - PubMed
Smith 1998 {published data only}
    1. Smith, N. H, Cron, S, Valdez, L. M, Chappell, C. L, & White, A. C, Jr. Combination drug therapy for cryptosporidiosis in AIDS. J. Infect. Dis. 1998;178(3):900‐903. - PubMed
Sprinz 1998 {published data only}
    1. Sprinz, E, Mallman, R, Barcellos, S, Silbert, S, Schestatsky, G, & Bem, D. D. AIDS‐related cryptosporidial diarrhoea: an open study with roxithromycin. J Antimicrob.Chemother 1998;41(Suppl B):85‐91. - PubMed
Uip 1998 {published data only}
    1. Uip, D. E, Lima, A. L, Amato, V. S, Boulos, M, Neto, V. A, & Bem, D. D. Roxithromycin treatment for diarrhoea caused by Cryptosporidium spp. in patients with AIDS. J Antimicrob.Chemother 1998;41(Suppl B):93‐97. - PubMed
Woolf 1987 {published data only}
    1. Woolf, G. M, Townsend, M, & Guyatt, G. Treatment of cryptosporidiosis with spiramycin in AIDS. An "N of 1" trial. J Clin.Gastroenterol 1987;9(6):632‐634. - PubMed

Additional references

Abrahamsen 2004
    1. Abrahamsen, M.S, Templeton TJ, Enomoto, S, Abrahante, JE, Zhu, G, Lancto CA, Deng M, Liu C, Widmer G, Tzipori G, Buck GA, Xu P, Bankier AT, Dear PH, Konfortov BA, Spriggs HF, Iyer L, Anantharaman V, Aravind L, Kapur V. Complete genome sequence of the apicomplexan, Cryptosporidium parvum. Science 2004;304(5669):441‐445. - PubMed
Carr 1998
    1. Carr A, Marriot D, Field A, Vasak E, Cooper DA. Treatment of HIV‐1‐associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998;351:256‐261. - PubMed
CDC 1995
    1. CDC. Cryptosporidium in water: CDC guidelines on how to protect yourself. Centers for Disease Control and Prevention. AIDS Treat News 1995;227:7‐8. - PubMed
Cicirello 1997
    1. Cicirello, H, Kehl KS, Addiss DG, Chusid MJ, Glass RI, Davis JP, Havens PL. Cryptosporidiosis in children during a massive waterborne outbreak in Milwaukee, Wisconsin: clinical, laboratory and epidemiologic findings. Epidemiol Infect 1997;119:53‐60. - PMC - PubMed
Crabb 1998
    1. Crabb, J. Antibody‐based immunotherapy for cryptosporidiosis. Adv. Parasitol. 1998;40:121‐149. - PubMed
Current 1991
    1. Current, WL, Garcia LS. Cryptosporidiosis. Clin. Microbiol. Rev. 1991;4(3):325‐358. - PMC - PubMed
Fewtrell 2005
    1. Fewtrell, L, Kaufmann RB, Kay D, Enanoria W, Haller L, Colford JM Jr. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta‐analysis. Lancet Infect. Dis. 2005;5(1):42‐52. - PubMed
Grube 1997
    1. Grube, H, Ramratnam B, Ley C, Flanigan TP. Resolution of AIDS associated cryptosporidiosis after treatment with indinavir. Am. J. Gastroenterol 1997;92(4):726. - PubMed
Havelaar 2003
    1. Havelaar A, Boonyakarnkul T, Cunliffe D, et al. Guidelines for Drinking Water Quality Water Borne Pathogens. Vol. Third Edition, WHO, 2003.
Hunter 2000
    1. Hunter, PR. Advice on the response from public and environmental health to the detection of cryptosporidial oocysts in treated drinking water. PHLS Advisory Committee on Water and the Environment. Comm. Dis. Pub. Health. 2000;3(1):24‐27. - PubMed
Hunter 2002
    1. Hunter, PR, Nichols. Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients. Clin. Microbiol. Rev. 2002;15(1):145‐154. - PMC - PubMed
Jadad 1996
    1. Jadad, AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control. Clin. Trials. 1996;17(1):1‐12. - PubMed
Juranek 1995
    1. Juranek, DD. Cryptosporidiosis: sources of infection and guidelines for prevention. Clin.Infect.Dis. 1995;21(Suppl 1):S57‐61. - PubMed
Kaplan 2002
    1. Kaplan, JE, Masur H, Holmes KK. Guidelines for preventing opportunistic infections among HIV‐infected persons‐‐2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm.Rep. 2002;51(RR‐8):1‐52. - PubMed
Mac Kenzie 1994
    1. Mac Kenzie, WR, Hoxie NJ, Proctor ME, Gradus MS, Blair KA, Peterson DE, Kazmierczak JJ, Addiss DG, Fox KR, Rose JB. A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply. N. Engl. J. Med. 1994;331(3):161‐167. - PubMed
Maggi 2000
    1. Maggi, P, Larocca AM, Quarto M, Serio G, Brandonisio O, Angarano G, Pastore G. Effect of antiretroviral therapy on cryptosporidiosis and microsporidiosis in patients infected with human immunodeficiency virus type 1. Eur. J Clin. Microbiol. Infect.Dis 2000;19(3):213‐217. - PubMed
McLauchlin 2000
    1. McLauchlin, J, Amar C, Pedraza‐Diaz S, Nichols GL. Molecular epidemiological analysis of Cryptosporidium spp. in the United Kingdom: results of genotyping Cryptosporidium spp. in 1,705 fecal samples from humans and 105 fecal samples from livestock animals. J. Clin. Microbiol 2000;38(11):3984‐3990. - PMC - PubMed
Mead 2002
    1. Mead, JR. Cryptosporidiosis and the challenges of chemotherapy. Drug Resist. Updat. 2002;5(1):47‐57. - PubMed
Miao 2000
    1. Miao, YM, Awad‐El‐Kariem FM, Franzen C, Ellis DS, Muller A, Counihan HM, Hayes PJ, Gazzard BG. Eradication of cryptosporidia and microsporidia following successful antiretroviral therapy. J.Acquir.Immune.Defic.Syndr 2000;25(2):124‐129. - PubMed
Morgan‐Ryan 2002
    1. Morgan‐Ryan, UM, Fall A, Ward LA, Hijjawi N, Sulaiman I, Fayer R, Thompson RC, Olson M, Lal A, Xiao L. Cryptosporidium hominis n. sp. (Apicomplexa: Cryptosporidiidae) from Homo sapiens. J Eukaryot. Microbiol 2002;49(6):433‐440. - PubMed
Robinson 2002
    1. Robinson, KA, Dickersin K. Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. Int, J. Epidemiol. 2002;31(1):150‐153. - PubMed
Striepen 2004
    1. Striepen, B, Pruijssers AJ, Huang J, Li C, Gubbels MJ, Umejiego NN, Hedstrom L, Kissinger JC. Gene transfer in the evolution of parasite nucleotide biosynthesis. Proc. Natl. Acad. Sci. U.S.A 2004;101(9):3154‐3159. - PMC - PubMed
Theodos 1998
    1. Theodos, CM, Griffiths JK, D'Onfro J, Fairfield A, Tzipori S. Efficacy of nitazoxanide against Cryptosporidium parvum in cell culture and in animal models. Antimicrob. Agents Chemother 1998;42(8):1959‐1965. - PMC - PubMed
Umejiego 2004
    1. Umejiego, NN, Li C, Riera T, Hedstrom L, Striepen B. Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design. J. Biol. Chem. 2004;279(39):40320‐40327. - PubMed

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