High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial

BMC Infectious Diseases, Dec 2009

Background Treatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children. Methods We performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo. Results Sixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation. Conclusion We found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction. Trial Registration The trial was registered as ISRCTN41089957.

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High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial

BMC Infectious Diseases High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial Beatrice Amadi 1 Mwiya Mwiya 1 Sandie Sianongo 1 Lara Payne 1 Angela Watuka 1 Max Katubulushi 1 Paul Kelly 0 1 0 Institute of Cell and Molecular Science, Barts & The London School of Medicine, Queen Mary University of London , London , UK 1 Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine , Lusaka , Zambia Background: Treatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children. Methods: We performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo. Results: Sixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation. Conclusion: We found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction. Trial Registration: The trial was registered as ISRCTN41089957. - Background Cryptosporidiosis is an important cause of morbidity and mortality in malnourished children [1,2] and in children with AIDS [2]. In immunocompetent children cryptosporidiosis is a frequent cause of diarrhoea [3], and even these episodes which are usually of limited duration can have long-term consequences [4]. However, treatment remains difficult and unsatisfactory, with no drugs having any proven efficacy except nitazoxanide [5-7]. We have previously reported that three day treatment with the antiparasitic drug nitazoxanide was effective in treatment of HIV-seronegative children but demonstrated insignificant activity in HIV-seropositive children [8]. There is an urgent need for effective treatment for cryptosporidiosis in HIV-infected children [9]. We postulated that the performance of this drug in such patients could be improved by a higher dosage and by giving a longer course of treatment. We report here the results of a randomised controlled trial to evaluate this hypothesis in the same setting as our earlier study. The doses of nitazoxanide chosen were double those used in the previous study, and the duration was increased from 3 to 14 days. Ethics approval was obtained from the University of Zambia Research Ethics Committee. The trial was registered as ISRCTN41089957. Methods We carried out a double-blind, randomised, placebo controlled trial in paediatric patients shown to be positive for both HIV and cryptosporidiosis, in the children's diarrhoea/malnutrition ward of the University Teaching Hospital, Lusaka. Children were included if between 1 and 11 years of age, if positive in at least 2 of 3 stool samples for Cryptosporidium spp. (oocysts identified using auramine phenol staining), if they had had diarrhoea with 3 or more unformed stools daily, and if HIV seropositive as confirmed by the Capillus Rapid Test (Trinity Biotech, Ireland). If Cryptosporidium spp. oocysts were present in the initial screening but not in the baseline samples, the patient was excluded unless they tested positive for oocysts within one week from this first sample. Children were excluded if they had a bacterial cause for diarrhoea or if positive for Entamoeba histolytica or Giardia lamblia by the TriageĀ® Parasitic Panel (Biosite Diagnostics, San Diego, CA). Other exclusion criteria were a history of investigational drug therapy within one month prior to enrolment, or other recognised anti-protozoal therapy within two weeks prior to enrolment. Children who were moribund were not randomised and gravely ill were observed for a period of 1-2 weeks prior to randomisation. Study procedures At the initial visit a complete medical history was reviewed to evaluate conformity with inclusion and exclusion criteria. A physical exam (...truncated)


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Beatrice Amadi, Mwiya Mwiya, Sandie Sianongo, Lara Payne, Angela Watuka, Max Katubulushi, Paul Kelly. High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial, BMC Infectious Diseases, 2009, pp. 195, 9, DOI: 10.1186/1471-2334-9-195