No abstract

BackgroundTreatment 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.MethodsWe 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.ResultsSixty 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.ConclusionWe 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 RegistrationThe trial was registered as ISRCTN41089957.

Although intestinal and systemic infections did not differ for HIV-seropositive and HIV-seronegative children, HIV influenced nutritional states of all children. Cryptosporidiosis and marasmus were associated with higher mortality.

In four crowded townships of Lusaka, Zambia, the prevalence of cryptosporidiosis in 222 children with diarrhea was 18%, with marked temporal and geographic variation over the course of one rainy season. Using data on the finding of oocysts of Cryptosporidium parvum in urban water supplies, the areas under study were categorized as high or low risk. Prevalence of cryptosporidiosis in children with diarrhea was higher in high risk areas after stratification by early/late stage of the rains (Mantel-Haenszel odds ratio [OR] ϭ 2.9, 95% confidence interval [CI] ϭ 1.3, 6.7; P ϭ 0.008). Cryptosporidiosis was not associated with keeping animals, nutritional status, or parental education, but was apparently more common in breast fed children (OR ϭ 2.7, 95% CI ϭ 1.1, 6.9; P ϭ 0.01), although the proportion of exclusively breast fed children was not measured. Since most of these infections were of short duration, we conclude that transmission of C. parvum can vary dynamically within one city and over short periods of time, and that water-borne contamination may be a substantial influence.