To determine the response of the small intestinal mucosa to environmental conditions, we studied changes in mucosal architecture and function in a longitudinal cohort study in African adults. Over three consecutive years, 238 adults submitted monthly stool samples for parasitologic and bacteriologic analysis and underwent an annual endoscopic jejunal biopsy for mucosal morphometry. Absorption and permeability assays were performed on the same day as the enteroscopy. Variation in mucosal architecture and function was correlated with environmental factors and stool microbiology. The whole cohort had structural and functional evidence of tropical enteropathy, but structure and function were only weakly correlated. There were marked changes over time, and seasonal variation was observed in villous height (16%), xylose recovery (16%), and permeability (28%). Asymptomatic intestinal infections were common. Enteropathy was more severe in participants with Citrobacter rodentium or hookworm ova in the stool sample taken one month before the investigations were performed.

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.

Background: Diarrheal disease remains a major contributor to morbidity and mortality in Africa, but host defense against intestinal infection is poorly understood and may depend on nutritional status. Objective: To test the hypothesis that defense against intestinal infection depends on micronutrient status, we undertook a randomized controlled trial of multiple micronutrient supplementation in a population where there is borderline micronutrient deficiency. Design: All consenting adults (≥18 y) living in a carefully defined sector of Misisi, Lusaka, Zambia, were included in a cluster-randomized (by household), double-blind, placebo-controlled trial with a midpoint crossover. There were no exclusion criteria. Participants were given a daily tablet containing 15 micronutrients at just above the recommended nutrient intake or placebo. The primary endpoint was the incidence of diarrhea; secondary endpoints were severe episodes of diarrhea, respiratory infection, nutritional status, CD4 count, and mortality. Results: Five hundred participants were recruited and followed up for 3.3 y (10 846 person-months). The primary endpoint, incidence of diarrhea (1.4 episodes/y per person), did not differ with treatment allocation. However, severe episodes of diarrhea were reduced in the supplementation group (odds ratio: 0.50; 95% CI: 0.26, 0.92; P = 0.017). Mortality was reduced in HIV-positive participants from 12 with placebo to 4 with supplementation (P = 0.029 by log-rank test), but this was not due to changes in CD4 count or nutritional status. Conclusion: Micronutrient supplementation with this formulation resulted in only modest reductions in severe diarrhea and reduced mortality in HIV-positive participants. The trial was registered as ISRCTN31173864.