Search

Abstract 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.

Abstract Background The HIV epidemic in sub-Saharan Africa has had a major impact on infectious disease, and there is currently great interest in the impact of HIV on intestinal barrier function. A three year longitudinal cohort study in a shanty compound in Lusaka, Zambia, carried out before anti-retroviral therapy was widely available, was used to assess the impact of HIV on susceptibility to intestinal infectious disease. We measured the incidence and seasonality of intestinal infection and diarrhoea, aggregation of disease in susceptible individuals, clustering by co-habitation and genetic relatedness, and the disease-to-infection ratio. Methods Adults living in a small section of Misisi, Lusaka, were interviewed every two weeks to ascertain the incidence of diarrhoea. Monthly stool samples were analysed for selected pathogens. HIV status and CD4 count were determined annually. Results HIV seroprevalence was 31% and the prevalence of immunosuppression (CD4 count 200 cells/μL or less) was 10%. Diarrhoea incidence was 1.1 episodes per year and the Incidence Rate Ratio for HIV infection was 2.4 (95%CI 1.7–3.3; p < 0.001). The disease-to-infection ratio was increased at all stages of HIV infection. Aggregation of diarrhoea in susceptible individuals was observed irrespective of immunosuppression, but there was little evidence of clustering by co-habitation or genetic relatedness. There was no evidence of aggregation of asymptomatic infections. Conclusion HIV has an impact on intestinal infection at all stages, with an increased disease-to-infection ratio. The aggregation of disease in susceptible individuals irrespective of CD4 count suggests that this phenomenon is not a function of cell mediated immunity.

Abstract Background Mortality in Zambian AIDS patients is high, especially in patients with diarrhoea, and there is still unacceptably high mortality in Zambian patients just starting anti-retroviral therapy. We set out to determine if high concentrations of serum cytokines correlate with mortality. Methods Serum samples from 30 healthy controls (HIV seropositive and seronegative) and 50 patients with diarrhoea (20 of whom died within 6 weeks) were analysed. Concentrations of tumour necrosis factor receptor p55 (TNFR p55), macrophage migration inhibitory factor (MIF), interleukin (IL)-6, IL-12, interferon (IFN)-γ and C-reactive protein (CRP) were measured by ELISA, and correlated with mortality after 6 weeks follow-up. Results Apart from IL-12, concentrations of all cytokines, TNFR p55 and CRP increased with worsening severity of disease, showing highly statistically significant trends. In a multivariable analysis high TNFR p55, IFN-γ, CRP and low CD4 count (CD4 count Conclusion High serum concentrations of TNFR p55, IFN-γ, CRP and low CD4 count correlated with disease severity and short-term mortality in HIV-infected Zambian adults with diarrhoea. These factors were better predictors of survival than BMI. Understanding the cause of TNFR p55, IFN-γ and CRP elevation may be useful in development of interventions to reduce mortality in AIDS patients with chronic diarrhoea in Africa.