Susceptibility to intestinal infection and diarrhoea in Zambian adults in relation to HIV status and CD4 count

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/microL 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.

Figure 1

Seasonal variation in diarrhoea and in eight intestinal infections. The seasons (each of 2 months) are shown along the x axis (1 May, June; 2 July, August; 3 September, October; 4 November, December; 5 January, February; 6 March, April) and the incidence of that infection per 'season' on the y axis. Rainfall is November-March, so shigellosis is commoner in the dry season and aeromoniasis during the rains. Infections which are listed in Table 1 and not shown here did not display seasonality.

Figure 2

Risk of intestinal infection and diarrhoeal disease in the whole cohort, and according to HIV status and CD4 count. Fig 2A shows the absolute risk of intestinal infection per month, irrespective of symptoms, for pathogens using the restrictive definition (see Methods), and Fig 2B shows the absolute risk of infection per month, irrespective of symptoms, using the more open definition. Fig 2C shows the percentage of intestinal infections associated with diarrhoea (i.e. disease-to-infection ratio) using the restrictive definition. Fig 2D shows the disease-to-infection ratio using the more open definition.