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

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.

Reduced gene expression of intestinal alpha-defensins predicts diarrhea in a cohort of African adults.

BACKGROUND: Human defensin (HD) 5 and HD6, both Paneth cell alpha-defensins, contribute to the antimicrobial barrier against intestinal infection. We have previously demonstrated that levels of both HD5 and HD6 mRNA were reduced in adults living in urban Zambia, compared with those in adults living in London. The aim of the present study was to determine, during 2 years of follow-up, whether alpha-defensin expression in Zambian adults is related to susceptibility to diarrhea. METHODS: We analyzed intestinal biopsy samples from a longitudinal cohort study conducted in 83 Zambian adults by quantitative reverse-transcription polymerase chain reaction, Western blotting, immunohistochemistry, and in situ hybridization, and we measured the incidence of diarrhea. RESULTS: Levels of HD5 and HD6 mRNA in Paneth cells varied between participants, over time, and seasonally and were strongly correlated with mucosal architecture. Gene expression was almost exclusively restricted to Paneth cells. The median (interquartile range) HD5 mRNA level was 6.0 (5.6-6.7) log10 transcripts/microg of total RNA among 18 participants who experienced diarrhea within 2 months after biopsy-sample collection, compared with 6.8 (6.2-7.3) log10 transcripts/microg of total RNA among 94 participants who did not (P=.006). A similar observation was made for HD6. CONCLUSIONS: These data indicate that intestinal alpha-defensin expression is dynamic and seasonal and suggest that susceptibility to intestinal infection is related to alpha-defensin expression.

Primary mycobacterial skin infection: A summary

The commonest pathogenic skin mycobacteria in many areas of the world is still Mycobacterium leprae. This mycobacteria, which grows best at skin temperatures 31(graus)C-33(graus)C, often involves nerve twigs and trunks. In addition to producing skin lesionms, it can cause motor and sensory deficits. The mycobacteria has been cultivated in the laboratory only in animal models.

Control of a type 1 poliomyelitis epidemic in British Guiana, 1962-63, with trivalent oral poliovirus vaccine. II Virological aspects

Epidemics of paralytic poliomyelitis has been reported with increasing frequency in the Caribbean area over the last decade. During the first weeks of a type 1 poliomyelitis epidemic in British Guiana in the winter of 1962-63, it was possible to study "wild" poliovirus infections in pre-school children, and to obtain information concerning the effectiveness of a country-wide control programme using trivalent oral poliovirus vaccine. Serological studies indicated that many Guianese children had had previous asymptomatic poliovirus infections by school age. However, there were more children with antibodies to types 2 and 3 than with antibodies to type 1. Following the first of two feedings of trivalent vaccine, there were significant increases in the percentage of children with poliovirus antibodies. Though begun only three weeks after the hospitalization of several paralysed children, a rectal-swab survey indicated that in some areas over one-third of the pre-school children were excreting "wild" poliovirus. In one area of the country, where only 2 percent of the children were excreting poliovirus type 1, vaccine feeding seemed most effective in containing the epidemic. These results support the suggestion that to be successful an epidemic control programme in a developing tropical country should be rapidly organized and completed (AU)