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ABSTRACT: 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.
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.
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.
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.
BMC Gastroenterology 01/2009; 9:7. · 2.42 Impact Factor
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Veronica Mulenga,
Deborah Ford,
A Sarah Walker,
Darlington Mwenya, James Mwansa,
Frederick Sinyinza,
Kennedy Lishimpi,
Andrew Nunn,
Stephen Gillespie,
Ali Zumla,
Chifumbe Chintu,
Diana M Gibb
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ABSTRACT: Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.
CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups.
Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)].
Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.
AIDS 02/2007; 21(1):77-84. · 6.24 Impact Factor
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Veronica Mulenga,
Deborah Ford,
A Sarah Walker,
Darlington Mwenya, James Mwansa,
Frederick Sinyinza,
Kennedy Lishimpi,
Andrew Nunn,
Stephen Gillespie,
Ali Zumla,
Chifumbe Chintu,
Diana M Gibb,
the CHAP Trial Team
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ABSTRACT: Background: Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear.
Methods: CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups.
Results: Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)].
Conclusions: Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.
AIDS 01/2007; 21(1):77-84. · 6.24 Impact Factor
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Mary Shilalukey Ngoma,
Mutinta Nalubamba,
Sumbukeni Kowa,
Dominic Minyoi,
Joseph Mubanga, James Mwansa,
John Musuku,
Chifumbe Chintu,
Ganapati Bhat,
Thomas Kapakala,
Peter Mumba,
Khange Nyalungwe
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ABSTRACT: The last successfully treated case of congenital trypanosomiasis in Zambia was in October 1978, with detailed analysis of immunoglobulins, illustrating the waning of blood and serum levels of IgA, IgG, and IgM during treatment, up to 99 days after treatment. Twenty-five years later, we report on a case of congenital trypanosomiasis. The disease is now rare and can be missed or dismissed as retroviral disease, particularly in adults. The main unusual symptoms were the prolonged intermittent convulsions in an otherwise well infant. Management of the disease is now more interdisciplinary, resources for laboratory support are fewer, lumbar puncture is more relevant, and antitrypanosomal drugs are more difficult to obtain. The mother died within one week of hospitalization and the infant initially responded to three doses of suramin and 3 weeks of melsopropol. Convulsions ceased during the second round of melsopropol. Unfortunately, the infant died of nosocomial infection.
Journal of Tropical Pediatrics 12/2004; 50(6):377-8. · 1.39 Impact Factor
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Paul Kelly,
Ian Menzies,
Roger Crane,
Isaac Zulu,
Carole Nickols,
Roger Feakins, James Mwansa,
Victor Mudenda,
Max Katubulushi,
Steve Greenwald,
Michael Farthing
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ABSTRACT: 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.
The American journal of tropical medicine and hygiene 05/2004; 70(4):412-9. · 2.59 Impact Factor
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ABSTRACT: Mycoplasma contamination of the licensed anthrax vaccine administered to military personnel has been suggested as a possible cause of Persian Gulf illness. Vaccine samples tested by nonmilitary laboratories were negative for viable mycoplasma and mycoplasma DNA and did not support its survival. Mycoplasma contamination of anthrax vaccine should not be considered a possible cause of illness.
Emerging infectious diseases 02/2002; 8(1):92-3. · 6.17 Impact Factor
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ABSTRACT: Persistent diarrhoea is a major cause of morbidity and mortality in AIDS patients, and consequently an important public health problem in sub-Saharan Africa. Although intestinal protozoa and bacteria are detected in many of these patients, a substantial proportion of disease remains unexplained even after intensive investigation. HEp-2 cell adherent Escherichia coli have been described in AIDS patients with persistent diarrhoea, but their contribution to the overall burden of disease is not yet defined. We studied HEp-2 cell adherence of E. coli isolates from 116 adult Zambian AIDS patients and 153 healthy controls obtained in 1993 or 1998-99. Enteroaggregative, enteropathogenic, and diffusely adherent phenotypes were observed in E. coli isolates from both AIDS patients and controls, but cytotoxic phenotypes were only isolated from the AIDS patients. There was no evidence of seasonality in the frequency of isolation, and there was no evidence of long-term carriage. Light and electron microscopy of distal duodenal biopsies did not reveal any bacteria closely associated with the brush border. Isolates were less susceptible to amoxycillin, tetracycline, and sulfonamides than to newer antibiotics. Enterovirulent E. coli appear to contribute to intestinal disease in AIDS patients in Zambia but asymptomatic carriage is common. Antibiotic trials should be carried out.
Transactions of the Royal Society of Tropical Medicine and Hygiene 97(5):573-6. · 2.16 Impact Factor
