Effectiveness of cotrimoxazole prophylaxis on mortality in adults with tuberculosis in rural South Africa.

BACKGROUND: Adults with dual tuberculosis (TB) and HIV infection have a poor outcome. Studies in West Africa suggest that cotrimoxazole prophylaxis may reduce this mortality. OBJECTIVE: To evaluate the effectiveness of cotrimoxazole in reducing mortality in adults with active TB, irrespective of HIV status, in a high prevalence setting. DESIGN: Cohort study using historical controls. METHODS: Adults treated for TB between 1998 and 2000 were traced and vital status at 6 months ascertained (2004: control group). All adults starting treatment for TB between June 2001 and June 2002 were offered cotrimoxazole prophylaxis 960 mg once daily for 6 months during TB treatment irrespective of HIV status (1321: intervention group). Mortality, adverse reactions and adherence were compared between intervention and control groups. RESULTS: HIV seroprevalence in patients with TB at the start of the intervention was estimated to be 78%. Mortality at 6 months was 29% lower in the group given cotrimoxazole than in the control group. The number needed to treat to prevent one death during the period of TB treatment was 24. The benefit was seen across all types of TB but was only evident in new patients; patients being retreated had similar outcomes in both groups. Adverse events were infrequent and minor, with only two participants having treatment stopped for this reason. CONCLUSION: Cotrimoxazole prophylaxis for all adults with TB, irrespective of HIV status, in an area of high HIV seroprevalence may be a feasible, safe and effective way to reduce mortality for the duration of treatment.

HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa.

BACKGROUND: Malaria and HIV are two of the most important diseases facing Africa. It remains uncertain whether HIV-related immunosuppression adversely affects the clinical outcome of malaria. OBJECTIVE: To measure the association between HIV status and outcome from malarial infection in adults living in a region of unstable malaria transmission. DESIGN: Observational cohort study. SETTING: Four community clinics and the Government hospital in Hlabisa district, KwaZulu-Natal, South Africa; a region of high HIV prevalence. METHODS: Consecutive febrile adults were screened for malaria with a rapid antigen test. Those with malaria provided blood spots for HIV testing, a thick blood film for confirmation of malaria and clinical data. Outcome was established following management according to South African government guidelines. RESULTS: Malaria was microscopically confirmed in 613. HIV prevalence was 29.9% (180/613); 110 (18%) had severe/complicated malaria and 28 (4.6%) died. HIV-infected patients were more likely to vomit or be confused and were more likely to be admitted to hospital (P = 0.05). In patients admitted to hospital, HIV infection was associated with severe/complicated malaria [adjusted odds ratio (OR) 2.3; 95% confidence interval (CI), 1.4-3.9] and with death (OR 7.5; 95% CI, 2.2-25.1). Acidosis and coma were also strong independent risk factors for death. CONCLUSION: HIV infection had an unexpectedly large association with the outcome of falciparum malaria in a region of unstable transmission. Both diseases are widespread in Africa and these results add to the body of knowledge suggesting an interaction of significant public health importance between HIV and malaria in Africa.

Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence.

BACKGROUND: Malaria and HIV are important pediatric problems in sub-Saharan Africa. It is uncertain how HIV-related immunosuppression and malaria interact in children. We aimed to describe associations among HIV status, presentation and outcome from malaria in children from Hlabisa district, KwaZulu-Natal, South Africa, a region of high HIV prevalence and unstable Plasmodium falciparum transmission. METHODS: Consecutive febrile children were screened for malaria with a rapid antigen test. After consent was given, clinical data were recorded, and blood spots were obtained for HIV antibody testing. Cases were managed according to national guidelines. RESULTS: Malaria was diagnosed in 663 children, of whom 10.1% were HIV antibody-positive. Semiquantitative asexual and sexual stage parasitemia densities were unrelated to HIV status. Overall 161 children were hospitalized; 19 (12%) were <1 year old; and 41 (25%) had severe/complicated malaria. Severe disease presented more frequently in HIV antibody-positive than in HIV-uninfected children (P = 0.05), particularly in those >1 year old with coma (P = 0.02) and hypoglycemia (P = 0.05). Receiving parenteral antibiotics was associated with severe disease (odds ratio, 3.0; 95% confidence interval, 1.3 to 6.7) whereas a low white blood cell count (<4 x 10(6)/l) was associated with nonsevere disease (odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Seven children (4.3%) died. Coma, age <1 year and low white blood cell count were the clearest predictors of poor outcome. CONCLUSION: HIV infection was associated with severe/complicated malaria, although the magnitude of the effect may be relatively small. Given that both malaria and HIV are widespread in Africa, even small effects may generate significant morbidity and mortality and major public health consequences.