Functional adrenal insufficiency among critically ill patients with human immunodeficiency virus in a resource-limited setting.

BACKGROUND: Functional adrenal insufficiency (FAI) is associated with increased mortality and is defined as subnormal cortisol production during acute severe illness. METHODS: After screening 200 adult patients admitted in the medical emergency unit of Mulago Hospital, Kampala, Uganda, 113 critically ill HIV-infected adults not receiving corticosteroids were enrolled after obtaining informed consent to determine the prevalence and factors associated with FAI. RESULTS: Functional adrenal insufficiency, defined in this study as morning total serum cortisol level of 3%) occurred in 52% (11 of 21) patients with FAI compared to 24% (22 of 92) patients with normal adrenal function (p= 0.01). Factors predicting FAI on multivariate analysis were use of rifampicin and eosinophilia. The mortality rate among patients with FAI (19%) was not significantly different when compared to that among patients with a normal cortisol response (33%) (p=0.221). Hyponatremia, hypoglycemia, hyperkalemia, postural hypotension and the use of ketoconazole were not associated with FAI in this study. CONCLUSION: The diagnosis of FAI should be considered in severely ill patients with stage IV HIV disease using rifampicin or those found to have unexplained eosinophilia. Further studies to determine benefits of corticosteroids in critically ill HIV patients are needed in this setting.

Urban malaria: primary caregivers' knowledge, attitudes, practices and predictors of malaria incidence in a cohort of Ugandan children.

OBJECTIVES: To assess malaria-related knowledge, attitude and practices (KAP) among primary caregivers, to identify associations between primary caregivers' characteristics and positive KAP towards malaria, and to identify independent predictors of childhood malaria incidence in an urban setting. METHODS: Children aged 6 months to 5 years living in Kampala, Uganda were enrolled as part of a longitudinal study on antimalarial therapy. Primary caregivers of 307 children were interviewed and information was collected on demographics, malaria-related KAP, environmental and household factors. Malaria incidence was measured prospectively using passive surveillance. RESULTS: A total of 90% of respondents reported mosquitoes and/or malaria as the cause of fever. Caregivers reported that if their child had fever, 63% would go to a clinic or hospital as their first action and 97% as their first or second action. Only 38% knew that chloroquine was the recommended first-line treatment for malaria and 29% knew the correct dose. Preventive measures for malaria were reported in 45% of households but only 25% reported using bednets. Higher levels of education for the caregiver were associated with positive malaria-related KAP. Malaria incidence varied widely. The following were independent predictors of malaria incidence: (1). Children aged 24-41 months at enrolment had a higher incidence of malaria. (2). Reported bednet or chemoprophylaxis use reduced the incidence of malaria. (3). A child's place of residence was associated with incidence. (4). Children from households using open water sources had a higher incidence than those using closed sources. CONCLUSION: Primary caregivers were knowledgeable about malaria and used modern health care facilities but knew less about the proper administration of antimalarials and had limited use of preventive measures. Malaria incidence was associated with child's age at enrolment, geography, source of water and the use of preventive measures.

Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.

BACKGROUND: New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda. METHODS: We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol. FINDINGS: 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate. INTERPRETATION: Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.