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Summaryobjective To identify risk factors for in-hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda. results Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty-two per cent were children <16 years of age with a male ⁄ female ratio of 2.2. The overall case-fatality rate during pentavalent antimonial (n = 1641) or conventional amphotericin B treatment (n = 217) was 3.7%. There was no difference in the case-fatality rate between treatment groups (P > 0.20). The main risk factors for in-hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug-related adverse events. The case-fatality rate among patients >45 years of age was strikingly high (29.0%).

Background and methodologyDue to geographic overlap of malaria and visceral leishmaniasis (VL), co-infections may exist but have been poorly investigated. To describe prevalence, features and risk factors for VL-malaria co-infections, a case-control analysis was conducted on data collected at Amudat Hospital, Uganda (2000–2006) by Médecins sans Frontières. Cases were identified as patients with laboratory-confirmed VL and malaria at hospital admission or during hospitalization; controls were VL patients with negative malaria smears. A logistic regression analysis was performed to study the association between patients' characteristics and the occurrence of the co-infection.ResultsOf 2414 patients with confirmed VL, 450 (19%) were positively diagnosed with concomitant malaria. Most co-infected patients were males, residing in Kenya (69%). While young age was identified by multivariate analysis as a risk factor for concurrent VL and malaria, particularly the age groups 0–4 (odds ratio (OR): 2.44; 95% confidence interval (CI): 1.52–3.92) and 5–9 years (OR: 2.23, 95% CI: 1.45-3-45), mild (OR: 0.53; 95% CI: 0.32–0.88) and moderate (OR: 0.45; 95% CI: 0.27–0.77) anemia negatively correlated with the co-morbidity. VL patients harboring skin infections were nearly three times less likely to have the co-infection (OR: 0.35; 95% CI: 0.17–0.72), as highlighted by the multivariate model. Anorexia was slightly more frequent among co-infected patients (OR: 1.71; 95% CI: 0.96–3.03). The in-hospital case-fatality rate did not significantly differ between cases and controls, being 2.7% and 3.1% respectively (OR: 0.87; 95% CI: 0.46–1.63).ConclusionsConcurrent malaria represents a common condition among young VL patients living in the Pokot region of Kenya and Uganda. Although these co-morbidities did not result in a poorer prognosis, possibly due to early detection of malaria, a positive trend towards more severe symptoms was identified, indicating that routine screening of VL patients living in malaria endemic-areas and close monitoring of co-infected patients should be implemented.

African sleeping sickness (SS) is a severe, potentially lethal parasitic disease. The treatments of choice are the antiparasitic agents suramin, which is adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis of patient with SS before, during, and after therapy with suramin and/or melarsoprol, in two sequential stages. First, we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test (250 µg i.v.) to assess the maximal adrenocortical responsiveness of 69 patients with SS and 38 normal controls. We demonstrated paradoxically subnormal Cortisol responses before suramin therapy [net Cortisol response 60 min after stimulation: 10.5 ± 2.9 (mean ± SE) vs. 17.5 ± 1.0 µg/dl for controls, p = 0.004], with 27% of the patients falling within the adrenal insufficiency range (stimulated cortisol concentration <20 µg/dl). These responses subsequently and unexpectedly improved with suramin and/or melarsoprol therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test (100 µg i.v.) in 68 additional patients with SS and 14 control subjects to examine whether the glucocorticoid deficiency observed was primary and/or secondary. Compared to controls, the ACTH and Cortisol responses to hCRH were blunted (ACTH after 60 min: 29 ± 7 vs. 58 ± 8 pg/ml in controls, p = 0.014; cortisol: 15.2 ± 1.5 vs. 19.6 ± 0.7 µg/dl, p = 0.018), suggesting the presence of secondary adrenal insufficiency. There was improvement of both ACTH and cortisol responsiveness to hCRH with therapy, with cortisol recovery occurring before ACTH, suggesting an additional primary component of adrenal dysfunction in these patients. Plasma concentrations of tumor necrosis factor (TNF)-Α (16.0 ± 4.1 vs. 2.9 ± 1.4 pg/ml in controls, p = 0.003) and interleukin (IL)-6 (19.2 ± 7.3 vs. 1.3 ± 0.2 pg/ml, p = 0.0001), but not IL-1Β (2.0 ± 0.2 vs. 0.9 ± 0.2, p = NS), were elevated when adrenocrotical function impairment and disease activity were at their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentrations and maximal Cortisol concentrations during hCRH testing (TNF-Α: r = –0.31, p = 0.003; IL-6: r = –0.34, p = 0.002). We conclude that unmedicated SS is associated with significant impairment of adrenocortical function which is reversed with suramin and/or melarsoprol therapy in the majority of patients. This impairment may be due to the elevated plasma cytokine concentrations, and may represent a natural adaptation of the HPA axis in inflammatory states. A controlled therapeutic trial is necessary to demonstrate whether supplemental glucocorticoids could be beneficial in SS.

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