SummaryBackgroundSevere malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa. Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality. We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.MethodsThis open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15 years) with severe falciparum malaria were randomly assigned to parenteral artesunate or parenteral quinine. Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.Findings5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine. All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63–0·90; relative reduction 22·5%, 95% CI 8·1–36·9; p=0·0022). Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49–0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66–0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64–0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients. Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43–0·91; p=0·0134). Artesunate was well tolerated, with no serious drug-related adverse effects.InterpretationArtesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.FundingThe Wellcome Trust.

This review outlines the association between tuberculosis and diabetes, focusing on epidemiology, physiopathology, clinical aspects, diagnosis and treatment, and evaluates future perspectives, with particular attention to developing countries.

Background. Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria.Methods. HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status.Results. HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P < .001). In an age- and antimalarial treatment–adjusted logistic regression model, significant, independent predictors for death were renal impairment, acidosis, parasitemia, and plasma PfHRP2 concentration.Conclusions. Severe malaria in HIV-coinfected patients presents with higher parasite burden, more complications, and comorbidity, and carries a higher case fatality rate. Early identification of HIV coinfection is important for the clinical management of severe malaria.

ObjectiveTuberculosis (TB) remains a major global health issue, ranking in the top ten causes of death worldwide. A deep understanding of factors influencing poor treatment outcomes may allow the development of additional treatment strategies, focused on the most vulnerable groups. Aims of the study were: (i) to evaluate the treatment outcome among TB subjects followed in an outpatient setting and (ii) to analyze factors associated with treatment failure in newly diagnosed patients with pulmonary TB in Beira, the second largest city of Mozambique.ResultsA total of 301 TB adult patients (32.6% females) were enrolled. Among them, 62 (20.6%) experienced a treatment failure over a 6 months follow-up. On multivariate model, being males (O.R. = 1.73; 95% CI 1.28–2.15), absence of education (O.R. = 1.85; 95% CI 1.02–2.95), monthly income under 50 dollars (O.R. = 1.74; 95% CI 1.24–2.21) and being employed (O.R. = 1.57; 95% CI 1.21–1.70), low body mass index values (O.R. = 1.42; 95% CI 1.18–1.72) and HIV status (O.R. = 1.42; 95% CI 1.10–1.78) increased the likelihood of therapy failure over 6 months of follow-up. In this study, patients who need more medical attention were young males, malnourished, with low income and low educational degree and HIV positive. These subjects were more likely to fail therapy.

IntroductionData regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scarce. DM screening among TB patients in Mozambique was carried out.MethodsThe study was implemented from January to August 2016 in three Urban Health Centers in Beira, Mozambique and recruited adult (>18 years) patients newly diagnosed with pulmonary TB.ResultsThree hundred and one patients were enrolled (67.4%, males mean age 31.7(SD 11 years). Diabetes was diagnosed in only 3 patients (1%) and impaired glucose tolerance (IGT) in an additional 6 subjects (2%).ConclusionA lower than expected prevalence of DM was observed, which could be explained by the lack of traditional risk factors for DM (overweight, age over 45 years, hypertension and smoking) in Mozambique.

In malaria-endemic areas, Plasmodium falciparum parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental parasitemia. We assessed whether the plasma Plasmodium falciparum DNA concentration is a useful datum for distinguishing uncomplicated from severe malaria in African children and Asian adults. P. falciparum DNA concentrations were measured by real-time polymerase chain reaction (PCR) in 224 African children (111 with uncomplicated malaria and 113 with severe malaria) and 211 Asian adults (100 with uncomplicated malaria and 111 with severe malaria) presenting with acute falciparum malaria. The diagnostic accuracy of plasma P. falciparum DNA concentrations in identifying severe malaria was 0.834 for children and 0.788 for adults, similar to that of plasma P. falciparum HRP2 levels and substantially superior to that of parasite densities (P < .0001). The diagnostic accuracy of plasma P. falciparum DNA concentrations plus plasma P. falciparum HRP2 concentrations was significantly greater than that of plasma P. falciparum HRP2 concentrations alone (0.904 for children [P = .004] and 0.847 for adults [P = .003]). Quantitative real-time PCR measurement of parasite DNA in plasma is a useful method for diagnosing severe falciparum malaria on fresh or archived plasma samples.

Co-infection between malaria and HIV has major public health implications. The aims of this study were to assess the malaria prevalence and to identify predictors of positivity to malaria Test in HIV positive patients admitted to the health center São Lucas of Beira, Mozambique. A retrospective cross-sectional study was performed from January 2016 to December 2016. Overall, 701 adult HIV patients were enrolled, positivity to malaria test was found in 232 (33.0%). These patients were found to be more frequently unemployed (76.3%), aged under 40 (72.0%), with a HIV positive partner (22.4%) and with a CD4 cell count <200 (59.9%). The following variables were predictors of malaria: age under 40 (O.R. = 1.56; 95%CI: 1.22–2.08), being unemployed (O.R. = 1.74; 95%CI: 1.24–2.21), irregularity of cotrimoxazole prophylaxis’s (O.R. = 1.42; 95%CI: 1.10–1.78), CD4 cell count <200 (O.R. = 2.01; 95%CI: 1.42–2.32) and tuberculosis comorbidity (O.R. = 1.58; 95%CI: 1.17–2.79). In conclusion, high malaria prevalence was found in HIV patients accessing the out-patients centre of São Lucas of Beira. Our findings allowed us to identify the profile of HIV patients needing more medical attention: young adults, unemployed, with a low CD4 cell count and irregularly accessing to ART and cotrimoxazole prophylaxis.

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