Juliet Mwanga‐Amumpaire

BACKGROUND: Data from the largest randomized, controlled trial for the treatment of children hospitalized with severe malaria were used to identify such predictors of a poor outcome from severe malaria. METHODS: African children (<15 years) with severe malaria participated in a randomized comparison of parenteral artesunate and parenteral quinine in 9 African countries. Detailed clinical assessment was performed on admission. Parasite densities were assessed in a reference laboratory. Predictors of death were examined using a multivariate logistic regression model. RESULTS: Twenty indicators of disease severity were assessed, out of which 5 (base deficit, impaired consciousness, convulsions, elevated blood urea, and underlying chronic illness) were associated independently with death. Tachypnea, respiratory distress, deep breathing, shock, prostration, low pH, hyperparasitemia, severe anemia, and jaundice were statistically significant indicators of death in the univariate analysis but not in the multivariate model. Age, glucose levels, axillary temperature, parasite density, heart rate, blood pressure, and blackwater fever were not related to death in univariate models. CONCLUSIONS: Acidosis, cerebral involvement, renal impairment, and chronic illness are key independent predictors for a poor outcome in African children with severe malaria. Mortality is markedly increased in cerebral malaria combined with acidosis. Clinical Trial Registration. ISRCTN50258054.

BACKGROUND: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. METHODS AND FINDINGS: Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. CONCLUSIONS: Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children.

Background and objectives: Knowledge of local and regional antimicrobial resistance (AMR) is important for clinical decision making. However, surveillance capacity for AMR is lacking throughout East Africa, and current AMR data are sparse. We sought to address this gap by summarising all available high-quality data on AMR in the East Africa region.Method: We searched the PubMed database and African Journals Online archives in April and May 2015 using the search term ‘antimicrobial resistance AND sub-Saharan Africa’ to find articles published from 2005 onwards. Only full-text articles in English were included.Results: We included 12 published articles in our analysis. Most articles were on bloodstream infections, hospital-based and cross-sectional in design; a majority described either community- or hospital-acquired infections. High levels of AMR to commonly-used antibiotics were reported, including 50% – 100% resistance to ampicillin and cotrimoxazole infections, emerging resistance to gentamicin (20% – 47%) and relatively high levels of resistance to ceftriaxone (46% – 69%) among Gram-negative infections. Much of the resistance was reported to be in Klebsiella species and Escherichia coli. Among Gram-positive infections, extensive resistance was reported to ampicillin (100%), gentamicin and ceftriaxone (50% – 100%), with methicillin-resistant Staphylococcus aureus prevalence ranging from 2.6% – 4.0%.Conclusion: Overall, bacterial resistance was reported among commonly-used antibiotics (ampicillin, gentamicin and ceftriaxone), raising concern that these antibiotics may no longer be useful for treating moderate or severe bacterial infections in East Africa. Thus, empirical treatment of bacterial infections needs to be reconsidered and guided by local assessment of AMR. Improvements in the limited amount of quality data and lack of harmonisation in assessing the burden of AMR are also needed.

BACKGROUND: Quantification of human interactions relevant to infectious disease transmission through social contact is central to predict disease dynamics, yet data from low-resource settings remain scarce. METHODS: We undertook a social contact survey in rural Uganda, whereby participants were asked to recall details about the frequency, type, and socio-demographic characteristics of any conversational encounter that lasted for ≥5 min (henceforth defined as 'contacts') during the previous day. An estimate of the number of 'casual contacts' (i.e. < 5 min) was also obtained. RESULTS: In total, 566 individuals were included in the study. On average participants reported having routine contact with 7.2 individuals (range 1-25). Children aged 5-14 years had the highest frequency of contacts and the elderly (≥65 years) the fewest (P < 0.001). A strong age-assortative pattern was seen, particularly outside the household and increasingly so for contacts occurring further away from home. Adults aged 25-64 years tended to travel more often and further than others, and males travelled more frequently than females. CONCLUSION: Our study provides detailed information on contact patterns and their spatial characteristics in an African setting. It therefore fills an important knowledge gap that will help more accurately predict transmission dynamics and the impact of control strategies in such areas.