Person:

Dzik, Walter

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov).

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.

Objective: Anaemia affects the majority of children in sub-Saharan Africa (SSA). Previous studies of risk factors for anaemia have been limited by sample size, geography and the association of many risk factors with poverty. In order to measure the relative impact of individual, maternal and household risk factors for anaemia in young children, we analysed data from all SSA countries that performed haemoglobin (Hb) testing in the Demographic and Health Surveys. Design and setting This cross-sectional study pooled household-level data from the most recent Demographic and Health Surveys conducted in 27 SSA between 2008 and 2014. Participants: 96 804 children age 6–59 months. Results: The prevalence of childhood anaemia (defined as Hb <11 g/dL) across the region was 59.9%, ranging from 23.7% in Rwanda to 87.9% in Burkina Faso. In multivariable regression models, older age, female sex, greater wealth, fewer household members, greater height-for-age, older maternal age, higher maternal body mass index, current maternal pregnancy and higher maternal Hb, and absence of recent fever were associated with higher Hb in tested children. Demographic, socioeconomic factors, family structure, water/sanitation, growth, maternal health and recent illnesses were significantly associated with the presence of childhood anaemia. These risk factor groups explain a significant fraction of anaemia (ranging from 1.0% to 16.7%) at the population level. Conclusions: The findings from our analysis of risk factors for anaemia in SSA underscore the importance of family and socioeconomic context in childhood anaemia. These data highlight the need for integrated programmes that address the multifactorial nature of childhood anaemia.