Complex interactions between malaria and malnutrition: a systematic literature review.

BACKGROUND: Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition. METHODS: Database searches were conducted in PubMed, Global Health and Cochrane Libraries and articles published in English, French or Spanish between Jan 1980 and Feb 2018 were accessed and screened. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale and the risk of bias across studies was assessed using the GRADE approach. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline were followed. RESULTS: Of 2945 articles screened from databases, a total of 33 articles were identified looking at the association between malnutrition and risk of malaria and/or the impact of malnutrition in antimalarial treatment efficacy. Large methodological heterogeneity of studies precluded conducting meaningful aggregated data meta-analysis. Divergent results were reported on the effect of malnutrition on malaria risk. While no consistent association between risk of malaria and acute malnutrition was found, chronic malnutrition was relatively consistently associated with severity of malaria such as high-density parasitemia and anaemia. Furthermore, there is little information on the effect of malnutrition on therapeutic responses to artemisinin combination therapies (ACTs) and their pharmacokinetic properties in malnourished children in published literature. CONCLUSIONS: The evidence on the effect of malnutrition on malaria risk remains inconclusive. Further analyses using individual patient data could provide an important opportunity to better understand the variability observed in publications by standardising both malaria and nutritional metrics. Our findings highlight the need to improve our understanding of the pharmacodynamics and pharmacokinetics of ACTs in malnourished children. Further clarification on malaria-malnutrition interactions would also serve as a basis for designing future trials and provide an opportunity to optimise antimalarial treatment for this large, vulnerable and neglected population. TRIAL REGISTRATION: PROSPERO CRD42017056934 .

Progression of stunting and its predictors among school-aged children in western Kenya.

OBJECTIVE: The objectives of this study were (1) to assess whether a cohort of school-aged children experiences progression of stunting over a 2-y-period of observation and (2) to identify baseline nutritional and body composition risk factors for the progression of stunting. METHODS: As part of a large-scale, randomized controlled trial assessing the impact of insecticide-treated bednets (ITNs) on nutritional status, we longitudinally followed a cohort of school-aged children over a 2-y-period in western Kenya. Anthropometric measurements were made at four time points from which Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and body mass index (BMIZ) were calculated. Two measures of body composition, upper arm fat area and upper arm muscle area, were derived from mid-upper arm circumference (MUAC) and triceps skinfold thickness. RESULTS: Subjects experienced a mean change in HAZ from baseline to 9 months of -0.16 [-0.19, -0.13], from baseline to 16 months of -0.18 [-0.22, -0.15], and from baseline to 24 months of -0.36 [-0.41, -0.31]. Thus, the average individual's change in HAZ at the three follow-up time points is significantly less than zero, meaning that, on average, the cohort is deviating further from NCHS reference medians over time. The baseline nutritional measure that explained the greatest amount of variance in the progression of stunting was the upper arm muscle area Z-score (F=8.1; P=0.005). CONCLUSIONS: This longitudinal study provides further evidence from a distinct ecological setting regarding the progression of undernutrition during middle childhood in the developing world. It suggests that school-aged children in the developing world do not experience catch-up growth or remain stable. Rather, they continue to deviate from NCHS standards, accruing greater height deficits with age. In addition, absolute lean body mass explained the most variability in the progression of stunting, which supports cross-sectional findings from other studies.

Recognition of pallor associated with severe anaemia by primary caregivers in western Kenya.

OBJECTIVES: To explore which pallor signs and symptoms of severe anaemia could be recognized by primary caregivers following minimal instructions. METHODS: Data from three community-based cross-sectional surveys were used. Test characteristics to predict haemoglobin (Hb) concentrations < 5 and < 7 g/dl were compared for different combinations of pallor signs (eyelid, tongue, palmar and nailbed) and symptoms. RESULTS: Pallor signs and haemoglobin levels were available for 3782 children under 5 years of age from 2609 households. Comparisons of the sensitivity and specificity at a range of haemoglobin cut-offs showed that Hb < 5 g/dl was associated with the greatest combined sensitivity and specificity for pallor at any anatomical site (sensitivity = 75.6%, specificity = 63.0%, Youden index = 38.6). Higher or lower haemoglobin cut-offs resulted in more children being misclassified. Similar results were obtained for all individual pallor sites. Combining a history of soil eating with pallor at any site improved the sensitivity (87.8%) to detect Hb < 5 g/dl with a smaller reduction in specificity (53.3%; Youden index 41.1). Other combinations including respiratory signs or poor feeding resulted in lower accuracy. CONCLUSION: Primary caregivers can recognize severe anaemia (Hb < 5 g/dl) in their children, but only with moderate accuracy. Soil eating should be considered as an additional indicator of severe anaemia. The effect of training caretakers to improve recognition of severe anaemia and care-seeking behaviour at the household level should be assessed in prospective community-based studies.

Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX.

A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene, with a guanine to adenine nucleotide change at position -308, TNF2 is associated with increased TNF-alpha production. TNF2 homozygotes have a higher risk of severe disease and/or death due to cerebral malaria and other infectious diseases. We investigated the impact of this allele on malaria morbidity and mortality in young children who participated in an immuno-epidemiologic cohort study of malaria in an area of intense perennial Plasmodium falciparum transmission in western Kenya. A total of 1,048 children were genotyped. Poisson regression and Cox proportional hazards models were used to determine the relationship between TNF-308 variants and morbidity and mortality. The gene frequencies of the TNF1 and TNF2 alleles were 0.90 and 0.10, respectively. TNF2 homozygosity was associated with pre-term birth when compared with TNF1 homozygotes [relative risk (RR) 7.3, 95% CI, 2.85-18.9, P = 0.002) and heterozygotes (RR 6.7, 95% CI 2.0-23.0, P = 0.008). Among children born prematurely, the TNF2 allele was significantly associated with a higher risk of death in infancy compared with TNF1 (RR 7.47, 95% CI 2.36-23.6). The risk of death was higher among TNF2 homozygotes than among heterozygotes. The TNF2 allele was significantly associated with high density P. falciparum parasitemia (RR 1.11, 95% CI 1.0-1.24). Among low birth weight children, the TNF2 allele was associated with severe anemia (RR 2.16, 95% CI 1.17-4.01) and showed a trend toward a risk for severe malaria anemia (RR 1.99, 95% CI 0.89-4.46). These data suggest that TNF2 is a risk factor for pre-term birth and early childhood mortality and malaria morbidity in children in this region. Further understanding of the pathogenic mechanisms underlying this association is required.