Sickle Cell Trait Protects Against Plasmodium falciparum Infection

Abstract

Although sickle cell trait protects against severe disease due to Plasmodium falciparum, it has not been clear whether sickle trait also protects against asymptomatic infection (parasitemia). To address this question, the authors identified 171 persistently smear-negative children and 450 asymptomatic persistently smear-positive children in Bancoumana, Mali (June 1996 to June 1998). They then followed both groups for 2 years using a cohort-based strategy. Among the 171 children with persistently negative smears, the median time for conversion to smear-positive was longer for children with sickle trait than for children without (274 vs. 108 days, P < 0.001; Cox hazard ratio = 0.56, 95% confidence interval: 0.33, 0.96; P = 0.036). Similar differences were found in the median times to reinfection after spontaneous clearance without treatment (365 days vs. 184 days; P = 0.01). Alternatively, among the 450 asymptomatic children with persistently positive smears, the median time for conversion to smear-negative (spontaneous clearance) was shorter for children with sickle trait than for children without (190 vs. 365 days; P = 0.02). These protective effects of sickle trait against asymptomatic P. falciparum infection under conditions of natural transmission were demonstrable using a cohort-based approach but not when the same data were examined using a cross-sectional approach.

Hemoglobin E and Glucose-6-Phosphate Dehydrogenase Deficiency and Plasmodium falciparum Malaria in the Chittagong Hill Districts of Bangladesh

“…In this study, we did not have enough severe malaria cases to analyze the association between severe disease and HbE status, but rather we compared those without infection to those who presented with mild clinical infection in a community setting. It is possible that the protective effects may only apply to reducing severe symptoms, a result found by Hutagalung and others, 11 rather than preventing infection or onset of 19 have suggested, it is possible that the cross-sectional analyses used were not robust enough to identify these differences and that a longitudinal approach was needed. The small sample size and lack of significance when comparing the marginal frequencies of hemoglobin status by malaria suggest that further research on this question is needed to fully understand the relationship of HbE and malaria.…”

Plasmodium falciparum infection in febrile Congolese children: prevalence of clinical malaria 10 years after introduction of artemisinin‐combination therapies

“…In 2015, the malaria global burden was estimated at 214 million cases resulting in 438 000 deaths . Children under five and women in their first pregnancy are at particular risk of complications and severe disease . The transmission and incidence rates of Plasmodium falciparum malaria are higher in sub‐Saharan Africa .…”

“…Children under five and women in their first pregnancy are at particular risk of complications and severe disease . The transmission and incidence rates of Plasmodium falciparum malaria are higher in sub‐Saharan Africa . Eighty eight percent of the malaria cases in 2015 occurred in the WHO African Region .…”

Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition

“…In addition, the AS genotype is underrepresented among children with severe malaria (6,7). Other studies have demonstrated faster clearance of asymptomatic infection in children with AS (8). However, despite the strong epidemiologic evidence of selection for AS, the biological mechanism underlying the protection against severe malaria is not completely understood.…”