Quantitative trait locus analysis of parasite density reveals that HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia

Abstract

BackgroundHaemoglobin S (HbS) is the gene known to confer the strongest advantage against malaria morbidity and mortality. Multiple HbS effects have been described resulting in protection against parasitaemia and reduction of severe malaria risk. This study aimed to explore HbS protection against severe malaria and Plasmodium falciparum parasitaemia in Angolan children exhibiting different severe malaria syndromes.MethodsA case–control study was designed with 430 malaria cases (n = 288 severe malaria and n = 142 uncomplicated malaria) and 319 uninfected controls, attending a central paediatric hospital in Luanda. Severe malaria syndromes were cerebral malaria (n = 130), severe malaria anaemia (n = 30) and hyperparasitaemia (n = 128). Quantitative trait locus analysis was carried out to study HbS association to parasite densities.ResultsPreviously reported HbS protection against severe malaria was confirmed in case–control analysis (P = 2 × 10−13) and corroborated by transmission disequilibrium test (P = 4 × 10−3). High parasite density protection conferred by HbS was detectable within severe malaria patients (P = 0.04). Stratifying severe malaria patients according parasite densities, it was found that HbS was highly associated to hyperparasitaemia protection (P = 1.9 × 10−9) but did not protect non-hyperparasitaemic children against severe malaria complications, namely cerebral malaria and severe malaria anaemia. Many studies have shown that HbS protects from severe malaria and controls parasite densities but the analysis further suggests that HbS protection against severe malaria syndromes was at a large extent correlated with control of parasitaemia levels.ConclusionsThis study supports the hypothesis that HbS confers resistance to hyperparasitaemia in patients exhibiting severe malaria syndromes and highlights that parasitaemia should be taken into account when evaluating HbS protection in severe malaria.

Iron deficiency anaemia among 6-to-36-month children from northern Angola

“…Newborn infants with sickle cell anaemia are reported to be healthy due to predominant production of fetal haemoglobin while in the uterus and neonatal period, but anaemia and haemolysis are evidenced after 4-6 months of age [68]. Also, the carriers of sickle cell trait (AS) were suggested to have a relative survival advantage over people with normal haemoglobin in regions where malaria is endemic, but this is neither absolute protection nor invulnerability to the disease [68,69].…”