Foetal haemoglobin and the dynamics of paediatric malaria

Abstract

BackgroundAlthough 80% of malaria occurs in children under five years of age, infants under six months of age are known to have low rates of infection and disease. It is not clear why this youngest age group is protected; possible factors include maternal antibodies, unique nutrition (breast milk), and the presence of foetal haemoglobin (HbF). This work aims to gain insight into possible mechanisms of protection, and suggest pathways for focused empirical work, by modelling a range of possible effects of foetal haemoglobin and other red blood cell (RBC) developmental changes on parasite dynamics in infants.MethodsA set of ordinary differential equations was created to investigate the leading hypotheses about the possible protective mechanisms of HbF-containing red blood cells, in particular whether HbF suppresses parasite population growth because parasite multiplication in individual RBCs is lower, slower or absent. The model also incorporated the intrinsic changes in blood volume and haematocrit that occur with age, and the possibility of parasite affinities for HbF-containing RBCs or reticulocytes.ResultsThe model identified several sets of conditions in which the infant remained protected, or displayed a much slower growth of parasitaemia in the first few months of life, without any intervening immune response. The most protective of the hypothesized mechanisms would be the inhibition of schizont division in foetal RBCs so that fewer merozoites are produced. The model showed that a parasite preference for HbF-containing RBCs increases protective effects for the host, while a preference for reticulocytes has little effect.ConclusionsThe results from this simple model of haematological changes in infants and their effects on Plasmodium falciparum infection dynamics emphasize the likely importance of HbF and RBC number as an explanatory factor in paediatric malaria, and suggest a framework for organizing related empirical research.

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda

“…The present results also fail to compare with conclusions from a study in Mali in which an age stratified analysis showed sickle trait-mediated malaria protection to be more evident in early childhood [ 39 ]. Possible explanations for the lower incidence of uncomplicated malaria among HBB wild types in the current study could relate to protection conferred by fetal hemoglobin and maternal antibodies during early childhood [ 40 – 42 ]. However the present study did not assess for the levels of fetal haemoglobin and maternal antibodies in infancy, thus other studies would be needed to confirm this relationship.…”

The relationship between Plasmodium infection, anaemia and nutritional status in asymptomatic children aged under five years living in stable transmission zones in Kinshasa, Democratic Republic of Congo

“…One might assume an intensive use of bed nets in that age group but there was no difference according to the use of ITNs within age groups. In younger children, especially under six months old, the presence of maternal antibodies may decrease the prevalence of PI and therefore of asymptomatic infection [ 53 , 54 ], while in older infants, over six months, when maternal protection wanes, asymptomatic infection may be uncommon as the lack of acquired anti-malaria immunity deviates these children immediately to symptomatic or even severe symptomatic malaria episodes, decreasing the prevalence of asymptomatic infection in these infants [ 55 , 56 ].…”

Uncomplicated Malaria in Children under 6 Months or Less than 5 Kg; How Prescribers in Ghana Manage it in the Absence of a National Policy

“…Demonstration of in-vitro malaria parasite growth inhibitory characteristics of lactoferrin and immunoglobin A (IgA) found in breast milk as well as maternal and infant sera has led others to hypothesize that infants are protected from malaria [8,9]. The assumption of infant's immunity against malaria was further boosted by studies that showed that high hemoglobin F concentration at birth inhibits malaria parasite's development in the first few months of human life [10,11]. This assumption of a sixmonth period of protection in a newborn in contradicted by other studies which found no relationship between presence of maternal antibodies and their protection against malaria in African infants [11,12].…”