Plasmodium falciparum Malaria in Children Aged 0-2 Years: The Role of Foetal Haemoglobin and Maternal Antibodies to Two Asexual Malaria Vaccine Candidates (MSP3 and GLURP)

Abstract

BackgroundChildren below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate-rich protein (GLURP), in children in their first two years of life in Burkina Faso and their risk of malaria.MethodsA cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2) on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography.ResultsA total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2) did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria.ConclusionsWe did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.

Dynamics of asymptomatic infections and symptomatic malaria show different temporal profiles among infants living in a high transmission area of Ghana

“…While seasonality and parasite density have been considered in some studies (39)(40)(41), antimalarial usage, microscopy or polymerase chain reaction detection methods and varying duration between initial detection of parasites and onset of symptoms ranging from three to twenty-one days, have also been used to define malaria in other studies (5,21,42). Consequently, the profiles obtained for infants in this study could change if our definitions followed any of the above.…”

“…The low incidence of symptomatic malaria below six months of age has been attributed to presence of fetal hemoglobin (14,15) and passively acquired maternal IgG (16). Also, malaria-specific antibodies at birth (in maternal and/or cord blood) have been associated with protection against some malaria parasite antigens but not others (16)(17)(18)(19)(20)(21).…”

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].…”

“…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]. Several other studies undertaken in health facilities and communities in some sub-Saharan countries showed a higher burden of disease in infants under 6 months than what is generally assumed and even if the antibodies provide some protection, it is shorter than the widely quoted six months [13,14].…”

Functional insight the role of plasmodium falciparum reticulocyte blinding like protein homologues : RH2B and RH5 during merozoites invasion

“…All these have failed in field trials as single antigen vaccines, suggesting a need for combinatorial vaccines that target multiple antigens present at different stages of the parasite's development (Schwartz et al, 2012, Tham et al, 2012. ME-TRAP combined with MSP-1 failed to significantly induce protection (Hodgson et al, 2014), nevertheless, the fused vaccine comprising of P. falciparum glutamate-rich protein (PfGLURP) and MSP-3 was able to induce cytophilic antibodies which affected parasite development (Kangoye et al, 2014, Baumann et al, 2012, Tamborrini et al, 2011. With all these parasite ligands, there are still limited numbers of recombinant or vectored vaccine candidates that have been shown to be efficacious in clinical trial (Hill, 2011.…”