Increased Susceptibility to Plasmodium falciparum in Infants is associated with Low, not High, Placental Malaria Parasitemia

Abstract

Risk of malaria in infants can be influenced by prenatal factors. In this study, the potential for placental parasitemia at delivery in predicting susceptibility of infants to Plasmodium falciparum (Pf) infections was evaluated. Seventy-two newborns of mothers who were placental malaria negative (PM−) and of mothers who were PM+ with below (PM+ Lo) and above (PM + Hi) median placental parasitemia, were actively monitored during their first year of life. Median time to first PCR-detected Pf infection was shorter in PM + Lo infants (2.8 months) than in both PM− infants (4.0 months, p = 0.002) and PM + Hi infants (4.1 months, p = 0.01). Total number of new infections was also highest in the PM + Lo group. Only 24% of infants experienced clinical malaria episodes but these episodes occurred earlier in PM + Lo infants than in PM + Hi infants (p = 0.05). The adjusted hazard ratio (95% CI) of having Pf infection was 3.9 (1.8-8.4) and 1.5 (0.7-3.4) for infants in the PM + Lo and PM + Hi groups, respectively. Collectively, low placental parasitemia was associated with increased susceptibility to malaria during infancy. Therefore, malaria in pregnancy preventive regimens, such as sulfadoxine-pyremethamine, that reduce but do not eliminate placental Pf in areas of drug resistance may increase the risk of malaria in infants.When pregnant women become infected with the mosquito-borne parasite Plasmodium falciparum (Pf), parasitized erythrocytes adhere to placental villi and accumulate in the intervillous spaces (IVS), causing a condition referred to as placental malaria (PM) 1 . In addition to eliciting adverse pregnancy outcomes 2 , PM has been identified as a risk factor for early childhood morbidity and mortality. In general, infants born to PM-positive (PM+) mothers have a shorter time to first Pf infection 3,4 and first clinical episode of malaria 5,6 , a higher incidence of Pf infections early in life 7 , lower hemoglobin levels 8 , and higher risk of dying 9 compared to infants of PM-negative (PM−) mothers. However, the risk of malaria is not homogeneous among infants of PM+ mothers, since some PM+ infants have similar risk outcomes as PM− infants 3,5,9-11 . There is therefore a need to identify specific prenatal factors associated with increased susceptibility to malaria in infants whose mothers had PM.Factors thought to be important in modifying the susceptibility of infants to malaria include maternal gravidity and the timing of occurrence of malaria during pregnancy. For example, infants born to multigravid Tanzanian women had their first microscopically detected infection 12 weeks earlier than infants of primigravid women 3 . Likewise, Gabonese infants born to multigravidae were approximately twice as likely to experience clinical episodes of malaria during the first 30 months of life than infants born to primigravidae 5 . Concerning the timing of infection during pregnancy, when maternal Pf infections occurred within 3 months prior to delivery, Ugandan infants were at a higher risk of infection than when mothers...

Placental Malaria

“…One study demonstrated that children born to mothers with placental malaria had a significantly higher odds of clinical malaria (OR, 4.1; 95% CI, 1.3-13.1) in the first year of life [54]. Another study found that clinical malaria episodes occurred earlier in children born to women with placental malaria than women with no placental malaria [57]. Congenital malaria, while rare, has been associated with placental malaria.…”

Composition of the gut microbiota transcends genetic determinants of malaria infection severity and influences pregnancy outcome

“…Furthermore, maternal malaria infection profoundly impacts the postnatal health and survival of the infants. Malaria-associated low birth weight is estimated to have a fatality rate of 37·5% [22], and infants born to malaria-infected women are more susceptible to malaria in early life [[23], [24], [25]]. Thus, understanding the pathogenesis of malaria in pregnancy is critical for improving maternal and child health outcomes in malarious regions.…”

Measuring antibody avidity to Plasmodium falciparum merozoite antigens using a multiplex immunoassay approach

“…Studies in high transmission areas have reported little or no increase in Ab avidity with age for EBA-175, MSP1, MSP2, and MSP3 [4][5][6][7][8][9]. Plasma used in this study was from infants and adults living in a rural village with perennial transmission who received an estimated 257 infectious mosquito bites/person/year [29,30]. Clearly, it would be interesting to investigate affinity maturation with age in this high transmission setting to determine if and when affinity maturation occurs.…”

“…A collection of de-identified, archival, plasma samples from malaria endemic regions of Cameroon with high transmission were used [29,30]. Samples included: plasma from 5 selected adults with known Ab levels for the antigens; 40 adults residing in Ngali II (pregnant women, non-pregnant women, males) who had been repeatedly infected with malaria and had developed high malarial immunity, and 57 12-month-old infants living in Ngali II who had just begun developing immunity to malaria [30].…”

“…A collection of de-identified, archival, plasma samples from malaria endemic regions of Cameroon with high transmission were used [29,30]. Samples included: plasma from 5 selected adults with known Ab levels for the antigens; 40 adults residing in Ngali II (pregnant women, non-pregnant women, males) who had been repeatedly infected with malaria and had developed high malarial immunity, and 57 12-month-old infants living in Ngali II who had just begun developing immunity to malaria [30]. Two pools of plasma were used as positive controls (PC), with PC consisting of plasma samples pooled from adults living in Ngali II village (a high malaria transmission area), Cameroon and positive control #2 (PC#2) including plasma pooled from pregnant women living in the same village [29].…”