Infections in Infants during the First 12 Months of Life: Role of Placental Malaria and Environmental Factors

Abstract

BackgroundThe association between placental malaria (PM) and first peripheral parasitaemias in early infancy was assessed in Tori Bossito, a rural area of Benin with a careful attention on transmission factors at an individual level.MethodologyStatistical analysis was performed on 550 infants followed weekly from birth to 12 months. Malaria transmission was assessed by anopheles human landing catches every 6 weeks in 36 sampling houses and season defined by rainfall. Each child was located by GPS and assigned to the closest anopheles sampling house. Data were analysed by survival Cox models, stratified on the possession of insecticide-treated mosquito nets (ITNs) at enrolment.Principal FindingsAmong infants sleeping in a house with an ITN, PM was found to be highly associated to first malaria infections, after adjusting on season, number of anopheles, antenatal care (ANC) visits and maternal severe anaemia. Infants born from a malaria infected placenta had a 2.13 fold increased risk to present a first malaria infection than those born from a non infected placenta ([1.24–3.67], p<0.01) when sleeping in a house with an ITN. The risk to present a first malaria infection was increased by 3.2 to 6.5, according to the level of anopheles exposure (moderate or high levels, compared to the absence of anopheles).ConclusionsFirst malaria infections in early childhood can be attributed simultaneously to both PM and high levels of exposure to infected anopheles. Protective measures as Intermittent Preventive Treatment during pregnancy (IPTp) and ITNs, targeted on both mothers and infants should be reinforced, as well as the research on new drugs and insecticides. In parallel, investigations on placental malaria have to be strengthened to better understand the mechanisms involved, and thus to protect adequately the infants high risk group.

Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

“…In parallel, epidemiological studies, including our own, have clearly documented the altered susceptibility of infants to P. falciparum infection or disease (11)(12)(13)(14)(15)(16). It has not been documented whether and how specific components of the innate immune system of such "tolerant" infants may contribute to their apparent inability to control the parasite.…”

“…In Benin, the study took place in the district of Come, Mono Province, located 70 km west of the economical capital, Cotonou. Malaria transmission in this area can be characterized as hyperendemic, with two peaks during the rainy seasons (April to July, September to November), and an entomological inoculation rate estimated at 35 to 60 infective bites per person per year (13). The STOPPAM study design has been described in detail elsewhere (37).…”

“…With an annual estimate of 50 million or more mothers at risk, pregnancy-associated malaria (PAM) due to Plasmodium falciparum is a well-recognized and well-described example of such an infection, representing a major public health burden measurable by the adverse pregnancy outcomes it causes (reviewed in references [6][7][8][9][10]. Quite apart from the association between PAM and low birth weight and the poor prognosis of survival that goes with it, a number of studies have documented the increased susceptibility to malaria of infants born to mothers with P. falciparum infection detected at delivery (11)(12)(13)(14)(15). PAM has also recently been shown to be associated with an increased risk of fever episodes of nonmalarial causes in infancy (16).…”

Pregnancy-associated malaria and malaria in infants: an old problem with present consequences

“…Congenital malaria rates range between 0.83 and 5.96% [17,25-29] in recent epidemiological studies. The introduction of molecular techniques has increased the detection of cord blood parasitaemia raising prevalence rates to 33% [30].…”

“…A more recent study in Mozambique found that infants born to women who had clinical malaria during pregnancy, or acute placental infection, had an increased risk of clinical malaria during infancy (OR = 1.96; 95% CI, 1.13–3.41, and OR = 4.63; 95% CI 2.10–10.24, respectively) [22]. Furthermore, a cohort study conducted in Tori Bossito (Benin) confirmed the link between PM and malaria in infants through consistent entomologic and environmental follow-up [17,23]. The study findings on infants sleeping in a house with an ITN confirmed the link between PM and malaria controlled for transmission intensity, seasonality, number of anopheles, antenatal care (ANC) visits, and maternal severe anaemia (AHR = 2.13; 95% CI 1.24–3.67) compared with infants whose mothers did not have placental malaria at delivery.…”