Mouse Anti-Sheep Erythrocyte Hybridoma [TSCD-SQ9-3-5]

BackgroundMalaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania.MethodsWe recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5kg), prematurity (live birth below 37weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes.ResultsAmong 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR)=1.75; 95% confidence interval (CI): 1.05-2.92; P=0.03) and in women who were anemic (OR=1.59; 95% CI: 1.20-2.11; P=0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR=0.33; 95% CI: 0.17-0.62; P=0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR=1.48; 95% CI: 1.03-2.11; P=0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR=1.30, 95% CI: 0.98-1.72, P=0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR=0.61, 95% CI: 0.43-0.88, P=0.01). Placental malaria was not associated with low birth weight or prematurity.ConclusionMalaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.

The mutation responsible for Duffy negativity, which impedesPlasmodium vivaxinfection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethalP.falciparumhave not succeeded in malarious zones. Here we present an evolutionary-epidemiological model of malaria which demonstrates that if adaptive immunity against the most virulent effects of malaria is gained rapidly by the host, mutations which prevent infectionper seare unlikely to succeed. Our results (i) explain the rarity of strain-transcendingP.falciparuminfection blocking adaptations in humans; (ii) make the surprising prediction that mutations which blockP.falciparuminfection are most likely to be found in populations experiencing low or infrequent malaria transmission, and (iii) predict that immunity against some of the virulent effects ofP.vivaxmalaria may be built up over the course of many infections. Author summary Malaria has profoundly influenced human evolution. However, humans have adapted to two major malaria parasites,Plasmodium falciparumandPlasmodium vivax, by strikingly different strategies. The Duffy negative blood group impairsP.vivaxentry to red blood cells and reduces the chance of becoming infected. No equivalent blocking adaption againstP.falciparumhas evolved to become widespread, despite the existence of candidate mutations. We show that rapidly gained adaptive immunity to malaria virulence limits the success of infection blocking mutations. This could account for humans' contrasting adaptations toP.falciparumandP.vivax. Our results highlight the critical role of adaptive immunity in determining how vertebrate hosts evolve in response to pathogen selection, and provide a new framework within which to understand this process.