Women Exposed to ‘P. falciparum’ Develop Mechanisms that Mitigate the Impact of Infection in Pregnancy

 The health impact of malaria in pregnancy is less severe in women living in high transmission regions, and this is due both to an increased immune response to the parasite (resistance) and to mechanisms that limit tissue damage associated to the infection (tolerance). These are the conclusions of a study led by ISGlobal, an institution supported by the “la Caixa” Foundation, and published in BMC Medicine. The results show that women exposed to the parasite develop mechanisms that mitigate the consequences of infection and suggest that when transmission intensity levels decrease, the adverse impact of malaria in pregnancy increases. 

Antibodies against the VAR2CSA protein of the malaria parasite Plasmodium falciparum play a protective role during pregnancy by preventing placental colonization by the parasite. This immune response (resistance) also reduces parasite densities below the detection limit by microscopy (submicroscopic infections). In addition, infected hosts can also limit parasite-induced damage without necessarily limiting the infection (parasite tolerance). Both resistance and tolerance determine disease progression and severity. However, it is still not clear whether one leads to another or whether they exist independently, especially among pregnant women.  

The aim of this study was to assess the clinical impact of P. falciparum infection in more than 1,700 pregnant women from four Sub-Saharan African countries with different malaria transmission intensities.  The team measured parasite prevalence (by molecular methods) and determined the proportion of submicroscopic infections and antibody levels (as indicators of resistance) and the relationship between parasite density and maternal haemoglobin levels and birthweight (as indicators of tolerance).   

The results indicate that Benin was the country with highest parasite prevalence (41%) and highest percentage of submicroscopic infections. In contrast, women from Mozambique, where prevalence is lowest (6%), had higher parasite densities and increased risk of premature birth. These results indicate that both resistance and parasite tolerance decrease in regions of low parasite transmission. They also suggest that the reduced severity of infections in women from highly endemic regions is not only mediated by the immune response to the parasite but also by mechanisms that prevent damage induced by the infection (tolerance).  

“We provide evidence that pregnant women exposed to the parasite develop mechanisms to minimise disease pathology, which together with immune responses can reduce the adverse impact of malaria in pregnancy” says Alfredo Mayor, coordinator of the study. “Distinguishing these two types of defence (resistance and tolerance) is important to understand how reductions in transmission intensity affect malaria disease” he adds. 

Reference:

Ndam NT, Mbuba E, González R, et al. Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities. BMC Medicine.  2017 Jul 17;15(1):130.