The epidemiology and consequences of maternal malaria: a review of immunological basis

Abstract

Millions of women who become pregnant in malaria-endemic areas are at increased risk of contracting malaria infection that jeopardises the outcome of pregnancy. The complication of this infection for mother and baby are considerable. In absence of any other reason, it was thought that the increased risk of infection during pregnancy was related to suppression of pre-existing malaria immunity. Although this concept is plausible, the significantly higher risk of maternal malaria and consequences in primigravidae compared with multigravidae suggests that there are more to mere immunosuppression in pregnancy. The mechanisms underlying some of the striking epidemiological and clinical features of malaria in pregnancy could be related to differences in the strains of parasite populations infecting pregnant women occasioned by the cyto-adherent properties of human placenta, presence or absence of anti-adhesion antibodies acquired from previous pregnancies or the elevated production of some pro-inflammatory cytokines in response to parasitisation of human placenta. Malaria infection of placenta causes a shift from Th2 to Th1 cytokine profile that may be detrimental to pregnancy. The increased susceptibility in the first pregnancy can be explained by the absence of anti-adhesion antibody in the primigravida that is being exposed for the first time to a different strain of malaria parasite sub-population that adhere exclusively to chondroitin sulphate A and hyaluronic acid (HA) in the placenta. In reviewing the epidemiology and consequences of maternal malaria, we have highlighted possible immunological and molecular basis that could account for the higher impact of malaria in pregnancy especially among primigravidae. These factors could be the basis for future research and vaccine formulation.

Introduction

Malaria, the most important parasitic disease of man, is endemic in 103 countries where more than 2000 million people live exposed to the infection (Menendez, 1995). An estimated 300–500 million cases of malaria each year result in about 1–2 million deaths, mainly in children less than 5 years of age living in sub-Saharan Africa (Snow et al., 1999, Snow et al., 2001). Besides children, some 24 million women that become pregnant each year in malaria-endemic regions are at increased risk of being infected with Plasmodium falciparum malaria and its associated complications (McGregor et al., 1983, Steketee et al., 1996b). In some sub-Saharan African countries endemic for malaria, almost half of all primigravidae will be parasitaemic at their first antenatal visit (Menendez, 1995). The complications of these infections, for the mother and baby are considerable and constitute one of Africa's major public health problems. The reasons for the increased susceptibility to malaria in pregnancy and its clinical manifestations are not as straightforward as has been reported previously. The previously held opinion that pregnancy depresses pre-existing immunity (Blacklock and Gordon, 1925, Ibanesebhor and Okolo, 1992) does not explain the differential impact of maternal malaria infection on primigravidae. The available data suggest that several mechanisms could be involved (Scherf et al., 2001, Beeson and Brown, 2002).

An extensive review of available data on immunological basis of the epidemiology and consequences of maternal malaria was carried out with the view of suggesting some therapeutic and control measures in this high-risk group.