Abstract
BackgroundPregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance.Methodology/FindingsHere we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r2 = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350×106 CD4+ T- cells/L having less opsonising antibodies (coef: −11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia.Conclusions/SignificanceThis flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV are indicated.
Highlights
In malaria-endemic areas, pregnancy increases susceptibility to infections by the malaria parasite Plasmodium falciparum
In this study an improved, high-throughput method has been developed in order to more accurately and rapidly estimate Fc-receptor mediated phagocytosis induced by P. falciparum malaria-specific antibodies
Such a method facilitates the measurement of functional antibodies to malaria variant surface antigens (VSA) in large sample sets
Summary
In malaria-endemic areas, pregnancy increases susceptibility to infections by the malaria parasite Plasmodium falciparum. During pregnancy the placenta expresses and exposes to the maternal blood circulation chondroitin sulphate A (CSA) and this is one of the favoured receptors for the binding of red cells infected with parasites expressing pregnancy-associated variant surface antigens (VSA) [4]. Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance
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