Low antibody levels to pregnancy-specific malaria antigens and heightened cytokine responses associated with severe malaria in pregnancy.

BACKGROUND: Pregnant women living in unstable malaria transmission settings may develop severe malaria (SM). The pathogenesis of SM in pregnancy is poorly understood. METHODS: To determine whether SM in pregnancy is associated with lower malarial antibody responses and higher cytokine responses, plasma samples were collected from 121 Sudanese pregnant women of whom 39 were diagnosed with SM. Antibodies to pregnancy-specific and non-pregnancy-specific Plasmodium falciparum variant surface antigens (VSA) and concentrations of cytokines TNF, IFNγ, IL-1ß, IL-6, IL-8 and IL-10 were measured. RESULTS: Pregnant women with SM demonstrated significantly lower antibody levels to pregnancy-specific VSA (P = .020) and higher plasma IFNγ (P = .020), IL-10 (P = .0002) and IL-6 levels (P < .0001) than uninfected pregnant women. Concentrations of inflammatory cytokines IL-1ß (P = .001), IL-6 (P = .004) and IL-8 (P = .020) were inversely correlated with antibodies to VAR2CSA-DBL5 in pregnant women with SM. Lower haemoglobin levels and higher parasite densities were associated with lack of pregnancy-specific antibodies (P = .028) and higher levels of inflammatory cytokines, in particular IL-6 and IL-8. CONCLUSIONS: Pregnant women with SM lack pregnancy-specific malaria immunity, and this correlates with heightened inflammatory cytokine concentrations, low haemoglobin levels and high parasite density, suggesting that failure of antibody to control parasitaemia may contribute to SM pathogenesis.

Acute-phase proteins in pregnant Sudanese women with severe Plasmodium falciparum malaria.

A case-control study was carried out in Kassala and Medani Maternity Hospitals in Sudan to investigate acute-phase proteins [haptoglobin, C-reactive protein (CRP), ferritin and albumin] in three groups of pregnant women (32 in each arm) comprising those with severe Plasmodium falciparum malaria or uncomplicated P. falciparum malaria and healthy controls. Whilst there was no significant difference in the levels of albumin and haptoglobin, ferritin and CRP levels were significantly higher in pregnant women with severe P. falciparum malaria. There were significant positive correlations between parasite count and haptoglobin, and medium positive correlations between parasite count and CRP.