Abstract:
Background: Resistance and tolerance to Plasmodium falciparum can determine the
progression of malaria disease. However, quantitative evidence of tolerance is still
limited. We investigated variations in the adverse impact of P. falciparum infections
among African pregnant women under different intensities of malaria transmission.
Methods: P. falciparum at delivery was assessed by microscopy, quantitative PCR
(qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant
women from Benin, Gabon, Kenya and Mozambique. Resistance was defined by the
proportion of submicroscopic infections and the levels of anti-parasite antibodies
quantified by Luminex, and tolerance by the relationship of pregnancy outcomes with
parasite densities at delivery.
Results: P. falciparum prevalence by qPCR in peripheral and/or placental blood of HIVuninfected Mozambican, Gabonese and Beninese women at delivery was 6% (21/340),
11% (28/257) and 41% (143/349), respectively. The proportion of peripheral
submicroscopic infections was higher in Benin (83%) than in Mozambique (60%) and
Gabon (55%; P = 0.033). Past or chronic placental P. falciparum infection was associated
with an increased risk of preterm birth in Mozambican newborns (OR = 7.05, 95% CI
1.79 to 27.82). Microscopic infections were associated with reductions in haemoglobin
levels at delivery among Mozambican women (-1.17 g/dL, 95% CI -2.09 to -0.24) as
well as with larger drops in haemoglobin levels from recruitment to delivery in
Mozambican (-1.66 g/dL, 95% CI -2.68 to -0.64) and Gabonese (-0.91 g/dL, 95% CI -
1.79 to -0.02) women. Doubling qPCR-peripheral parasite densities in Mozambican
women were associated with decreases in haemoglobin levels at delivery (-0.16 g/dL,
95% CI -0.29 to -0.02) and increases in the drop of haemoglobin levels (-0.29 g/dL, 95%
CI -0.44 to -0.14). Beninese women had higher anti-parasite IgGs than Mozambican
women (P < 0.001). No difference was found in the proportion of submicroscopic
infections nor in the adverse impact of P. falciparum infections in HIV-infected women
from Kenya (P. falciparum prevalence by qPCR: 9%, 32/351) and Mozambique (4%,
15/417).
Conclusions: The lowest levels of resistance and tolerance in pregnant women from
areas of low malaria transmission were accompanied by the largest adverse impact of P.
falciparum infections. Exposure-dependent mechanisms developed by pregnant women
to resist the infection and minimise pathology can reduce malaria-related adverse
outcomes. Distinguishing both types of defences is important to understand how
reductions in transmission can affect malaria disease.