Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities

TY - JOUR

T1 - Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities

AU - Ndam, Nicaise Tuikue

AU - Mbuba, Emmanuel

AU - González, Raquel

AU - Cisteró, Pau

AU - Kariuki, Simon

AU - Sevene, Esperança

AU - Rupérez, María

AU - Fonseca, Ana Maria

AU - Vala, Anifa

AU - Maculuve, Sonia

AU - Jiménez, Alfons

AU - Quintó, Llorenç

AU - Ouma, Peter

AU - Ramharter, Michael

AU - Aponte, John J

AU - Nhacolo, Arsenio

AU - Massougbodji, Achille

AU - Briand, Valerie

AU - Kremsner, Peter G

AU - Mombo-Ngoma, Ghyslain

AU - Desai, Meghna

AU - Macete, Eusebio

AU - Cot, Michel

AU - Menéndez, Clara

AU - Mayor, Alfredo

PY - 2017/7/17

Y1 - 2017/7/17

N2 - 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 HIV-uninfected 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.TRIAL REGISTRATION: ClinicalTrials.gov NCT00811421 . Registered 18 December 2008.

AB - 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 HIV-uninfected 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.TRIAL REGISTRATION: ClinicalTrials.gov NCT00811421 . Registered 18 December 2008.

KW - Adult

KW - Delivery, Obstetric

KW - Female

KW - Gabon

KW - HIV Infections/complications

KW - Humans

KW - Infant, Newborn

KW - Kenya

KW - Malaria, Falciparum/epidemiology

KW - Microscopy

KW - Mozambique

KW - Parturition

KW - Placenta

KW - Plasmodium falciparum/immunology

KW - Pregnancy

KW - Pregnancy Complications, Infectious

KW - Pregnancy Outcome

KW - Prevalence

KW - Real-Time Polymerase Chain Reaction

KW - Young Adult

U2 - 10.1186/s12916-017-0893-6

DO - 10.1186/s12916-017-0893-6

M3 - SCORING: Journal article

C2 - 28712360

VL - 15

SP - 130

JO - BMC MED

JF - BMC MED

SN - 1741-7015

IS - 1

ER -