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

BMC Medicine

Research Article

Anifa Vala¹  Eusebio Macete¹  Sonia Maculuve¹  Arsenio Nhacolo¹  Esperança Sevene²  Achille Massougbodji³  Llorenç Quintó³  Pau Cisteró⁴  Alfons Jiménez⁵  Clara Menéndez⁶  María Rupérez⁶  John J. Aponte⁶  Raquel González⁶  Alfredo Mayor⁶  Ana Maria Fonseca⁷  Emmanuel Mbuba⁸  Michel Cot⁹  Valerie Briand⁹  Nicaise Tuikue Ndam^1,10  Ghyslain Mombo-Ngoma^1,11  Peter G. Kremsner^1,11  Michael Ramharter^1,12  Simon Kariuki^1,13  Peter Ouma^1,13  Meghna Desai^1,14 

[1] Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique;Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique;Universidade Eduardo Mondlane, Maputo, Mozambique;Faculté des Sciences de la Santé (FSS), Université d’Aboméy Calavi, Cotonou, Benin;ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain;ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain;CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain;Centro de Investigação em Saúde da Manhiça (CISM), Maputo, Mozambique;ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain;Graduate Program in Areas of Basic and Applied Biology, Universidade do Porto, Porto, Portugal;Ifakara Health Institute (IHI), Bagamoyo Research and Training Centre (BRTC), Bagamoyo, Tanzania;Institut de Recherche pour le Développement (IRD), Paris, France;Institut de Recherche pour le Développement (IRD), Paris, France;COMUE Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France;Faculté des Sciences de la Santé (FSS), Université d’Aboméy Calavi, Cotonou, Benin;Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany;Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon;Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany;Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria;Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon;Kenya Medical Research Institute (KEMRI)/Centre for Global Health Research, Kisumu, Kenya;Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA;

关键词: Malaria;    Pregnancy;    Immunity;    Resistance;    Tolerance;   

DOI  :  10.1186/s12916-017-0893-6

 received in 2017-02-22, accepted in 2017-06-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundResistance 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.MethodsP. 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.ResultsP. 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).ConclusionsThe 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 registrationClinicalTrials.gov NCT00811421. Registered 18 December 2008.

【 授权许可】

CC BY   
© The Author(s). 2017