VAR2CSA Serology to Detect Plasmodium Falciparum Transmission Patterns in Pregnancy

Overview

Journal Emerg Infect Dis

Specialty Infectious Diseases

Date 2019 Sep 21

PMID 31538557

Citations 12

Authors

Ana Maria Fonseca

Raquel Gonzalez

Azucena Bardaji

Chenjerai Jairoce

Maria Ruperez

Alfons Jimenez

Llorenc Quinto

Pau Cistero

Anifa Vala

Charfudin Sacoor

Himanshu Gupta

Jennifer Hegewisch-Taylor

Joe Brew

Nicaise Tuikue Ndam

Simon Kariuki

Marta Lopez

Carlota Dobano

Chetan E Chitnis

Peter Ouma

Michael Ramharter

Salim Abdulla

John J Aponte

Achille Massougbodji

Valerie Briand

Ghyslain Mombo-Ngoma

Meghna Desai

Michel Cot

Arsenio Nhacolo

Esperanca Sevene

Eusebio Macete

Clara Menendez

Alfredo Mayor

Affiliations

Soon will be listed here.

Abstract

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of <2 years. Seroprevalence against these peptides reflected declines and rebounds of transmission in southern Mozambique during 2004-2012, reduced exposure associated with use of preventive measures during pregnancy, and local clusters of transmission that were missed by detection of P. falciparum infections. These data suggest that VAR2CSA serology can provide a useful adjunct for the fine-scale estimation of the malaria burden among pregnant women over time and space.

Citing Articles

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References

Bejon P, Williams T, Liljander A, Noor A, Wambua J, Ogada E . Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya. PLoS Med. 2010; 7(7):e1000304. PMC: 2897769. DOI: 10.1371/journal.pmed.1000304. View

Doritchamou J, Sabbagh A, Jespersen J, Renard E, Salanti A, Nielsen M . Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA. PLoS One. 2015; 10(9):e0137695. PMC: 4579133. DOI: 10.1371/journal.pone.0137695. View

Fowkes F, McGready R, Cross N, Hommel M, Simpson J, Elliott S . New insights into acquisition, boosting, and longevity of immunity to malaria in pregnant women. J Infect Dis. 2012; 206(10):1612-21. PMC: 3475637. DOI: 10.1093/infdis/jis566. View

Sepulveda N, Stresman G, White M, Drakeley C . Current Mathematical Models for Analyzing Anti-Malarial Antibody Data with an Eye to Malaria Elimination and Eradication. J Immunol Res. 2016; 2015:738030. PMC: 4684866. DOI: 10.1155/2015/738030. View

Fried M, Duffy P . Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996; 272(5267):1502-4. DOI: 10.1126/science.272.5267.1502. View

Aitken E, Mbewe B, Luntamo M, Kulmala T, Beeson J, Ashorn P . Antibody to P. falciparum in pregnancy varies with intermittent preventive treatment regime and bed net use. PLoS One. 2012; 7(1):e29874. PMC: 3267709. DOI: 10.1371/journal.pone.0029874. View

Andersen P, Nielsen M, Resende M, Rask T, Dahlback M, Theander T . Structural insight into epitopes in the pregnancy-associated malaria protein VAR2CSA. PLoS Pathog. 2008; 4(2):e42. PMC: 2242842. DOI: 10.1371/journal.ppat.0040042. View

Ndam N, Mbuba E, Gonzalez R, Cistero P, Kariuki S, Sevene E . Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities. BMC Med. 2017; 15(1):130. PMC: 5513247. DOI: 10.1186/s12916-017-0893-6. View

Brabin B, Romagosa C, Abdelgalil S, Menendez C, Verhoeff F, McGready R . The sick placenta-the role of malaria. Placenta. 2004; 25(5):359-78. DOI: 10.1016/j.placenta.2003.10.019. View

10.

Mogeni P, Omedo I, Nyundo C, Kamau A, Noor A, Bejon P . Effect of transmission intensity on hotspots and micro-epidemiology of malaria in sub-Saharan Africa. BMC Med. 2017; 15(1):121. PMC: 5492887. DOI: 10.1186/s12916-017-0887-4. View

11.

Willilo R, Molteni F, Mandike R, Mugalura F, Mutafungwa A, Thadeo A . Pregnant women and infants as sentinel populations to monitor prevalence of malaria: results of pilot study in Lake Zone of Tanzania. Malar J. 2016; 15(1):392. PMC: 4966757. DOI: 10.1186/s12936-016-1441-0. View

12.

Gonzalez R, Desai M, Macete E, Ouma P, Kakolwa M, Abdulla S . Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial. PLoS Med. 2014; 11(9):e1001735. PMC: 4172537. DOI: 10.1371/journal.pmed.1001735. View

13.

Nunes-Silva S, Gangnard S, Vidal M, Vuchelen A, Dechavanne S, Chan S . Llama immunization with full-length VAR2CSA generates cross-reactive and inhibitory single-domain antibodies against the DBL1X domain. Sci Rep. 2014; 4:7373. PMC: 5376981. DOI: 10.1038/srep07373. View

14.

Fonseca A, Quinto L, Jimenez A, Gonzalez R, Bardaji A, Maculuve S . Multiplexing detection of IgG against Plasmodium falciparum pregnancy-specific antigens. PLoS One. 2017; 12(7):e0181150. PMC: 5513451. DOI: 10.1371/journal.pone.0181150. View

15.

Menendez C, Bardaji A, Sigauque B, Romagosa C, Sanz S, Serra-Casas E . A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic. PLoS One. 2008; 3(4):e1934. PMC: 2277457. DOI: 10.1371/journal.pone.0001934. View

16.

Welch R, Anderson B, Litwin C . Rapid immunochromatographic strip test for detection of anti-K39 immunoglobulin G antibodies for diagnosis of visceral leishmaniasis. Clin Vaccine Immunol. 2008; 15(9):1483-4. PMC: 2546669. DOI: 10.1128/CVI.00174-08. View

17.

Naniche D, Serra-Casas E, Bardaji A, Quinto L, Dobano C, Sigauque B . Reduction of antimalarial antibodies by HIV infection is associated with increased risk of Plasmodium falciparum cord blood infection. J Infect Dis. 2012; 205(4):568-77. DOI: 10.1093/infdis/jir815. View

18.

Drakeley C, Cook J . Chapter 5. Potential contribution of sero-epidemiological analysis for monitoring malaria control and elimination: historical and current perspectives. Adv Parasitol. 2009; 69:299-352. DOI: 10.1016/S0065-308X(09)69005-9. View

19.

Ataide R, Mayor A, Rogerson S . Malaria, primigravidae, and antibodies: knowledge gained and future perspectives. Trends Parasitol. 2014; 30(2):85-94. DOI: 10.1016/j.pt.2013.12.007. View

20.

Salanti A, Staalsoe T, Lavstsen T, Jensen A, Sowa M, Arnot D . Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol. 2003; 49(1):179-91. DOI: 10.1046/j.1365-2958.2003.03570.x. View