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Development and validation of serological markers for detecting recent Plasmodium vivax infection

Rhea Longley 1, 2, 3 Michael White 4 Eizo Takashima 5 Jessica Brewster 1 Masayuki Morita 5 Fumie Matsuura 6 Thomas Obadia 4, 7 Zoe Liu 1, 2 Connie Li-Wai-Suen 1, 2 Wai-Hong Tham 2, 1 Julie Healer 2, 1 Christèle Huon 8 Chetan Chitnis 8 Wang Nguitragool 3 Wuelton Monteiro 9, 10 Carla Proietti 11, 12 Denise Doolan 11, 12 Andre Siqueira 13 Xavier Ding 14 Iveth Gonzalez 14 James Kazura 15 Marcus Lacerda 16 Jetsumon Sattabongkot 3 Takafumi Tsuboi 5 Ivo Mueller 1, 2, 4, *
* Corresponding author
1 WEHI - The Walter and Eliza Hall Institute of Medical Research
2 University of Melbourne
3 Mahidol University [Bangkok]
4 Malaria : parasites et hôtes - Malaria : parasites and hosts
5 Ehime University [Matsuyama]
6 CellFree Sciences Co., Ltd.
7 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
8 Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines
9 FMT-HVD - Fundação de Medicina Tropical Doutor Heitor Vieira Dourado
10 UEA - Universidade do Estado do Amazonas
11 JCU - James Cook University
12 Queensland Institute of Medical Research
13 FIOCRUZ - Fundação Oswaldo Cruz
14 FIND - Foundation for Innovative New Diagnostics
15 Center for Global Health and Diseases
16 ILMD - Instituto Leônidas e Maria Deane - Fiocruz Amazônia [Manaus, Brésil]
Abstract : A major gap in the Plasmodium vivax elimination toolkit is the identification of individuals carrying clinically silent and undetectable liver-stage parasites, called hypnozoites. This study developed a panel of serological exposure markers capable of classifying individuals with recent P. vivax infections who have a high likelihood of harboring hypnozoites. We measured IgG antibody responses to 342 P. vivax proteins in longitudinal clinical cohorts conducted in Thailand and Brazil and identified candidate serological markers of exposure. Candidate markers were validated using samples from year-long observational cohorts conducted in Thailand, Brazil and the Solomon Islands and antibody responses to eight P. vivax proteins classified P. vivax infections in the previous 9 months with 80% sensitivity and specificity. Mathematical models demonstrate that a serological testing and treatment strategy could reduce P. vivax prevalence by 59-69%. These eight antibody responses can serve as a biomarker, identifying individuals who should be targeted with anti-hypnozoite therapy.
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Rhea Longley, Michael White, Eizo Takashima, Jessica Brewster, Masayuki Morita, et al.. Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nature Medicine, Nature Publishing Group, 2020, 26 (5), pp.741-749. ⟨10.1038/s41591-020-0841-4⟩. ⟨pasteur-02612720⟩

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