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

Rhea J. Longley; Michael T. White; Eizo Takashima; Jessica Brewster; Masayuki Morita; Matthias Harbers; Thomas Obadia; Leanne J. Robinson; Fumie Matsuura; Zoe S.J. Liu; Connie S.N. Li-Wai-Suen; Wai Hong Tham; Julie Healer; Christele Huon; Chetan E. Chitnis; Wang Nguitragool; Wuelton Monteiro; Carla Proietti; Denise L. Doolan; Andre M. Siqueira; Xavier C. Ding; Iveth J. Gonzalez; James Kazura; Marcus Lacerda; Jetsumon Sattabongkot; Takafumi Tsuboi; Ivo Mueller

doi:10.1038/s41591-020-0841-4

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

Rhea J. Longley, Michael T. White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Thomas Obadia, Leanne J. Robinson, Fumie Matsuura, Zoe S.J. Liu, Connie S.N. Li-Wai-Suen, Wai Hong Tham, Julie Healer, Christele Huon, Chetan E. Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L. Doolan, Andre M. SiqueiraXavier C. Ding, Iveth J. Gonzalez, James Kazura, Marcus Lacerda, Jetsumon Sattabongkot, Takafumi Tsuboi, Ivo Mueller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

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.

Original language	English
Pages (from-to)	741-749
Number of pages	9
Journal	Nature Medicine
Volume	26
Issue number	5
DOIs	https://doi.org/10.1038/s41591-020-0841-4
Publication status	Published - 1 May 2020
Externally published	Yes

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Longley, R. J., White, M. T., Takashima, E., Brewster, J., Morita, M., Harbers, M., Obadia, T., Robinson, L. J., Matsuura, F., Liu, Z. S. J., Li-Wai-Suen, C. S. N., Tham, W. H., Healer, J., Huon, C., Chitnis, C. E., Nguitragool, W., Monteiro, W., Proietti, C., Doolan, D. L., ... Mueller, I. (2020). Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nature Medicine, 26(5), 741-749. https://doi.org/10.1038/s41591-020-0841-4

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title = "Development and validation of serological markers for detecting recent Plasmodium vivax infection",

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.",

author = "Longley, {Rhea J.} and White, {Michael T.} and Eizo Takashima and Jessica Brewster and Masayuki Morita and Matthias Harbers and Thomas Obadia and Robinson, {Leanne J.} and Fumie Matsuura and Liu, {Zoe S.J.} and Li-Wai-Suen, {Connie S.N.} and Tham, {Wai Hong} and Julie Healer and Christele Huon and Chitnis, {Chetan E.} and Wang Nguitragool and Wuelton Monteiro and Carla Proietti and Doolan, {Denise L.} and Siqueira, {Andre M.} and Ding, {Xavier C.} and Gonzalez, {Iveth J.} and James Kazura and Marcus Lacerda and Jetsumon Sattabongkot and Takafumi Tsuboi and Ivo Mueller",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2020",

month = may,

day = "1",

doi = "10.1038/s41591-020-0841-4",

language = "English",

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Longley, RJ, White, MT, Takashima, E, Brewster, J, Morita, M, Harbers, M, Obadia, T, Robinson, LJ, Matsuura, F, Liu, ZSJ, Li-Wai-Suen, CSN, Tham, WH, Healer, J, Huon, C, Chitnis, CE, Nguitragool, W, Monteiro, W, Proietti, C, Doolan, DL, Siqueira, AM, Ding, XC, Gonzalez, IJ, Kazura, J, Lacerda, M, Sattabongkot, J, Tsuboi, T & Mueller, I 2020, 'Development and validation of serological markers for detecting recent Plasmodium vivax infection', Nature Medicine, vol. 26, no. 5, pp. 741-749. https://doi.org/10.1038/s41591-020-0841-4

TY - JOUR

T1 - Development and validation of serological markers for detecting recent Plasmodium vivax infection

AU - Longley, Rhea J.

AU - White, Michael T.

AU - Takashima, Eizo

AU - Brewster, Jessica

AU - Morita, Masayuki

AU - Harbers, Matthias

AU - Obadia, Thomas

AU - Robinson, Leanne J.

AU - Matsuura, Fumie

AU - Liu, Zoe S.J.

AU - Li-Wai-Suen, Connie S.N.

AU - Tham, Wai Hong

AU - Healer, Julie

AU - Huon, Christele

AU - Chitnis, Chetan E.

AU - Nguitragool, Wang

AU - Monteiro, Wuelton

AU - Proietti, Carla

AU - Doolan, Denise L.

AU - Siqueira, Andre M.

AU - Ding, Xavier C.

AU - Gonzalez, Iveth J.

AU - Kazura, James

AU - Lacerda, Marcus

AU - Sattabongkot, Jetsumon

AU - Tsuboi, Takafumi

AU - Mueller, Ivo

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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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U2 - 10.1038/s41591-020-0841-4

DO - 10.1038/s41591-020-0841-4

M3 - Article

C2 - 32405064

AN - SCOPUS:85084626398

SN - 1078-8956

VL - 26

SP - 741

EP - 749

JO - Nature Medicine

JF - Nature Medicine

IS - 5

ER -

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

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