A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir

Dingyin Tao; Brent McGill; Timothy Hamerly; Tamaki Kobayashi; Prachi Khare; Amanda Dziedzic; Tomasz Leski; Andrew Holtz; Bruce Shull; Anne E. Jedlicka; Andrew Walzer; Paul D. Slowey; Christopher C. Slowey; Sandrine E. Nsango; David A. Stenger; Mike Chaponda; Modest Mulenga; Kathryn H. Jacobsen; David J. Sullivan; Sadie J. Ryan; Rashid Ansumana; William J. Moss; Isabelle Morlais; Rhoel R. Dinglasan

doi:10.1126/scitranslmed.aan4479

A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir

Dingyin Tao, Brent McGill, Timothy Hamerly, Tamaki Kobayashi, Prachi Khare, Amanda Dziedzic, Tomasz Leski, Andrew Holtz, Bruce Shull, Anne E. Jedlicka, Andrew Walzer, Paul D. Slowey, Christopher C. Slowey, Sandrine E. Nsango, David A. Stenger, Mike Chaponda, Modest Mulenga, Kathryn H. Jacobsen, David J. Sullivan, Sadie J. RyanRashid Ansumana, William J. Moss, Isabelle Morlais, Rhoel R. Dinglasan

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

Abstract

A large proportion of ongoing malaria parasite transmission is attributed to low-density subclinical infections not readily detected by available rapid diagnostic tests (RDTs) or microscopy. Plasmodium falciparum gametocyte carriage is subclinical, but gametocytemic individuals comprise the parasite reservoir that leads to infection of mosquitoes and local transmission. Effective detection and quantification of these carriers can help advance malaria elimination strategies. However, no point-of-need (PON) RDTs for gametocyte detection exist, much less one that can perform noninvasive sampling of saliva outside a clinical setting. Here, we report on the discovery of 35 parasite markers from which we selected a single candidate for use in a PON RDT. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. The test is capable of identifying submicroscopic carriage in both clinical and nonclinical settings and is compatible with archived saliva samples.

Original language	English (US)
Article number	eaan4479
Journal	Science translational medicine
Volume	11
Issue number	473
DOIs	https://doi.org/10.1126/scitranslmed.aan4479
State	Published - Jan 2 2019
Externally published	Yes

ASJC Scopus subject areas

Medicine(all)

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10.1126/scitranslmed.aan4479

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Tao, D., McGill, B., Hamerly, T., Kobayashi, T., Khare, P., Dziedzic, A., Leski, T., Holtz, A., Shull, B., Jedlicka, A. E., Walzer, A., Slowey, P. D., Slowey, C. C., Nsango, S. E., Stenger, D. A., Chaponda, M., Mulenga, M., Jacobsen, K. H., Sullivan, D. J., ... Dinglasan, R. R. (2019). A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir. Science translational medicine, 11(473), [eaan4479]. https://doi.org/10.1126/scitranslmed.aan4479

A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir. / Tao, Dingyin; McGill, Brent; Hamerly, Timothy; Kobayashi, Tamaki; Khare, Prachi; Dziedzic, Amanda; Leski, Tomasz; Holtz, Andrew; Shull, Bruce; Jedlicka, Anne E.; Walzer, Andrew; Slowey, Paul D.; Slowey, Christopher C.; Nsango, Sandrine E.; Stenger, David A.; Chaponda, Mike; Mulenga, Modest; Jacobsen, Kathryn H.; Sullivan, David J.; Ryan, Sadie J.; Ansumana, Rashid; Moss, William J.; Morlais, Isabelle; Dinglasan, Rhoel R.

In: Science translational medicine, Vol. 11, No. 473, eaan4479, 02.01.2019.

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

Tao, D, McGill, B, Hamerly, T, Kobayashi, T, Khare, P, Dziedzic, A, Leski, T, Holtz, A, Shull, B, Jedlicka, AE, Walzer, A, Slowey, PD, Slowey, CC, Nsango, SE, Stenger, DA, Chaponda, M, Mulenga, M, Jacobsen, KH, Sullivan, DJ, Ryan, SJ, Ansumana, R, Moss, WJ, Morlais, I & Dinglasan, RR 2019, 'A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir', Science translational medicine, vol. 11, no. 473, eaan4479. https://doi.org/10.1126/scitranslmed.aan4479

Tao, Dingyin ; McGill, Brent ; Hamerly, Timothy ; Kobayashi, Tamaki ; Khare, Prachi ; Dziedzic, Amanda ; Leski, Tomasz ; Holtz, Andrew ; Shull, Bruce ; Jedlicka, Anne E. ; Walzer, Andrew ; Slowey, Paul D. ; Slowey, Christopher C. ; Nsango, Sandrine E. ; Stenger, David A. ; Chaponda, Mike ; Mulenga, Modest ; Jacobsen, Kathryn H. ; Sullivan, David J. ; Ryan, Sadie J. ; Ansumana, Rashid ; Moss, William J. ; Morlais, Isabelle ; Dinglasan, Rhoel R. / A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir. In: Science translational medicine. 2019 ; Vol. 11, No. 473.

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title = "A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir",

abstract = "A large proportion of ongoing malaria parasite transmission is attributed to low-density subclinical infections not readily detected by available rapid diagnostic tests (RDTs) or microscopy. Plasmodium falciparum gametocyte carriage is subclinical, but gametocytemic individuals comprise the parasite reservoir that leads to infection of mosquitoes and local transmission. Effective detection and quantification of these carriers can help advance malaria elimination strategies. However, no point-of-need (PON) RDTs for gametocyte detection exist, much less one that can perform noninvasive sampling of saliva outside a clinical setting. Here, we report on the discovery of 35 parasite markers from which we selected a single candidate for use in a PON RDT. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. The test is capable of identifying submicroscopic carriage in both clinical and nonclinical settings and is compatible with archived saliva samples.",

author = "Dingyin Tao and Brent McGill and Timothy Hamerly and Tamaki Kobayashi and Prachi Khare and Amanda Dziedzic and Tomasz Leski and Andrew Holtz and Bruce Shull and Jedlicka, {Anne E.} and Andrew Walzer and Slowey, {Paul D.} and Slowey, {Christopher C.} and Nsango, {Sandrine E.} and Stenger, {David A.} and Mike Chaponda and Modest Mulenga and Jacobsen, {Kathryn H.} and Sullivan, {David J.} and Ryan, {Sadie J.} and Rashid Ansumana and Moss, {William J.} and Isabelle Morlais and Dinglasan, {Rhoel R.}",

note = "Funding Information: The project was funded, in part, by a TEDCO Maryland Innovation Initiative award (120701) and a Bill & Melinda Gates Foundation (OPP 1054413) to R.R.D. T.L., A.H., D.A.S., and R.A. were supported by the Chemical Biological Technologies Directorate from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA). However, any opinions, findings, conclusions, or other recommendations expressed here are those of the authors and do not necessarily reflect the views of the DTRA. Publisher Copyright: Copyright {\textcopyright} 2019 The Authors, some rights reserved.",

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doi = "10.1126/scitranslmed.aan4479",

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AU - Tao, Dingyin

AU - McGill, Brent

AU - Hamerly, Timothy

AU - Kobayashi, Tamaki

AU - Khare, Prachi

AU - Dziedzic, Amanda

AU - Leski, Tomasz

AU - Holtz, Andrew

AU - Shull, Bruce

AU - Jedlicka, Anne E.

AU - Walzer, Andrew

AU - Slowey, Paul D.

AU - Slowey, Christopher C.

AU - Nsango, Sandrine E.

AU - Stenger, David A.

AU - Chaponda, Mike

AU - Mulenga, Modest

AU - Jacobsen, Kathryn H.

AU - Sullivan, David J.

AU - Ryan, Sadie J.

AU - Ansumana, Rashid

AU - Moss, William J.

AU - Morlais, Isabelle

AU - Dinglasan, Rhoel R.

N1 - Funding Information: The project was funded, in part, by a TEDCO Maryland Innovation Initiative award (120701) and a Bill & Melinda Gates Foundation (OPP 1054413) to R.R.D. T.L., A.H., D.A.S., and R.A. were supported by the Chemical Biological Technologies Directorate from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA). However, any opinions, findings, conclusions, or other recommendations expressed here are those of the authors and do not necessarily reflect the views of the DTRA. Publisher Copyright: Copyright © 2019 The Authors, some rights reserved.

PY - 2019/1/2

Y1 - 2019/1/2

N2 - A large proportion of ongoing malaria parasite transmission is attributed to low-density subclinical infections not readily detected by available rapid diagnostic tests (RDTs) or microscopy. Plasmodium falciparum gametocyte carriage is subclinical, but gametocytemic individuals comprise the parasite reservoir that leads to infection of mosquitoes and local transmission. Effective detection and quantification of these carriers can help advance malaria elimination strategies. However, no point-of-need (PON) RDTs for gametocyte detection exist, much less one that can perform noninvasive sampling of saliva outside a clinical setting. Here, we report on the discovery of 35 parasite markers from which we selected a single candidate for use in a PON RDT. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. The test is capable of identifying submicroscopic carriage in both clinical and nonclinical settings and is compatible with archived saliva samples.

AB - A large proportion of ongoing malaria parasite transmission is attributed to low-density subclinical infections not readily detected by available rapid diagnostic tests (RDTs) or microscopy. Plasmodium falciparum gametocyte carriage is subclinical, but gametocytemic individuals comprise the parasite reservoir that leads to infection of mosquitoes and local transmission. Effective detection and quantification of these carriers can help advance malaria elimination strategies. However, no point-of-need (PON) RDTs for gametocyte detection exist, much less one that can perform noninvasive sampling of saliva outside a clinical setting. Here, we report on the discovery of 35 parasite markers from which we selected a single candidate for use in a PON RDT. We performed a cross-sectional, multi-omics study of saliva from 364 children with subclinical infection in Cameroon and Zambia and produced a prototype saliva-based PON lateral flow immunoassay test for P. falciparum gametocyte carriers. The test is capable of identifying submicroscopic carriage in both clinical and nonclinical settings and is compatible with archived saliva samples.

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A saliva-based rapid test to quantify the infectious subclinical malaria parasite reservoir

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