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Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand

Thailand is aiming for malaria elimination by the year 2030. However, the high proportion of asymptomatic infections and the presence of the hidden hypnozoite stage of Plasmodium vivax are impeding these efforts. We hypothesized that a validated surveillance tool utilizing serological markers of rec...

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Autores principales: Chotirat, Sadudee, Nekkab, Narimane, Kumpitak, Chalermpon, Hietanen, Jenni, White, Michael T., Kiattibutr, Kirakorn, Sa-angchai, Patiwat, Brewster, Jessica, Schoffer, Kael, Takashima, Eizo, Tsuboi, Takafumi, Harbers, Matthias, Chitnis, Chetan E., Healer, Julie, Tham, Wai-Hong, Nguitragool, Wang, Mueller, Ivo, Sattabongkot, Jetsumon, Longley, Rhea J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279756/
https://www.ncbi.nlm.nih.gov/pubmed/34276583
http://dx.doi.org/10.3389/fmicb.2021.643501
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author Chotirat, Sadudee
Nekkab, Narimane
Kumpitak, Chalermpon
Hietanen, Jenni
White, Michael T.
Kiattibutr, Kirakorn
Sa-angchai, Patiwat
Brewster, Jessica
Schoffer, Kael
Takashima, Eizo
Tsuboi, Takafumi
Harbers, Matthias
Chitnis, Chetan E.
Healer, Julie
Tham, Wai-Hong
Nguitragool, Wang
Mueller, Ivo
Sattabongkot, Jetsumon
Longley, Rhea J.
author_facet Chotirat, Sadudee
Nekkab, Narimane
Kumpitak, Chalermpon
Hietanen, Jenni
White, Michael T.
Kiattibutr, Kirakorn
Sa-angchai, Patiwat
Brewster, Jessica
Schoffer, Kael
Takashima, Eizo
Tsuboi, Takafumi
Harbers, Matthias
Chitnis, Chetan E.
Healer, Julie
Tham, Wai-Hong
Nguitragool, Wang
Mueller, Ivo
Sattabongkot, Jetsumon
Longley, Rhea J.
author_sort Chotirat, Sadudee
collection PubMed
description Thailand is aiming for malaria elimination by the year 2030. However, the high proportion of asymptomatic infections and the presence of the hidden hypnozoite stage of Plasmodium vivax are impeding these efforts. We hypothesized that a validated surveillance tool utilizing serological markers of recent exposure to P. vivax infection could help to identify areas of ongoing transmission. The objective of this exploratory study was to assess the ability of P. vivax serological exposure markers to detect residual transmission “hot-spots” in Western Thailand. Total IgG levels were measured against a panel of 23 candidate P. vivax serological exposure markers using a multiplexed bead-based assay. A total of 4,255 plasma samples from a cross-sectional survey conducted in 2012 of endemic areas in the Kanchanaburi and Ratchaburi provinces were assayed. We compared IgG levels with multiple epidemiological factors that are associated with an increased risk of P. vivax infection in Thailand, including age, gender, and spatial location, as well as Plasmodium infection status itself. IgG levels to all proteins were significantly higher in the presence of a P. vivax infection (n = 144) (T-test, p < 0.0001). Overall seropositivity rates varied from 2.5% (PVX_097625, merozoite surface protein 8) to 16.8% (PVX_082670, merozoite surface protein 7), with 43% of individuals seropositive to at least 1 protein. Higher IgG levels were associated with older age (>18 years, p < 0.05) and males (17/23 proteins, p < 0.05), supporting the paradigm that men have a higher risk of infection than females in this setting. We used a Random Forests algorithm to predict which individuals had exposure to P. vivax parasites in the last 9-months, based on their IgG antibody levels to a panel of eight previously validated P. vivax proteins. Spatial clustering was observed at the village and regional level, with a moderate correlation between PCR prevalence and sero-prevalence as predicted by the algorithm. Our data provides proof-of-concept for application of such surrogate markers as evidence of recent exposure in low transmission areas. These data can be used to better identify geographical areas with asymptomatic infection burdens that can be targeted in elimination campaigns.
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spelling pubmed-82797562021-07-15 Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand Chotirat, Sadudee Nekkab, Narimane Kumpitak, Chalermpon Hietanen, Jenni White, Michael T. Kiattibutr, Kirakorn Sa-angchai, Patiwat Brewster, Jessica Schoffer, Kael Takashima, Eizo Tsuboi, Takafumi Harbers, Matthias Chitnis, Chetan E. Healer, Julie Tham, Wai-Hong Nguitragool, Wang Mueller, Ivo Sattabongkot, Jetsumon Longley, Rhea J. Front Microbiol Microbiology Thailand is aiming for malaria elimination by the year 2030. However, the high proportion of asymptomatic infections and the presence of the hidden hypnozoite stage of Plasmodium vivax are impeding these efforts. We hypothesized that a validated surveillance tool utilizing serological markers of recent exposure to P. vivax infection could help to identify areas of ongoing transmission. The objective of this exploratory study was to assess the ability of P. vivax serological exposure markers to detect residual transmission “hot-spots” in Western Thailand. Total IgG levels were measured against a panel of 23 candidate P. vivax serological exposure markers using a multiplexed bead-based assay. A total of 4,255 plasma samples from a cross-sectional survey conducted in 2012 of endemic areas in the Kanchanaburi and Ratchaburi provinces were assayed. We compared IgG levels with multiple epidemiological factors that are associated with an increased risk of P. vivax infection in Thailand, including age, gender, and spatial location, as well as Plasmodium infection status itself. IgG levels to all proteins were significantly higher in the presence of a P. vivax infection (n = 144) (T-test, p < 0.0001). Overall seropositivity rates varied from 2.5% (PVX_097625, merozoite surface protein 8) to 16.8% (PVX_082670, merozoite surface protein 7), with 43% of individuals seropositive to at least 1 protein. Higher IgG levels were associated with older age (>18 years, p < 0.05) and males (17/23 proteins, p < 0.05), supporting the paradigm that men have a higher risk of infection than females in this setting. We used a Random Forests algorithm to predict which individuals had exposure to P. vivax parasites in the last 9-months, based on their IgG antibody levels to a panel of eight previously validated P. vivax proteins. Spatial clustering was observed at the village and regional level, with a moderate correlation between PCR prevalence and sero-prevalence as predicted by the algorithm. Our data provides proof-of-concept for application of such surrogate markers as evidence of recent exposure in low transmission areas. These data can be used to better identify geographical areas with asymptomatic infection burdens that can be targeted in elimination campaigns. Frontiers Media S.A. 2021-06-29 /pmc/articles/PMC8279756/ /pubmed/34276583 http://dx.doi.org/10.3389/fmicb.2021.643501 Text en Copyright © 2021 Chotirat, Nekkab, Kumpitak, Hietanen, White, Kiattibutr, Sa-angchai, Brewster, Schoffer, Takashima, Tsuboi, Harbers, Chitnis, Healer, Tham, Nguitragool, Mueller, Sattabongkot and Longley. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Chotirat, Sadudee
Nekkab, Narimane
Kumpitak, Chalermpon
Hietanen, Jenni
White, Michael T.
Kiattibutr, Kirakorn
Sa-angchai, Patiwat
Brewster, Jessica
Schoffer, Kael
Takashima, Eizo
Tsuboi, Takafumi
Harbers, Matthias
Chitnis, Chetan E.
Healer, Julie
Tham, Wai-Hong
Nguitragool, Wang
Mueller, Ivo
Sattabongkot, Jetsumon
Longley, Rhea J.
Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title_full Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title_fullStr Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title_full_unstemmed Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title_short Application of 23 Novel Serological Markers for Identifying Recent Exposure to Plasmodium vivax Parasites in an Endemic Population of Western Thailand
title_sort application of 23 novel serological markers for identifying recent exposure to plasmodium vivax parasites in an endemic population of western thailand
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279756/
https://www.ncbi.nlm.nih.gov/pubmed/34276583
http://dx.doi.org/10.3389/fmicb.2021.643501
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