Population heterogeneity in Plasmodium vivax relapse risk

Eva Stadler; Deborah Cromer; Somya Mehra; Adeshina I. Adekunle; Jennifer A. Flegg; Nicholas M. Anstey; James A. Watson; Cindy S. Chu; Ivo Mueller; Leanne J. Robinson; Timothy E. Schlub; Miles P. Davenport; David S. Khoury

doi:10.1371/journal.pntd.0010990

Population heterogeneity in Plasmodium vivax relapse risk

Eva Stadler, Deborah Cromer, Somya Mehra, Adeshina I. Adekunle, Jennifer A. Flegg, Nicholas M. Anstey, James A. Watson, Cindy S. Chu, Ivo Mueller, Leanne J. Robinson, Timothy E. Schlub, Miles P. Davenport, David S. Khoury

Global and Tropical Health

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

10 Citations (Scopus)

64 Downloads (Pure)

Abstract

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P. vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P. vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P. vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P. vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.

Original language	English
Article number	e0010990
Journal	PLoS Neglected Tropical Diseases
Volume	16
Issue number	12
DOIs	https://doi.org/10.1371/journal.pntd.0010990
Publication status	Published - 1 Dec 2022

Bibliographical note

Funding Information:
This work was funded by the Australian Research Council (ARC; https://www.arc.gov.au) (grants DP120100064 & DP180103875 (to DSK, MPD, DC) and DP200100747 (to JAF)) and the National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au) of Australia (grants 1082022 (to MPD, DC), 1173528 (to DC), 1141921 (to DSK), 1080001 and 1173027 (to MPD) and Senior Principal Research Fellowship 1135820 (to NMA)). LJR is supported by NHMRC (https://www.nhmrc.gov.au) Career Development Fellowship (GNT1161627). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022 Stadler et al.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pntd.0010990

67542972-oaFinal published version, 2.66 MBLicence: CC BY
67542972-oaE-pub ahead of print, 2.66 MBLicence: CC BY

Cite this

@article{5fd7536b380d4d37a84e26d1b4e176ef,

title = "Population heterogeneity in Plasmodium vivax relapse risk",

abstract = "A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P. vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P. vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P. vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P. vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.",

author = "Eva Stadler and Deborah Cromer and Somya Mehra and Adekunle, {Adeshina I.} and Flegg, {Jennifer A.} and Anstey, {Nicholas M.} and Watson, {James A.} and Chu, {Cindy S.} and Ivo Mueller and Robinson, {Leanne J.} and Schlub, {Timothy E.} and Davenport, {Miles P.} and Khoury, {David S.}",

note = "Funding Information: This work was funded by the Australian Research Council (ARC; https://www.arc.gov.au) (grants DP120100064 & DP180103875 (to DSK, MPD, DC) and DP200100747 (to JAF)) and the National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au) of Australia (grants 1082022 (to MPD, DC), 1173528 (to DC), 1141921 (to DSK), 1080001 and 1173027 (to MPD) and Senior Principal Research Fellowship 1135820 (to NMA)). LJR is supported by NHMRC (https://www.nhmrc.gov.au) Career Development Fellowship (GNT1161627). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022 Stadler et al.",

year = "2022",

month = dec,

day = "1",

doi = "10.1371/journal.pntd.0010990",

language = "English",

volume = "16",

journal = "PLoS Neglected Tropical Diseases",

issn = "1935-2727",

publisher = "Public Library of Science (PLoS)",

number = "12",

}

TY - JOUR

T1 - Population heterogeneity in Plasmodium vivax relapse risk

AU - Stadler, Eva

AU - Cromer, Deborah

AU - Mehra, Somya

AU - Adekunle, Adeshina I.

AU - Flegg, Jennifer A.

AU - Anstey, Nicholas M.

AU - Watson, James A.

AU - Chu, Cindy S.

AU - Mueller, Ivo

AU - Robinson, Leanne J.

AU - Schlub, Timothy E.

AU - Davenport, Miles P.

AU - Khoury, David S.

N1 - Funding Information: This work was funded by the Australian Research Council (ARC; https://www.arc.gov.au) (grants DP120100064 & DP180103875 (to DSK, MPD, DC) and DP200100747 (to JAF)) and the National Health and Medical Research Council (NHMRC; https://www.nhmrc.gov.au) of Australia (grants 1082022 (to MPD, DC), 1173528 (to DC), 1141921 (to DSK), 1080001 and 1173027 (to MPD) and Senior Principal Research Fellowship 1135820 (to NMA)). LJR is supported by NHMRC (https://www.nhmrc.gov.au) Career Development Fellowship (GNT1161627). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022 Stadler et al.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P. vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P. vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P. vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P. vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.

AB - A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P. vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P. vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P. vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P. vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.

UR - http://www.scopus.com/inward/record.url?scp=85145491659&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0010990

DO - 10.1371/journal.pntd.0010990

M3 - Article

C2 - 36534705

AN - SCOPUS:85145491659

SN - 1935-2727

VL - 16

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

IS - 12

M1 - e0010990

ER -

Population heterogeneity in Plasmodium vivax relapse risk

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this