The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China

Abstract Background With the recent certification by World Health Organization that the People’s Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People’s Republic of China over the last 7 decades. Of the four widespread species of human malaria...

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Main Authors: Guo-Jing Yang, Le-Yuan Shang, Xiao-Nong Zhou, Tamsin E. Lee, Bo Bi, Michael White, Thomas A. Smith, Melissa A. Penny
Format: Article
Language:English
Published: BMC 2022-01-01
Series:BMC Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12916-021-02214-y
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author Guo-Jing Yang
Le-Yuan Shang
Xiao-Nong Zhou
Tamsin E. Lee
Bo Bi
Michael White
Thomas A. Smith
Melissa A. Penny
author_facet Guo-Jing Yang
Le-Yuan Shang
Xiao-Nong Zhou
Tamsin E. Lee
Bo Bi
Michael White
Thomas A. Smith
Melissa A. Penny
author_sort Guo-Jing Yang
collection DOAJ
description Abstract Background With the recent certification by World Health Organization that the People’s Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People’s Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. Methods We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People’s Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. Results P. vivax parasites from the seven studies of five southern and central provinces in the People’s Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10–19 days) or long-incubation (228–371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman’s rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. Conclusions Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.
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spelling doaj.art-482cf22526b146d285d474f75cc1c7a52022-12-21T17:33:50ZengBMCBMC Medicine1741-70152022-01-0120111410.1186/s12916-021-02214-yThe empirical support for the radical cure strategy for eliminating Plasmodium vivax in ChinaGuo-Jing Yang0Le-Yuan Shang1Xiao-Nong Zhou2Tamsin E. Lee3Bo Bi4Michael White5Thomas A. Smith6Melissa A. Penny7Key Laboratory of Tropical Translational Medicine of Ministry of Education, the First Affiliated Hospital, Hainan Medical UniversityHenan Center for Disease Control and PreventionNational Health Commission Key Laboratory on Biology of Parasite and Vector, National Institute of Parasitic Diseases, Chinese Center for Disease Control and PreventionSwiss Tropical and Public Health InstituteKey Laboratory of Tropical Translational Medicine of Ministry of Education, the First Affiliated Hospital, Hainan Medical UniversityInstitut Pasteur, Université de Paris, G5 Épidémiologie et Analyse des Maladies Infectieuses, Département de Santé GlobaleSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteAbstract Background With the recent certification by World Health Organization that the People’s Republic of China is malaria-free, it is timely to consider how elimination of malaria was completed in People’s Republic of China over the last 7 decades. Of the four widespread species of human malaria, Plasmodium vivax was the last to be eliminated by the national program of China. Understanding the incubation periods and relapses patterns of P. vivax through historical data from China is relevant for planning disease elimination in other malaria-endemic countries, with residual P. vivax malaria. Methods We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People’s Republic of China. The studies had at least two years of follow-up. We categorized P. vivax incubation patterns via cluster analysis and investigated relapse studies by adapting a published within-host relapse model for P. vivax temperate phenotypes. Each model was fitted using the expectation-maximization (EM) algorithm initialized by hierarchical model-based agglomerative clustering. Results P. vivax parasites from the seven studies of five southern and central provinces in the People’s Republic of China covering geographies ranging from the south temperate to north tropical zones. The parasites belonged to two distinct phenotypes: short- (10–19 days) or long-incubation (228–371 days). The larger the sporozoite inoculation, the more likely short incubation periods were observed, and with more subsequent relapses (Spearman’s rank correlation between the number of inoculated sporozoites and the number of relapses of 0.51, p-value = 0.0043). The median of the posterior distribution for the duration of the first relapse interval after primary infection was 168.5 days (2.5% quantile: 89.7; 97.5% quantile: 227.69 days). The predicted survival proportions from the within-host model fit well to the original relapse data. The within-host model also captures the hypnozoite activation rates and relapse frequencies, which consequently influences the transmission possibility of P. vivax. Conclusions Through a within-host model, we demonstrate the importance of clearance of hypnozoites. A strategy of two rounds of radical hypnozoite clearance via mass drug administration (MDA) deployed during transmission (summer and autumn) and non-transmission (late spring) seasons had a pronounced effect on outbreaks during the malaria epidemics in China. This understanding can inform malaria control strategies in other endemic countries with similar settings.https://doi.org/10.1186/s12916-021-02214-yPlasmodium vivaxEliminationPeople’s Republic of ChinaStrategyModel
spellingShingle Guo-Jing Yang
Le-Yuan Shang
Xiao-Nong Zhou
Tamsin E. Lee
Bo Bi
Michael White
Thomas A. Smith
Melissa A. Penny
The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
BMC Medicine
Plasmodium vivax
Elimination
People’s Republic of China
Strategy
Model
title The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
title_full The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
title_fullStr The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
title_full_unstemmed The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
title_short The empirical support for the radical cure strategy for eliminating Plasmodium vivax in China
title_sort empirical support for the radical cure strategy for eliminating plasmodium vivax in china
topic Plasmodium vivax
Elimination
People’s Republic of China
Strategy
Model
url https://doi.org/10.1186/s12916-021-02214-y
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