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, 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 Methods We collated data from both published and unpublished malaria parasite inoculation experiments conducted between 1979 and 1988 with parasites from different regions of the People’s Republic of China.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.

Epidemiologic changes of infectious diseases in the post-SARS era in China, 2004–2018

“…It is worth noting that, through regional and inter-departmental cooperation, such as the Five Middle Provinces and Three Southern Provinces Malaria Joint Control and Prevention Programme, and the improvement of the reference laboratory system for malaria diagnosis, and the implementation of the ‘1–3-7’ malaria surveillance and response strategy, China was certified by WHO in 2021 as the 40th malaria free country. However, continued increase in imported cases is a current challenge [ 7 – 9 ]. In contrast to the sharp decline in indigenous cases, imported malaria cases showed an explosive growth, with the percentage rising from 16.2% in 2004 to 99.9% in 2017 [ 10 ].…”

Spatiotemporal and Seasonal Trends of Class A and B Notifiable Infectious Diseases in China: Retrospective Analysis

“…After nearly 70 years of battling malaria (since 1949), a milestone of 0 indigenous malaria cases was achieved in 2017 [40,41]. In June 2021, China was officially awarded a malaria-free certification by the WHO, making it the first country in the WHO Western Pacific Region to be certified in more than 3 decades [42]. During our research period, there were only a few small-scale regional outbreaks of malaria in Yunnan and Anhui provinces (Figure S13 in Multimedia Appendix 1).…”