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Plasmodium vivax (P. vivax) is the most geographically distributed malaria parasite, and causes severe morbidity (1). Historically, P. vivax was the dominant parasite species in China for several decades (2). Since the National Action Plan for Malaria Elimination was launched in 2010 (3), domestic vivax malaria cases have steadily declined, while the proportion of imported vivax malaria cases has increased. To date, the epidemiological status and characteristics of P. vivax in the malaria elimination phase have not been adequately studied. The objective of this study was to analyze the epidemiological characteristics of P. vivax between 2013 and 2020 in China. The individual data of vivax malaria cases were collected to analyze the demographic characteristics, time distribution of cases and source infection countries of imported cases. The results revealed that the last domestic vivax malaria case was reported in Yunnan Province in 2016, and that hundreds of imported vivax cases were still reported every year, mainly from Southeast Asia. Men who worked outdoors were at high risk of P. vivax infection. This study suggests that P. vivax remains a key point of focus in the elimination or after elimination phase. Adaptive and updated strategies focusing on P. vivax should be considered.
Although P. vivax was endemic in China, the incidence of malaria had decreased to an estimated 2/100,000 in 2000, due to the widespread use of antimalarial drugs, unprecedented socioeconomic changes, and urbanization implemented nationwide since the 1980s (4). From 2004 to 2012, vivax malaria cases accounted for 76.9% of all reported malaria cases. Between 2001 and 2006 there was a resurgence of P. vivax malaria in central China, mainly caused by climate warming, which led to extending malaria transmission, with increasing vectorial capacity of Anopheles sinensis (An. sinensis) and low capacity of diagnosis leading to an accumulation of infectious sources (5). This resurgence was controlled by targeted mass drug administration (MDA) and case management (5). As most areas in central and southern China are susceptible areas where An. sinensis is prevalent, the imported P. vivax malaria may pose a high risk of malaria transmission re-establishment in these malaria-free localities during the transmission season (6).
Data on vivax malaria cases, including demographic information (age, sex, and occupation), diagnosis, case classification, interval between onset and diagnosis, and source infection of malaria from 31 provincial-level administrative divisions (PLADs), were collected via the Parasitic Diseases Information Reporting Management System (PDIRMS) during 2013–2020. Data from Hong Kong, Macao, and Taiwan were not included in the study. Demographic data were analyzed using Microsoft Excel 2010 and SAS (version 9.4, SAS Institute Inc, NC, USA). Differences between groups were evaluated by chi-squared test and Kruskal-Wallis test. Differences were considered statistically significant at P<0.05.
From January 1, 2013 to December 31, 2020, a total of 23,114 malaria cases were recorded from 31 PLADs via PDIRMS, among them 4,817 vivax malaria cases were reported, including 138 domestic cases and 4,679 imported cases. Meanwhile, 120 malaria-associated deaths were reported during this period (Figure 1A). Yunnan Province reported the last domestic P. vivax case in 2016, which was also the last domestic malaria case in China. No domestic cases have been reported in the country since 2017. From 2013 to 2020, the proportion of P. vivax remained above 20%, except in 2018 and 2019. The number of vivax malaria cases gradually declined, from 935 in 2013 to 234 in 2020 (Figure 1A). The number of domestic P. vivax cases decreased from 68 in 2013 to 1 in 2016. In addition, among all the reported vivax malaria cases, 179 were recurrent cases, accounting for 3.7% of the total. The interval from last malaria infection to recurrence among different sources was significantly different (P<0.01).
Figure 1.The PLADs of P. vivax malaria in China, 2013–2020. (A) Number of total malaria cases, vivax malaria cases, and deaths in China, 2013–2020. (B) Monthly distribution of imported and domestic vivax malaria cases based on sex, 2013–2020. (C) Provincial distribution of reported P. vivax in China, 2013–2020.
Abbreviations: PLADs=provincial-level administrative divisions; P. vivax=Plasmodium vivax.The monthly distribution of imported and domestic vivax malaria cases exhibited a seasonal trend (Figure 1B). The peak was in the period from May to August. Most P. vivax cases occurred in males (88.2%, 4,249/4,817) and in the 19–59 age group (91.8%, 4,421/4,817). The proportion of males among domestic cases (72.5%, 100/138) was lower than that among imported cases (88.7%, 4,149/4,679), which indicated that the majority of the population working abroad was male. Furthermore, most vivax malaria cases occurred among people working outdoors (43.0%, 1,307/4,817), who were at high risk of exposure to outdoor biting vectors including construction workers, farmers, open mine workers, drivers, field engineers, etc. Of the 4,817 reported malaria cases, 68.1% (n=3,281) were diagnosed in a health facility of a city or county center for disease control and prevention (CDC)/hospital, while 19.4% were diagnosed in a township hospital (Table 1). Moreover, 89.8% were diagnosed and confirmed by PCR in the provincial malaria diagnosis reference laboratory. The median interval between the illness onset and the first visit to the doctor was different between domestic cases and imported cases (P<0.05), which were 3 days [interquartile range (IQR): 1–6] and 2 days (IQR: 0–4), respectively. The median interval between the first visit to the doctor and the final diagnosis was 0 days (IQR: 0–4).
Item 2013 2014 2015 2016 2017 2018 2019 2020 P-value† IMP IND IMP IND IMP IND IMP IND IMP IMP IMP IMP Total 867 68 798 45 836 24 685 1 573 397 289 234 Sex <0.001 Female 61 20 47 11 86 7 97 0 105 57 47 30 Male 806 48 751 34 750 17 588 1 468 340 242 204 Age group (years) 0.072 <5 3 0 6 3 9 0 9 1 10 4 1 2 5–18 28 14 17 3 35 5 38 0 35 20 10 17 19–59 832 47 766 37 776 18 615 0 510 353 263 204 ≥60 4 7 9 2 16 1 23 0 18 20 15 11 Occupation <0.001 Outdoors NA NA NA NA 80 1 233 0 379 272 190 152 Indoors NA NA NA NA 13 0 34 0 34 39 33 13 Unclear* NA NA NA NA 21 1 84 0 125 77 63 38 Missing NA NA NA NA 722 22 334 1 35 7 3 31 Diagnosis health facility <0.001 Provincial-level CDC 38 3 21 0 1 0 7 0 5 2 1 0 Provincial-level hospital 48 2 45 0 49 2 58 0 38 33 23 12 City-level CDC 37 1 25 0 18 0 11 0 9 3 3 2 City-level hospital 140 6 124 3 125 5 141 0 135 104 72 53 County-level CDC 307 16 301 19 253 11 166 1 98 68 33 22 County-level hospital 133 17 149 13 152 1 143 0 106 96 83 76 Township hospital 90 20 73 8 197 5 153 0 170 89 68 62 Village clinic 12 1 4 1 5 0 0 0 1 1 5 6 Private clinic 61 2 56 1 36 0 6 0 11 1 1 1 Missing 1 0 0 0 0 0 0 0 0 0 0 0 PCR confirmation <0.001 Yes 625 51 714 38 772 22 647 1 547 385 289 233 No 242 17 84 7 64 2 38 0 26 12 0 1 Abbreviations: NA=not available; IMP=imported cases; IND=domestic cases; PCR=polymerase chain reaction.
* Unclear indicates that the risk exposure could not be estimated in populations such as children, retirees, students, unemployed persons, etc. Missing data were not included in the statistical analysis.
† P value was calculated by chi-squared test or Kruskal-Wallis test.Table 1. Demographic characteristics of the reported vivax malaria cases in China (2013–2020).
Most imported vivax malaria cases were from Southeast Asia (63.8%, 2,986/4,679), followed by East Africa (16.1%, 753/4,679), Central Africa (6.5%, 304/4,679), West Africa (5.1%, 240/4,679), and South Asia (5.1%, 237/4,679) (
Supplementary Table S1 ). Among these cases, the major source countries were Myanmar, Ethiopia, and Indonesia, accounting for 54.5%, 13.0%, and 5.2%, respectively. In addition, most vivax malaria cases were reported from Yunnan Province (52.7%), followed by Sichuan (10.3%), Henan (5.0%), and Guangxi (4.6%) PLADs (Figure 1C). -
The results of this study showed that the number of vivax malaria cases in China declined significantly during 2013–2020 (Figure 1A and Table 1). The last domestic vivax case was reported in 2016 and hundreds of imported vivax cases have been recorded annually. China was certified malaria-free by the World Health Organization (WHO) in 2021 since there had been no domestic cases for more than three years. Malaria elimination in China has largely been achieved through China’s “1-3-7” approach along with an adaptive malaria elimination strategy (6-7). P. vivax is more difficult to eliminate or control than P. falciparum and other species because it has dormant liver forms (hypnozoites) in its lifecycle (8). P. vivax patients may relapse due to the activation of hypnozoites and become a new source of transmission, even after the schizonts of P. vivax have been removed from the blood.
P. vivax remained the predominant species in China, and several interventions focused primarily on P. vivax elimination in the journey of malaria elimination phase, such as radical cure in the following spring, target MDA and adaptive case finding, and a focus-based surveillance system (4). The last domestic P. vivax case was reported in 2016, and since then there have been no reported domestic cases. However, hundreds of imported vivax malaria cases have been reported annually (Table 1), mainly due to the increasing number of Chinese workers or business people working abroad, especially from Southeast Asia and Africa, where malaria is highly endemic (
Supplementary Table S1 ). In addition, the difference in sex ratio between domestic and imported cases indicated the population working abroad was predominantly male, especially those working outdoors, which was consistent with the previous study (6). The decrease in imported cases in 2020 was caused by the COVID-19 international travel restrictions (9). Additionally, a proportion of recurrent imported vivax malaria cases were identified in this study, which may be due to differences in radical treatment strategies, glucose-6-phosphate dehydrogenase (G6PD) deficiency rate, treatment adherence, and drug resistance in the infection source countries (10), suggesting that G6PD detection before treatment and supervised medication for imported vivax malaria cases are required.China has been a malaria-free country, however An. sinensis, the major malaria vector in China, is prevalent in most parts of country (4,6). In the post-elimination phase, several challenges need to be considered to prevent re-transmission of vivax malaria through imported malaria cases. First, this study showed that the duration between disease outbreak and first doctor visit was slightly longer in areas with reported domestic cases, such as Yunnan Province, reflecting the residents’ lack of knowledge, attitudes, and practices regarding malaria treatment-seeking. Health education on malaria among the high-risk population is needed. Second, the capability for malaria diagnosis in health facilities was unbalanced at different levels. More training and refresher training should be conducted for case detection and diagnosis, especially in health facilities at the city or county levels. In addition, submicroscopic or asymptomatic patients with lower parasitemia were not diagnosed using RDT or microcopy, which is still a challenge in malaria elimination. Third, early detection and diagnosis with appropriate treatment and radical cure in the following spring should be maintained for imported P. vivax patients to prevent relapse or recurrence. The radical cure rate was relatively higher in China, which might be caused by the spring radical treatment in the following year, although the dosage of 8-day primaquine in China was different compared with 14-day primaquine recommended by WHO. Fourth, the “1-3-7” approach was well implemented nationwide, and made an important contribution to achieving the national goal of elimination. However, the strategies and approaches should be updated or adapted, with a focus on imported cases, to prevent recurrence of malaria in the post-eradication phase.
The study was subject to some limitations. First, the source countries of 31 imported vivax cases were not available. Second, recurrent vivax cases were not analyzed in this study because no methods were available to distinguish recurrent vivax cases from new infections or recrudescence.
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No conflicts of interest.
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