
==== Front
JMIR Public Health Surveill
JMIR Public Health Surveill
JPH
publichealth
9
JMIR Public Health and Surveillance
2369-2960
JMIR Publications Toronto, Canada

39212596
10.2196/52089
52089
Malaria Surveillance and Prevention
Infectious Diseases (non-STD/STI)
Public (e)Health, Digital Epidemiology and Public Health Informatics
Longitudinal and Cohort Studies in Public Health
Epidemiology
Descriptive Epidemiology and Population Size Estimates
Original Paper
Profile and Determinants for Complications of Imported Malaria in 5 Chinese Provinces From 2014 to 2021: Retrospective Analysis
http://orcid.org/0009-0008-2566-247X
Liu Bowen BMed 12*iliubw@163.com

http://orcid.org/0000-0001-7034-3402
Zhang Tao MMSc 3*ahcdczt@126.com

http://orcid.org/0000-0002-1211-9362
Wang Duoquan PhD 12456wangdq@nipd.chinacdc.cn

http://orcid.org/0000-0003-2290-7335
Xia Shang PhD 12456sxia@nipd.chinacdc.cn

http://orcid.org/0000-0002-1486-0883
Li Weidong MMSc 3ahcdclwd@163.com

http://orcid.org/0000-0002-7710-9587
Zhang Xiaoxi PhD 12zhangxiaoxi@sjtu.edu.cn

http://orcid.org/0009-0007-3013-6151
Wang Shuxun MPH 12wangshuxun@sjtu.edu.cn

http://orcid.org/0000-0002-1595-9965
Guo Xiao-Kui PhD 12xkguo@shsmu.edu.cn

http://orcid.org/0000-0003-1417-8427
Zhou Xiao-Nong PhD 12456zhouxn1@chinacdc.cn

http://orcid.org/0000-0003-3172-5218
Li Shizhu PhD 12456lisz@chinacdc.cn

1 School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 One Health Center, Shanghai Jiao Tong University-The University of Edinburgh, Shanghai, China
3 Anhui Provincial Center for Disease Control and Prevention, Hefei, Anhui Province, China
4 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
5 NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
6 WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China
Mavragani Amaryllis
ShizhuLiPhD, National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, No.207 Rui Jin Er Road, Shanghai, 200025, China, 86 021-64311779; lisz@chinacdc.cn
* these authors contributed equally

None declared.

2024
30 8 2024
10 e5208923 8 2023
15 6 2024
17 6 2024
Copyright © Bowen Liu, Tao Zhang, Duoquan Wang, Shang Xia, Weidong Li, Xiaoxi Zhang, Shuxun Wang, Xiao-Kui Guo, Xiao-Nong Zhou, Shizhu Li. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org)
2024
https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.

Abstract

Background

In 2021, the World Health Organization officially declared the People’s Republic of China as malaria-free. However, despite this milestone achievement, the continued occurrence of severe and fatal cases of imported malaria in China, due to globalization and increased international communication, remains a significant public health concern.

Objective

The aim of this study was to elucidate the epidemiological characteristics of imported malaria in 5 Chinese provinces from 2014 to 2021 and to identify the factors that influence complications in imported malaria cases. The findings will provide a basis for enhancing prevention and control measures, thereby consolidating China’s achievements in malaria elimination.

Methods

A case-based retrospective study was performed, using surveillance data collected from the representative provinces of China from 2014 to 2021. Epidemiological characteristics were analyzed using descriptive statistics. Logistic regression was used to identify the factors influencing the occurrence of complications.

Results

A total of 5559 malaria cases were included during the study period. The predominant species was Plasmodium falciparum (3940/5559, 70.9%), followed by Plasmodium ovale (1054/5559, 19%), Plasmodium vivax (407/5559, 7.3%), Plasmodium malariae (157/5559, 2.8%), and 1 case of Plasmodium knowlesi. Most of the cases were male (5343/5559, 96.1%). The complication rates for P falciparum and P ovale were 11.4% and 3.3%, respectively. Multivariate logistic regression analysis of the relevant factors of malaria complications revealed potential protective factors, including a previous infection by Plasmodium (P<.001; odds ratio [OR] 0.512, 95% CI 0.422‐0.621), and risk factors, including increased age (P=.004; OR 1.014, 95% CI 1.004‐1.024), misdiagnosis at the first clinical visit (P<.001; OR 3.553, 95% CI 2.886‐4.375), and the time interval from onset to treatment (P=.001; OR 1.026, 95% CI 1.011‐1.042). Subgroup analyses identified risk factors associated with P falciparum, which include advanced age (P=.004; OR 1.015, 95% CI 1.005‐1.026), initial misdiagnosis during the first clinical visit (P<.001; OR 3.549, 95% CI 2.827‐4.455), the time interval from onset to treatment (P<.001; OR 1.043, 95% CI 1.022‐1.063), and a delay of more than 3 days from the first treatment to diagnosis (P<.001; OR 2.403, 95% CI 1.823‐3.164). Additionally, the risk factors pertaining to P ovale involve misdiagnosis at the initial clinical visit (P=.01; OR 2.901, 95% CI 1.336‐6.298), the time interval from onset to treatment (P=.002; OR 1.095, 95% CI 1.033‐1.160), and the duration from the initial treatment to diagnosis (P=.43; OR 1.032, 95% CI 0.953‐1.118). Previous infections can prevent the progression of both P falciparum and P ovale.

Conclusions

This study showed that the increasing proportion of P ovale in recent years should not be ignored. Furthermore, there is a need to improve diagnostic awareness, enhance the capacity of medical institutions, and provide health education for high-risk groups.

Keywords

imported malaria
epidemiological characteristics
complications
influencing factors
China
==== Body
pmcIntroduction

Malaria is an infectious disease that continues to pose a significant threat to human health in tropical and subtropical areas [1]. It is listed as 1 of the 3 major infectious diseases by the World Health Organization (WHO), alongside HIV/AIDS and tuberculosis [2]. According to the 2023 World Malaria Report [3] issued by the WHO, malaria remained endemic in 85 countries in 2022 with approximately 249 million cases, leading to 608,000 deaths. The African region has the highest burden of malaria globally, accounting for 93.6% of the global cases in 2022. In fact, the world’s progress toward malaria elimination has stalled since 2017, and the number of cases has rebounded [4]. The incidence of malaria has been on the rise since 2017, notably increasing from 218 million to 233 million cases between 2019 and 2022. The resurgence of malaria cases may pose spillover risks to other nonendemic countries. Consequently, regions without endemic malaria, particularly nations that have recently attained elimination, should remain vigilant against this potential threat and strengthen surveillance of imported malaria [5].

Malaria is one of the most widespread infectious diseases in China, with a long history of endangering people’s physical and mental health. China has implemented a comprehensive set of tailored policies and measures to combat malaria, designed for its specific circumstances [6]. Different departments have collaborated and operated jointly under government leadership to assume responsibility for prevention and control efforts [7]. After 70 years of efforts, China was certified by the WHO as a malaria-free country on June 30, 2021. However, with ongoing globalization and the promotion of the Belt and Road Initiative and China-Africa cooperation strategy, the cross-border flow of people has become more frequent, and overseas sources of infection continue to be imported. Imported malaria poses a significant threat to the consolidation of China's achievements in malaria elimination [8]. Obviously, until malaria is eradicated globally, China still needs to pay attention to the risk of imported malaria, as the introduction of Plasmodium parasites may lead to the re-establishment of malaria. This has already been observed in countries where malaria has been successfully eliminated [9-12]. Continuous surveillance in China is used to address the potential impact of imported malaria, a crucial component of the global malaria ecosystem [13]. Before the outbreak of COVID-19, the annual number of imported malaria cases in China was approximately 3000 [14]. The main origin of infection was Africa, with Plasmodium falciparum being the predominant species, and with fatal cases due to P falciparum occasionally reported [14]. Moreover, dynamic surveillance data have indicated an increased trend of non-falciparum malaria infection among the imported malaria cases in China [15-18]. However, previous studies mainly focused on P falciparum, and the study on the clinical outcome of non-falciparum malaria was neglected [1920]. Surveillance data in China are supported by reliable clinical diagnosis, which can help to improve the understanding of the field.

This was a retrospective case-based study that used malaria surveillance data from 5 provinces of China from January 1, 2014, to December 31, 2021. Epidemiological characteristics, diagnosis, and treatment were analyzed. Factors influencing complications of malaria cases were explored. The findings provide evidence that will be valuable in optimizing the management strategy of imported malaria cases.

Methods

Study Design and Data Sources

The provinces of Anhui, Henan, Hubei, Zhejiang, and Guangxi Zhuang Autonomous Region, China, were selected for this study, according to the epidemics and retransmission risk of imported malaria [21]. Zhejiang is an economically developed province where international communications are frequent, which has a high risk of imported cases [22]. Guangxi is a border province in southern China, where numerous labor workers journey to Africa for gold mining [23]. Historically, malaria was highly prevalent in the provinces of Anhui, Henan, and Hubei [24-26], which means high receptivity, namely, a relatively high risk of re-establishment of malaria. The provinces of Anhui, Hubei, Henan, Zhejiang, and Guangxi (hereinafter referred to as “the five provinces”) were chosen as the study sites.

The data of the imported cases were collected from January 1, 2014, to December 31, 2021, from the 5 provinces using the infectious disease information reporting management system and parasitic disease information reporting management system [21]. We included only cases with singular Plasmodium infections and well-documented complications; mixed infections were excluded from the analysis. The collected information included general demographic characteristics, source of infection, the reason for travel, date of onset, first visit unit and time, first visit results, laboratory diagnosis results, types of complications, treatment drugs, and others. Before treating imported malaria cases in the study, blood samples were collected, and the presence of Plasmodium species was confirmed by microscope examination and polymerase chain reaction at the provincial reference laboratories, in compliance with national criteria for malaria diagnosis [27].

Definition of Malaria Complications and Imported Malaria

The definition of malaria complications is that during the course of the disease, other diseases or clinical manifestations induced by malaria were present, but the underlying diseases of the patients were not included. These included brain damage, acute respiratory distress syndrome, shock, hemolysis, severe renal damage, pulmonary edema, severe anemia, acidosis, liver damage, gastrointestinal damage, and others [28].

In this study, the term “imported malaria” refers to individuals who have been diagnosed with malaria parasites in their blood through diagnostic tests, as well as those who have contracted the infection outside of China.

Statistical Analyses

The case database was established using Microsoft Excel 2021, and IBM SPSS Statistics v26.0 software was used for statistical analyses. The epidemiological characteristics, diagnosis and treatment processes, complications, and other variables of the imported malaria cases were descriptively analyzed. Continuous variables were described as the mean (χ-) and SD if they were normally distributed, and as medians and IQRs otherwise. Qualitative data are presented as ratios or percentages (%).

Logistic regression was used to identify the factors influencing the occurrence of complications as the dependent variable. The Box-Tidwell method was used to test the linear relationship between the continuous independent variable and the logit (p) of the dependent variable. If the linear relationship was not satisfied, the variable was transformed into a categorical variable. Univariate analysis was used to screen statistically significant independent variables, which were included in the multivariate model for analysis. Further subgroup analysis was carried out according to malaria species (P falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, and Plasmodium knowlesi) to identify the influencing factors of complications of different malaria species. Two-sided tests were used for statistical analysis with α=.05.

Ethical Considerations

This study was approved by the ethical review committee of the National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (No.20190115). Since all data were deidentified from the National Information System for Parasitic Disease Control and Prevention, informed consent was waived. Additionally, the authors obtained permission to access and use the data, ensuring adherence to data usage policies and ethical standards.

Results

The study received funding in January 2022, and the survey was conducted from June to July 2022. The study included a total of 5559 cases of imported malaria from 5 provinces of China between 2014 and 2021.

Epidemiological Profile

During the study period, a total of 5559 cases of imported malaria were included, including 3940 cases of P falciparum, 1054 cases of P ovale, 407 cases of P vivax, 157 cases of P malariae, and 1 case of P knowlesi. Most of the cases (5343/5559, 96.1%) were male. The mean age (in years) of the patients was 40 (SD 9.9; range 1‐75). There were 5 children, accounting for 0.1% (5/5559) of the total, who were under 15 years old. The ages of these children were 1, 2, 9, 14, and 15 years. Most of the cases were migrant workers (81.6%, 4536/5559). Of the imported cases, 96.1% (5344/5559) were from Africa. The nations with the highest number of cases were Ghana (843/5559, 15.2%), followed by Nigeria (669/5559, 12%) and Cameroon (551/5559, 9.9%). The full details are provided in Figure 1 and Table 1.

Figure 1. Number of imported malaria cases in 5 provinces of China from 2014 to 2021.

Table 1. Characteristics of patients with imported malaria in 5 provinces of China from 2014 to 2021 (N=5559).

Characteristics	Patients	
Gender		
 Male, n (%)	5343 (96.1)	
 Female, n (%)	216 (3.9)	
 Age (years), mean (SD)	40 (9.9)	
Species, n (%)		
 Plasmodium vivax	407 (7.3)	
 Plasmodium falciparum	3940 (70.9)	
 Plasmodium malariae	157 (2.8)	
 Plasmodium ovale	1054 (19)	
 Plasmodium knowlesi	1 (0)	
Purpose of travel, n (%)		
 Labor	4536 (81.6)	
 Official duties or business	878 (15.8)	
 Others	145 (2.6)	
Previous infection a , n (%)		
 Yes	3982 (71.6)	
 No	1577 (28.4)	
Origin of infection b , n (%)		
 Africa	5344 (96.1)	
 Oceania	13 (0.2)	
 Asia	194 (3.5)	
 South America	8 (0.1)	
a Previous infection: People who have been infected with Plasmodium, regardless of the species.

b Origin of infection: One case was Turk. Turkey is a trans-Eurasian country. It is included in Asia because Europe is not malaria-endemic.

Diagnosis and Treatment

The majority (3582/5559, 64.4%) of the imported malaria cases initially visited medical institutions at or below the county level. Standard treatments were almost always provided (5467/5559, 98.3%). However, 25.6% (1421/5559) of the imported malaria cases did not receive standard treatments on their first visit. Complications occurred in 9% (500/5559) of the cases, as detailed in Table 2.

Table 2. Diagnosis and treatment of patients with imported malaria in 5 provinces of China from 2014 to 2021 (N=5559).

Variables	Patients	
Misdiagnosis at the first visit, n (%)	
	Yes	1421 (25.6)	
	No	4138 (74.4)	
Standard treatmenta , n (%)	
	Yes	5467 (98.3)	
	No	92 (1.7)	
The level of the first medical visit unit, n (%)	
	Country hospital and below	3582 (64.4)	
	Municipal hospital	1260 (22.7)	
	Provincial hospital	588 (10.6)	
	Others	129 (2.3)	
Antimalarial drugs, n (%)	
	Chloroquine plus primaquine	311 (5.6)	
	Artemisinin-based combination therapy	1697 (30.5)	
	Injectable artemisininb	1388 (25.0)	
	Combination therapyc	2072 (37.3)	
	Others	91 (1.6)	
Complication	
	Yes, n (%)	500 (9.0)	
	No, n (%)	5059 (91.0)	
	Time from symptom onset to first time of treatment (days), median (IQR)	1 (0-3)d	
	Time from the first time of treatment to diagnosis (days), median (IQR)	0 (0-2)d	
a Standard treatment: Conform to the standard of use of antimalarial drugs (WS/T 485‐2016).

b Injectable artemisinin: Artemisinin is designed for injection into the body.

c Combination therapy: The treatment of malaria involves the use of two or more medicines.

d A score of 0 was assigned if the patient sought medical attention on the day of symptom onset or was diagnosed on the day of medical attention.

Distribution of Complications

Complications occurred for all 4 common species of malaria. The most frequently involved protozoan was P falciparum (449/3940, 11.4%), followed by P ovale (35/1054, 3.3%), P vivax (12/407, 2.9%), and P malariae (4/157, 2.5%). The proportion of complications of P falciparum was the highest, and that of non-falciparum malaria was similar (P=.84). The 449 cases with complications for P falciparum included 68 cases (68/449, 15.1%) with impaired consciousness, 76 cases (76/449, 16.9%) with hepatic damage and 47 cases (47/449, 10.5%) with severe anemia. Four cases of impaired consciousness occurred for both P ovale and P vivax infections. Full details are provided in Table 3.

Table 3. Complications in patients with imported malaria in 5 provinces of China from 2014 to 2021.

Complications	Plasmodium vivax, n (%)	Plasmodium falciparum, n (%)	Plasmodium malariae, n (%)	Plasmodium ovale, n (%)	
Impaired consciousness	4 (33)	68 (15.1)	0 (0)	4 (11)	
Acute respiratory distress syndrome	0 (0)	5 (1.1)	0 (0)	0 (0)	
Shock	0 (0)	18 (4)	0 (0)	2 (6)	
Hemolysis	0 (0)	12 (2.7)	0 (0)	0 (0)	
Renal impairment	0 (0)	4 (0.9)	0 (0)	0 (0)	
Pulmonary edema	0 (0)	2 (0.4)	0 (0)	0 (0)	
Severe anemia	1 (8)	47 (10.5)	0 (0)	2 (6)	
Acidosis	0 (0)	2 (0.4)	0 (0)	0 (0)	
Hepatic damage	1 (8)	76 (16.9)	2 (50)	10 (29)	
Gastrointestinal damage	2 (17)	37 (8.2)	0 (0)	4 (11)	
Othersa	4 (33)	178 (39.6)	2 (50)	13 (37)	
Total	12 (100)	449 (100)	4 (100)	35 (100)	
a Others: Other diseases caused by Plasmodium do not include underlying diseases.

Analysis of Factors Influencing Complications

Univariate analysis results showed that a previous history of Plasmodium infection was a protective factor, while gender (male), age (years), misdiagnosis at the first visit, time from symptom onset to first time of treatment (days), and time from the first time of treatment to diagnosis (days) were factors associated with complications. Multivariate analysis showed that a previous history of Plasmodium infection reduced the risk of complications (odds ratio [OR] 0.512, 95% CI 0.422‐0.621). Factors increasing the risk of complications were age (1.4% increased risk for every year; OR 1.014, 95% CI 1.004‐1.024), misdiagnosis at the first visit (OR 3.553, 95% CI 2.886‐4.375), and delay between the onset of illness and visit (2.6% per day; OR 1.026, 95% CI 1.011‐1.042). The full details are provided in Table 4.

Table 4. Logistic regression analyses of complications of patients with imported malaria in 5 provinces of China from 2014 to 2021.

Category	Crude	Adjusted	
	P value	Odds ratio (95% CI)	P value	Odds ratio (95% CI)	
Gendera	.04	0.651 (0.433-0.979)	.01	0.667 (0.436-1.021)	
Age (years)	.01	1.012 (1.003-1.022)	.004	1.014 (1.004-1.024)	
Misdiagnosis at the first visit	<.001	4.023 (3.334-4.854)	<.001	3.553 (2.886-4.375)	
Previous infectionb	<.001	0.418 (0.347-0.504)	<.001	0.512 (0.422-0.621)	
Time from symptom onset to first time of treatment (days)	.02	1.017 (1.002-1.032)	.001	1.026 (1.011-1.042)	
Time from the first time of treatment to diagnosis (days)	<.001	1.065 (1.047-1.084)	.15	1.015 (0.995-1.035)	
a Gender: Female patients used as controls.

b Previous infection: People who have ever been infected with Plasmodium, regardless of the species.

Subgroup analyses were performed to identify the influential factors for P falciparum and P ovale. Due to an insufficient sample size for complications, P vivax, P malariae, and P knowlesi were not included. The univariate analysis results showed that the factors influencing complications of P ovale were previous infection, misdiagnosis at the first visit, time from symptom onset to first time of treatment (days), and time from the first time of treatment to diagnosis (days). The influencing factors of P falciparum included previous infection, age (years), misdiagnosis at the first visit, time from symptom onset to the first time of treatment (days), and time from the first time of treatment to diagnosis exceeding 3 days.

Multiple logistic regression analysis results revealed that previous infection decreased the risk of complications of P ovale (OR 0.444, 95% CI 0.199‐0.990) and P falciparum (OR 0.597, 95% CI 0.485‐0.735). Misdiagnosis at the first visit increased the risk of complications of P ovale (OR 2.901, 95% CI 1.336‐6.298) and P falciparum (OR 3.549, 95% CI 2.827‐4.455), as did each day in the time from symptom onset to the first time of treatment, with a 9.5% daily increase for P ovale (OR 1.095, 95% CI 1.033‐1.160) and 4.3% for P falciparum (OR 1.043, 95% CI 1.022‐1.063). Age was also a risk factor for increased risk of complications for P falciparum, with a 1.5% yearly increase (OR 1.015, 95% CI 1.005‐1.026). Finally, the time from the first time of treatment to diagnosis exceeding 3 days increases the risk of complications of P falciparum (OR 2.403, 95% CI 1.823‐3.164). The full details are provided in Table 5.

Table 5. Logistic regression analyses of risk factors for complications of different parasite species of imported malaria in 5 provinces of China from 2014 to 2021.

Variables	Crude	Adjusted	
	P value	Odds ratio (95% CI)	P value	Odds ratio (95% CI)	
Plasmodiumfalciparum	
	Misdiagnosis at the first visit	<.001	4.410 (3.601-5.400)	<.001	3.549 (2.827-4.455)	
	Age (years)	.01	1.013 (1.003-1.023)	.004	1.015 (1.005-1.026)	
	Previous infection	<.001	0.483 (0.396-0.590)	<.001	0.597 (0.485-0.735)	
	Time from symptom onset to first-time of treatment (days)	.004	1.029 (1.009-1.048)	<.001	1.043 (1.022-1.063)	
	Time from the first time of treatment to diagnosis exceeding 3 days	<.001	4.889 (3.893-6.141)	<.001	2.403 (1.823-3.164)	
Plasmodiumovale	
	Misdiagnosis at the first visit	.001	3.168 (1.607-6.246)	.01	2.901 (1.336-6.298)	
	Previous infection	.02	0.382 (0.175-0.835)	.047	0.444 (0.199-0.990)	
	Time from symptom onset to first time of treatment (days)	.01	1.077 (1.017-1.139)	.002	1.095 (1.033-1.160)	
	Time from the first time of treatment to diagnosis (days)	.02	1.075 (1.013-1.141)	.43	1.032 (0.953-1.118)	

Discussion

Principal Findings

The prevalence of P falciparum still predominates, while the proportion of P ovale has increased among imported malaria cases in China. This trend may indicate the underestimation of P ovale malaria in Africa and nonstandardized treatments in at-risk populations. Additionally, our findings indicate that P ovale can lead to severe complications, including brain damage. Health care providers in China should continually enhance their awareness and diagnostic abilities pertaining to imported malaria in order to improve patient outcomes.

According to the dynamic surveillance data, a total of 5559 cases of imported malaria were included in the 5 provinces during this study period, 3940 (70.9%) cases involving P falciparum and 1054 (19%) cases involving P ovale. The number of P falciparum cases still ranks first, and the proportion of P ovale cases has increased, consistent with the data-related domestic studies in recent years [1516]. In contrast, the monitoring data from Italy from 2011 to 2017 indicated that the proportion of imported P ovale is only approximately 5% (range 3%‐8%), and P falciparum was the most frequent species identified, with 78% (range 69%‐84%) of infections over the study period [29]. The surveillance of all imported malaria cases in Bulgaria from 2000 to 2020 also showed that P falciparum accounted for the highest proportion (64.65%), followed by P vivax (28.45%) and P ovale (3.45%) [30]. Furthermore, a study from the European surveillance reported that P falciparum accounted for the majority of those cases (n=28,070, 89%). P ovale, P malariae, and P vivax represented 6%, 3%, and 2% of the infections, respectively [31]. The increased prevalence of P ovale among imported malaria in China may reflect the underestimated prevalence of P ovale malaria in Africa, unstandardized treatments, using more sensitive and accurate nucleic acid detection methods, and other factors. Further studies are needed to explore the underlying causes of the changes in the epidemic situation of malaria. These data will help inform the optimizations and adjustments of control measures for imported malaria in China.

This study scrutinized the complications of malaria and the influential factors. Among the 5559 imported malaria cases, 500 (9%) complications were observed. Complications were reported for all 4 species. The protozoan that was most frequently associated was P falciparum, with similar rates for non-falciparum malaria. The comparative data reveal that the situation of P falciparum is more complicated and serious. Four cases of brain damage were reported for both P vivax and P ovale. This is the same as reported elsewhere [3233]: both P vivax and P ovale can lead to severe cases, can induce adverse clinical outcomes, and can be lethal. Thus, further observational studies on the clinical characteristics of non-falciparum and standardized treatments are needed to provide new evidence for the management of imported malaria cases.

Multivariate logistic regression analysis showed that previous infection by Plasmodium offered protection against the complications of imported malaria. Patients who had previously been infected with Plasmodium may have acquired partial immunity, which decreases the risk of complications [34]. However, it depends on the factor of time as the level of acquired immunity decreases over time. In addition, previous infection by Plasmodium can increase a person’s awareness of malaria-related symptoms. When patients exhibit symptoms resembling a Plasmodium infection, they are more likely to consider the possibility of having Plasmodium if they have been previously infected. This may instill a strong awareness of active medical treatment and timely and effective treatments [35]. Contrary to previous infection by Plasmodium, age is a risk factor for complications. With increasing age, the body’s various functions and resistance decline [36], which increases the possibility of complications. However, this may also be due to the fact that the imported malaria cases mainly concern young and middle-aged people.

The findings of this study also emphasize the importance of initial diagnosis. If the diagnosis is not correct at the first visit, the patient may not be treated in time. The resulting delay may result in various complications. The times from symptom onset to the first time of treatment and from the first time of treatment to diagnosis are important risk factors for complications, which are related to the prolonged course of the disease. The current findings echo the serious consequences of delay in medical care seeking and diagnosis of malaria cases that have been previously reported [3738]. Further subgroup analysis showed that the prolonged time from onset to first time of treatment was a risk factor for the complications of P ovale, while no statistical association was found between the time from the first time of treatment to diagnosis and the complications of P ovale. This may be due to the low density of parasites in the blood of the infected individual and the relatively mild clinical symptoms [2839]. Therefore, patients often fail to seek timely medical treatment after the onset of the disease, resulting in a prolonged interval between symptom onset and medical treatments. However, for P falciparum, both the prolonged time from symptom onset to the first time of treatment and from the first time of treatment to diagnosis are risk factors for complications. This is due to the rapid clinical progress of P falciparum, which repeatedly replicates over the course of 48 h inside erythrocytes, resulting in exponential growth and rapid disease progression [4041]; the delay from symptom onset to diagnosis has an important impact on the development of the disease.

Study Limitations

There are several limitations to this study. The data were obtained from a routine surveillance system, and the study was retrospective. The possibility of recall bias cannot be discounted. Moreover, the complications of malaria are complex, and different epidemiological investigators may not record all clinical complications. Furthermore, it is important to note that this study did not encompass border areas, so the findings may not be directly applicable to those regions. In border areas, the prevention and control of malaria rely more on effective information communication [42].

Conclusions

While P falciparum represents the highest proportion among the 5 malaria species and exhibits a higher fatality rate in comparison to the other species [43], it is crucial to acknowledge the importance of the other malaria species. In recent years, the proportion of imported P ovale has been on the rise, and serious complications can endanger patient survival. Diagnostic awareness and the capacity of medical institutions must be improved. The present findings emphasize the importance of initial diagnosis. Strengthening the team of professionals is crucial [44]. In addition, the challenge of complications associated with imported malaria indicates the need for health education for risk groups.

Acknowledgments

We thank the staff members of the municipal and county Centers for Disease Control and Prevention for their contribution to data collection. Generative AI was not used in any part of composing the manuscript.

This research was funded by National Natural Science Foundation of China (No. 32161143036), the National Special Science and Technology Project for Major Infectious Diseases of China (Grant No. 2016ZX10004222-004), and Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (2023-2025) Key Discipline Project (No. GWVI-11.1-12).

Abbreviations

OR odds ratio

WHO World Health Organization

Authors’ Contributions: All the authors listed have made substantial, direct, and intellectual contributions to the work and approved it for publication. BL, TZ, DW, and SL designed the study and guided the methodology; BL, TZ, and DW wrote the first draft; TZ and DW were responsible for data collection; BL, TZ, and DW were responsible for data input and analysis; and SX, WL, XZ, SW, XKG, XNZ, and SL critically reviewed, discussed, and modified the manuscript. All authors read and approved the final manuscript.

Data Availability: The data sets generated during and/or analyzed during this study are available from the corresponding author upon reasonable request.
==== Refs
References

1. Zhang C Yang R Wu L et al Survey of malaria vectors on the Cambodia, Thailand and China-Laos borders Malar J Dec 30 2022 21 1 399 doi 10.1186/s12936-022-04418-w Medline 36585690
2. Makam P Matsa R “Big Three” infectious diseases: tuberculosis, malaria and HIV/AIDS Curr Top Med Chem 2021 21 31 2779 2799 doi 10.2174/1568026621666210916170417 Medline 34530712
3. World malaria report 2023 World Health Organization 2023 URL https://www.who.int/publications/i/item/9789240086173 Accessed 20-08-2024
4. World malaria report 2022 World Health Organization 2022 URL https://www.who.int/publications/i/item/9789240064898 Accessed 20-08-2024
5. Global technical strategy for malaria 2016-2030, 2021 update World Health Organization 2021 URL https://www.who.int/publications/i/item/9789240031357 Accessed 20-08-2024
6. Yin JH Zhang L Feng XY Xia ZG Evolution of anti-malaria policies and measures in P.R. China for achieving and sustaining malaria-free Front Public Health Mar 2023 11 1094859 doi 10.3389/fpubh.2023.1094859 Medline 36935657
7. Feng X Huang F Yin J Wang R Xia Z Key takeaways from China’s success in eliminating malaria: leveraging existing evidence for a malaria-free world BMJ Glob Health Apr 2022 7 4 e008351 doi 10.1136/bmjgh-2021-008351 Medline 35487673
8. Feng J Xia ZG Vong S Yang WZ Zhou SS Xiao N Preparedness for malaria resurgence in China: case study on imported cases in 2000-2012 Adv Parasitol 2014 86 231 265 doi 10.1016/B978-0-12-800869-0.00009-3 Medline 25476887
9. An Q Li Y Sun Z Gao X Wang H Seasonal prediction of the distribution of three major malaria vectors in China: based on an ecological niche model PLoS Negl Trop Dis 01 2024 18 1 e0011884 doi 10.1371/journal.pntd.0011884 Medline 38236812
10. Danis K Lenglet A Tseroni M Baka A Tsiodras S Bonovas S Malaria in Greece: historical and current reflections on a re-emerging vector borne disease Travel Med Infect Dis 01 2013 11 1 8 14 doi 10.1016/j.tmaid.2013.01.001 Medline 23434287
11. Krüger A Rech A Su XZ Tannich E Two cases of autochthonous Plasmodium falciparum malaria in Germany with evidence for local transmission by indigenous Anopheles plumbeus Trop Med Int Health Dec 2001 6 12 983 985 doi 10.1046/j.1365-3156.2001.00816.x Medline 11737834
12. Santa-Olalla Peralta P Vazquez-Torres MC Latorre-Fandos E et al First autochthonous malaria case due to Plasmodium vivax since eradication, Spain, October 2010 Euro Surveill Oct 14 2010 15 41 19684 doi 10.2807/ese.15.41.19684-en Medline 20961517
13. Global Malaria Programme operational strategy 2024-2030 World Health Organization 2024 URL https://www.who.int/publications/i/item/9789240090149 Accessed 20-08-2024
14. Li Z Jun F Zhigui X Shuisen Z Analysis of the characteristics of malaria epidemic in China in 2019 and progress of elimination Chin J Parasitol Parasit Dis 2020 38 2 133 138 doi 10.12140/j.issn.1000-7423.2020.02.001
15. Zhu M Zhang C Zhang Y et al An epidemiological analysis of imported malaria in Shanghai during a COVID-19 outbreak Malar J Aug 25 2022 21 1 245 doi 10.1186/s12936-022-04273-9 Medline 36008837
16. Liu P Shen L Wang S et al Increasing proportions of relapsing parasite species among imported malaria in China’s Guangxi Province from Western and Central Africa Travel Med Infect Dis Sep 2021 43 102130 doi 10.1016/j.tmaid.2021.102130 Medline 34166802
17. Li W Zhang X Feng J et al Evaluation of the combination of rapid diagnostic tests and microscopy for imported malaria surveillance in Anhui Province, China Acta Trop Oct 2021 222 106042 doi 10.1016/j.actatropica.2021.106042 Medline 34252385
18. Zhang T Wang S Wang D et al Epidemiological profile of Plasmodium ovale spp. imported from Africa to Anhui Province, China, 2012-2019 Malar J 01 6 2021 20 1 15 doi 10.1186/s12936-020-03551-8 Medline 33407463
19. Tomassi MV D’Abramo A Vita S et al A case of severe Plasmodium ovale malaria with acute respiratory distress syndrome and splenic infarction in a male traveller presenting in Italy Malar J Apr 4 2024 23 1 93 doi 10.1186/s12936-024-04911-4 Medline 38575935
20. Kayiba NK Nitahara Y Tshibangu-Kabamba E et al Malaria infection among adults residing in a highly endemic region from the Democratic Republic of the Congo Malar J Mar 18 2024 23 1 82 doi 10.1186/s12936-024-04881-7 Medline 38500094
21. Zhang T Wang D Qian Y et al Profile and determinants of delayed care-seeking and diagnosis among patients with imported malaria: a retrospective study in China, 2014-2021 Infect Dis Poverty Dec 22 2022 11 1 125 doi 10.1186/s40249-022-01050-3 Medline 36550586
22. Linong Y Wei R Hualiang C Shengrong X Shunrong Y Kegen Y Molecular epidemiological characteristics of malaria cases in Zhejiang Zhejiang Prev Med 2009 21 10 1 3 doi 10.19485/j.cnki.issn1007-0931.2009.10.001
23. Qiuli X Kangming L Zhiqin Y et al Hospitalization costs and influencing factors of imported malaria patients in Guangxi Zhuang Autonomous Region and Yunnan Province Chin J Schistosomiasis Control 2021 33 2 154 161 doi 10.16250/j.32.1374.2020312
24. Xian X Tao Z Jingjing J Weidong L Malaria control and elimination in Anhui Province Trop Dis Parasitol 2020 18 2 65 69 doi 10.3969/j.issn.1672-2302.2020.02.001
25. Zhang H Zhang Q Yang C et al Progress and scientific and technological achievements of malaria elimination in Henan Province Henan J Prev Med 2019 30 10 721 725 doi 10.13515/j.cnki.hnjpm.1006-8414.2019.010.001
26. Jing X Dongni W Hong Z et al Malaria control and elimination in Hubei Province Chin J Parasitol Parasit Dis 2021 39 5 565 571 doi 10.12140/j.issn.1000-7423.2021.05.001
27. National Health and Family Planning Commission of China Diagnosis of malaria URL http://www.nhc.gov.cn/ewebeditor/uploadfile/2015/12/20151208094408183.pdf Accessed 10-09-2022
28. Writing Group of National Medical Center for Infectious Diseases Lanjuan L Wenhong Z Jianrong H Qi G Guidelines for the diagnosis and treatment of malaria Chin J Parasitol Parasit Dis 2022 40 4 419 427 doi 10.12140/j.issn.1000-7423.2022.04.001
29. Dorrucci M Boccolini D Bella A et al Malaria surveillance system and hospital discharge records: assessing differences in Italy, 2011-2017 database analysis Travel Med Infect Dis 07 2022 48 102322 doi 10.1016/j.tmaid.2022.102322 Medline 35367383
30. Kaftandjiev I Harizanov R Rainova I et al Epidemiological and clinical characteristics of imported malaria in Bulgaria: a retrospective study of а 21-year period Travel Med Infect Dis Sep 2022 49 102400 doi 10.1016/j.tmaid.2022.102400 Medline
31. Gossner CM Hallmaier-Wacker L Briet O et al Arthropod-borne diseases among travellers arriving in Europe from Africa, 2015 to 2019 Euro Surveill Feb 2023 28 7 2200270 doi 10.2807/1560-7917.ES.2023.28.7.2200270 Medline 36795503
32. Trivedi S Chakravarty A Neurological complications of malaria Curr Neurol Neurosci Rep Aug 2022 22 8 499 513 doi 10.1007/s11910-022-01214-6 Medline 35699901
33. Groger M Fischer HS Veletzky L Lalremruata A Ramharter M A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria Malar J Mar 11 2017 16 1 112 doi 10.1186/s12936-017-1759-2 Medline 28284211
34. Lau YL Lee WC Tan LH et al Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome Malar J Nov 4 2013 12 1 24180319 doi 10.1186/1475-2875-12-389 Medline 24180319
35. Lu G Cao Y Chen Q Zhu G Müller O Cao J Care-seeking delay of imported malaria to China: implications for improving post-travel healthcare for migrant workers J Travel Med 07 14 2022 29 4 taab156 doi 10.1093/jtm/taab156 Medline 34581417
36. Mühlberger N Jelinek T Behrens RH et al Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID surveillance data Clin Infect Dis Apr 15 2003 36 8 990 995 doi 10.1086/374224 Medline 12684911
37. Hoffmeister B Aguilar Valdez AD Hypertension is associated with an increased risk for severe imported falciparum malaria: a tertiary care hospital based observational study from Berlin, Germany Malar J Dec 6 2019 18 1 410 doi 10.1186/s12936-019-3007-4 Medline 31810471
38. Yanli G Yiqing X Shiying Z Mingzhen H Epidemiological characteristics and case diagnosis of malaria in Changzhou from 2010 to 2020 Trop Dis Parasito 2022 20 2 69 75 doi 10.3969/j.issn.1672-2302.2022.02.003
39. Garcia LS Malaria Clin Lab Med Mar 2010 30 1 93 129 doi 10.1016/j.cll.2009.10.001 20513543
40. Junying G Ning J Mechanism of action of heparin/Hepari sulfide in the invasion of red blood cells by Plasmodium falciparum parasite Sci China Life Sci 2021 51 5 518 524 doi 10.1360/SSV-2020-0383
41. Maier AG Matuschewski K Zhang M Rug M Plasmodium falciparum Trends Parasitol Jun 2019 35 6 481 482 doi 10.1016/j.pt.2018.11.010 Medline 30595467
42. Saldanha R Mosnier É Barcellos C et al Contributing to elimination of cross-border malaria through a standardized solution for case surveillance, data sharing, and data interpretation: development of a cross-border monitoring system JMIR Public Health Surveill Sep 1 2020 6 3 e15409 doi 10.2196/15409 Medline 32663141
43. Li Z Boyu Y Zhigui X Jianhai Y Analysis of malaria epidemic characteristics in China in 2021 Chinese Journal of Parasitology and Parasitic Diseases 2022 40 2 135 139 doi 10.12140/j.issn.1000-7423.2022.02.001
44. Liu H Zhou YW Deng Y et al Historical review of malaria control and elimination in the border areas of China: a case study of Yunnan Province Adv Parasitol 2022 116 33 67 doi 10.1016/bs.apar.2021.12.001 Medline 35752449
