Epidemiological characteristics of Plasmodium malariae malaria in China: a malaria that should not be neglected post elimination.

BACKGROUND: Plasmodium malariae was always neglected compared with P. falciparum and P. vivax. In the present study, we aimed to describe the epidemiology of reported cases infected with P. malariae in the past decade to raise awareness of the potential threat of this malaria parasite in China. METHODS: Individual data of malaria cases infected with P. malariae reported in China in the past decade were collected via the China Information System for Disease Control and Prevention and Parasitic Diseases Information Reporting Management System, to explore their epidemiological characteristics. Pearson Chi-square tests or Fisher's Exact Test was used in the statistical analysis. RESULTS: From 2013 to 2022, a total of 581 P. malariae cases were reported in China, and mainly concentrated in 20-59 years old group (P < 0.001), and there was no significant trend in the number of cases reported per month. Moreover, four kinds of P. malariae cases were classified, including 567 imported cases from 41 countries in 8 regions and distributed in 27 provinces (autonomous regions, municipalities) in China, six indigenous cases in a small outbreak in Hainan, seven recurrent cases in Guangdong and Shanghai, and one induced case in Shanghai, respectively. In addition, only 379 cases (65.2%) were diagnosed as malaria on the first visit (P < 0.001), and 413 cases (71.1%) were further confirmed as P. malariae cases (P = 0.002). Meanwhile, most cases sought healthcare first in the health facilities at the county and prefectural levels, but only 76.7% (161/210) and 73.7% (146/198) cases were diagnosed as malaria, and the accuracy of confirmed diagnosis as malaria cases infected with P. malariae was only 77.2% (156/202) and 69.9% (167/239) in these health facilities respectively. CONCLUSIONS: Even though malaria cases infected with P. malariae didn't account for a high proportion of reported malaria cases nationwide, the threat posed by widely distributed imported cases, a small number of indigenous cases, recurrent cases and induced case cannot be ignored in China. Therefore, it is necessary to raise awareness and improve the surveillance and response to the non-falciparum species such as P. malariae, and prevent the reestablishment of malaria transmission after elimination.

Imported malaria from land bordering countries in China: A challenge in preventing the reestablishment of malaria transmission.

OBJECTIVE: No indigenous malaria cases have been reported since 2017 in China, but a large number of imported cases are still reported every year, including those from the land bordering countries. To characterize their epidemiological profiles will provide evidence for the development of appropriate strategies to effectively address the challenges of border malaria in the post-elimination phase. METHODS: Individual-level data of imported malaria cases from the land bordering countries were collected from 2017 to 2021 in China via the web-based surveillance systems, and analyzed by SPSS, ArcGIS and WPS software, to explore their epidemiological profiles. RESULTS: A total of 1170 malaria cases imported into China from six of the fourteen land bordering countries were reported between 2017 and 2021 with a decline trend. Overall, cases were widely distributed in 31-97 counties from 11 to 21 provinces but mainly in Yunnan. Moreover, these imported cases were mainly infected with P. vivax (94.8%), and a total of 68 recurrent cases were reported in 6-14 counties from 4 to 8 provinces. In addition, nearly 57.1% of the total reported cases could seek healthcare within 2 days of getting sick, and 71.3% of the reported cases could be confirmed as malaria on the day they sought medical care. CONCLUSIONS: China still needs to attach great importance to the risk and challenge of the imported malaria from bordering countries particularly from Myanmar in preventing reestablishment of malaria transmission in the post-elimination phase. It is necessary not only to strengthen collaboration and cooperation with the bordering countries, but also coordinate multiple departments at home to improve malaria surveillance and response system and prevent the reestablishment of malaria transmission in China.

Establishing and applying an adaptive strategy and approach to eliminating malaria: practice and lessons learnt from China from 2011 to 2020.

ABSTRACTOn 30 June 2021, China was certified malaria-free by the World Health Organization. In this study, the evolution, performance, outcomes, and impact of China's adaptive strategy and approach for malaria elimination from 2011 to 2020 were analysed using 10-year data. The strategy and approach focused on timely detection and rapid responses to individual cases and foci. Indigenous cases declined from 1,308 in 2011 to 36 in 2015, and the last one was reported from Yunnan Province in April 2016, although thousands of imported cases still occur annually. The "1-3-7" approach was implemented successfully between 2013 and 2020, with 100% of cases reported within 24 h, 94.5% of cases investigated within three days of case reporting, and 93.4% of foci responses performed within seven days. Additionally, 81.6% of patients attended the first healthcare visit within 1-3 days of onset and 58.4% were diagnosed as malaria within three days of onset, in 2017-2020. The adaptive strategy and approach, along with their universal implementation, are most critical in malaria elimination. In addition to strengthening surveillance on drug resistance and vectors and border malaria collaboration, a further adapted three-step strategy and the corresponding "3-3-7" model are recommended to address the risks of re-transmission and death by imported cases after elimination. China's successful practice and lessons learnt through long-term efforts provide a reference for countries moving towards elimination.

Epidemiologic Analysis of Efforts to Achieve and Sustain Malaria Elimination along the China-Myanmar Border.

Malaria cases have dramatically declined in China along the Myanmar border, attributed mainly to adoption of the 1-3-7 surveillance and response approach. No indigenous cases have been reported in China since 2017. Counties in the middle and southern part of the border area have a higher risk for malaria importation and reestablishment after elimination.

High Frequency Mutations in pfdhfr and pfdhps of Plasmodium falciparum in Response to Sulfadoxine-Pyrimethamine: A Cross-Sectional Survey in Returning Chinese Migrants From Africa.

Background: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against Plasmodium falciparum infection. However, increasing SP resistance (SPR) of P. falciparum affects the therapeutic efficacy of SP, and pfdhfr (encoding dihydrofolate reductase) and pfdhps (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of pfdhfr and pfdhps in P. falciparum isolated from infected Chinese migrant workers returning from Africa. Methods: In total, 159 blood samples from P. falciparum-infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in pfdhfr and pfdhps were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview. Results: High frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in pfdhfr, respectively. A triple mutation (IRN) in pfdhfr was the most prevalent haplotype (86.83%). Six point mutations were detected in pfdhps DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The pfdhps K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in pfdhps. In total, 5 haplotypes of the pfdhfr gene and 13 haplotypes of the pfdhps gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the pfdhfr-pfdhps combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA). Conclusion: A high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous in vitro molecular monitoring of Sulfadoxine-Pyrimethemine combined in vivo therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.

A retrospective analysis of malaria epidemiological characteristics in Yingjiang County on the China-Myanmar border.

Yingjiang County, which is on the China-Myanmar border, is the main focus for malaria elimination in China. The epidemiological characteristics of malaria in Yingjiang County were analysed in a retrospective analysis. A total of 895 malaria cases were reported in Yingjiang County between 2013 and 2019. The majority of cases occurred in males (70.7%) and individuals aged 19-59 years (77.3%). Plasmodium vivax was the predominant species (96.6%). The number of indigenous cases decreased gradually and since 2017, no indigenous cases have been reported. Malaria cases were mainly distributed in the southern and southwestern areas of the county; 55.6% of the indigenous cases were reported in Nabang Township, which also had the highest risk of imported malaria. The "1-3-7" approach has been implemented effectively, with 100% of cases reported within 24 h, 88.9% cases investigated and confirmed within 3 days and 98.5% of foci responded to within 7 days. Although malaria elimination has been achieved in Yingjiang County, sustaining elimination and preventing the re-establishment of malaria require the continued strengthening of case detection, surveillance and response systems targeting the migrant population in border areas.

Operational research capacity building through the Structured Operational Research Training Initiative (SORT-IT) in China: implementation, outcomes and challenges.

BACKGROUND: Chinese Center for Disease Control and Prevention (China CDC) introduced the Structured Operational Research Training Initiative (SORT IT) into China to build a special capacity and equip public health professionals with an effective tool to support developing countries in strengthening their operational research. The paper aims to investigate and analyze the implementation, outcomes and challenges of the first cycle of SORT IT in China. MAIN TEXT: As a result of the successful implementation, SORT IT China, Cycle 1 has demonstrated fruitful outputs as exemplified by the 18-month follow-up to the post-training initiatives of the twelve participants, who all achieved the four milestones required by SORT IT. Eleven of twelve (92%) manuscripts generated that focused on the prevention and control of malaria, influenza, HIV/AIDS, hepatitis B, schistosomiasis, tuberculosis and Japanese encephalitis were published by peer-reviewed international journals with the impact factor ranging from 2.6 to 4.8. The most up-to-date citation count on February 19, 2021 was 53 times out of which 31 times were cited by Science Citation Index papers with 94.827 impact factor in total. Six senior professionals from China CDC also facilitated the whole SORT IT training scheme as co-mentors under the guidance of SORT IT mentors. The twelve participants who gained familiarity with the SORT IT courses and training principles are likely become potential mentors for future SORT IT, but they as the non-first language speakers/users of English also faced the challenge in thoroughly understanding the modules delivered in English and writing English academically to draft the manuscripts. CONCLUSION: The outcomes from the first cycle of SORT IT in China have led to studies contributing to narrowing the knowledge gap among numerous public health challenges nationally and internationally. It is believed the researchers who participated will continue to apply the skills learned within their domain and help build the training capacity for future operational research courses both in China and in developing countries with similar needs.

Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China.

BACKGROUND: The emergence and spread of multidrug resistance poses a significant risk to malaria control and eradication goals in the world. There has been no indigenous malaria cases reported in China since 2017, and China is approaching national malaria elimination. Therefore, anti-malarial drug resistance surveillance and tracking the emergence and spread of imported drug-resistant malaria cases will be necessary in a post-elimination phase in China. METHODS: Dried blood spots were obtained from Plasmodium falciparum-infected cases returned from Africa to China between 2012 and 2015, prior to anti-malarial drug treatment. Whole DNA were extracted and known polymorphisms relating to drug resistance of pfcrt, pfmdr1 gene, and the propeller domain of pfk13 were evaluated by nested PCR and sequencing. The haplotypes and prevalence of these three genes were evaluated separately. Chi-squared test and Fisher's exact test were used to evaluate differences among the different sub-regions of Africa. A P value < 0.05 was used to evaluate differences with statistical significance. The maps were created using ArcGIS. RESULTS: A total of 731 P. falciparum isolates were sequenced at the pfcrt locus. The wild type CVMNK was the most prevalent haplotype with prevalence of 62.8% and 29.8% of the isolates showed the triple mutant haplotype CVIET. A total of 434 P. falciparum isolates were successfully sequenced and pfmdr1 allelic variants were observed in only codons 86, 184 and 1246. Twelve haplotypes were identified and the prevalence of the wild type pfmdr1 NYD was 44.1%. The single mutant pfmdr1 in codons 86 and 184 was predominant but the haplotype NYY with single mutation in codon 1246 was not observed. The double mutant haplotype YFD was common in Africa. About 1,357 isolates were successfully sequenced of pfk13-propeller domain, the wild type was found in 1,308 samples (96.4%) whereby 49 samples (3.6%) had mutation in pfk13. Of 49 samples with pfk13 mutations, 22 non-synonymous and 4 synonymous polymorphic sites were confirmed. The A578S was the most common mutation in pfk13-propeller domain and three mutations associated with artemisinin resistance (M476I, R539T, P553L) were identified in three isolates. CONCLUSION: This study provides evidence that could give insight into potential issues with anti-malarial drug resistance to inform national drug policy in China in order to treat imported cases.

From control to elimination: a spatial-temporal analysis of malaria along the China-Myanmar border.

BACKGROUND: Malaria cases have declined significantly along the China-Myanmar border in the past 10 years and this region is going through a process from control to elimination. The aim of this study is to investigate the epidemiology of malaria along the border, will identify challenges in the progress from control to elimination. METHODS: National reported malaria cases from China and Myanmar, along with the data of 18 Chinese border counties and 23 townships in Myanmar were obtained from a web-based diseases information reporting system in China and the national malaria control program of Myanmar, respectively. Epidemiological data was analyzed, including the number of reported cases, annual parasite index and proportion of vivax infection. Spatial mapping of the annual parasite index (API) at county or township level in 2014 and 2018 was performed by ArcGIS. The relationship of malaria endemicity on both sides of the border was evaluated by regression analysis. RESULTS: The number of reported malaria cases and API declined in the border counties or townships. In 2014, 392 malaria cases were reported from 18 Chinese border counties, including 8.4% indigenous cases and 91.6% imported cases, while the highest API (0.11) was occurred in Yingjiang County. There have been no indigenous cases reported since 2017, but 164 imported cases were reported in 2018 and 97.6% were imported from Myanmar. The average API in 2014 in 23 Myanmar townships was significantly greater than that of 18 Chinese counties (P < 0.01). However, the API decreased significantly in Myanmar side from 2014 to 2018 (P < 0.01). The number of townships with an API between 0 and 1 increased to 15 in 2018, compared to only five in 2014, while still four townships had API > 10. Plasmodium vivax was the predominant species along the border. The number of reported malaria cases and the proportion of vivax infection in the 18 Chinese counties were strongly correlated with those of the 23 Myanmar townships (P < 0.05). CONCLUSIONS: Malaria elimination is approaching along the China-Myanmar border. However, in order to achieve the malaria elimination in this region and prevent the re-establishment of malaria in China after elimination, continued political, financial and scientific commitment is required.

No evidence of amplified Plasmodium falciparum plasmepsin II gene copy number in an area with artemisinin-resistant malaria along the China-Myanmar border.

BACKGROUND: The emergence and spread of artemisinin resistance in Plasmodium falciparum poses a threat to malaria eradication, including China's plan to eliminate malaria by 2020. Piperaquine (PPQ) resistance has emerged in Cambodia, compromising an important partner drug that is widely used in China in the form of dihydroartemisinin (DHA)-PPQ. Several mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 (k13) are associated with artemisinin resistance and have arisen spread in the Great Mekong subregion, including the China-Myanmar border. Multiple copies of the plasmepsin II/III (pm2/3) genes, located on chromosome 14, have been shown to be associated with PPQ resistance. METHODS: The therapeutic efficacy of DHA-PPQ for the treatment of uncomplicated P. falciparum was evaluated along the China-Myanmar border from 2010 to 2014. The dry blood spots samples collected in the efficacy study prior DHA-PPQ treatment and from the local hospital by passive detection were used to amplify k13 and pm2. Polymorphisms within k13 were genotyped by capillary sequencing and pm2 copy number was quantified by relative-quantitative real-time polymerase chain reaction. Treatment outcome was evaluated with the World Health Organization protocol. A linear regression model was used to estimate the association between the day 3 positive rate and k13 mutation and the relationship of the pm2 copy number variants and k13 mutations. RESULTS: DHA-PPQ was effective for uncomplicated P. falciparum infection in Yunnan Province with cure rates > 95%. Twelve non synonymous mutations in the k13 domain were observed among the 268 samples with the prevalence of 44.0% and the predominant mutation was F446I with a prevalence of 32.8%. Only one sample was observed with multi-copies of pm2, including parasites with and without k13 mutations. The therapeutic efficacy of DHA-PPQ was > 95% along the China-Myanmar border, consistent with the lack of amplification of pm2. CONCLUSION: DHA-PPQ for uncomplicated P. falciparum infection still showed efficacy in an area with artemisinin-resistant malaria along the China-Myanmar border. There was no evidence to show PPQ resistance by clinical study and molecular markers survey. Continued monitoring of the parasite population using molecular markers will be important to track emergence and spread of resistance in this region.

Genomic Epidemiology of Antimalarial Drug Resistance in Plasmodium falciparum in Southern China.

Emerging artemisinin resistance in Southeast Asia poses a significant risk to malaria control and eradication goals, including China's plan to eliminate malaria nationwide by 2020. Plasmodium falciparum was endemic in China, especially in Southern China. Parasites from this region have shown decreased susceptibility to artemisinin and delayed parasite clearance after artemisinin treatment. Understanding the genetic basis of artemisinin resistance and identifying specific genetic loci associated with this phenotype is crucial for surveillance and containment of resistance. In this study, parasites were collected from clinical patients from Yunnan province and Hainan island. The parasites were genotyped using a P. falciparum-specific single nucleotide polymorphism (SNP) microarray. The SNP profiles examined included a total of 27 validated and candidate molecular markers of drug resistance. The structure of the parasite population was evaluated by principal component analysis by using the EIGENSOFT program, and ADMIXTURE was used to calculate maximum likelihood estimates for the substructure analysis. Parasites showed a high prevalence of resistance haplotypes of pfdhfr and pfdhps and moderate prevalence of pfcrt. There was no mutation identified on pfmdr1. Candidate SNPs on chromosomes 10, 13, and 14 that were associated with delayed parasite clearance showed a low prevalence of mutants. Parasites from Southern China were clustered and separated from those from Southeast Asia. Parasites from Yunnan province were substructured from parasites from Hainan island. This study provides evidence for a genomic population with drug resistance in Southern China and also illustrates the utility of SNP microarrays for large-scale parasite molecular epidemiology.

Monitoring and evaluation of intervals from onset of fever to diagnosis before "1-3-7" approach in malaria elimination: a retrospective study in Shanxi Province, China from 2013 to 2018.

BACKGROUND: China's 1-3-7 approach was extensively implemented to monitor the timeframe of case reporting, case investigation and foci response in the malaria elimination. However, activities before diagnosis and reporting (before '1') would counteract the efficiency of 1-3-7 approach but few data have evaluated this issue. This study aims to evaluate the timelines between onset of fever and diagnosis at healthcare facilities in Shanxi Province. METHODS: Routine data were extracted from IDIRMS and NMISM database from 2013 to 2018. Time intervals between onset of fever and healthcare-seeking and between healthcare-seeking and diagnosis were calculated. Each of the documented malaria cases was geo-coded and paired to the county-level layers of polygon. RESULTS: A total of 90 cases were reported in 2013-2018 in Shanxi Province, and 73% of cases reported at provincial health facilities. All malaria cases were imported from Africa (90%) and Southeast Asia (10%) especially around the Chinese Spring Festival (n = 46, 51%). The median days between fever and healthcare-seeking and between healthcare-seeking and diagnosis of malaria were 3 and 2, respectively. CONCLUSIONS: The current "1-3-7" approach is well executed in Shanxi Province, but delays intervals observed in case finding before 1-3-7 approach occurred in all levels of facilities in Shanxi Province, which imply that more efforts are highlighted for timely case finding. Health education should be provided for improving awareness of healthcare-seeking, and various technical training aiming at the physicians should be carried out to improve diagnosis of malaria.

Imported malaria cases in former endemic and non-malaria endemic areas in China: are there differences in case profile and time to response?

BACKGROUND: China has achieved zero indigenous malaria case report in 2017. However, along with the increasing of international cooperation development, there is an increasing number of imported malaria cases from Chinese nationals returning from malaria-affected countries. Previous studies have focused on malaria endemic areas in China. There is thus limited information on non-endemic areas in China, especially on the performance of malaria surveillance and response in health facilities. METHODS: A comparative retrospective study was carried out based on routine malaria surveillance data collected from 2013 to 2017. All imported malaria cases reported within the mainland of China were included. Variables used in the comparative analysis between cases in former endemic and former non-endemic areas, included age, gender and occupation, destination of overseas travel, Plasmodium species and patient health outcome. Monthly aggregated data was used to compare seasonal and spatial characteristics. Geographical distribution and spatial-temporal aggregation analyses were conducted. Time to diagnosis and report, method of diagnosis, and level of reporting/diagnosing health facilities were used to assess performance of health facilities. RESULTS: A total of 16 733 malaria cases, out of which 90 were fatal, were recorded in 31 provinces. The majority of cases (96.2%) were reported from former malaria endemic areas while 3.8% were reported from former non-malaria endemic areas. Patients in the age class from 19 to 59 years and males made the highest proportion of cases in both areas. There were significant differences between occupational categories in the two areas (P <  0.001). In former endemic areas, the largest proportion of cases was among outdoor workers (80%). Two peaks (June, January) and three peaks (June, September and January) were found in former endemic and former non-endemic areas, respectively. Time between the onset of symptoms and diagnosis at clinics was significantly different between the two areas at different level of health facilities (P <  0.05). CONCLUSIONS: All the former non-endemic areas are now reporting imported malaria cases. However, the largest proportion of imported cases is still reported from former endemic areas. Health facilities in former endemic areas outperformed those in former non-endemic areas. Information, treatment, and surveillance must be provided for expatriates while capacity building and continuous training must be implemented at health facilities in China.

Monitoring of malaria vectors at the China-Myanmar border while approaching malaria elimination.

BACKGROUND: Tengchong County was one of the counties located at the China-Myanmar border with high malaria incidence in the previous decades. As the pilot county for malaria elimination at the border area, Tengchong County is aiming to be the first county to achieve malaria elimination goal. A cross-sectional entomological survey was carried out to evaluate the feasibility of elimination approach and assess the receptivity of malaria reintroduction. METHODS: Light traps associated with live baits were used to investigate the abundance of adult mosquitoes in nine villages in Tengchong County. Light traps were set to collect adult mosquitoes in both human houses and cowsheds from dusk till dawn in each site. RESULTS: A total of 4948 adult Anopheles mosquitoes were collected from May to December in two villages. Of the mosquitoes were captured, 24.2% were in human houses and 75.8% in cowsheds. The peak of abundance occurred in July for An. sinensis and in September-October for An. minimus (s.l.) Ten Anopheles species were collected, the most prevalent being An. sinensis (50.3%), An. peditaeniatus (31.6%) and An. minimus (s.l.) (15.8%), contributing to 97.6% of the sample. Potential breeding sites were also investigated and a total of 407 larvae were collected, with An. sinensis (50.1%) and An. minimus (s.l.) (46.2%) as predominant species. Ponds and rice fields were the two preferred breeding sites for Anopheles mosquitoes; however, the difference between the number of adults and larvae captured suggest other breeding sites might exist. Both An. sinensis and An. minimus (s.l.) were found zoophilic with human blood index as 0.21 and 0.26, respectively. No Plasmodium positive Anopheles specimens were found by PCR among 4,000 trapped mosquitoes. CONCLUSIONS: Although no indigenous malaria cases have been reported in Tengchong County since 2013, there is still a risk from the presence of vectors in the context of human population movements from neighboring malaria endemic areas. The presence of An. sinensis, associated to rice fields, is particularly worrying. Sustained entomological surveillance is strongly suggested even after malaria elimination certification.

Ready for malaria elimination: zero indigenous case reported in the People's Republic of China.

BACKGROUND: Malaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed. METHODS: A retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS. RESULTS: From 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n = 4262; 2016, n = 3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection. CONCLUSION: Malaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries.

Mobile population dynamics and malaria vulnerability: a modelling study in the China-Myanmar border region of Yunnan Province, China.

BACKGROUND: The China-Myanmar border region presents a great challenge in malaria elimination in China, and it is essential to understand the relationship between malaria vulnerability and population mobility in this region. METHODS: A community-based, cross-sectional survey was performed in five villages of Yingjiang county during September 2016. Finger-prick blood samples were obtained to identify asymptomatic infections, and imported cases were identified in each village (between January 2013 and September 2016). A stochastic simulation model (SSM) was used to test the relationship between population mobility and malaria vulnerability, according to the mechanisms of malaria importation. RESULTS: Thirty-two imported cases were identified in the five villages, with a 4-year average of 1 case/year (range: 0-5 cases/year). No parasites were detected in the 353 blood samples from 2016. The median density of malaria vulnerability was 0.012 (range: 0.000-0.033). The average proportion of mobile members of the study population was 32.56% (range: 28.38-71.95%). Most mobile individuals lived indoors at night with mosquito protection. The SSM model fit the investigated data (χ2 = 0.487, P = 0.485). The average probability of infection in the members of the population that moved to Myanmar was 0.011 (range: 0.0048-0.1585). The values for simulated vulnerability increased with greater population mobility in each village. CONCLUSIONS: A high proportion of population mobility was associated with greater malaria vulnerability in the China-Myanmar border region. Mobile population-specific measures should be used to decrease the risk of malaria re-establishment in China.

Receptivity to malaria in the China-Myanmar border in Yingjiang County, Yunnan Province, China.

BACKGROUND: The re-establishment of malaria has become an important public health issue in and out of China, and receptivity to this disease is key to its re-emergence. Yingjiang is one of the few counties with locally acquired malaria cases in the China-Myanmar border in China. This study aimed to understand receptivity to malaria in Yingjiang County, China, from June to October 2016. METHODS: Light-traps were employed to capture the mosquitoes in 17 villages in eight towns which were categorized into four elevation levels: level 1, 0-599 m; level 2, 600-1199 m; level 3, 1200-1799 m; and level 4, > 1800 m. Species richness, diversity, dominance and evenness were used to picture the community structure. Similarity in species composition was compared between different elevation levels. Data of seasonal abundance of mosquitoes, human biting rate, density of light-trap-captured adult mosquitoes and larvae, parous rate, and height distribution (density) of Anopheles minimus and Anopheles sinensis were collected in two towns (Na Bang and Ping Yuan) each month from June to October, 2016. RESULTS: Over the study period, 10,053 Anopheles mosquitoes were collected from the eight towns, and 15 Anopheles species were identified, the most-common of which were An. sinensis (75.4%), Anopheles kunmingensis (15.6%), and An. minimus (3.5%). Anopheles minimus was the major malaria vector in low-elevation areas (< 600 m, i.e., Na Bang town), and An. sinensis in medium-elevation areas (600-1200 m, i.e., Ping Yuan town). In Na Bang, the peak human-biting rate of An. minimus at the inner and outer sites of the village occurred in June and August 2016, with 5/bait/night and 15/bait/night, respectively. In Ping Yuan, the peak human-biting rate of An. sinensis was in August, with 9/bait/night at the inner site and 21/bait/night at the outer site. The two towns exhibited seasonal abundance with high density of the two adult vectors: The peak density of An. minimus was in June and that of An. sinensis was in August. Meanwhile, the peak larval density of An. minimus was in July, but that of An. sinensis decreased during the investigation season; the slightly acidic water suited the growth of these vectors. The parous rates of An. sinensis and An. minimus were 90.46 and 93.33%, respectively. CONCLUSIONS: The Anopheles community was spread across different elevation levels. Its structure was complex and stable during the entire epidemic season in low-elevation areas at the border. The high human-biting rates, adult and larval densities, and parous rates of the two Anopheles vectors reveal an exceedingly high receptivity to malaria in the China-Myanmar border in Yingjiang County.

Prevalence of Clinical and Subclinical Plasmodium falciparum and Plasmodium vivax Malaria in Two Remote Rural Communities on the Myanmar-China Border.

Malaria infections may be symptomatic, leading to treatment, or "asymptomatic," typically detected through active surveillance, and not leading to treatment. Malaria elimination may require purging both types of infection. Using detection methods with different sensitivities, we conducted a cross-sectional study in two rural communities located along the border between China's Yunnan Province and Myanmar's Shan and Kachin States, to estimate the prevalence of asymptomatic and symptomatic malaria. In Mong Pawk, all infections detected were asymptomatic, and the prevalence of Plasmodium falciparum was 0.3%, 4.3%, 4.0%, and 7.8% by light microscopy, rapid diagnostic test (RDT), conventional polymerase chain reaction (cPCR), and multiplexed real-time PCR (RT-PCR), respectively, and Plasmodium vivax prevalence was 0% by all detection methods. In Laiza, of 385 asymptomatic participants, 2.3%, 4.4%, and 12.2% were positive for P. vivax by microscopy, cPCR, and RT-PCR, respectively, and 2.3% were P. falciparum-positive only by RT-PCR. Of 34 symptomatic participants in Laiza, 32.4% were P. vivax-positive by all detection methods. Factors associated with infection included gender (males higher than females, P = 0.014), and young age group (5-17 age group compared with others, P = 0.0024). Although the sensitivity of microscopy was adequate to detect symptomatic infections, it missed the vast majority (86.5%) of asymptomatic infections. Although molecular detection methods had no advantage over standard microscopy or RDT diagnosis for clinically apparent infections, malaria elimination along the Myanmar-China border will likely require highly sensitive surveillance tools to identify asymptomatic infections and guide targeted screen-and-treat interventions.

Malaria in China, 2011-2015: an observational study.

OBJECTIVE: To ascertain the trends and burden of malaria in China and the costs of interventions for 2011-2015. METHODS: We analysed the spatiotemporal and demographic features of locally transmitted and imported malaria cases using disaggregated surveillance data on malaria from 2011 to 2015, covering the range of dominant malaria vectors in China. The total and mean costs for malaria elimination were calculated by funding sources, interventions and population at risk. FINDINGS: A total of 17 745 malaria cases, including 123 deaths (0.7%), were reported in mainland China, with 15 840 (89%) being imported cases, mainly from Africa and south-east Asia. Almost all counties of China (2855/2858) had achieved their elimination goals by 2015, and locally transmitted cases dropped from 1469 cases in 2011 to 43 cases in 2015, mainly occurring in the regions bordering Myanmar where Anopheles minimus and An. dirus are the dominant vector species. A total of United States dollars (US$) 134.6 million was spent in efforts to eliminate malaria during 2011-2015, with US$ 57.2 million (43%) from the Global Fund to Fight AIDS, Tuberculosis and Malaria and US$ 77.3 million (57%) from the Chinese central government. The mean annual investment (US$ 27 million) per person at risk (574 million) was US$ 0.05 (standard deviation: 0.03). CONCLUSION: The locally transmitted malaria burden in China has decreased. The key challenge is to address the remaining local transmission, as well as to reduce imported cases from Africa and south-east Asia. Continued efforts and appropriate levels of investment are needed in the 2016-2020 period to achieve elimination.