Epidemiological and clinical characteristics of the chikungunya outbreak in Ruili City, Yunnan Province, China.

Chikungunya fever is an acute infectious disease caused by the chikungunya virus (CHIKV) that is characterized by fever, rash, and joint pain. CHIKV has infected millions of people in Africa, Asia, America, and Europe since it re-emerged in the Indian Ocean region in 2004. Here, we report an outbreak of Chikungunya fever that occurred in Ruili of Yunnan Province, a city located on the border between China and Myanmar, in September 2019. The outbreak lasted for three months from September to December. Overall, 112 cases were confirmed by a real-time reverse-transcription polymerase chain reaction in the Ruili People's Hospital, and they showed apparent temporal, spatial, and population aggregation. Among them, 91 were local cases distributed in 19 communities of Ruili City, and 21 were imported cases. The number of female patients was higher than that of male patients, and most patients were between 20 and 60 years old. The main clinical manifestations included joint pain (91.96%), fever (86.61%), fatigue (58.04%), chills (57.14%), rash (48.21%), headache (39.29%), and so forth. Biochemical indexes revealed increased C-reactive protein (63.39%), lymphopenia (57.17%), increased hemoglobin (33.04%), neutrophilia (28.57%), and thrombocytopenia (16.07%). Phylogenetic analysis of the complete sequences indicated that the CHIKV strains in this outbreak belonged to the Indian Ocean clade of the East/Central/South African genotype. We speculated that this chikungunya outbreak might be caused by CHIKV-infected persons returning from Myanmar, and provided a reference for the formulation of effective treatment and prevention measures.

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.

Axl Deficiency Promotes the Neuroinvasion of Japanese Encephalitis Virus by Enhancing IL-1α Production from Pyroptotic Macrophages.

Japanese encephalitis virus (JEV) is a flavivirus that causes Japanese encephalitis (JE), which has an unclear pathogenesis. Despite vaccination, thousands of deaths attributed to JE are reported annually. In this study, we report that mice deficient for Axl, a receptor tyrosine kinase that plays multiple roles in flaviviral infection, displayed greater mortality upon JEV infection. The effect of Axl deficiency on JEV infection was mediated by markedly elevated serum interleukin-1α (IL-1α) levels, which devastated the blood-brain-barrier and promoted viral neuroinvasion within 24 h postinfection. Using an in situ infection model, we showed that dead macrophages were the primary source of observed increased serum IL-1α levels. Axl deficiency enhanced cell death and caused pyroptosis in 80% of JEV-infected macrophages by disrupting phosphatidylinositol 3-kinase (PI3K)-Akt signaling. Intriguingly, the primary effector released by pyroptotic macrophages in our model was IL-1α rather than IL-1ß. Finally, we assessed the effect of an IL-1α antagonist and demonstrated that it effectively prevented the incidence of JE. Our results indicate that Axl plays a protective role in JEV infection, identify IL-1α released by pyroptotic macrophages as a crucial factor promoting JEV neuroinvasion, and suggest that an IL-1α antagonist may be a candidate for JE therapy.IMPORTANCE Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes Japanese encephalitis (JE), the most commonly diagnosed viral encephalitis worldwide. The fatality rate of JE is 20%, and nearly half of the surviving patients develop neuropsychiatric sequelae. Axl is a receptor tyrosine kinase that plays multiple roles in flaviviral infections. Currently, the involvement of Axl in JEV infection remains enigmatic. In this study, we demonstrate that Axl impedes the pathogenesis of severe JE in mice by maintaining blood-brain-barrier (BBB) integrity and restricting viral neuroinvasion. Furthermore, serum IL-1α is a key mediator of this process and is primarily released by JEV-infected pyroptotic macrophages to elicit BBB breakdown, while an IL-1α antagonist can effectively reduce the incidence of severe JE. Our work uncovers the protective role of Axl in antagonizing severe JE and shows that the use of an IL-1α antagonist may be a promising tactic to prevent severe JE.

Seven decades towards malaria elimination in Yunnan, China.

BACKGROUND: Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People's Democratic Republic, Myanmar, and Viet Nam. METHODS: Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). RESULTS: A malaria elimination campaign in the 1950-1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the '1-3-7' surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. CONCLUSIONS: Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.

Intensive surveillance, rapid response and border collaboration for malaria elimination: China Yunnan's ''3 + 1''strategy.

BACKGROUND: Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission. MAIN TEXT: Strategy 1: Intensive interventions within 2.5 km-wide perimeter along the border to prevent border-spill malaria. The area within 2.5 km along the international border is the travel radius of anopheline mosquitoes. Comprehensive interventions should include: (1) proactive and passive case detection, (2) intensive vector surveillance, (3) evidence-based vector control, and (4) evidence-based preventative treatment with anti-malarial drugs. Strategy 2: Community-based malaria detection and screening of migrants and travellers in frontier townships. Un-permitted travellers cross borders frequently and present in frontier townships. Maintenance of intensified malaria surveillance should include: (1) passive malaria detection in the township hospitals, (2) seek assistance from villager leaders and health workers to monitor cross border travellers, and refer febrile patients to the township hospitals and (3) the county's Centre for Disease Control and Prevention maintain regular proactive case detection. Strategy 3: Universal coverage of malaria surveillance to detect malaria cues. Passive detection should be consolidated into the normal health service. Health services personnel should remain vigilant to ensure universal coverage of malaria detection and react promptly to any malaria cues. Strategy + 1: Strong collaborative support with neighbouring countries. Based on the agreement between the two countries, integrated control strategies should be carried out to reduce malaria burden for both countries. There should be a clear focus on the border areas between neighbouring countries. CONCLUSION: The 3 + 1 strategy is an experience summary of border malaria control and elimination, and then contributed to malaria elimination in Yunnan's border areas, China. Nevertheless, Yunnan still has remaining challenges of re-establishment of malaria transmission in the border areas, and the 3 + 1 strategy should still be carried out.

Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

Genetic polymorphism of merozoite surface proteins 1 and 2 of Plasmodium falciparum in the China-Myanmar border region.

BACKGROUND: Malaria is a major public health problem in the China-Myanmar border region. The genetic structure of malaria parasite may affect its transmission model and control strategies. The present study was to analyse genetic diversity of Plasmodium falciparum by merozoite surface proteins 1 and 2 (MSP1 and MSP2) and to determine the multiplicity of infection in clinical isolates in the China-Myanmar border region. METHODS: Venous blood samples (172) and filter paper blood spots (70) of P. falciparum isolates were collected from the patients of the China-Myanmar border region from 2006 to 2011. The genomic DNA was extracted, and the msp1 and msp2 genes were genotyped by nested PCR using allele-specific primers for P. falciparum. RESULTS: A total of 215 P. falciparum clinical isolates were genotyped at the msp1 (201) and msp2 (204), respectively. For the msp1 gene, MAD20 family was dominant (53.49%), followed by the K1 family (44.65%), and the RO33 family (12.56%). For the msp2 gene, the most frequent allele was the FC27 family (80.93%), followed by the 3D7 family (75.81%). The total multiplicity of infection (MOI) of msp1 and msp2 was 1.76 and 2.21, with a prevalence of 64.19% and 72.09%, respectively. A significant positive correlation between the MOI and parasite density was found in the msp1 gene of P. falciparum. Sequence analysis revealed 38 different alleles of msp1 (14 K1, 23 MAD20, and 1 RO33) and 52 different alleles of msp2 (37 3D7 and 15 FC27). CONCLUSION: The present study showed the genetic polymorphisms with diverse allele types of msp1 and msp2 as well as the high MOI of P. falciparum clinical isolates in the China-Myanmar border region.

Identification of a Newly Isolated Getah Virus in the China-Laos Border, China.

In this study, we isolated a virus strain (YN12031) from specimens of Armigeres subalbatus collected in the China-Laos border. BHK-21 cells infected with YN12031 exhibited an evident cytopathic effect (CPE) 32 h post-infection. The virus particles were spherical, 70 nm in diameter, and enveloped; they also featured surface fibers. Molecular genetic analysis revealed that YN12031 was closely related to alpha viruses such as Chikungunya virus and Sindbis virus, and located in the same clade as MM2021, the prototype of Getahvirus (GETV) isolated in Malaysia in 1955. Phylogenetic analysis of the E2 and capsid genes further revealed that YN12031 was located in the same clade as the Russian isolate LEIV/16275/Mag. Analysis of the homology of nucleotides and amino acids in the coding area and E2 gene demonstrated that the YN12031 isolated from the China-Laos border (tropical region) was related closest to the LEIV/16275/Mag isolate obtained in Russia (North frigid zone area) among other isolates studied. These results suggest that GETV can adapt to different geographical environments to propagate and evolve. Thus, strengthening the detection and monitoring of GETV and its related diseases is very crucial.

[Species Identification and Sequence Analysis of Plasmodium spp. in Border Areas of Yunnan Province by 18S rRNA-based Nested PCR]

Objective: To analyze blood samples from patients with falciparum malaria and vivax malaria in border areas of Yunnan Province, using 18S rRNA-based nested PCR, and compare 18S rRNA sequences. Methods: Blood or filter blood samples with positive microscopic results for Plasmodium falciparum or P. vivax infection were collected from Laza, Nankajiang, Mangdong and Nawei of Myanmar, and from Mengla, Tengchong and Yingjiang of Yunnan Province between 2004 and 2011. 18S rRNA-based nested PCR was conducted on the samples, and PCR products were sequenced and blasted. Phylogenetic tree was constructed using the neighbor-joining method with MEGA software (version 6.06). Results: Microscopic examination revealed P. falciparum infection in 256 samples and P. vivax infection in 219 samples. The 18S rRNA-based PCR further confirmed P. falciparum infection in 242 samples, P. vivax infection in 176 samples, and mixed infection in 57 samples. The consistency rate was 81.7% （388/475） between microscopic and PCR results. The inconsistency rate significantly correlated with parasite density （Spearman's r=-0.408， P<0.05）. Sequence alignment revealed 11 and 10 homologous sequences for P. falciparum and P. vivax 18S rRNA gene, comprising 2.9%（6/205） and 22.5%（27/120） variable sites, respectively. The 18S rRNA of P. falciparum clustered with that from Cameroon（GenBank accession number KC428742）, but was distantly related with the S-type 18S rRNA from the Netherlands （U36465） and Brazil （U36466 and U36467）. The 18S rRNA of P. vivax clustered with A-type 18S rRNA from Thailand （U07367）, but was distantly related with the C-type 18S rRNA from Thailand（U07368）. Conclusion: Nested PCR revealed mixed infection in 57 samples among those identified with single infection by microscopy. There is no significant difference in 18S rRNA sequence in seven counties/cities in Yunnan Province.

[Evaluation on Malaria Hotspots in Yingjiang County of the China-Myanmar Border Area in 2015].

Objective: To understand the control status of malaria at hotspots in Yingjiang County and provide measures for malaria elimination in the China-Myanmar border areas of Yunnan Province. Methods: A survey was made in 4 villages with indigenous malaria cases or imported cases in Nabang and Tongbiguan of Yingjiang County in Yunnan Province in June and July 2015. Peripheral blood samples were collected from the neighboring residents around patients and examined by malaria rapid diagnostic test （RDT）. The results were further verified by nested-PCR. Mosquitoes were collected by overnight trapping with light traps in Jingpo, Lilisu, Jiema, and Mengxiangyang villages or by human landing catches in Jingpo and Lisu villages. Nested-PCR was performed on part of the captured Anopheles minimus to detect the malaria parasites. Results: One hundred and ninety-four filter blood samples were collected from 11 malaria cases in two sites. All were detected to be negative for Plasmodium by RDT. In contrast, two samples originated from Jingpo and Lisu villages with indigenous cases were detected to be positive for Plasmodium vivax by nested-PCR. A total of 2 374 mosquitoes were captured, belonging to 22 species of 4 genera: Anopheles, Culex, Aedes and Armigeres. The mosquitoes were predominated by genus Culex, followed by genus Anopheles（11.33%, 269/2 374） which was dominated by A. minimus（49.07%, 132/269）, then was A. sinensis（4.09%, 11/269）, A. maculatus（2.23%, 6/269）, A. jeyporiensis（0.74%, 2/269）and so on. The mean indoor man-biting rate of mosquitoes was 5.78 and 3.20 per person per hour for Jingpo and Lisu villages, and the mean outdoor man-biting rate of mosquitoes was 2.30 per person per hour for Lisu Village. The 14 A. minimus were negative for sporozoite infection as detected by nested-PCR. Conclusion: Nested-PCR showed that there are asymptomatic Plasmodium carriers in Yingjiang's border area of Yunnan Province. Four major mosquito species as malaria vectors exist with A. minimus as the dominant one.

[Study on the Resistance of Culex tritaeniorhynchus to DDT and Deltamethrin in Yunnan Province].

OBJECTIVE: To investigate the resistance level of Culex tritaeniorhynchus to DDT and deltamethrin in Yunnan Province. METHODS: Adult Culex tritaeniorhynchus samples were collected in Zhaoyang District of Zhaotong City, Mangshi County of Dehong Prefecture, Yuanjiang County of Yuxi City, Jiangcheng and Menglian County of Puer City. The susceptibility of Cx. tritaeniorhynchus to DDT and deltamethrin were tested by bioassay method. The resistance level was judged by adjusted mortality. RESULTS: Culex tritaeniorhynchus collected from Zhaoyang, Mangshi, Jiangcheng, Menglian, and Yuanjiang, and exposed to DDT for 1 h, the mortality after 24 hours was 51.1%, 86.8%, 35.4%, 21.0%, and 4.6%, respectively; the resistant grade in Mangshi was maybe resistance(M), and the others 4 sites were resistance (R). The range of KT, to DDT was from 18.76 min to 395.65 min. The mortality of the mosquitoes from the five sites to deltamethrin was 36.9%, 59.2%, 43.1%, 34.1%, and 3.3%, respectively; the resistant grade was R in all sites, and the range of KT50 was 8.69-715.37 min. CONCLUSION: Culex tritaeniorhynchus in Yunnan Province shows simultaneously resistant to DDT and deltamethrin, and therefore the insecticiding strategy should be adjusted.

A household randomized, controlled trial of the efficacy of 0.03% transfluthrin coils alone and in combination with long-lasting insecticidal nets on the incidence of Plasmodium falciparum and Plasmodium vivax malaria in Western Yunnan Province, China.

BACKGROUND: Mosquito coils are the most commonly used household insecticidal product in the world with sales exceeding 50 billion coils, used by two billion people worldwide annually. Despite strong evidence that coils prevent mosquito bites a systematic review concluded that there is no evidence that burning mosquito coils prevents malaria acquisition. Therefore, the current trial was designed to measure and compare prevention of malaria infection by mosquito coils or long-lasting insecticidal net (LLIN) or a combination of the two in Yunnan, China in the Greater Mekong sub-region. METHODS: A four-arm single blind household-randomized design was chosen as coils emanate insecticide throughout the household. Households enrolled at baseline were randomly allocated by the lottery method to one of the four intervention arms: (i) nothing, (ii) 0.03% transfluthrin coils alone, (iii) deltamethrin long-lasting insecticide treated nets, (LLINs) alone or (iv) a combination of transfluthrin coils and deltamethrin LLINs. All household members were recruited to the study, with only those households excluded with pregnant or breastfeeding mothers, members with chest complaints or allergies or members that regularly slept away from home. The main outcome of interest was Plasmodium falciparum malaria prevalence detected by rapid diagnostic tests (RDTs) during six repeated monthly cross-sectional surveys. The secondary outcome of interest was the effect on Plasmodium vivax prevalence detected in the same way. RESULTS: A total of 2,052 households were recruited into the study, comprising 7,341 individuals The odds ratios of testing positive by RDT with P. falciparum or P. vivax were >75% lower for all intervention arms compared with the control arm. Coils alone provided 77% protection (95% CI: 50%-89%), LLINs provided 91% protection (95% CI: 72%-97%) and the combination of coils and LLINs provided 94% protection (95% CI: 77%-99%) against P. falciparum compared with the control arm. There was no statistically significant difference between the protective efficacies of the different interventions. CONCLUSIONS: This is the first robust clinical evaluation of transfluthrin mosquito coils as a means to reduce malaria and the high degree of infection prevented would indicate they represent a potentially highly effective tool, which could be integrated into larger vector control programmes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00442442, March 2007.

[Identification of mammalian blood meals in anopheline mosquitoes from four counties of Yunnan Province by multiple PCR].

From June to August 2012, the blood-sucking mosquitoes were captured around cattle-sheds and human houses in Yuanjiang County, Qiaojia County, Yongshan County, and Jinghong City of Yunan Province. Blood samples from mosquitoes were collected on filter paper. Multiplex PCR assay was used to detect the blood meal samples. Among the 145 mosquitoes captured, 123 were Anopheles sinensis (84.8%) and 22 A. minimus (15.2%). Among the blood samples, corresponding bands were amplified in 134 samples. The result showed that the blood meals were from pigs (n = 104), cows (n = 22), dogs (n = 4), human (n=2), cow and pig (n = 1), pig and human (n = 1). Human blood index of A. sinensis and A. minimus was 0.018 and 0.045, respectively.

[Research progress on the sugar-feeding behavior of mosquitoes and its application in mosquito control].

The energy of the physiological activities for both male and female mosquitoes is provided by feeding sugar outdoors. The attractive toxic sugar bait (ATSB) was developed according to the behavior, and showed a good result in reducing mosquito population size. This paper introduces the progress on the sugar-feeding behavior of mosquitoes and application in vector-borne disease control.

[In vitro sensitivity of Plasmodium falciparum isolates from China-Myanmar border region to chloroquine, piperaquine and pyronaridine].

OBJECTIVE: To assess the in vitro sensitivity of Plasmodium falciparum to chloroquine, piperaquine and pyronaridine in China-Myanmar border area. METHODS: Fifty-one blood specimens of P. falciparum isolates were collected from Laza City of Myanmar during September to December in 2009, and the sensitivity of the parasites to the drugs was detected by Rieckmann's in vitro microtest. RESULTS: Among the 42 blood samples with valid results of sensitivity test, the resistance rate to chloroquine, piperaquine and pyronaridine was 95.2%, 7.1%, and 54.8%, with a corresponding 50% inhibition dose (IDn) of 320.5, 128.2, and 96.0 nmol/L, respectively. Pyronaridine-resistant P. falciparum exhibited some degree of cross-resistance to chloroquine [91.3%(21/23)] and piperaquine [13.0% (3/23)], and chloroquine-resistant P. falciparum showed cross-resistance to piperaquine [7.5%(3/40)] and pyronaridine [52.5%(21/40)]. High level of cross-resistance was present to chloroquine (100%) and pyronaridine (100%) in piperaquine resistant P. falciparum. CONCLUSION: In Laza City, P. falciparum shows high resistance to chloroquine, half isolates are resistant to pyronaridine, and most isolates are still sensitive to piperaquine.

Historical review of malaria control and elimination in the border areas of China: A case study of Yunnan Province.

To understand how malaria could be eliminated in the original hyperendmic area for malaria along international borders in Yunnan Province, malaria situation and control were described on the basis of seven phases. At last the experiences and lessons of the program that reduced border malaria from hyperendmicity to malaria-free status were summarized. Malaria control and elimination area were particularly difficult in the Yunnan border. The achievement can be attributed to high political commitment, strategic and technical innovations based on the actual locality, effective collaboration and communication with neighbouring countries to carry out cross border interventions. Other border areas might perform their own pilot interventions based on their local context, including malaria burden, governing system, health service structure contextualized based on their socioeconomic development and ecology, and then a local decision could be made according to their own trial results.

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.

Malaria: elimination tale from Yunnan Province of China and new challenges for reintroduction.

BACKGROUND: Eradication of infectious disease is the sanctified public health and sustainable development goal around the world. MAIN BODY: Three antimalarial barriers were developed to control imported malarial cases, and an effective surveillance strategy known as the "1-3-7 approach" was developed to eliminate malaria from the Chinese population. From 2011 to 2019, 5254 confirmed malaria cases were reported and treated in Yunnan Province, China. Among them, 4566 cases were imported from other countries, and 688 cases were indigenous from 2011 to 2016. Since 2017, no new local malarial case has been reported in China. Thus, malaria has been completely eliminated in Yunnan Province. However, malaria is detected in overseas travellers on a regular basis, such as visitors from neighbouring Myanmar. CONCLUSION: Hence, the strategies should be further strengthened to maintain a robust public health infrastructure for disease surveillance and vector control programs in border areas. Such programs should be supported technically and financially by the government to avert the possibility of a malarial resurgence in Yunnan Province.

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.

Genetic diversity and population structure of Aedes aegypti after massive vector control for dengue fever prevention in Yunnan border areas.

Dengue fever is a mosquito-borne disease caused by the dengue virus. Aedes aegypti (Ae. Aegypti) is considered the primary vector of Dengue virus transmission in Yunnan Province, China. With increased urbanization, Ae. aegypti populations have significantly increased over the last 20 years. Despite all the efforts that were made for controlling the virus transmission, especially on border areas between Yunnan and Laos, Vietnam, and Myanmar (dengue-endemic areas), the epidemic has not yet been eradicated. Thus, further understanding of the genetic diversity, population structure, and invasive strategies of Ae. aegypti populations in the border areas was vital to uncover the vector invasion and distribution dynamic, and essential for controlling the infection. In this study, we analyzed genetic diversity and population structure of eight adult Ae. Aegypti populations collected along the border areas of Yunnan Province in 2017 and 2018. Nine nuclear microsatellite loci and mitochondrial DNA (mtDNA) sequences were used to achieve a better understanding of the genetic diversity and population structure. One hundred and fourteen alleles were found in total. The polymorphic information content value, together with the expected heterozygosity (He) and observed heterozygosity (Ho) values showed high genetic diversity in all mosquito populations. The clustering analysis based on Bayesian algorithm, the UPGMA and DAPC analysis revealed that all the eight Ae. aegypti populations can be divided into three genetic groups. Based on the mtDNA results, all Ae. aegypti individuals were divided into 11 haplotypes. The Ae. aegypti populations in the border areas of Yunnan Province presented with high genetic diversity, which might be ascribed to the continuous incursion of Ae. aegypti.