Cooperative Sentinel Surveillance of Malaria in Laiza and Nearby Areas of Myanmar and Importation Threat Monitoring - China, 2019-2023.

Introduction: Laiza and nearby areas (LNA) in Myanmar are identified as the primary malaria hotspots in the bordering regions of Yunnan Province, China. Methods: Six sentinel surveillance sites were established at the China-Myanmar border in LNA to monitor malaria. Data from 2019 was used as a baseline to analyze malaria incidence and trends in LNA and Myanmar, as well as the importation of malaria cases into China from 2019 to 2023. Results: Plasmodium vivax was the predominant species, representing 99.95% (14,060/14,066) of confirmed malaria cases in LNA. A total of 8,356 malaria cases were identified in 2023, with an annual parasite incidence (API) of 19.78 per 100 person-years. Compared to 2019, the incidence rate ratio was 21.47 (95% confidence interval: 18.84, 24.48), indicating that the API in 2023 was 21.47 times higher than that in 2019. In Yunnan, out of 1,016 reported cases, 545 imported cases (53.64%) originated from LNA and spread to 18 (13.95%) out of 129 counties. Ten provinces in China, including Yunnan, reported imported malaria cases from LNA in Myanmar. Conclusions: The increase in population, particularly among internally displaced persons, along with inadequate healthcare services, has led to a notable resurgence of malaria in LNA. This resurgence poses a risk to preventing the re-emergence of malaria transmission in China. There is an urgent need for novel collaborative policies, as well as financial and technical assistance, to enhance malaria control efforts in LNA, Myanmar.

Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region.

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.

Screening for malaria infection in residents on the China-Myanmar border: RDT, microscopy and PCR / 中国热带医学

@#Abstract: Objective To compare the screening effects of RDT, microscopy and PCR for malaria among residents in low malaria areas and elimination areas, and to investigate the presence of malaria in residents of border Villages in Cangyuan Va County and asymptomatic infections in surrounding areas, providing a basis for preventing re-introduction of malaria after elimination. Methods From August 2020 to March 2021, the fingertip blood of the investigated subjects was collected from three survey sites in the border area between China and Myanmar, namely Banlao Township in Cangyuan Va Autonomous County of Lincang City, Banwai District, Mengmao County, the Second Special Zone of Shan State, Myanmar, Yongmo and Dayan Township, Nandeng Special Zone, the Second Special Zone of Shan State, Myanmar. The malaria parasite antigen detection test kit, malaria parasite microscopic examination, fluorescent quantitative PCR and nested PCR were used to detect the asymptomatic infection of malaria parasites. Results A total of 1 040 blood samples were collected, including 606 from China and 434 from Myanmar, with 506 males and 534 females. Among them, , there were 51 individuals aged 0 to <5 years, 283 aged 5 to < years, 187 aged 15 to < years, 232 aged 30 to <45 years, 205 aged 45 to < years, and 82 aged ≥60 years. All 1 040 people tested negative for plasmodium antigen detection kit. One case of Plasmodium vivax detected by plasmodium microscopic etiology, with a detection rate of 0.10%. One case of P. vivax was also detected by fluorescent quantitative PCR and nested PCR, with a detection rate of 0.10%. Among them, one case of P. vivax was detected in Banwai District, Mengmao County, the Second Special Zone of Shan State, Myanmar, with a detection rate of 0.35%. The detection rates of malaria parasites in Banlao Township in Cangyuan Va Autonomous County of Lincang City, Yunnan Province and Yongmo Township and Dayan Township, Nandeng Special District, the Second Special Zone of Shan State, Myanmar were both 0. The difference in the detection rate of malaria parasites among the three survey sites was not statistically significant (χ2 =2.682, P>0.05). The asymptomatic P. vivax infection was detected in a 6-year-old girl from Banwai District, Mengmao County, the Second Special Zone of Shan State, Myanmar. Conclusions RDT is not suitable for malaria screening in low malaria area and elimination area. Microscopic examination and PCR can be used for malaria screening, but PCR operation is complex and costly. In surrounding areas outside of China, malaria is still prevalent, while there is no source of malaria infection in border villages of Cangyuan Va County. However, there is a risk of importation, and timely and effective measures should be taken to prevent reintroduction and transmission.

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.

Malaria from hyperendemicity to elimination along international borders in Yunnan, China during 2003‒2020: a case study.

BACKGROUND: Border malaria is one of the most intractable problems hindering malaria elimination worldwide. Movement of both the human population and anopheline mosquitoes infected with Plasmodium spp. can cause cross-border malaria transmission. The Yunnan border area was still hyperendemic for malaria in the early part of this century. The objective of this case study was to analyze the strategies, interventions and impacts of malaria control and elimination in the Yunnan border area. MAIN TEXT: A total of 10,349 malaria cases and 17.1 per 10,000 person-years of annual parasite incidence (API) were reported in the border area in 2003. Based on natural village-based stratification, integrated interventions, including mass drug administration for radical cures and preventive treatment, clinically presumptive treatment of all febrile patients for malaria and indoor residual spraying or dipping bed nets with insecticides were successfully carried out from 2003 to 2013. The overall API was reduced to 0.6 per 10,000 person-years by 2013, while effective cross-border collaboration interventions dramatically reduced the malaria burden in the neighbouring border areas of Myanmar. From 2014 forward, the comprehensive strategy, including universal coverage of surveillance to detect malaria cases, a rapid response to possible malaria cases and effective border collaboration with neighbouring areas, successfully eliminated malaria and prevented reintroduction of malaria transmission in the Yunnan border area. CONCLUSIONS: In Yunnan malaria burden has successfully reduced by dynamically accurate stratification and comprehensive interventions; and then the region achieved elimination and prevented reintroduction of malaria transmission through intensive surveillance, rapid response and border collaboration. Other border areas should perform their own intervention trials to develop their own effective strategy.

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.

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.

In situ formation of a biomimetic lipid membrane triggered by an aggregation-enhanced photoligation chemistry.

Nature or synthetic systems that can self-assemble into biomimetic membranes and form compartments in aqueous solution have received extensive attention. However, these systems often have the problems of requiring complex processes or lacking of control in simulating lipid synthesis and membrane formation of cells. This paper demonstrates a conceptually new strategy that uses a photoligation chemistry to convert nonmembrane molecules to yield liposomes. Lysosphingomyelin (Lyso) and 2-nitrobenzyl alcohol derivatives (NBs) are used as precursors and the amphiphilic character of Lyso promotes the formation of mixed aggregates with NBs, bringing the lipid precursors into close proximity. Light irradiation triggers the conversion of NBs into reactive aldehyde intermediates, and the preassembly facilitates the efficient and specific ligation between aldehyde and Lyso amine over other biomolecules, thereby accelerating the synthesis of phospholipids and forming membrane compartments similar to natural lipids. The light-controllable transformation represents the use of an external energy stimulus to form a biomimetic phospholipid membrane, which has a wide range of applications in medicinal chemistry, synthetic biological and abiogenesis.

Malaria Risk Map Using Spatial Multi-Criteria Decision Analysis along Yunnan Border During the Pre-elimination Period.

In moving toward malaria elimination, finer scale malaria risk maps are required to identify hotspots for implementing surveillance-response activities, allocating resources, and preparing health facilities based on the needs and necessities at each specific area. This study aimed to demonstrate the use of multi-criteria decision analysis (MCDA) in conjunction with geographic information systems (GISs) to create a spatial model and risk maps by integrating satellite remote-sensing and malaria surveillance data from 18 counties of Yunnan Province along the China-Myanmar border. The MCDA composite and annual models and risk maps were created from the consensus among the experts who have been working and know situations in the study areas. The experts identified and provided relative factor weights for nine socioeconomic and disease ecology factors as a weighted linear combination model of the following: ([Forest coverage × 0.041] + [Cropland × 0.086] + [Water body × 0.175] + [Elevation × 0.297] + [Human population density × 0.043] + [Imported case × 0.258] + [Distance to road × 0.030] + [Distance to health facility × 0.033] + [Urbanization × 0.036]). The expert-based model had a good prediction capacity with a high area under curve. The study has demonstrated the novel integrated use of spatial MCDA which combines multiple environmental factors in estimating disease risk by using decision rules derived from existing knowledge or hypothesized understanding of the risk factors via diverse quantitative and qualitative criteria using both data-driven and qualitative indicators from the experts. The model and fine MCDA risk map developed in this study could assist in focusing the elimination efforts in the specifically identified locations with high risks.

Spatiotemporal Trends of Malaria in Relation to Economic Development and Cross-Border Movement along the China-Myanmar Border in Yunnan Province.

The heterogeneity and complexity of malaria involves political and natural environments, socioeconomic development, cross-border movement, and vector biology; factors that cannot be changed in a short time. This study aimed to assess the impact of economic growth and cross-border movement, toward elimination of malaria in Yunnan Province during its pre-elimination phase. Malaria data during 2011-2016 were extracted from 18 counties of Yunnan and from 7 villages, 11 displaced person camps of the Kachin Special Region II of Myanmar. Data of per-capita gross domestic product (GDP) were obtained from Yunnan Bureau of Statistics. Data were analyzed and mapped to determine spatiotemporal heterogeneity at county and village levels. There were a total 2,117 malaria cases with 85.2% imported cases; most imported cases came from Myanmar (78.5%). Along the demarcation line, malaria incidence rates in villages/camps in Myanmar were significantly higher than those of the neighboring villages in China. The spatial and temporal trends suggested that increasing per-capita GDP may have an indirect effect on the reduction of malaria cases when observed at macro level; however, malaria persists owing to complex, multi-faceted factors including poverty at individual level and cross-border movement of the workforce. In moving toward malaria elimination, despite economic growth, cooperative efforts with neighboring countries are critical to interrupt local transmission and prevent reintroduction of malaria via imported cases. Cross-border workers should be educated in preventive measures through effective behavior change communication, and investment is needed in active surveillance systems and novel diagnostic and treatment services during the elimination phase.

Phototriggered labeling and crosslinking by 2-nitrobenzyl alcohol derivatives with amine selectivity.

Here we report the use of 2-nitrobenzyl alcohol (NB) as a photoreactive group with amine selectivity and explore its applications for photoaffinity labeling and crosslinking of biomolecules. This work confirms that NB is an efficient photoreactive group and has great potential in drug discovery, chemical biology and protein engineering.

Light-responsive polymersomes with a charge-switch for targeted drug delivery.

Unlike the traditional block amphiphilic polymersomes, we herein report a lipid-like amphiphilic polymer that self-assembles into photo-responsive polymersomes for drug delivery. The introduction of a quaternary ammonium moiety not only provides a hydrophilic segment of the polymersomes, but also enables electrostatic adsorption with folic acid, thus achieving the targeting of cancer cells with overexpression of folate receptor. Upon light irradiation, the photocleavage reaction of the o-nitrobenzyl moiety disintegrates polymersomes by changing the polymer structure from cationic amphiphilic state to zwitterionic hydrophilic state, thus realizing photo-triggered drug release. The data showed that anticancer drugs (doxorubicin hydrochloride, DOX·HCl) can be loaded into the hydrophilic cavity of polymersomes and controllably released by photo-induced disintegration of polymersomes. Cellular assay showed that the active targeting of folic acid and photo-triggered release endowed the DOX-loaded polymersomes with a higher cytotoxicity to HeLa cells. Such cationic polymersomes provide a novel strategy for designing effective and intelligent drug carriers, and have potential application as a novel integrated platform for targeted drug delivery.

A well-defined unimolecular channel facilitates chloride transport.

A unimolecular ion channel was optimized by functionalization with a new type of rigid-rod oligomer. The macrocycle pendant endows chloride selectivity and the fluorescence feature and suitable length of the rod facilitates the visual insertion of channels into the lipid bilayer, resulting in efficient ion transport with an EC50 value of 0.36 µM.

Assessment of malaria control consultation and service posts in Yunnan, P. R. China.

BACKGROUND: This paper seeks to assess the function of malaria control consultation and service posts (MCCSPs) that are located on the border areas of Yunnan province, P.R. China, as a strategy for eliminating malaria among the mobile and migrant population in these areas. METHODS: A retrospective descriptive analytical study was conducted. Blood smear examinations conducted at all MCCSPs in Yunnan from 2008 to 2014 were analysed. A cross-sectional survey was conducted in 2014 to understand how the MCCSPs function and to elucidate the quality of the blood smear examinations that they conduct. RESULTS: Out of the surveyed MCCSPs, 66 % (39/59), 22 % (13/59), and 12 % (7/59) were attached to local township hospitals, village health clinics, and the county centre for disease control and prevention or private clinics, respectively. More than 64 % (38/59) of the posts' staff were part-time workers from township hospitals and village health facilities. Less than 31 % (18/59) of the posts' staff were full-time workers. A total of 35 positive malaria cases were reported from seven MCCSPs in 2014. Four MCCSPs were unable to perform their functions due to under staffing in 2014. There was a small fluctuation in blood smear examinations from January 2008 to June 2009, with two peaks during the period from July 2009 to October 2010. The number of blood smear examinations has been increasing since 2011. The yearly mean number of blood smear examinations in each post increased from 44 per month in 2011 to 109 per month in 2014, and the number of positive malaria cases detected by blood smear examinations has declined (χ 2 = 90.67, P = 0.000). The percentage of people from Yingjiang county getting blood smear examinations increased between 2008 and 2014, while percentages of the mobile population including Myanmar people, people from other provinces, and people from other Yunnan counties getting blood smear examinations decreased. CONCLUSION: MCCSPs face challenges in the phase of malaria elimination in Yunnan, China. New case detection strategies should be designed for MCCSPs taking into account the current trends of migration.

[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.

[Efficacy of Capture and Ligation Probe-PCR with#br# Pooling Strategy in Detection of Plasmodium spp.].

The capture and ligation probe-PCR（CLIP-PCR） with pooling strategy method and microscopy were applied on 100 clinical samples（7 positive and 93 negative samples） from the malaria reference laboratory in Yunnan Province. By calculating the detection rate, sensitivity, specificity, detection time and detection cost, the efficacy of the CLIP-PCR with pooling strategy method in detecting Plasmodium spp. was evaluated. The CLIP-PCR with matrix pooling strategy successfully detected Plasmodium spp. in all the 7 positive samples. Its sensitivity and specificity relative to the microscopy as a gold standard were both 100%. The detection time for all the samples by CLIP-PCR was 5.0 h, 85.0% shorter than that by microscopy（33.3 h）, and the detection cost was 300 yuan, 75.0% less than that by microscopy （1 000 yuan）.