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Objective: Prospective studies of encephalitis are rare in regions where encephalitis is prevalent, such as low middle‐income Southeast Asian countries. We compared the diagnostic yield of local and advanced tests in cases of pediatric encephalitis in Myanmar. Methods: Children with suspected subacute or acute encephalitis at Yangon Children's Hospital, Yangon, Myanmar, were prospectively recruited from 2016–2018. Cohort 1 (n = 65) had locally available diagnostic testing, whereas cohort 2 (n = 38) had advanced tests for autoantibodies (ie, cell‐based assays, tissue immunostaining, studies with cultured neurons) and infections (ie, BioFire FilmArray multiplex Meningitis/Encephalitis multiplex PCR panel, metagenomic sequencing, and pan‐viral serologic testing [VirScan] of cerebrospinal fluid). Results: A total of 20 cases (13 in cohort 1 and 7 in cohort 2) were found to have illnesses other than encephalitis. Of the 52 remaining cases in cohort 1, 43 (83%) had presumed infectious encephalitis, of which 2 cases (4%) had a confirmed infectious etiology. Nine cases (17%) had presumed autoimmune encephalitis. Of the 31 cases in cohort 2, 23 (74%) had presumed infectious encephalitis, of which one (3%) had confirmed infectious etiology using local tests only, whereas 8 (26%) had presumed autoimmune encephalitis. Advanced tests confirmed an additional 10 (32%) infections, 4 (13%) possible infections, and 5 (16%) cases of N‐methyl‐D‐aspartate receptor antibody encephalitis. Interpretation: Pediatric encephalitis is prevalent in Myanmar, and advanced technologies increase identification of treatable infectious and autoimmune causes. Developing affordable advanced tests to use globally represents a high clinical and research priority to improve the diagnosis and prognosis of encephalitis. ANN NEUROL 2023;93:615–628 [ABSTRACT FROM AUTHOR]

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight‐based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co‐infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro‐costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow‐up. SVR was achieved in 680/803 (84.6%) by intention‐to‐treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non‐PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real‐world estimate of $1250. High SVR rates were achieved for non‐PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real‐world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population. [ABSTRACT FROM AUTHOR]

• The use of point–of–care (POC) assays for HCV detection and diagnosis in Myanmar (a developing and low resource setting) was established. • There was a strong positive correlation coefficient between GeneXpert and Roche, r (155) = 0.96, (p <0.001). • GeneXpert and ABL methods showed a good level of agreement with the standard roche real time HCV assay. • The mean difference and 95 % limits of agreement were -0.28 and −0.7 to 0.2 IU/mL, and -0.063 and −1.4 to 1.3 Log10IU/mL for GeneXpert and ABL, respectively. Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real–time HCV testing and results especially to at–risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene–HCV assays against the gold standard and reference method Roche real–time HCV in Myanmar. Blood samples from 158 high–risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland–Altman analyses. There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p <0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries. [ABSTRACT FROM AUTHOR]

The coordination of development efforts and ecological conservation in China's border regions is a significant challenge due to the overlap of biodiversity hotspots, ecologically fragile zones, and impoverished areas. Achieving the harmonious integration of ecological preservation and economic development relies on the fundamental assessment of ecological security (ES). However, comprehensive assessments of ES in border regions remain limited. This study introduces a new index, the multivariate ecological security index (MESI), which integrates ecosystem vigor, organization, elasticity, services and risk. Here, the MESI was utilized to assess the temporal and spatial changes in ES and its associated impact factors in the China-Myanmar border region (CMBR) from 2000 to 2020. The MESI provides a clear representation of the actual ES status in the CMBR, exhibiting a significant correlation with the eco-environmental quality index (EEQI; p < 0.01). The ES status exhibited notable spatial heterogeneity in the CMBR, consisting primarily of both relatively safe and safe levels, which accounted for approximately 85% of the total area. From 2000 to 2020, the CMBR experienced a gradual improvement in ES status, with the area experiencing an increase in the ES level accounting for 23.41% of the total area, which exceeded the proportion of the area experiencing a decrease in the ES level (4.71%). The combined impact of multiple factors exerted a greater influence on ES than did individual factors alone. Notably, human factors increasingly influenced the ES status during the study period. The results of this study provide valuable insights for ecological preservation and sustainable management in the CMBR, and the MESI can be extended to assess the ES of other regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Mosquito-based arbovirus surveillance can serve as an early warning in evaluating the status of mosquito-borne virus prevalence and thus prevent local outbreaks. Although Tengchong County in Yunnan Province-which borders Myanmar-is abundant and diverse in mosquitoes, very few mosquito-based arbovirus investigations have been conducted in the recent decade. Herein, this study aims to evaluate the presence and the diffusion of mosquito-borne pathogens, currently prevalent in this region., Methods: We collected 9486 mosquitoes, representing eight species, with Culex tritaeniorhynchus and Anopheles sinensis as the dominant species, during high mosquito activity seasons (July-October) in Tengchong, in 2018. Samples collected from 342 pools were tested using reverse-transcription PCR to determine the species, distribution, and infection rates of virus and parasite, and further analyze their genotypes, phylogenetic relationships, infection rate, and potential pathogenicity., Results: Fifteen Japanese encephalitis virus (JEV) strains from Cx. tritaeniorhynchus pools were detected. Seven strains of insect-specific flaviviruses (ISFVs), including two Aedes flavivirus (AeFV) and Yunnan Culex flavivirus strains each, one Culex theileri flavivirus, Yamadai flavivirus (YDFV) and Anopheles-associated flavivirus (AAFV) strains each were detected in Aedes albopictus, Cx. tritaeniorhynchus, Cx. vagans, Cx. pseudovihnui, and An. sinensis pools, respectively. The whole-genome was successfully amplified in one strain of JEV and AeFV each. Phylogenetic analysis using the E gene placed all the newly detected JEV strains into the GI-b genotype. They showed highly nucleotide identities, and were most closely related to the strain detected in Tengchong in 2010. The comparison of the E protein of JEV strains and vaccine-derived strain, showed six amino residue differences. The bias-corrected maximum likelihood estimation values (and 95% confidence interval) for JEV in Cx. tritaeniorhynchus collected in Tengchong in 2018 were 2.4 (1.4-3.9)., Conclusions: A potential Japanese encephalitis epidemic focus with the abundance of host mosquitoes and high JEV infection rate was observed in Tengchong. In addition, at least five species of ISFVs co-circulate in this area. This study highlights the importance of widespread and sustained mosquito-based arbovirus surveillance in local areas to prevent the transmission of JEV, and other emerging/re-emerging mosquito-borne pathogens.

Background: HIV-transmitted drug resistance (TDR) is found in antiretroviral therapy (ART)-naïve populations infected with HIV-1 with TDR mutations and is important for guiding future first- and second-line ART regimens. We investigated TDR and its effect on CD4 count in ART-naïve youths from the China-Myanmar border near the Golden Triangle to better understand TDR and effectively guide ART., Methods: From 2009 to 2017, 10,832 HIV-1 infected individuals were newly reported along the Dehong border of China, 573 ART-naïve youths (16 ~ 25 y) were enrolled. CD4 counts were obtained from whole blood samples. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and jpHMM recombination prediction tool were used to determine genotypes. TDR mutations (TDRMs) were analyzed using the Stanford Calibrated Population Resistance tool., Results: The most common infection route was heterosexuals (70.51%), followed by people who inject drugs (PWID, 19.20%) and men who have sex with men (MSM) (8.90%). The distribution of HIV genotypes mainly included the unique recombinant form (URF) (44.08%), 38.68% were CRFs, 13.24% were subtype C and 4.04% were subtype B. The prevalence of TDR increased significantly from 2009 to 2017 (3.48 to 9.48%) in ART-naïve youths (4.00 to 13.16% in Burmese subjects, 3.33 to 5.93% in Chinese subjects), and the resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 3.49, 2.62, and 0.52%, respectively. Most (94.40%, n = 34) of HIV-1-infected patients with TDRM had mutation that conferred resistance to a single drug class. The most common mutations Y181I/C and K103N, were found in 7 and 9 youths, respectively. The mean CD4 count was significantly lower among individuals with TDRMs (373/mm 3 vs. 496/mm 3 , p = 0.013)., Conclusions: The increase in the prevalence of HIV-1 TDR increase and a low CD4 count of patients with TDRMs in the China-Myanmar border suggests the need for considering drug resistance before initiating ART in HIV recombination hotspots.

To reveal the genetic diversity of Babesia microti and Theileria orientalis in Southwest China, we conducted a molecular survey of piroplasms in hard ticks in a China-Myanmar border county. Host infesting and questing ticks were collected from Tengchong County in 2013 and 2014. Piroplasm infection in ticks was detected by PCR, and then, phylogenetic analysis was conducted to study the genetic diversity of the pathogens identified in ticks. All in all, six piroplasm species comprising of B. microti; B. orientalis; a novel Babesia species designated Babesia sp. Tengchong, China; T. orientalis; T. luwenshuni; and an as yet undescribed piroplasmid species referred to as Piroplasmid sp. Tengchong, China, have been identified after screening goat- and cattle-attached ticks. In addition, B. bigemina has been identified by screening questing ticks. Phylogenetic analysis based on the 18S rRNA and partial β-tubulin gene revealed two novel potentially zoonotic genotypes designated B. microti Tengchong-Type A and B. The T. orientalis genotypes identified in the present study represent the seven known genotypes 1-5, 7, and N3 as revealed by phylogenetic analysis of 18S rRNA and MPSP genes. Importantly, an additional genotype designated N4 has also been identified in this study, which brings the number of recognized T. orientalis genotypes to a total of twelve. Thus, besides the two novel species, Babesia sp. Tengchong, China, closely related to Babesia species isolated from yak and Piroplasmid sp. Tengchong, China, our study demonstrates that additional novel B. microti and T. orientalis genotypes exist in Southwest China.

Background: Many tick species have great morphological similarity and are thus grouped into species complexes. Molecular methods are therefore useful in the classification and identification of ticks. However, little is known about the genetic diversity of hard ticks in China, especially at the subspecies level. Tengchong is one of the epidemic foci of tick-borne diseases in China, but the tick species inhabiting the local area are still unknown., Methods: Eighteen villages in Tengchong County, China, were selected for sampling carried out from September to October 2014. Infesting hard ticks were removed from the body surface of domestic animals and questing ticks were collected from grazing fields. After morphological identification, molecular characteristics of each tick species were analyzed based on both 16S rRNA and cytochrome c oxidase subunit 1 (cox1) gene fragments., Results: Six tick species were identified based on morphology: Rhipicephalus microplus, R. haemaphysaloides, Ixodes ovatus, Haemaphysalis longicornis, H. shimoga and H. kitaokai. Phylogenetic analysis using the cox1 gene revealed that R. microplus ticks from the present study belong to clade C. For tick samples of both R. haemaphysaloides and I. ovatus, three phylogenetic groups were recognized, and the intergroup genetic distances exceeded the usual tick species boundaries. Haemaphysalis longicornis ticks were clustered into two separate clades based on the cox1 gene. For ticks from both H. shimoga and H. kitaokai, two phylogenetic groups were recognized based on the phylogenetic analysis of the 16S rRNA gene, and the intergroup genetic distances also exceeded the known boundaries for closely related tick species., Conclusions: According to molecular analyses, new species or subspecies closely related to R. haemaphysaloides, I. ovatus, H. shimoga and H. kitaokai probably exist in the China-Myanmar border Tengchong County, or these ticks form species complexes with highly divergent mitochondrial lineages. Morphological comparisons are warranted to further confirm the taxonomic status of these tick species.

Cholera, caused by Vibrio cholerae , remains a global threat to public health. In Myanmar, the availability of published information on the occurrence of the disease is scarce. We report here that cholera incidence in Mandalay generally exhibited a single annual peak, with an annual average of 312 patients with severe dehydration over the past 5 years (since 2011) and was closely associated with the rainy season. We analyzed cholera outbreaks, characterized 67 isolates of V. cholerae serogroup O1 in 2015 from patients from Mandalay, and compared them with 22 V. cholerae O1 isolates (12 from Mandalay and 10 from Yangon) in 2014. The isolates carried the classical cholera toxin B subunit ( ctxB ), the toxin-coregulated pilus A ( tcpA ) of Haitian type, and repeat sequence transcriptional regulator ( rstR ) of El Tor type. Two molecular typing methods, pulsed-field gel electrophoresis and multiple-locus variable-number tandem repeat analysis (MLVA), differentiated the 89 isolates into seven pulsotypes and 15 MLVA profiles. Pulsotype Y15 and one MLVA profile (11, 7, 7, 16, 7) were predominantly found in the isolates from cholera outbreaks in Mandalay, 2015. Pulsotypes Y11, Y12, and Y15 with some MLVA profiles were detected in the isolates from two remote areas, Mandalay and Yangon, with temporal changes. These data suggested that cholera spread from the seaside to the inland area in Myanmar.

Objective: To reveal the distribution and composition of malaria-transmitting vectors on the western part of China-Myanmar border., Methods: An entomological survey of malaria vectors was carried out in six villages of Yingjiang County and Xidong County on China-Myanmar border between August and September, 2008. Mosquitoes in human dwellings and cattle sheds were collected by overnight trapping with ovitrap light. The mosquitoes were firstly identified morphologically, and then Anopheles minimus A and C, An. aconitus, and An. jeyporiensis were identified by using multiplex PCR. Some mosquitoes were selected to extract the total genomic DNA, and detect sporozoites by nested PCR., Results: A total of 4571 mosquitoes were captured with 54.32% (2483/4571) of anopheline mosquitoes. There was significant difference in Anopheles species composition in human dwellings and cattle sheda The main species in human dwellings were An. kochi, An. minimus, and An. sinensis, while the principal species in cattle sheds consist of An. kochi (223), An. annularis (184), An. vagus (131), and An jeyporiensis (129). Furthermore, the composition in human dwellings of villages with and without cattle was significantly different. An. minimus (260) and An. kochi (49) werethe most important species in villages with cattle, whereas An. kochi (481) and An. sinensis (124) were the key species in villages without cattle. A total of 1075 mosquitoes were examined for sporozoites and 9 mosquitoes were found to be infected. Only three species, Le. An. minimus (7/408), An aconiaus (1/125) and An. pseudowillmori (1/101) were infected with malaria parasite. All sporozoites were identified as Plasmodium falcipoarum by sequencing, the target fragment was 204 bp., Conclusion: The species composition of mosquitoes is complex in the study sites on the western part of China-Myanmar border, and An. minimus is the major malaria vector. Additionally, An. aconitus and An.pseudowillmori are also confirmed as potential malaria vector in this area.

Background: Co-infection with HIV and HCV and/or HBV is highly prevalent in intravenous drug users (IDUs). Because of the proximity to the "Golden Triangle", HIV prevalence among the IDUs is very high in the China-Myanmar border region. However, there are few studies about co-infection with HIV and HCV and/or HBV, especially in the region that belongs to Myanmar., Methods: 721 IDUs, including 403 Chinese and 318 Burmese, were investigated for their HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) serological status. Statistical analysis was performed to evaluate the differences of the epidemic situation between the Chinese IDUs and the Burmese IDUs., Results: Among the Chinese IDUs and the Burmese IDUs, HCV infection was the most prevalent (69.0% vs 48.1%, P<0.001), followed by HBV (51.6% vs 43.1%, P<0.05) and HIV (33.7% vs 27.0%, P>0.05). Besides, there were more HIV-HBV co-infected IDUs (20.1% vs 11.3%, P<0.005), and HIV-HCV co-infected IDUs (31.8% vs 23.9%, P<0.05) in China than in Myanmar, as well as HIV-HBV-HCV triple infection (19.1% vs 10.4%, P<0.005)., Conclusion: Co-infection with HIV and HCV and/or HBV is highly prevalent among the IDUs in the China-Myanmar border region. The HIV epidemic appears to be in a downward trend, compared with previous reports. However, all infections were more prevalent among the Chinese IDUs than among the Burmese.