Seroepidemiologic Survey of Crimean-Congo Hemorrhagic Fever Virus in Logging Communities, Myanmar.

Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Asia, infecting many animal hosts, but CCHFV has not been reported in Myanmar. We conducted a seroepidemiologic survey of logging communities in Myanmar and found CCHFV exposure was common (9.8%) and exposure to wild animal blood and body fluids was associated with seropositivity.

Anthropogenic interferences lead to gut microbiome dysbiosis in Asian elephants and may alter adaptation processes to surrounding environments.

Human activities interfere with wild animals and lead to the loss of many animal populations. Therefore, efforts have been made to understand how wildlife can rebound from anthropogenic disturbances. An essential mechanism to adapt to environmental and social changes is the fluctuations in the host gut microbiome. Here we give a comprehensive description of anthropogenically induced microbiome alterations in Asian elephants (n = 30). We detected gut microbial changes due to overseas translocation, captivity and deworming. We found that microbes belonging to Planococcaceae had the highest contribution in the microbiome alterations after translocation, while Clostridiaceae, Spirochaetaceae and Bacteroidia were the most affected after captivity. However, deworming significantly changed the abundance of Flavobacteriaceae, Sphingobacteriaceae, Xanthomonadaceae, Weeksellaceae and Burkholderiaceae. These findings may provide fundamental ideas to help guide the preservation tactics and probiotic replacement therapies of a dysbiosed gut microbiome in Asian elephants. More generally, these results show the severity of anthropogenic activities at the level of gut microbiome, altering the adaptation processes to new environments and the subsequent capability to maintain normal physiological processes in animals.

Morphological and molecular identification of cyathostomine gastrointestinal nematodes of Murshidia and Quilonia species from Asian elephants in Myanmar.

Gastrointestinal nematode parasites have long been recognized in Asian elephants. The most common parasites belong to the subfamily Cyathostominae of the family Strongylidae, which are small to medium-sized with a cylindrical buccal capsule surrounded by coronal leaflets. Diagnostic keys of such parasites are provided from old illustrations in the form of line drawings. However, there very few photomicrographs and no genetic information of these parasites exist. In the present study we obtained adult worm specimens from faeces of Asian elephants after anthelmintic treatment in two elephant camps in Myanmar. Here, we provided photomicrographs for five cyathostomine parasites, Murshidia falcifera, Murshidia indica, Murshidia neveulemairei, Quilonia renniei, and Quilonia travancra almost 100 years after their original drawings. In addition, we determined the mitochondrial cytochrome c oxidase subunit I (COI) gene sequences of these species. Phylogenetic analysis of the COI genes of Murshidia and Quilonia species from Asian and African elephants revealed parasite speciation in each elephant host. The present study also indicated that several Murshidia and Quilonia species were widely distributed in Asian elephants in Myanmar, providing new insight into control strategies and evolution of cyathostomine gastrointestinal parasites in elephants.

First record and analysis of the COI gene of Cobboldia elephantis obtained from a captive Asian elephant from Myanmar.

The stomach bot fly species in Asian elephants has long been known as Cobboldia elephantis. However, there is no genetic information available for this species to date. Here, we report that a third-instar fly larva was excreted from a captive Asian elephant four months after export from an elephant camp in Myanmar to a zoological garden in Japan. Morphological characteristics of the larva were coincident with published descriptions of C. elephantis. The mitochondrial cytochrome c oxidase subunit I (COI) gene was amplified from the larva by PCR using primers modified from those designed for DNA barcoding of insects and amphibians. The COI gene of C. elephantis showed 76.6 % and 83.6 % identity at the nucleotide and amino acid levels, respectively, to that of C. loxodontis, the stomach bot fly species in African elephants. Phylogenetic analysis of the COI genes of several stomach bot fly species revealed that the two Cobboldia species formed a clade separate from the stomach bot fly species found in rhinoceros and equids.

Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease in Asian Elephant Calves in Logging Camps, Myanmar.

In recent years, an alarming number of cases of lethal acute hemorrhagic disease have occurred in Asian elephant calves raised in logging camps in Myanmar. To determine whether these deaths were associated with infection by elephant endotheliotropic herpesvirus (EEHV), we conducted diagnostic PCR subtype DNA sequencing analysis on necropsy tissue samples collected from 3 locations. We found that EEHV DNA from 7 PCR loci was present at high levels in all 3 calves and was the same EEHV1A virus type that has been described in North America, Europe, and other parts of Asia. However, when analyzed over 5,610 bp, the strains showed major differences from each other and from all previously characterized EEHV1A strains. We conclude that these 3 elephant calves in Myanmar died from the same herpesvirus disease that has afflicted young Asian elephants in other countries over the past 20 years.

New elephant crisis in Asia-Early warning signs from Myanmar.

In the southern Bago Yoma mountain range in Myanmar, Asian elephants are being killed at a disturbing rate. This emerging crisis was identified initially through a telemetry study when 7 of 19 of collared elephants were poached within a year of being fitted with a satellite-GPS collar. Subsequent follow up of ground teams confirmed the human caused death or disappearance of at least 19 elephants, including the seven collared individuals, within a 35 km2 area in less than two years. The carcasses of 40 additional elephants were found in areas located across south-central Myanmar once systematic surveys began by our team and collaborators. In addition to the extreme rate of loss, this study documents the targeting of elephants for their skin instead of the more common ivory, an increasing trend in Myanmar. Intensive research programs focused on other conservation problems identified this issue and are now encouraging local authorities to prioritize anti-poaching efforts and improve conservation policies within the country. Myanmar represents one of the last remaining countries in Asia with substantial wildlands suitable for elephants. Increasing rates of human-elephant conflict and poaching events in this country pose a dire threat to the global population.

Acceptability of Peer-Delivered HIV Testing and Counselling Among Men Who Have Sex with Men (MSM) and Transgender Women (TW) in Myanmar.

Men who have sex with men (MSM) and transgender women (TW) are a priority population for HIV prevention in Myanmar but report sub-optimal HIV testing frequency. Previous studies have shown that peer involvement in HIV testing can normalize stigmatized sexualities and reduce barriers to testing. We explored the acceptability of peer-delivered HIV testing among 425 undiagnosed MSM and TW in Yangon and Mandalay. An overwhelming majority of participants (86%) reported being 'comfortable/very comfortable' with peer-delivered HIV testing. Logistic regression identified reporting sexual identity as Apone [adjusted odds ratio (aOR) 3.8; 95% CI 1.2-11.7], recent HIV testing (aOR 3.1; 95% CI 1.4-6.5), reporting a high likelihood of HIV acquisition (aOR 3.6; 95% CI 1.7-7.6), and reporting ≥ 5 casual partners in the past 3 months (aOR 0.2; 95% CI 0.1-0.6) as associated with peer-delivered HIV testing acceptability. Given ongoing HIV vulnerability among MSM and TW in Myanmar, peer-delivered testing may offer prevention benefits by increasing testing rates and identifying undiagnosed infection earlier.

A tool compound targeting the core binding factor Runt domain to disrupt binding to CBFß in leukemic cells.

The core binding factor (CBF) gene RUNX1 is a target of chromosomal translocations in leukemia, including t(8;21) in acute myeloid leukemia (AML). Normal CBF function is essential for activity of AML1-ETO, product of the t(8;21), and for survival of several leukemias lacking RUNX1 mutations. Using virtual screening and optimization, we developed Runt domain inhibitors which bind to the Runt domain and disrupt its interaction with CBFß. On-target activity was demonstrated by the Runt domain inhibitors' ability to depress hematopoietic cell formation in zebrafish embryos, reduce growth and induce apoptosis of t(8;21) AML cell lines, and reduce progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells. Runt domain inhibitors had similar effects on murine and human T cell acute lymphocytic leukemia (T-ALL) cell lines. Our results confirmed that Runt domain inhibitors might prove efficacious in various AMLs and in T-ALL.

Willingness to use HIV pre-exposure prophylaxis among gay men, other men who have sex with men and transgender women in Myanmar.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has emerged as a key component of contemporary HIV combination prevention strategies. To explore the local suitability of PrEP, country-specific acceptability studies are needed to inform potential PrEP implementation. In the context of Myanmar, in addition to resource constraints, HIV service access by gay men, other men who have sex with men, and transgender women (GMT) continues to be constrained by legislative and community stigma and marginalization. We aimed to determine PrEP acceptability among GMT in Myanmar and explore the factors associated with willingness to use PrEP. METHODS: GMT were recruited in Yangon and Mandalay through local HIV prevention outreach programmes in November and December 2014. Quantitative surveys were administered by trained peer educators and collected data on demographics, sexual risk, testing history and PrEP acceptability. A modified six-item PrEP acceptability scale classified self-reported HIV undiagnosed GMT as willing to use PrEP. Multivariable logistic regression identified factors associated with willingness to use PrEP. RESULTS: Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%). PrEP acceptability was high, with 270 (62%) GMT classified as willing to use PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05-3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82; 95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94; 95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The association between never or only occasionally using condoms with casual partners and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00-4.10). GMT who reported concern about side effects and long-term use of PrEP were less likely (aOR = 0.35; 95%CI = 0.21-0.59) to be willing to use PrEP. CONCLUSIONS: This is the first study to assess PrEP acceptability in Myanmar. Findings suggest PrEP is an acceptable prevention option among GMT in Myanmar, providing they are not required to pay for it. Implementation/demonstration projects are needed to explore the feasibility and cost-effectiveness of PrEP as a prevention option for GMT in Myanmar.

Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells.

The transcription factor RUNX1 is frequently mutated in myelodysplastic syndrome and leukemia. RUNX1 mutations can be early events, creating preleukemic stem cells that expand in the bone marrow. Here we show, counterintuitively, that Runx1-deficient hematopoietic stem and progenitor cells (HSPCs) have a slow growth, low biosynthetic, small cell phenotype and markedly reduced ribosome biogenesis (Ribi). The reduced Ribi involved decreased levels of rRNA and many mRNAs encoding ribosome proteins. Runx1 appears to directly regulate Ribi; Runx1 is enriched on the promoters of genes encoding ribosome proteins and binds the rDNA repeats. Runx1-deficient HSPCs have lower p53 levels, reduced apoptosis, an attenuated unfolded protein response, and accordingly are resistant to genotoxic and ER stress. The low biosynthetic activity and corresponding stress resistance provides a selective advantage to Runx1-deficient HSPCs, allowing them to expand in the bone marrow and outcompete normal HSPCs.

Condom use among male migrant workers in dry zone, Myanmar.

OBJECTIVE: To study the factors associated with condom use among male Myanmar migrant workers in Pakokku, Myanmar MATERIAL AND METHOD: This cross-sectional study used two stages cluster sampling with probability proportional to size (PPS) method to collect samples. During 1-14 February 2010, 324 male Myanmar migrant workers between 18 and 60 years of age were asked to complete face-to-face structured interview on knowledge, perception, cues to action, peer influence and sexual behaviors. Data were analyzed by descriptive statistics, Chi-square test and Fishers exact test. RESULTS: Results revealed that 71.0 percent of respondents were under young and middle adult age and 66.7 percent were married. It showed that 11.1 percent of the respondents used condom regularly with spouse or girlfriends or sex workers during the past year There were associations between age (p = 0.006), marital status (p < 0.001), educational level (p = 0.014), monthly income (p = 0.015), level of knowledge on HIV/AIDS (p = 0.017), perceived susceptibility of getting HIV/ AIDS (p = 0.024) and condom use. No associations were noted between occupation, duration of career; duration of each trip, perceived severity, perceived benefit, perceived barrier, cues to action, peer influence and condom use. CONCLUSION: With low proportion of regular condom use among study group, behavior change, communication interventions and strengthening of the 100.0% Targeted Condom Promotion Project are recommended to promote perception and knowledge about HIV/AIDS and condom use among male migrant workers.

Structure of the AML1-ETO NHR3-PKA(RIIα) complex and its contribution to AML1-ETO activity.

AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIα)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIα). Based on this structure, a key residue in AML1-ETO for PKA(RIIα) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIα) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.