Trends in HIV incidence following scale-up of harm reduction interventions among people who inject drugs in Kachin, Myanmar, 2008-2020: analysis of a retrospective cohort dataset.

Background: People who inject drugs (PWID) in Kachin, Myanmar, have a high HIV prevalence (>40%), but there is no data on incidence. We used HIV testing data from three harm reduction drop-in centres (DIC) in Kachin (2008-2020) to determine HIV incidence trends among PWID and associations with intervention uptake. Methods: Individuals were HIV-tested at first DIC visit and periodically thereafter, during which demographic and risk behaviour data were collected. Two DIC provided opioid agonist therapy (OAT) from 2008. Monthly DIC-level needle/syringe provision (NSP) data was available from 2012. Site-level 6-monthly NSP coverage was denoted low, high, or medium if it was below the lower quartile, above upper quartile, between these quartiles of provision levels over 2012-2020, respectively. HIV incidence was estimated by linking subsequent test records for those initially testing HIV-negative. Associations with HIV incidence were examined using Cox regression. Findings: Follow-up HIV testing data was available for 31.4% (2227) of PWID initially testing HIV-negative, with 444 incident HIV infections during 6266.5 person years (py) of follow-up. Overall HIV incidence was 7.1 per 100 py (95% confidence interval 6.5-7.8), which decreased from 19.3 (13.3-28.2) in 2008-11 to 5.2 per 100 py (4.6-5.9) in 2017-20. In the full PWID incidence dataset after adjustment for various factors, recent (≤6 weeks) injecting (aHR 1.74, 1.35-2.25) and needle sharing (aHR 2.00, 1.48-2.70) were associated with higher incidence, while longer injection careers were associated with reduced incidence (aHR 0.54, 0.34-0.86, for 2-5 yrs vs <2 yrs). In a reduced dataset including data on OAT access and NSP coverage (2012-2020 for two DIC providing OAT), being on OAT during follow-up was associated with reduced HIV incidence (aHR 0.36, 0.27-0.48, compared to never being on OAT) as was high NSP coverage (aHR 0.64, 0.48-0.84, compared to medium syringe coverage). Interpretation: Although HIV incidence is high among PWID in Kachin, data suggests it has decreased since the scale-up in harm reduction interventions. Funding: US NIH, Médecins du Monde.

Co-Development of a Web Application (COVID-19 Social Site) for Long-Term Care Workers ("Something for Us"): User-Centered Design and Participatory Research Study.

BACKGROUND: Improving confidence in and uptake of COVID-19 vaccines and boosters among long-term care workers (LTCWs) is a crucial public health goal, given their role in the care of elderly people and people at risk. While difficult to reach with workplace communication interventions, most LTCWs regularly use social media and smartphones. Various social media interventions have improved attitudes and uptake for other vaccines and hold promise for the LTCW population. OBJECTIVE: We aimed to develop a curated social web application (interactive website) to increase COVID-19 vaccine confidence (a 3-arm randomized trial is underway). METHODS: Following user-centric design and participatory research approaches, we undertook the following 3 steps: (1) content identification, (2) platform development, and (3) community building. A LTCW and stakeholder advisory group provided iterative input. For content identification (step 1), we identified topics of concern about COVID-19 vaccines via desktop research (published literature, public opinion polls, and social media monitoring), refined by interviewing and polling LTCWs. We also conducted a national online panel survey. We curated and fact-checked posts from popular social media platforms that addressed the identified concerns. During platform development (step 2), we solicited preferences for design and functionality via interviews and user experience testing with LTCWs. We also identified best practices for online community building (step 3). RESULTS: In the interviews (n=9), we identified 3 themes: (1) LTCWs are proud of their work but feel undervalued; (2) LTCWs have varying levels of trust in COVID-19-related information; and (3) LTCWs would welcome a curated COVID-19 resource that is easy to understand and use-"something for us". Through desktop research, LTCW interviews, and our national online panel survey (n=592) we found that participants are interested in information about COVID-19 in general, vaccine benefits, vaccine risks, and vaccine development. Content identification resulted in 434 posts addressing these topic areas, with 209 uploaded to the final web application. Our LTCW poll (n=8) revealed preferences for personal stories and video content. The platform we developed is an accessible WordPress-based social media web application, refined through formal (n=3) and informal user experience testing. Users can sort posts by topic or subtopic and react to or comment on posts. To build an online community, we recruited 3 LTCW "community ambassadors" and instructed them to encourage discussion, acknowledge concerns, and offer factual information on COVID-19 vaccines. We also set "community standards" for the web application. CONCLUSIONS: An iterative, user-centric, participatory approach led to the launch of an accessible social media web application with curated content for COVID-19 vaccines targeting LTCWs in the United States. Through our trial, we will determine if this approach successfully improves vaccine confidence. If so, a similar social media resource could be used to develop curated social media interventions in other populations and with other public health goals.

Point-prevalence surveys of antimicrobial consumption and resistance at a paediatric and an adult tertiary referral hospital in Yangon, Myanmar.

BACKGROUND: Antimicrobial resistance is increasingly prevalent worldwide. The inappropriate use of antimicrobials, including in the hospital setting, is considered a major driver of antimicrobial resistance. AIM: To inform improvements in antimicrobial stewardship, we undertook point prevalence surveys of antimicrobial prescribing at Yangon Children's Hospital and Yangon General Hospital in Yangon, Myanmar. METHODS: We conducted our surveys using the Global Point-Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) method. All inpatients who were prescribed an antimicrobial on the day of the survey were included in the analysis. FINDINGS: We evaluated a total of 1,980 patients admitted to two hospitals during December 2019. Of these, 1,255 (63.4%) patients were prescribed a total of 2,108 antimicrobials. Among antimicrobials prescribed, 722 (34.3%) were third-generation cephalosporins, the most commonly prescribed antimicrobial class. A total of 940 (44.6%) antimicrobials were prescribed for community-acquired infection, and 724 (34.3%) for surgical prophylaxis. Of 2,108 antimicrobials, 317 (15.0%) were prescribed for gastrointestinal tract prophylaxis, 305 (14.5%) for skin, soft tissue, bone and joint prophylaxis, and 303 (14.4%) for pneumonia treatment. A stop or review date was documented for 350 (16.6%) antimicrobial prescriptions, 673 (31.9%) antimicrobial prescriptions were guideline compliant, and 1,335 (63.3%) antimicrobials were administered via the parenteral route. Of 1,083 antimicrobials prescribed for a therapeutic use, 221 (20.4%) were targeted therapy. CONCLUSION: Our findings underscore the need to update and expand evidence-based guidelines for antimicrobial use, promote the benefits of targeted antimicrobial therapy, and support the implementation of hospital-based antimicrobial stewardship programmes at the hospitals surveyed.

Genomic Tracking of SARS-CoV-2 Variants in Myanmar.

In December 2019, the COVID-19 disease started in Wuhan, China. The WHO declared a pandemic on 12 March 2020, and the disease started in Myanmar on 23 March 2020. In December 2020, different variants were brought worldwide, threatening global health. To counter those threats, Myanmar started the COVID-19 variant surveillance program in late 2020. Whole genome sequencing was done six times between January 2021 and March 2022. Among them, 83 samples with a PCR threshold cycle of less than 25 were chosen. Then, we used MiSeq FGx for sequencing and Illumina DRAGEN COVIDSeq pipeline, command line interface, GISAID, and MEGA version 7 for data analysis. In January 2021, no variant was detected. The second run, during the rise of cases in June 2021, showed Alpha, Delta, and Kappa variants. The third and the fourth runs in August and December showed only a Delta variant. Omicron and Delta variants were detected during the fifth run in January 2022. The sixth run in March 2022 showed only Omicron BA.2. Amino acid mutation at the receptor binding domain of Spike glycoprotein started since the second run coupling with high transmission, recurrence, and vaccine escape. We also found the mutation at the primer targets used in current RT-PCR platforms, but there was no mutation at the existing antiviral drug targets. The occurrence of multiple variants and mutations claimed vigilance at ports of entry and preparedness for effective control measures. Genomic surveillance with the observation of evolutionary data is required to predict imminent threats of the current disease and diagnose emerging infectious diseases.

Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer.

BACKGROUND: Chemoresistance is one of the main problems in treatment of cancer. Periostin (PN) is a stromal protein which is mostly secreted from cancer associated fibroblasts in the tumor microenvironment and can promote cancer progression including cell survival, metastasis, and chemoresistance. The main objective of this study was to develop an anti-PN peptide from the bacteriophage library to overcome PN effects in breast cancer (BCA) cells. METHODS: A twelve amino acids bacteriophage display library was used for biopanning against the PN active site. A selected clone was sequenced and analyzed for peptide primary structure. A peptide was synthesized and tested for the binding affinity to PN. PN effects including a proliferation, migration and a drug sensitivity test were performed using PN overexpression BCA cells or PN treatment and inhibited by an anti-PN peptide. An intracellular signaling mechanism of inhibition was studied by western blot analysis. Lastly, PN expressions in BCA patients were analyzed along with clinical data. RESULTS: The results showed that a candidate anti-PN peptide was synthesized and showed affinity binding to PN. PN could increase proliferation and migration of BCA cells and these effects could be inhibited by an anti-PN peptide. There was significant resistance to doxorubicin in PN-overexpressed BCA cells and this effect could be reversed by an anti-PN peptide in associations with phosphorylation of AKT and expression of survivin. In BCA patients, serum PN showed a correlation with tissue PN expression but there was no significant correlation with clinical data. CONCLUSIONS: This finding supports that anti-PN peptide is expected to be used in the development of peptide therapy to reduce PN-induced chemoresistance in BCA.

A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar.

Data on causes of community-onset bloodstream infection in Myanmar are scarce. We aimed to identify etiological agents of bloodstream infections and patterns of antimicrobial resistance among febrile adolescents and adults attending Yangon General Hospital (YGH), Yangon, Myanmar. We recruited patients ≥12 years old with fever ≥38°C who attended YGH from 5 October 2015 through 4 October 2016. A standardized clinical history and physical examination was performed. Provisional diagnoses and vital status at discharge was recorded. Blood was collected for culture, bloodstream isolates were identified, and antimicrobial susceptibility testing was performed. Using whole-genome sequencing, we identified antimicrobial resistance mechanisms of Enterobacteriaceae and sequence types of Enterobacteriaceae and Streptococcus agalactiae. Among 947 participants, 90 (9.5%) had bloodstream infections (BSI) of which 82 (91.1%) were of community-onset. Of 91 pathogens isolated from 90 positive blood cultures, we identified 43 (47.3%) Salmonella enterica including 33 (76.7%) serovar Typhi and 10 (23.3%) serovar Paratyphi A; 20 (22.0%) Escherichia coli; 7 (7.7%) Klebsiella pneumoniae; 6 (6.6%), Staphylococcus aureus; 4 (4.4%) yeasts; and 1 (1.1%) each of Burkholderia pseudomallei and Streptococcus agalactiae. Of 70 Enterobacteriaceae, 62 (88.6%) were fluoroquinolone-resistant. Among 27 E. coli and K. pneumoniae, 18 (66.6%) were extended-spectrum beta-lactamase (ESBL)-producers, and 1 (3.7%) each were AmpC beta-lactamase- and carbapenemase-producers. Fluoroquinolone resistance was associated predominantly with mutations in the quinolone resistance-determining region. blaCTX-M-15 expression was common among ESBL-producers. Methicillin-resistant S. aureus was not detected. Fluoroquinolone-resistant, but not multiple drug-resistant, typhoidal S. enterica was the leading cause of community-onset BSI at a tertiary hospital in Yangon, Myanmar. Fluoroquinolone and extended-spectrum cephalosporin resistance was common among other Enterobactericeae. Our findings inform empiric management of severe febrile illness in Yangon and indicate that measures to prevent and control enteric fever are warranted. We suggest ongoing monitoring and efforts to mitigate antimicrobial resistance among community-onset pathogens.

Use of Augmented Reality in Reconstructive Microsurgery: A Systematic Review and Development of the Augmented Reality Microsurgery Score.

BACKGROUND: Augmented reality (AR) uses a set of technologies that overlays digital information into the real world, giving the user access to both digital and real-world environments in congruity. AR may be specifically fruitful in reconstructive microsurgery due to the dynamic nature of surgeries performed and the small structures encountered in these operations. The aim of this study was to conduct a high-quality preferred reporting items for systematic reviews and meta-analyses (PRISMA) and assessment of multiple systematic reviews 2 (AMSTAR 2) compliant systematic review evaluating the use of AR in reconstructive microsurgery. METHODS: A systematic literature search of Medline, EMBASE, and Web of Science databases was performed using appropriate search terms to identify all applications of AR in reconstructive microsurgery from inception to December 2018. Articles that did not meet the objectives of the study were excluded. A qualitative synthesis was performed of those articles that met the inclusion criteria. RESULTS: A total of 686 articles were identified from title and abstract review. Five studies met the inclusion criteria. Three of the studies used head-mounted displays, one study used a display monitor, and one study demonstrated AR using spatial navigation technology. The augmented reality microsurgery score was developed and applied to each of the AR technologies and scores ranged from 8 to 12. CONCLUSION: Although higher quality studies reviewing the use of AR in reconstructive microsurgery is needed, the feasibility of AR in reconstructive microsurgery has been demonstrated across different subspecialties of plastic surgery. AR applications, that are reproducible, user-friendly, and have clear benefit to the surgeon and patient, have the greatest potential utility. Further research is required to validate its use and overcome the barriers to its implementation.

Molecular mechanisms of antimicrobial resistance and phylogenetic relationships of Salmonella enterica isolates from febrile patients in Yangon, Myanmar.

BACKGROUND: Enteric fever is common in southeast Asia. However, there is little information on the circulating Salmonella enterica strains causing enteric fever in Myanmar. METHODS: We performed antimicrobial susceptibility testing and whole genome sequencing on S. enterica bloodstream isolates from febrile patients aged ≥12 y attending two hospitals in Yangon, Myanmar, from 5 October 2015 through 4 October 2016. We identified the serovar of S. enterica, determined antimicrobial susceptibility and the molecular mechanisms of resistance. We analysed phylogenetic relationships among Myanmar S. enterica isolates and those with isolates from neighbouring countries. RESULTS: Of 73 S. enterica isolated, 39 (53%) were serovar Typhi and 34 (47%) were Paratyphi A. All isolates were susceptible to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole but resistant to ciprofloxacin. We identified mutations in chromosomal genes gyrA, gyrB and parC as responsible for fluoroquinolone resistance. All S. enterica Typhi isolates were of 4.3.1 subclade (formerly known as H58) and formed two closely related genotypic clusters; both clusters were most closely related to isolates from India from 2012. All S. enterica Paratyphi A were lineage C, clade C4 and were closely related. CONCLUSION: Our study describes currently circulating S. enterica serovars in Myanmar, the genetic basis of their antimicrobial resistance and provides a genotypic framework for epidemiologic study.

Microbiome dataset from the upper respiratory tract of patients living with HIV, HIV/TB and TB from Myanmar.

This article contains microbiome data from the upper respiratory tract of patients living with HIV/TB, HIV and TB from Meiktila, a town in Myanmar where there is a high incidence of HIV and TB. Microbiomes were compared for HIV/TB infected and healthy adults from the same population. We collected nasopharyngeal and oropharyngeal swabs from a total of 33 participants (Healthy {5}, HIV/TB {8}, HIV {14}, and TB {6}). DNA was extracted from the swabs and subjected to custom single step 16s rRNA sequencing on an Illumina MiSeq platform. The sequencing data is available via http://www.ncbi.nlm.nih.gov/bioproject/ PRJNA432583.

Prevalence and associated risk factors of Strongyloides stercoralis infection in Lower Myanmar.

BACKGROUND: Strongyloidiasis is prevalent in Southeast Asian regions along with other soil-transmitted helminthiases, but only limited present-day data was available for Myanmar. METHODS: A prevalence survey for Strongyloides stercoralis infection was conducted among villagers in rural areas of three townships located in the Lower Myanmar during 2014-2016 by agar plate culture method in combination with specific identification by molecular assays. Risk factors associated with S. stercoralis infection were assessed by analyzing questionnaires obtained from study participants. RESULTS: Strongyloides stercoralis was identified in 40 out of 703 participants (5.7% overall prevalence). The highest prevalence (14.4%) was observed in Htantabin, while other two communities (Thabaung and Thanlyin) had much lower prevalence (2.2 and 2.5%, respectively). Infection was relatively rare (1.2%) in younger generations under 20 years compared to older generations (9.5%). Even in Htantabin, none of the female residents under age 40 (n = 33) had infection. In adult Htantabin residents, those who answered that they do not wear shoes regularly had an elevated risk of infection (odds ratio = 2.50, 95% confidence interval = 1.03-6.08). CONCLUSIONS: This study showed that there is still an on-going transmission of strongyloidiasis in Lower Myanmar. It is highly desirable that the soil should be free of fecal contamination by improving the management of fecal waste. Meanwhile, health education to promote shoe-wearing would be beneficial to reduce the risk of transmission, especially for those who have frequent and intense contact with soil.

Current Status of Research Ethics Capacity in Myanmar.

Myanmar has recently surfaced from total military rule and efforts at conducting research to enhance the health of the population has increased during the recent democratization process, both from the military and civil sectors as well as support from international agencies. International guidelines mandate that such research requires prior ethics review in accordance with international standards. Previous commentators have expressed concerns, however, regarding the degree of adequate training in research ethics for investigators, the optimal functioning of Research Ethics Committees (RECs), and the extent of responsible conduct in research in low and middle-income countries. Such concerns might also be applicable to Myanmar, especially since it has recently emerged from a long period of military rule where there has been lack of basic freedoms and human rights abuses. We herein review the current gaps in research ethics capacity in Myanmar, the status of the existing RECs and the current efforts to establish training programs to enhance capacity in research ethics.

Associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence: A systematic review and meta-analysis.

OBJECTIVE: The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent. METHODS: For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger's statistical tests. RESULTS: We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis. CONCLUSIONS: Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.

An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples.

BACKGROUND: Highly sensitive, scalable diagnostic methods are needed to guide malaria elimination interventions. While traditional microscopy and rapid diagnostic tests (RDTs) are suitable for the diagnosis of symptomatic malaria infection, more sensitive tests are needed to screen for low-density, asymptomatic infections that are targeted by interventions aiming to eliminate the entire reservoir of malaria infection in humans. METHODS: A reverse transcription polymerase chain reaction (RT- PCR) was developed for multiplexed detection of the 18S ribosomal RNA gene and ribosomal RNA of Plasmodium falciparum and Plasmodium vivax. Simulated field samples stored for 14 days with sample preservation buffer were used to assess the analytical sensitivity and specificity. Additionally, 1750 field samples from Southeastern Myanmar were tested both by RDT and ultrasensitive RT-PCR. RESULTS: Limits of detection (LoD) were determined under simulated field conditions. When 0.3 mL blood samples were stored for 14 days at 28 °C and 80% humidity, the LoD was less than 16 parasites/mL for P. falciparum and 19.7 copies/µL for P. vivax (using a plasmid surrogate), about 10,000-fold lower than RDTs. Of the 1739 samples successfully evaluated by both ultrasensitive RT-PCR and RDT, only two were RDT positive while 24 were positive for P. falciparum, 108 were positive for P. vivax, and 127 were positive for either P. vivax and/or P. falciparum using ultrasensitive RT-PCR. CONCLUSIONS: This ultrasensitive RT-PCR method is a robust, field-tested screening method that is vastly more sensitive than RDTs. Further optimization may result in a truly scalable tool suitable for widespread surveillance of low-level asymptomatic P. falciparum and P. vivax parasitaemia.

Infiltrating syringomatous adenoma of the nipple: clinical presentation and literature review.

Infiltrating syringomatous adenoma of the nipple is a rare neoplasm of the breast. Syringomatous adenoma of the nipple is often misdiagnosed because clinical examination and mammographic findings of syringomatous adenoma of the nipple mimic carcinoma. Despite its benign behavior, syringomatous adenoma of the nipple usually shows infiltrative expansile proliferation into adjacent tissue and underlying breast tissue. Up until now, to our knowledge, there has been no reported case of regional or distant metastasis. Histologically and clinically, syringomatous adenoma of the nipple is often confused with tubular carcinoma as well as low-grade adenosquamous carcinoma of the breast. Special attention given to this tumor by pathologists and clinicians can avoid misdiagnosis and unnecessary treatment.

Reversible posterior leukoencephalopathy syndrome in a child treated with bevacizumab.

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Hypertension is a well-recognized, common side effect of VEGF blocking agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been described as a rare but serious consequence of bevacizumab administration. We present a case of a 6-year-old child with refractory hepatoblastoma who developed hypertensive crisis, seizures and MRI changes consistent with RPLS while receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely resolved without neurologic sequelae with stringent blood-pressure control. Better understanding of risk for RPLS, prompt recognition and aggressive management will be required as bevacizumab gains wider use in pediatrics.