Mr. Thesis

Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus
========================

The largest monkeypox virus (MPXV) outbreak described so far in non-endemic countries was identified in May 20221-6. Here, shotgun metagenomics allowed the rapid reconstruction and phylogenomic characterization of the first MPXV outbreak genome sequences, showing that this MPXV belongs to clade 3 and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018-2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. An in-depth mutational analysis suggests the action of host APOBEC3 in viral evolution as well as signs of potential MPXV human adaptation in ongoing microevolution. Our findings also indicate that genome sequencing may provide resolution to track the spread and transmission of this presumably-slow-evolving dsDNA virus.

https://www.nature.com/articles/s41591-022-01907-y

မျောက်​ကျောက်​ရောဂါကာကွယ်​ဆေးထိုးနှံခြင်း
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​မျောက်ကျောက်​ရောဂါကာကွယ်​ဆေးထိုးနှံခြင်း
နဲ့ပတ်သက်ပြီး ကမ္ဘာ့ကျန်းမာ​ရေးအဖွဲ့က ၁၄-၆-၂၀၂၂ ရက်​နေ့မှာ ကနဦးလမ်းညွန်ချက်ကို ထုတ်ပြန်ခဲ့ပါတယ်။ ဒီထုတ်ပြန်ချက်မှာ အဓိကအချက် ၅ချက်ပါပါတယ်။

အဲဒီအချက်​တွေက​တော့
၁။ လက်ရှိအ​ခြေအ​နေမှာ လူအများအပြားကို ကာကွယ်​ဆေးထိုးဖို့ မလိုအပ်သလို၊ မတိုက်တွန်းကြောင်း၊

၂။ ​ရောဂါရှိသူနဲ့ ထိ​တွေ့ထားသူ​တွေအ​နေနဲ့ ထိ​တွေ့ပြီး ၄ရက်အတွင်း post-exposure prophylaxis (PEP) လို့​ခေါ်တဲ့ ထိ​တွေ့ပြီး​​နောက်ရောဂါဖြစ်ပွားမှုကိုကာကွယ်နိုင်ဖို့ ကမ္ဘာကျန်းမာ​ရေးအဖွဲ့ကအသိအမှတ်ပြုထားတဲ့ကာကွယ်​ဆေးကိုထိုးနှံဖို့ တိုက်တွန်း​ကြောင်း၊

၃။ အလားတူ ​ရောဂါကူးစက်နိုင်​ခြေများတဲ့ ကျန်းမာ​ရေးဝန်ထမ်း​တွေ၊ ဓါတ်ခွဲစမ်းသပ်ရောဂါရှာ​ဖွေသူ​တွေ၊ ဒါ့အပြင် နိုင်ငံအလိုက် ချမှတ်ထားတဲ့မူဝါဒအရ​ ရောဂါကူးစက်နိုင်​ခြေရှိသူ​တွေ အ​နေနဲ့လည်း post-exposure prophylaxis (PEP) ယူဖို့ တိုက်တွန်း​​ကြောင်း၊

၄။ ကာကွယ်​ဆေးထိုးစီမံချက်ကို အ​ကောင်အထည်မ​ဖော်ခင် ​ရောဂါရှာ​ဖွေစစ်​ဆေးမှု၊ ထိ​တွေ့လူနာရှာ​ဖွေ​ဖော်ထုတ်မှု၊ ကျန်းမာ​​ရေးအသိပညာ​ပေးမှု၊ ကာကွယ်​ဆေးရဲ့​ဘေးကင်းစိတ်ချရမှုနဲ့ အာနိသင်ရှိမှု​တွေကို စနစ်တကျသု​တေသနပြု​လေ့လာသုံးသပ်မှု ​ဆောင်ရွက်ဖို့ လိုအပ်​ကြောင်း၊

၅။ ကာကွယ်​ဆေးထိုးသင့်၊ မထိုးသင့် ဆုံးဖြတ်တဲ့​နေရာမှာ လူတစ်ဦးချင်းဆီအတွက် ​အကျိုး၊ အပြစ် ​သေချာစစ်​ဆေးတွက်ချက်ဖို့လိုအပ်​ကြောင်း၊ စတာ​တွေဖြစ်ပါတယ်။

အခုအချိန်အထိ မြန်မာနိုင်ငံမှာ ​မျောက်​ကျောက်​ရောဂါကူးစက်ခံရသူ တစ်ဦးတစ်​ယောက်မှမရှိ​သေး​ကြောင်း ကျန်းမာ​ရေးဝန်ကြီးဌာနကထုတ်ပြန်ထားပါတယ်။

​မေတ္တာဖြင့်
​ဒေါက်တာဇင်​ဇေယျာဝင်း
၁၅-၆-၂၀၂၂

Identification of a new HCV subtype 6xg among injection drug users in Kachin, Myanmar

Abstract
Characterizing HCV genetic diversity not only allows us to trace its origin and evolutionary history, but also provides valuable insights into diagnosis, prevention and therapy of HCV infection. Although eight HCV genotypes and 86 subtypes have been classified, there are still some HCV variants that need to be assigned. The genotype 6 is the most diverse HCV genotype and mainly prevalent in Southeast Asia. In this study, we identified a new HCV subtype 6xg from injection drug users (IDUs) in Kachin, Myanmar. A distinctive feature of 6xg from other subtypes of the genotype 6 was a Lys insertion in NS5A gene, which changes the RRKR/K motif into RRKKR/K. Bayesian analyses showed that HCV 6xg originated during 1984-1988, and experienced a rapid population expansion during 2005-2009. We characterized HCV subtype profile among IDUs in this region, and detected six HCV subtypes, including 1a (12%), 3a (12%), 3b (24%), 6n (16%), 6xa (20%), and 6xg (12%). Importantly, we found that HCV subtype distribution in Kachin was very similar to that in Dehong prefecture of Yunnan, but very distinct from those in other regions of Myanmar and Yunnan, indicating that the China-Myanmar border region shared a unique HCV subtype pattern. The appearance of 6xg and the unique HCV subtype profile among IDUs in the China-Myanmar border region have significant epidemiological and public health implications.

To cite: Zheng YT, Ye M, Chen X, Wang Y, Duo L, Zhang C. Identification of a new HCV subtype 6xg among injection drug users in Kachin, Myanmar. Frontiers in Microbiology. 2019;10:814.

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Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow

Abstract

Background
Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts.
Methods
Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012.
Results
A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6–97.9) in Myawaddy and 98.3% (95% CI 88.7–99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855–0.876), with low inter-population differentiation (F ST 0.016–0.026, P < 0.05).
Conclusions
Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.

To cite: Htun MW, Mon NC, Aye KM, Hlaing CM, Kyaw MP, Handayuni I, Trimarsanto H, Bustos D, Ringwald P, Price RN, Auburn S. Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow. Malaria journal. 2017 Dec;16(1):281.

Hard-to-Reach Villages in Myanmar: Challenges in Access to Health Services and Interim Solutions

Abstract

Background: After decades of under investment in health system, strengthening primary health care becomes a central focus of Myanmar’s National Health Plan (2017- 2020). In 2011, a health systems strengthening programme was piloted in 20 hard-to-reach townships of Myanmar with support from the Vaccine Alliance. Programme reached the hard-to-reach population with outreach health services, and introduced Hospital Equity Fund to provide free hospitalbased MCH services for poor mothers and children. Prior to its implementation, a baseline assessment was conducted in 2010 and early 2011 and after 2 years, in 2013, programme performance was assessed. This paper reviews the baseline health system situation of 20 hard-to-reach townships in 2010 and assesses programme outputs in 2013. Further, it draws key lessons from implementing interim strategy of primary health care strengthening, to inform current primary health care reform in Myanmar.
Method: Findings from baseline assessment of 20 hard-to-reach townships in 2010-2011 are reviewed to understand township health system situation. Programme outputs after 2 years, in 2013, are assessed through routine monitoring data and reports review, in-depth interviews of total 48 key informants from two selected townships who are township medical officers and basic health staffs, and field observations by the authors.
Results: Baseline assessment uncovered large gaps and multiple challenges that impeded delivery of primary health service in hard-to-reach areas of Myanmar. For example, shortage and misdistribution of primary health workers, lack of essential medicines, equipment, infrastructure and allowances hampered the delivery of outreach and static primary health services. Only 7% of rural health centers met the 13-health workers standard; while 19% of sub centres did not have sheltered premises for service provision. Poverty, low education, financial, geographical and social barriers were key demand side barriers. After two years, in 20 townships, statistics showed increased rates of antenatal care in 19 townships, Skilled Birth Attendants in 15 townships, and coverage of 2nd dose of Tetanus Toxoid and BCG in 11 townships. The Hospital Equity Fund prevented 1,327 potential maternal deaths through obstetric emergency.
Conclusion: Outreach services in low resource setting can ensure improved access to essential health services for the hard-to reach population. While investment in Interim strategy such as outreach services and hospital equity fund demonstrates positive changes in primary health care indicators, it should be gradually replaced by a sustainable primary health care system, for progressive realization of universal health coverage.

To cite: Wangmo S, Patcharanarumol W, Nwe ML, Tangcharoensathien V. Hard-to-Reach Villages in Myanmar: Challenges in Access to Health Services and Interim Solutions. Quality in Primary Care. 2017 Jul 3;25(4).

Influenza A(H9N2) Virus, Myanmar, 2014–2015

Routine surveillance of influenza A virus was conducted in Myanmar during 2014–2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

To cite: Lin TN, Nonthabenjawan N, Chaiyawong S, Bunpapong N, Boonyapisitsopa S, Janetanakit T, Mon PP, Mon HH, Oo KN, Oo SM, Win MM. Influenza A (H9N2) Virus, Myanmar, 2014–2015. Emerging infectious diseases. 2017 Jun;23(6):1041.

Surgical Mask vs N95 Respirator for Preventing Influenza Among Health Care Workers

Abstract

Context: Data about the effectiveness of the surgical mask compared with the N95 respirator for protecting health care workers against influenza are sparse. Given the likelihood that N95 respirators will be in short supply during a pandemic and not available in many countries, knowing the effectiveness of the surgical mask is of public health importance.

Objective: To compare the surgical mask with the N95 respirator in protecting health care workers against influenza.

Design, Setting, and Participants: Noninferiority randomized controlled trial of 446 nurses in emergency departments, medical units, and pediatric units in 8 tertiary care Ontario hospitals.

Intervention: Assignment to either a fit-tested N95 respirator or a surgical mask when providing care to patients with febrile respiratory illness during the 2008-2009 influenza season.

Main Outcome Measures: The primary outcome was laboratory-confirmed influenza measured by polymerase chain reaction or a 4-fold rise in hemagglutinin titers. Effectiveness of the surgical mask was assessed as noninferiority of the surgical mask compared with the N95 respirator. The criterion for noninferiority was met if the lower limit of the 95% confidence interval (CI) for the reduction in incidence (N95 respirator minus surgical group) was greater than −9%.

Results: Between September 23, 2008, and December 8, 2008, 478 nurses were assessed for eligibility and 446 nurses were enrolled and randomly assigned the intervention; 225 were allocated to receive surgical masks and 221 to N95 respirators. Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, −0.73%; 95% CI, −8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of −9%.

Conclusion: Among nurses in Ontario tertiary care hospitals, use of a surgical mask compared with an N95 respirator resulted in noninferior rates of laboratory-confirmed influenza.

To cite:
Loeb M, Dafoe N, Mahony J, John M, Sarabia A, Glavin V, Webby R, Smieja M, Earn DJ, Chong S, Webb A. Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial. Jama. 2009 Nov 4;302(17):1865-71.

Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes

Abstract

The recent emergence of both chikungunya and Zika viruses in the Americas has significantly expanded their distribution and has thus increased the possibility that individuals may become infected by more than one Aedes aegypti-borne virus at a time. Recent clinical data support an increase in the frequency of coinfection in human patients, raising the likelihood that mosquitoes could be exposed to multiple arboviruses during one feeding episode. The impact of coinfection on the ability of relevant vector species to transmit any of these viruses (that is, their vector competence) has not been determined. Thus, we here expose Ae. aegypti mosquitoes to chikungunya, dengue-2 or Zika viruses, both individually and as double and triple infections. Our results show that these mosquitoes can be infected with and can transmit all combinations of these viruses simultaneously. Importantly, infection, dissemination and transmission rates in mosquitoes are only mildly affected by coinfection.

To cite
Rückert C, Weger-Lucarelli J, Garcia-Luna SM, Young MC, Byas AD, Murrieta RA, Fauver JR, Ebel GD. Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes. Nature Communications. 2017;8.

Malaria epidemiology in central Myanmar: identification of a multi-species asymptomatic reservoir of infection
Abstract

Background
The spread of artemisinin-resistant Plasmodium falciparum is a global health concern. Myanmar stands at the frontier of artemisinin-resistant P. falciparum. Myanmar also has the highest reported malaria burden in Southeast Asia; it is integral in the World Health Organization’s plan to eliminate malaria in Southeast Asia, yet few epidemiological data exist for the general population in Myanmar.
Methods
This cross-sectional, probability household survey was conducted in Phyu township, Bago Region (central Myanmar), during the wet season of 2013. Interviewers collected clinical and behavioural data, recorded tympanic temperature and obtained dried blood spots for malaria PCR and serology. Plasmodium falciparum positive samples were tested for genetic mutations in the K13 region that may confer artemisinin resistance. Estimated type-specific malaria PCR prevalence and seroprevalence were calculated, with regression analysis to identify risk factors for seropositivity to P. falciparum. Data were weighted to account for unequal selection probabilities.
Results
1638 participants were sampled (500 households). Weighted PCR prevalence was low (n = 41, 2.5%) and most cases were afebrile (93%). Plasmodium falciparum was the most common species (n = 19. 1.1%) and five (26%) P. falciparum samples harboured K13 mutations. Plasmodium knowlesi was detected in 1.0% (n = 16) and Plasmodium vivax was detected in 0.4% (n = 7). Seroprevalence was 9.4% for P. falciparum and 3.1% for P. vivax. Seroconversion to P. falciparum was 0.003/year in the whole population, but 16-fold higher in men over 23 years old (LR test p = 0.016).
Discussion
This is the first population-based seroprevalence study from central Myanmar. Low overall prevalence was discovered. However, these data suggest endemic transmission continues, probably associated with behavioural risk factors amongst working-age men. Genetic mutations associated with P. falciparum artemisinin resistance, the presence of P. knowlesi and discrete demographic risk groups present opportunities and challenges for malaria control. Responses targeted to working-age men, capable of detecting sub-clinical infections, and considering all species will facilitate malaria elimination in this setting.

To cite
Ghinai I, Cook J, Hla TT, Htet HM, Hall T, Lubis IN, Ghinai R, Hesketh T, Naung Y, Lwin MM, Latt TS. Malaria epidemiology in central Myanmar: identification of a multi-species asymptomatic reservoir of infection. Malaria journal. 2017 Jan 5;16(1):16.

Influenza A(H9N2) Virus, Myanmar, 2014–2015

Abstract
Routine surveillance of influenza A virus was conducted in Myanmar during 2014–2015. Influenza A(H9N2) virus was isolated in Shan State, upper Myanmar. Whole-genome sequencing showed that H9N2 virus from Myanmar was closely related to H9N2 virus of clade 4.2.5 from China.

To cite
Lin TN, Nonthabenjawan N, Chaiyawong S, Bunpapong N, Boonyapisitsopa S, Janetanakit T, Mon PP, Mon HH, Oo KN, Oo SM, Win MM. Influenza A (H9N2) Virus, Myanmar, 2014–2015. Emerging infectious diseases. 2017 Jun;23(6):1041.

A Report on Upgraded Seismic Monitoring Stations in Myanmar: Station Performance and Site Response

Abstract
Myanmar is in a tectonically complex region between the eastern edge of the Himalayan collision zone and the northern end of the Sunda megathrust. Until recently, earthquake monitoring and research efforts have been hampered by a lack of modern instrumentation and communication infrastructure. In January 2016, a major upgrade of the Myanmar National Seismic Network (MNSN; network code MM) was undertaken to improve earthquake monitoring capability. We installed five permanent broadband and strong‐motion seismic stations and real‐time data telemetry using newly improved cellular networks. Data are telemetered to the MNSN hub in Nay Pyi Taw and archived at the Incorporated Research Institutions for Seismology Data Management Center. We analyzed station noise characteristics and site response using noise and events recorded over the first six months of station operation. Background noise characteristics vary across the array, but indicate that the new stations are performing well. MM stations recorded more than 20 earthquakes of M≥4.5 within Myanmar and its immediate surroundings, including an M 6.8 earthquake located northwest of Mandalay on 13 April 2016 and the Mw 6.8 Chauk event on 24 August 2016. We use this new dataset to calculate horizontal‐to‐vertical spectral ratios, which provide a preliminary characterization of site response of the upgraded MM stations.
To cite: Thiam HN, Htwe YM, Kyaw TL, Tun PP, Min Z, Htwe SH, Aung TM, Lin KK, Aung MM, de Cristofaro J, Franke M. A Report on Upgraded Seismic Monitoring Stations in Myanmar: Station Performance and Site Response. Seismological Research Letters. 2017 Mar 22.

Effect of misoprostol on the pharmacokinetics of sustained release diclofenac in Myanmar healthy male volunteers
Htet Htet Aung, Aye Soe, Nu Nu Aye

Abstract
Background: Sustained release diclofenac (diclofenac SR) is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis.Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR.
Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers.
Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 µg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC). Pharmacokinetic parameters such as area under concentration-time curve (AUC0-∞), peak plasma concentration (Cmax), time to achieve peak plasma concentration (Tmax), absorption half-life (T½(ab)), elimination half-life (T1/2(el)), absorption rate constant (Kab), and elimination rate constant (Kel) were determined.
Results: With misoprostol, the mean AUC0-∞ of diclofenac SR was significantly reduced from 12.11±5.25µg/mL×hr to 4.17±2.72µg/mL×hr (p0.05). The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el) was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05). The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05).
Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

To cite: Aung HH, Soe A, Aye NN. Effect of misoprostol on the pharmacokinetics of sustained release diclofenac in Myanmar healthy male volunteers. Siriraj Medical Journal. 2017 Mar 24;69(2):75-9.