Publications by authors named "Latt Latt Kyaw"

7 Publications

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Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study.

Lancet Glob Health 2022 07;10(7):e989-e1002

National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

Background: Encephalitis is a worldwide public health issue, with a substantially high burden among children in southeast Asia. We aimed to determine the causes of encephalitis in children admitted to hospitals across the Greater Mekong region by implementing a comprehensive state-of-the-art diagnostic procedure harmonised across all centres, and identifying clinical characteristics related to patients' conditions.

Methods: In this multicentre, observational, prospective study of childhood encephalitis, four referral hospitals in Cambodia, Vietnam, Laos, and Myanmar recruited children (aged 28 days to 16 years) who presented with altered mental status lasting more than 24 h and two of the following minor criteria: fever (within the 72 h before or after presentation), one or more generalised or partial seizures (excluding febrile seizures), a new-onset focal neurological deficit, cerebrospinal fluid (CSF) white blood cell count of 5 per mL or higher, or brain imaging (CT or MRI) suggestive of lesions of encephalitis. Comprehensive diagnostic procedures were harmonised across all centres, with first-line testing was done on samples taken at inclusion and results delivered within 24 h of inclusion for main treatable causes of disease and second-line testing was done thereafter for mostly non-treatable causes. An independent expert medical panel reviewed the charts and attribution of causes of all the included children. Using multivariate analyses, we assessed risk factors associated with unfavourable outcomes (ie, severe neurological sequelae and death) at discharge using data from baseline and day 2 after inclusion. This study is registered with, NCT04089436, and is now complete.

Findings: Between July 28, 2014, and Dec 31, 2017, 664 children with encephalitis were enrolled. Median age was 4·3 years (1·8-8·8), 295 (44%) children were female, and 369 (56%) were male. A confirmed or probable cause of encephalitis was identified in 425 (64%) patients: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71, 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. Diagnosis was made within 24 h of admission to hospital for 83 (13%) of 664 children. 119 (18%) children had treatable conditions and 276 (42%) had conditions that could have been preventable by vaccination. At time of discharge, 153 (23%) of 664 children had severe neurological sequelae and 83 (13%) had died. In multivariate analyses, risk factors for unfavourable outcome were diagnosis of M tuberculosis infection upon admission (odds ratio 3·23 [95% CI 1·04-10·03]), coma on day 2 (2·90 [1·78-4·72]), supplementary oxygen requirement (1·89 [1·25-2·86]), and more than 1 week duration between symptom onset and admission to hospital (3·03 [1·68-5·48]). At 1 year after inclusion, of 432 children who were discharged alive from hospital with follow-up data, 24 (5%) had died, 129 (30%) had neurological sequelae, and 279 (65%) had completely recovered.

Interpretation: In southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region.

Funding: Institut Pasteur, Institut Pasteur International Network, Fondation Merieux, Aviesan Sud, INSERM, Wellcome Trust, Institut de Recherche pour le Développement (IRD), and Fondation Total.
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July 2022

Operational experiences associated with the implementation of near point-of-care early infant diagnosis of HIV in Myanmar: a qualitative study.

BMC Health Serv Res 2021 Aug 23;21(1):863. Epub 2021 Aug 23.

Burnet Institute, Melbourne, Australia.

Background: Timely diagnosis and early initiation of life-saving antiretroviral therapy are critical factors in preventing mortality among HIV-infected infants. However, resource-limited settings experience numerous challenges associated with centralised laboratory-based testing, including low rates of testing, complex sample referral pathways and unacceptably long turnaround times for results. Point-of-care (POC) HIV testing for HIV-exposed infants can enable same-day communication of results and early treatment initiation for HIV-infected infants. However, complex operational issues and service integration can limit utility and must be well understood prior to implementation. We explored and documented the challenges and enabling factors in implementing the POC Xpert® HIV-1 Qual test (Cepheid, Sunnyvale, CA, USA) for early infant diagnosis (EID) as part of routine services in four public hospitals in Myanmar.

Methods: This sub-study was part of a randomised controlled stepped-wedge trial (Australian and New Zealand Clinical Trials Registry, number 12616000734460) designed to investigate the impact of POC testing for EID in Myanmar and Papua New Guinea. Infants recruited during the intervention phase underwent POC testing at the participating hospitals as part of routine care. Semi-structured interviews with 23 caregivers, 12 healthcare providers and 10 key informants were used to explore experiences of POC-EID testing. The research team and hospital staff documented and discussed implementation challenges throughout the study.

Results: Overall, caregivers and healthcare workers were satisfied with the short turnaround time of the POC test. Occasional delays in POC testing were mostly attributable to late receipt of samples by laboratory technicians and communication constraints among healthcare staff. Hospital staff valued technical assistance from the research group and the National Health Laboratory. Despite staff shortages and infrastructure challenges such as unreliable electricity supply and cramped space, healthcare workers and caregivers found the implementation of the POC test to be feasible at pilot sites.

Conclusions: As plans for national scale-up evolve, there needs to be a continual focus on staff training, communication pathways and infrastructure. Other models of care, such as allowing non-laboratory-trained personnel to perform POC testing, and cost effectiveness should also be evaluated.
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August 2021

Evolutionary analysis of human respiratory syncytial virus collected in Myanmar between 2015 and 2018.

Infect Genet Evol 2021 09 18;93:104927. Epub 2021 May 18.

Infectious Diseases Research Center of Niigata University in Myanmar (IDRC), 1-757, Asahahimachi-dori, Chuo-ku, Niigata-shi, Niigata 951-8510, Japan. Electronic address:

We studied genetic variation in the second hypervariable region (HVR) of the G gene of human respiratory syncytial virus (HRSV) from 1701 nasal swab samples collected from outpatients with acute respiratory infections at two general hospitals in the cities Yangon and Pyinmana in Myanmar from 2015 to 2018. HRSV genotypes were characterized using phylogenetic trees constructed using the maximum likelihood method. Time-scale phylogenetic tree analyses were performed using the Bayesian Markov chain Monte Carlo method. In total, 244 (14.3%) samples were HRSV-positive and were classified as HRSV-A (n = 84, 34.4%), HRSV-B (n = 158, 64.8%), and co-detection of HRSV-A/HRSV-B (n = 2, 0.8%). HRSV epidemics occurred seasonally between July (1.9%, 15/785) and August (10.5%, 108/1028), with peak infections in September (35.8%, 149/416) and October (58.2%, 89/153). HRSV infection rate was higher in children ≥1 year of age than in those <1 year of age (70.5% vs. 29.5%). The most common HRSV symptoms in children were cough (80%-90%) and rhinorrhea (70%-100%). The predominant genotypes were ON1for HRSV-A (78%) and BA9 for HRSV-B (64%). Time to the most recent common ancestor was 2014 (95% highest posterior density [HPD], 2012-2015) for HRSV-A ON1 and 2009 (95% HPD, 2004-2012) for HRSV-B BA9. The mean evolutionary rate (substitutions/site/year) for HRSV-B (2.12 × 10, 95% HPD, 8.53 × 10-3.63 × 10) was slightly higher than that for HRSV-A (1.39 × 10, 95% HPD, 6.03 × 10-2.12 × 10). The estimated effective population size (diversity) for HRSV-A increased from 2015 to 2016 and declined in mid-2018, whereas HRSV-B diversity was constant in 2015 and 2016 and increased in mid-2017. In conclusion, the dominant HRSV-A and HRSV-B genotypes in Myanmar were ON1 and BA9, respectively, between 2015 and 2018. HRSV-B evolved slightly faster than HRSV-A and exhibited unique phylogenetic characteristics.
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September 2021

Caregiver experience and perceived acceptability of a novel near point-of-care early infant HIV diagnostic test among caregivers enrolled in the PMTCT program, Myanmar: A qualitative study.

PLoS One 2020 30;15(10):e0241245. Epub 2020 Oct 30.

The Kirby Institute for Infection and Immunity in Society, UNSW Sydney, Sydney, Australia.

Background: The majority of HIV infection among children occurs through mother-to-child transmission. HIV exposed infants are recommended to have virological testing at birth or 4-6 weeks of age but challenges with centralized laboratory-based testing in Myanmar result in low testing rates and delays in result communication and treatment initiation. Decentralized point-of-care (POC) testing when integrated in prevention of mother-to-child transmission of HIV (PMTCT) services, can be an alternative to increase coverage of early infant diagnosis (EID) and timely engagement in HIV treatment and care.

Aim: This paper aims to explore experiences of caregivers of HIV-exposed infants enrolled in the PMTCT program in Myanmar and the perceived acceptability of point-of-care EID testing compared to conventional centralised laboratory-based testing.

Methods: This is a sub-study of the cluster randomised controlled stepped-wedge trial (Trial registration number: ACTRN12616000734460) that assessed the impact of near POC EID testing using Xpert HIV-1 Qual assay in four public hospitals in Myanmar. Caregivers of infants who were enrolled in the intervention phase of the main study, had been tested with both Xpert and standard of care tests and had received the results were eligible for this qualitative study. Semi-structured interviews were conducted with 23 caregivers. Interviews were audio recorded, transcribed verbatim and translated into English. Thematic data analysis was undertaken using NVivo 12 Software (QSR International).

Results: The majority of caregivers were satisfied with the quality of care provided by PMTCT services. However, they encountered social and financial access barriers to attend the PMTCT clinic regularly. Mothers had concerns about community stigma from the disclosure of their HIV status and the potential consequences for their infants. While medical care at the PMTCT clinics was free, caregivers sometimes experienced financial difficulties associated with out-of-pocket expenses for childbirth and transportation. Some caregivers had to choose not to attend work (impacting their income) or the adult antiretroviral clinic in order to attend the paediatric PMTCT clinic appointment. The acceptability of the Xpert testing process was high among the caregiver participants and more than half received the Xpert result on the same day as testing. Short turnaround time of the near POC EID testing enabled the caregivers to find out their infants' HIV status quicker, thereby shortening the stressful waiting time for results.

Conclusion: Our study identified important access challenges facing caregivers of HIV exposed infants and high acceptability of near POC EID testing. Improving the retention rate in the PMTCT and EID programs necessitates careful attention of program managers and policy makers to these challenges, and POC EID represents a potential solution.
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December 2020

Epidemic of influenza A(H1N1)pdm09 analyzed by full genome sequences and the first case of oseltamivir-resistant strain in Myanmar 2017.

PLoS One 2020 4;15(3):e0229601. Epub 2020 Mar 4.

National Health Laboratory, Department of Medical Services, Ministry of Health and Sports, Yangon, Yangon Region, Myanmar.

A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017-2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar.
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June 2020

Phylogeographic analysis of human influenza A and B viruses in Myanmar, 2010-2015.

PLoS One 2019 10;14(1):e0210550. Epub 2019 Jan 10.

Division of International Health, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi-dori, Chuo-ku, Niigata, Niigata, Japan.

We investigated the circulation patterns of human influenza A and B viruses in Myanmar between 2010 and 2015 by analyzing full HA genes. Upper respiratory tract specimens were collected from patients with symptoms of influenza-like illness. A total of 2,860 respiratory samples were screened by influenza rapid diagnostic test, of which 1,577 (55.1%) and 810 (28.3%) were positive for influenza A and B, respectively. Of the 1,010 specimens that were positive for virus isolation, 370 (36.6%) were A(H1N1)pdm09, 327 (32.4%) were A(H3N2), 130 (12.9%) B(Victoria), and 183 (18.1%) were B(Yamagata) viruses. Our data showed that influenza epidemics mainly occurred during the rainy season in Myanmar. Our three study sites, Yangon, Pyinmana, and Pyin Oo Lwin had similar seasonality and circulating type and subtype of influenza in a given year. Moreover, viruses circulating in Myanmar during the study period were closely related genetically to those detected in Thailand, India, and China. Phylogeographic analysis showed that A(H1N1)pdm09 viruses in Myanmar originated from Europe and migrated to other countries via Japan. Similarly, A(H3N2) viruses in Myanmar originated from Europe, and disseminated to the various countries via Australia. In addition, Myanmar plays a key role in reseeding of influenza B viruses to Southeast Asia and East Asia as well as Europe and Africa. Thus, we concluded that influenza virus in Myanmar has a strong link to neighboring Asian countries, Europe and Oceania.
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October 2019

Ensuring accurate testing for human immunodeficiency virus in Myanmar.

Bull World Health Organ 2015 Jan 24;93(1):42-6. Epub 2014 Oct 24.

JICA Major Infectious Disease Control Project II, Yangon, Myanmar .

Problem: Until 2005, the quality of rapid diagnostic human immunodeficiency virus (HIV) testing was not monitored and no regular technical support was provided to hospital laboratories in Myanmar.

Approach: The national reference laboratory introduced a national external quality assessment scheme. The scheme involved (i) training laboratory technicians in HIV testing and in the requirements of the quality assessment system; (ii) implementing a biannual proficiency panel testing programme; (iii) on-site assessments of poorly-performing laboratories to improve testing procedures; and (iv) development of national guidelines.

Local Setting: In 2011, a total of 422 public hospitals in Myanmar had laboratories providing HIV tests. In addition, private laboratories supported by nongovernmental organizations (NGOs) conducted HIV testing.

Relevant Changes: The scheme was started in 65 public laboratories in 2005. In 2012, it had expanded nationwide to 347 laboratories, including 33 NGO laboratories. During the expansion of the scheme, laboratory response rates were greater than 90% and the proportion of laboratories reporting at least one aberrant result improved from 9.2% (6/65) in 2005 to 5.4% (17/316) in 2012.

Lessons Learnt: National testing guidelines and a reference laboratory are needed to successfully implement quality assurance of HIV testing services. On-site assessments are crucial for all participating laboratories and the only source for insight on the causes of aberrant results; lessons that the reference laboratory can share nationally. Proficiency testing helps laboratory technicians to maintain HIV testing skills by ensuring that they regularly encountered HIV-positive samples.
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January 2015