Myanmar Health Sciences Research Journal
Original Articles :
Myanamr Health Research Registration 2024; 36(1-3): 1-9.
DOI:

Drug Susceptibility Profile, Genetic Determinants and Treatment Outcomes of Newly Diagnosed Pulmonary Tuberculosis Patients Attending Two Township TB Centers in Yangon, Myanmar

Wah Wah Aung, Phyu Win Ei, Zaw Myint, Wint Wint Nyunt, Myat Htut Nyunt, Mi Mi Htwe, Su Mon Win1, Yu Paing Thet1 & Naw Zar Htoo1

Myanmar Health Sciences Research Journal 2024, 36(1-3):1-9

ABSTRACT
Myanmar is one of the 30 highest burden countries for tuberculosis (TB) and multidrug/rifampicin (RIF)-resistant TB (MDR/RR-TB) worldwide. Anti-TB drug susceptibility and genetic determinants information such as lineage and resistance-associated gene mutations play an important role in determining treatment outcomes. A prospective observational study was carried out on newly diagnosed pulmonary TB patients at Hlaingtharyar and Shwepyithar Township TB Centers, Yangon, Myanmar during 2020-2022. TB patients were registered for drug susceptible TB (DS-TB) or MDR/RR-TB treatment regimens according to routine diagnostic GeneXpert MTB/RIF results. Sputum samples were collected to perform sputum smear microscopy and culture using Lowenstein Jensen media at the enrolment and follow-up visits up to end treatment. Phenotypic drug susceptibility testing (DST) using Mycobacterial Growth Indicator Tube (MGIT) method was performed on Mycobacterium tuberculosis isolated from enrol sputum samples. Genome sequencing using Illumina Miseq platform was conducted on a sub-set of M. tuberculosis isolates. Treatment responses were monitored and end-of-treatment outcomes of patients were evaluated. Of 126 patients (76 registered for DS-TB and 50 registered for MDR/RR-TB treatment regimens) who were eligible in the outcome analysis, phenotypic DST revealed 49 (38.9%) MDR-TB (resistant to at least RIF and isoniazid), 11 (8.7%) poly-resistance other than MDR, 9 (7.1%) mono-resistance and 2 (1.6%) MDR with fluroquinolone resistance, pre-extensively drug-resistant TB (pre-XDR-TB) patterns. Genome sequencing of 45 M. tuberculosis isolates showed 22 (48.9%) were harboring drug resistance-associated mutations.
RESULT
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INTRODUCTION
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Tuberculosis (TB) remains as the global health problem caused by a single infectious agent Mycobacterium tuberculosis complex. The World Health Organization (WHO) stated that TB is the second leading infectious disease killer worldwide, after COVID-19. It is also the leading killer of people and a major cause of deaths related to antimicrobial resistance. There was an estimated 10.6 million of TB occurrence worldwide with 410000 new cases of multidrug-resistant or rifampicin (RIF)-resistant TB (MDR/RR-TB) in 2022.1
SUPPLEMENTARY MATERIAL
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A prospective observational cohort study was conducted during 2020-2022 on newly diagnosed smear positive pulmonary TB, registered for DS-TB or MDR/RR-TB treatment according to the diagnostic Xpert MTB/RIF at Hlaingtharyar and Shwepyithar township TB Centres, Yangon. Based on 2019 National TB Program data, Yangon Region was the highest TB/MDR-TB prevalence Region. In this study, Hlaing-tharyar and Shwepyithar Township TB Centers were selected purposely because they were included in the top five high TB prevalence townships in Yangon Region. A total of 155 eligible patients were consecutively recruited after obtaining the written informed consents.
DISCUSSION
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An important component of WHO’s “END TB strategy” is preventing the spread of drug-resistant TB which leads to prolonged TB treatment and increased the risk of poor outcome.17 Country data of Myanmar showed proportion of MDR/RR-TB among new cases was 4.1%.1 The present study was conducted on 126 new pulmonary TB patients registered for DS-TB (n=76) and MDR/RR-TB (n=50) treatment in previously high prevalent townships in Yangon. Phenotypic DST profile revealed that 71 (56.3%) of study participants were resistant to any tested first- line and second-line anti-TB drugs including 27 (21.4%) total resistance to all five first-line drugs. Occurrence of MDR with other ant-TB drugs resistance, poly-resistance and pre-XDR pattern among newly diagnosed TB cases highlights the continuing problem of DR-TB in our population.
ACKNOWLEDGMENT
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This study was carried out by a research grant from Korea National Institute of Health, Republic of Korea. We acknowledged Dr. Seonghan Kim and Dr. Sungkyoung Lee, Korea National Institute of Health and Dr. Jong Seok Lee, International Tuberculosis Research Center for technical advice. We deeply thank study participants, TB coor-dinators, nurses, survey workers, Staff from Central National TB Program (Yangon Branch) and National Tuberculosis Reference Laboratory (Aungsan), laboratory team from Advanced Molecular Research Centre and admin and financial staff from Department of Medical Research.
CONFLICT OF INTEREST
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REFERENCES
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1. World Health Organization. Global tuber-culosis report 2023. Geneva: WHO, 2023. 2. National TB Program (Central-Yangon Branch). Yangon Region TB Profile 2020. NTP (Central-Yangon Branch); 2022. 3. World Health Organization. WHO console-dated guidelines on tuberculosis. Module 4: treatment-drug-susceptible tuberculosis treat-ment. Geneva: WHO, 2022. 4. World Health Organization. WHO console-dated guidelines on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treat-ment, 2022 update. Geneva: WHO, 2022. 5. National Tuberculosis Program and WHO country Office (Myanmar), Ministry of Health and Sports, Myanmar. Guidelines for management of drug resistant tuberculosis (DR-TB) in Myanmar. 2017.