Molecular Identification of Aedes, Armigeres, and Culex Mosquitoes (Diptera: Culicidae) Using Mitochondrial Cytochrome Oxidase Subunit I Genes in Myanmar.

PURPOSE: Mosquitoes are important vectors that carry disease-causing agents that can affect humans and animals. DNA barcoding is a complementary identification which can be used to validate morphological characterization of mosquito species. The objectives of this study were to identify the mitochondrial sequence of the COI gene and to construct a molecular phylogeny based on the genetic divergence of the mosquito species studied. METHODS: In this study, DNA extraction and the amplification of the mitochondrial cytochrome oxidase subunit I genes (COI) were performed on pooled mosquito samples collected in Nay Pyi Taw area, Myanmar. RESULTS: Fragments of the COI gene showed 99-100% identity with sequences of Aedes aegypti, Armigeres subalbatus, Culex pipiens complex, and Cx. quinquefasciatus, respectively, deposited in GenBank. This study categorized two haplotypes from each Ar. subalbatus and Cx. pipiens complex COI gene sequence, as well as three haplotypes from Cx. quinquefasciatus COI gene sequences. The highest haplotype diversity and nucleotide diversity were observed in the Ar. subalbatus population (Hd = 1.0000; π = 0.0033), followed by the Cx. pipiens complex and Cx. quinquefasciatus populations. CONCLUSION: This study provides useful information on the molecular identification and genetic diversity of mosquito vectors with medical and veterinary significance, which may assist in the improvement of mosquito control programs.

The first molecular confirmation of Culex pipiens complex as potential natural vectors of Dirofilaria immitis in Myanmar.

Dirofilariosis, known as one of the most widespread vector-borne zoonotic diseases, is caused by several different species of the nematodes of the genus Dirofilaria, which can be transmitted by Culex, Anopheles and Aedes mosquito vectors. In order to identify key vector mosquitoes of filarial parasites in Myanmar, mosquitoes were collected during three different seasons (summer, rainy and winter) in three townships in Nay Pyi Taw area, Myanmar. DNA extraction and polymerase chain reaction (PCR) analyses were conducted for 185 mosquito pools, with each pool containing 1-10 mosquitoes. Dirofilaria immitis was detected in 20 pools of Culex pipiens complex mosquitoes. The minimum infection rate of mosquitoes was found to be 16.33. The small subunit ribosomal RNA (12S rDNA) gene targeted PCR revealed that the sequences obtained were completely identical to the sequences of D. immitis derived from dogs in China, Brazil and France. The sequences obtained from mitochondrial cytochrome oxidase subunit I (COI) gene PCR exhibited 100% identity with the sequences of D. immitis derived from dogs in Bangladesh, Iran, Japan and Thailand, as well as humans in Iran and Thailand, and mosquitoes in Germany and Hungary. The findings of this study demonstrated that the mosquito species of Cx. pipiens complex are potential mosquito vectors for dirofilariosis in Myanmar.

Genomic Sequencing Profiles of Mycobacterium tuberculosis in Mandalay Region, Myanmar.

This study aimed to characterize whole-genome sequencing (WGS) information of Mycobacterium tuberculosis (Mtb) in the Mandalay region of Myanmar. It was a cross-sectional study conducted with 151 Mtb isolates obtained from the fourth nationwide anti-tuberculosis (TB) drug-resistance survey. Frequency of lineages 1, 2, 3, and 4 were 55, 65, 9, and 22, respectively. The most common sublineage was L1.1.3.1 (n = 31). Respective multi-drug resistant tuberculosis (MDR-TB) frequencies were 1, 1, 0, and 0. Four clusters of 3 (L2), 2 (L4), 2 (L1), and 2 (L2) isolates defined by a 20-single-nucleotide variant (SNV) cutoff were detected. Simpson's index for sublineages was 0.0709. Such high diversity suggests that the area probably had imported Mtb from many geographical sources. Relatively few genetic clusters and MDR-TB suggest there is a chance the future control will succeed if it is carried out properly.

Distribution of Mycobacterium tuberculosis Lineages and Drug Resistance in Upper Myanmar.

Mycobacterium tuberculosis complex (MTBC) is divided into 9 whole genome sequencing (WGS) lineages. Among them, lineages 1−4 are widely distributed. Multi-drug resistant tuberculosis (MDR-TB) is a major public health threat. For effective TB control, there is a need to obtain genetic information on lineages of Mycobacterium tuberculosis (Mtb) and to understand distribution of lineages and drug resistance. This study aimed to describe the distribution of major lineages and drug resistance patterns of Mtb in Upper Myanmar. This was a cross-sectional study conducted with 506 sequenced isolates. We found that the most common lineage was lineage 2 (n = 223, 44.1%). The most common drug resistance mutation found was streptomycin (n = 44, 8.7%). Lineage 2 showed a higher number of MDR-TB compared to other lineages. There were significant associations between lineages of Mtb and drug resistance patterns, and between lineages and geographical locations of Upper Myanmar (p value < 0.001). This information on the distribution of Mtb lineages across the geographical areas will support a lot for the better understanding of TB transmission and control in Myanmar and other neighboring countries. Therefore, closer collaboration in cross border tuberculosis control is recommended.

Entropy-Based Emotion Recognition from Multichannel EEG Signals Using Artificial Neural Network.

Humans experience a variety of emotions throughout the course of their daily lives, including happiness, sadness, and rage. As a result, an effective emotion identification system is essential for electroencephalography (EEG) data to accurately reflect emotion in real-time. Although recent studies on this problem can provide acceptable performance measures, it is still not adequate for the implementation of a complete emotion recognition system. In this research work, we propose a new approach for an emotion recognition system, using multichannel EEG calculation with our developed entropy known as multivariate multiscale modified-distribution entropy (MM-mDistEn) which is combined with a model based on an artificial neural network (ANN) to attain a better outcome over existing methods. The proposed system has been tested with two different datasets and achieved better accuracy than existing methods. For the GAMEEMO dataset, we achieved an average accuracy ± standard deviation of 95.73% ± 0.67 for valence and 96.78% ± 0.25 for arousal. Moreover, the average accuracy percentage for the DEAP dataset reached 92.57% ± 1.51 in valence and 80.23% ± 1.83 in arousal.

The fourth national tuberculosis prevalence survey in Myanmar.

Tuberculosis (TB) remains a significant cause of morbidity and mortality in Myanmar. The fourth National TB Prevalence Survey was conducted in 2017-2018 to determine the actual burden of TB not only at the national level but also for three subnational strata (the states, regions other than Yangon, and the Yangon region) and develop a more efficacious country strategy on TB care and control. One hundred and thirty eight clusters were selected by population proportionate sampling. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray (CXR) after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis (Mtb) by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF Ultra (Xpert), and culture (Ogawa media). Bacteriologically confirmed TB cases were defined by an expert panel. Of 75 676 eligible residents, 66 480 (88%) participated, and 10 082 (15%) screened positive for TB. Among these, 322 participants were defined as bacteriologically confirmed TB cases. Cough lasting for two weeks or longer, one of the criteria used for screening for symptoms, could detect only 14% (45/322) of the study cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 468 (95% CI: 391-546) per 100,000. The prevalence was much higher among males, the older age group, urban Yangon and remote villages. In-depth interview with the participants on TB treatment showed that none of them was diagnosed in a TB health centre (primary care facilities). The prevalence of TB in Myanmar is still high due to challenges such as uncontrolled urbanization, an ageing population, migration, and poor access to health facilities in remote areas. New screening and diagnostic tools might help to detect more TB patients. There is a need to lay greater emphasis on multisectoral approaches, decentralization and the integration of basic TB services into primary care facilities.

Prediction of epileptic seizures based on multivariate multiscale modified-distribution entropy.

Epilepsy is a common neurological disease that affects a wide range of the world population and is not limited by age. Moreover, seizures can occur anytime and anywhere because of the sudden abnormal discharge of brain neurons, leading to malfunction. The seizures of approximately 30% of epilepsy patients cannot be treated with medicines or surgery; hence these patients would benefit from a seizure prediction system to live normal lives. Thus, a system that can predict a seizure before its onset could improve not only these patients' social lives but also their safety. Numerous seizure prediction methods have already been proposed, but the performance measures of these methods are still inadequate for a complete prediction system. Here, a seizure prediction system is proposed by exploring the advantages of multivariate entropy, which can reflect the complexity of multivariate time series over multiple scales (frequencies), called multivariate multiscale modified-distribution entropy (MM-mDistEn), with an artificial neural network (ANN). The phase-space reconstruction and estimation of the probability density between vectors provide hidden complex information. The multivariate time series property of MM-mDistEn provides more understandable information within the multichannel data and makes it possible to predict of epilepsy. Moreover, the proposed method was tested with two different analyses: simulation data analysis proves that the proposed method has strong consistency over the different parameter selections, and the results from experimental data analysis showed that the proposed entropy combined with an ANN obtains performance measures of 98.66% accuracy, 91.82% sensitivity, 99.11% specificity, and 0.84 area under the curve (AUC) value. In addition, the seizure alarm system was applied as a postprocessing step for prediction purposes, and a false alarm rate of 0.014 per hour and an average prediction time of 26.73 min before seizure onset were achieved by the proposed method. Thus, the proposed entropy as a feature extraction method combined with an ANN can predict the ictal state of epilepsy, and the results show great potential for all epilepsy patients.

Genomic Profiling of Mycobacterium tuberculosis Strains, Myanmar.

Multidrug resistance is a major threat to global elimination of tuberculosis (TB). We performed phenotypic drug-susceptibility testing and whole-genome sequencing for 309 isolates from 342 consecutive patients who were given a diagnosis of TB in Yangon, Myanmar, during July 2016‒June 2018. We identified isolates by using the GeneXpert platform to evaluate drug-resistance profiles. A total of 191 (62%) of 309 isolates had rifampin resistance; 168 (88%) of these rifampin-resistant isolates were not genomically related, indicating the repeated emergence of resistance in the population, rather than extensive local transmission. We did not detect resistance mutations to new oral drugs, including bedaquiline and pretomanid. The current GeneXpert MTB/RIF system needs to be modified by using the newly launched Xpert MTB/XDR cartridge or line-probe assay. Introducing new oral drugs to replace those currently used in treatment regimens for multidrug-resistant TB will also be useful for treating TB in Myanmar.

Age and sex distribution of Mycobacterium tuberculosis infection and rifampicin resistance in Myanmar as detected by Xpert MTB/RIF.

BACKGROUND: Detection of tuberculosis disease (TB) and timely identification of Mycobacterium tuberculosis (Mtb) strains that are resistant to treatment are key to halting tuberculosis transmission, improving treatment outcomes, and reducing mortality. METHODS: We used 332,657 Xpert MTB/RIF assay results, captured as part of the Myanmar Data Utilization Project, to characterize Mtb test positivity and rifampicin resistance by both age and sex, and to evaluate risk factors associated with rifampicin resistance. RESULTS: Overall, 70% of individuals diagnosed with TB were males. Test positivity was higher among males (47%) compared to females (39%). The highest positivity by age occurred among individuals aged 16-20, with test positivity for females (65%) higher than for males (57%). Although a greater absolute number of males were rifampicin resistant, a greater proportion of females (11.4%) were rifampicin resistant as compared to males (9.3%). In the multivariate model, history of previous treatment, age less than 30, testing in the Yangon region, and female sex were significantly positively associated with rifampicin resistance after adjusting for HIV status and year test was performed. CONCLUSIONS: Our results indicate that young adults were more likely to test positive for TB and be identified as rifampicin resistant compared to older adults.

Measuring Catastrophic Costs Due to Tuberculosis in Myanmar.

BACKGROUND: This is the first survey to use the World Health Organization (WHO) methodology to document the magnitude and main drivers of tuberculosis (TB) patient costs in order to guide policies on cost mitigation and to produce a baseline measure for the percentage of TB-affected households experiencing catastrophic costs in Myanmar. METHODS: A nationally representative cross-sectional survey was administered to 1000 TB patients in health facilities from December 2015 to February 2016, focusing on costs of TB treatment (direct and indirect), household income, and coping strategies. A total cost was estimated for each household by extrapolating reported costs and comparing them to household income. If the proportion of total costs exceeded 20% of the annual household income, a TB-affected household was deemed to have faced catastrophic costs. RESULTS: 60% of TB-affected households faced catastrophic costs in Myanmar. On average, total costs were USD 759, and the largest proportion of this total was accounted for by patient time (USD 365), followed by food costs (USD 200), and medical expenses (USD 130). Low household wealth quintile and undergoing MDR-TB treatment were both significant predictors for households facing catastrophic costs. CONCLUSIONS: The high proportion of TB-affected households experiencing catastrophic costs suggests the need for TB-specific social protection programs in patient-centered healthcare. The survey findings have led the government and donors to increase support for MDR-TB patients. The significant proportion of total spending attributable to lost income and food or nutritional supplements suggests that income replacement programs and/or food packages may ameliorate the burdensome costs.

Sensitivity and specificity of tuberculosis signs and symptoms screening and adjunct role of social pathology characteristics in predicting bacteriologically confirmed tuberculosis in Myanmar.

BACKGROUND: Globally, using tuberculosis signs and symptoms (TB-SS) as a screening tool has become less important due to its low sensitivity and specificity. We analyzed data from the Myanmar National Tuberculosis (TB) prevalence survey in 2010. The various TB screening models were developed to predict TB by using logistic regression analysis, and their performance on TB prediction was compared by the measures of overall performance, calibration and discrimination ability, and sensitivity and specificity to determine whether social pathology characteristics could be used as a TB screening tool. RESULTS: Among 51,367 participants, 311 (0.6%) had bacteriologically confirmed TB, of which 37.2% were asymptomatic and 2% had a normal chest X-ray. Out of 32 various combinations of signs and symptoms, having any signs and symptoms gave the best sensitivity of 59.8% and specificity of 67.2%, but chest X-ray (CXR) alone gave the highest sensitivity (95.1%) and specificity (86.3%). The next best combination was cough only with a sensitivity of 24.4% and specificity of 85%. Other combinations had poor sensitivity (< 10%). Among various TB screening models, the overall performance R2 was higher in the combined models of social pathology and TB signs and symptoms as well as the social pathology model, compared to TB-SS models (> 10% versus < 3%), although all TB screening models were perfect to predict TB (Brier score = 0). The social pathology model shows a better calibration, more closer to 45° line of calibration plot with Hosmer-Lemeshow test p value = 0.787, than the combined models while it had a better discrimination ability in area under the curve, AUC = 80.4%, compared to TB-SS models with any signs and symptoms, AUC = 63.5% and with any cough, AUC = 57.1% (DeLong p value = 0.0001). Moreover, at the propensity score cutoff value ≥ 0.0053, the combined and social pathology models had sensitivity of ~ 80% and specificity of ~ 70%. The highest population attributable fraction to predict TB by social pathology characteristics was male gender (42.6%), age ≥ 55 years (31.0%), and underweight (30.4%). CONCLUSION: Over one-third of bacteriologically confirmed TB was asymptomatic. The conventional TB-SS screening tool using any TB signs and symptoms had a lower sensitivity and specificity compared to CXR and social pathology screening tools. The social pathology characteristics as TB screening tool had good calibration and can improve the discrimination ability to predict TB than TB-SS screenings and should be encouraged.

Combined Tuberculosis and Diabetes Mellitus Screening and Assessment of Glycaemic Control among Household Contacts of Tuberculosis Patients in Yangon, Myanmar.

BACKGROUND: This study aimed to identify the prevalence of diabetes mellitus (DM) and tuberculosis (TB) among household contacts of index TB patients in Yangon, Myanmar. METHOD: Household contacts were approached at their home. Chest X-ray and capillary blood glucose tests were offered based on World Health Organization and American Diabetes Association guidelines. Crude prevalence and odds ratios of DM and TB among household contacts of TB patients with and without DM were calculated. RESULTS: The overall prevalence of DM and TB among household contacts were (14.0%, 95% CI: 10.6-18.4) and (5%, 95% CI: 3.2-7.6), respectively. More than 25% of DM cases and almost 95% of TB cases among household contacts were newly diagnosed. Almost 64% of known DM cases among household contacts had poor glycaemic control. The risk of getting DM among household contacts of TB patients with DM was significantly higher (OR-2.13, 95% CI: 1.10-4.12) than those of TB patients without DM. There was no difference in prevalence of TB among household contacts of TB patients with and without DM. CONCLUSION: Significant proportions of the undetected and uncontrolled DM among household contacts of index TB patients indicate a strong need for DM screening and intervention in this TB-DM dual high-risk population.

Modified-Distribution Entropy as the Features for the Detection of Epileptic Seizures.

Epilepsy is one of the most common chronic neurological disorders, and therefore, diagnosis and treatment methods are urgently needed for these patients. Many methods and algorithms that can detect seizures in epileptic patients have been proposed. Electroencephalogram (EEG) is one of helpful tools for investigating epilepsy forms in patients, however, an expert in the neurological field must perform a visual inspection to identify a seizure. Such analyses require longer time because of the huge dataset recorded from many electrodes which are put on the human scalp. With the non-stationary nature of EEG, especially during the abnormality periods, entropy measures gain more interest in the field. In this work, by exploring the advantages of both reliable state-of-the-art entropies, fuzzy entropy and distribution entropy, a modified-Distribution entropy (mDistEn) for epilepsy detection is proposed. As the results, the proposed mDistEn method can successfully achieve the same consistency and better accuracy than using the state-of-the-art entropies. The mDistEn corresponds to higher Area Under the Curve (AUC) values compared with the fuzzy entropy and the distribution entropy and yields 92% classification accuracy.

HIV testing uptake and HIV positivity among presumptive tuberculosis patients in Mandalay, Myanmar, 2014-2017.

INTRODUCTION: The World Health Organization's framework for TB/HIV collaborative activities recommends provider-initiated HIV testing and counselling (PITC) of patients with presumptive TB. In Myanmar, PITC among presumptive TB patients was started at the TB outpatient department (TB OPD) in Mandalay in 2014. In this study, we assessed the uptake of PITC among presumptive TB patients and the number needed to screen to find one additional HIV positive case, stratified by demographic and clinical characteristics. METHOD: This was a cross-sectional study using routinely collected data of presumptive TB patients who registered for PITC services at the TB OPD between August 2014 and December 2017 in Mandalay. RESULT: Among 21,989 presumptive TB patients registered, 9,796 (44.5%) had known HIV status at registration and 2,763 (28.2%) were people already living with HIV (PLHIV). Of the remainder, 85.3% (10,401/12,193) were newly tested for HIV. Patients <55 years old, those registered in 2014, 2015 and 2017, those employed and those having a history of TB contact had higher uptakes of HIV testing. Among 10,401 patients tested for HIV, 213 (2.1%) patients were newly diagnosed with HIV and this included 147 (69.0%) who were not diagnosed as having TB. The overall prevalence of HIV (previously known and newly diagnosed) among presumptive TB patients was 14.8% (2,976/20,119). The number needed to screen to find one additional HIV case was 48: this number was lower (i.e., a higher yield) among patients aged 35-44 years and among those who were divorced or separated. CONCLUSION: Uptake of HIV testing among eligible presumptive TB patients was high with four out of five presumptive TB patients being tested for HIV. This strategy detected many additional HIV-positive persons, and this included those who were not diagnosed with TB. We strongly recommend that this strategy be implemented nationwide in Myanmar.

What Are the Barriers for Uptake of Antiretroviral Therapy in HIV-Infected Tuberculosis Patients? A Mixed-Methods Study from Ayeyawady Region, Myanmar.

Antiretroviral therapy (ART) coverage among HIV-infected tuberculosis (HIV-TB) patients has been suboptimal in Myanmar and the reasons are unknown. We aimed to assess the ART uptake among HIV-TB patients in public health facilities of Ayeyawady Region from July 2017-June 2018 and explore the barriers for non-initiation of ART. We conducted an explanatory mixed-methods study with a quantitative component (cohort analysis of secondary programme data) followed by a descriptive qualitative component (thematic analysis of in-depth interviews of 22 providers and five patients). Among 12,447 TB patients, 11,057 (89%) were HIV-tested and 627 (5.7%) were HIV-positive. Of 627 HIV-TB patients, 446 (71%) received ART during TB treatment (86 started on ART prior to TB treatment and rest started after TB treatment). Among the 181 patients not started on ART, 60 (33%) died and 41 (23%) were lost-to-follow-up. Patient-related barriers included geographic and economic constraints, poor awareness, denial of HIV status, and fear of adverse drug effects. The health system barriers included limited human resource, provision of ART on 'fixed' days only, weaknesses in counselling, referral and feedback mechanism, and clinicians' reluctance to start ART early due to concerns about immune reconstitution inflammatory syndrome. We urge the national TB and HIV programs to take immediate actions to improve the ART uptake.

Gaps in Implementing Bidirectional Screening for Tuberculosis and Diabetes Mellitus in Myanmar: An Operational Research Study.

In Myanmar from July 2018, as a pilot project in 32 townships, all tuberculosis (TB) patients aged ≥40 years were eligible for diabetes mellitus (DM) screening by random blood sugar (RBS) and all DM patients attending hospitals were eligible for TB screening. We assessed the bidirectional screening coverage of target groups through a cross sectional study involving secondary analysis of routine program data. From January to March 2019, of the 5202 TB patients enrolled, 48% were aged ≥40 years. Of those aged ≥40 years, 159 (6%) were known to have DM, and the remaining 2343 with unknown DM status were eligible for DM screening. Of these, 1280 (55%) were screened and 139 (11%) had high RBS values (≥200 mg/dL, as defined by the national program). There was no information on whether patients with high RBS values were linked to DM care. Of the total 8198 DM patients attending hospitals, 302 (3.7%) patients were tested for sputum smear and 147 (1.7%) were diagnosed with TB. In conclusion, only half of the eligible TB patients were screened for DM and the yield of TB cases among screened DM patients was high. There is an urgent need for improving and scaling up bidirectional screening in the country.

Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar.

Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%-6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%-24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.

Integration of drug safety monitoring in tuberculosis treatment programmes: country experiences.

New drugs and shorter treatments for drug-resistant tuberculosis (DR-TB) have become available in recent years and active pharmacovigilance (PV) is recommended by the World Health Organization (WHO) at least during the early phases of implementation, with active drug safety monitoring and management (aDSM) proposed for this. We conducted a literature review of papers reporting on aDSM. Up to 18 April, 2019, results have only been published from one national aDSM programme. Because aDSM is being introduced in many low- and middle-income countries, we also report experiences in introducing it into DR-TB treatment programmes, targeting the reporting of a restricted set of adverse events (AEs) as per WHO-recommended aDSM principles for the period 2014-2017. Early beneficial effects of active PV for TB patients include increased awareness about the occurrence, detection and management of AEs during TB treatment, and the increase of spontaneous reporting in some countries. However, because PV capacity is low in most countries and collaboration between national TB programmes and national PV centres remains weak, parallel and coordinated co-development of the capacities of both TB programmes and PV centres is needed.

Genotypes and genetic characters of Mycobacterium tuberculosis from Myanmar using three typing methods.

Knowledge on basic characteristics of Mycobacterium tuberculosis (MTB) is helpful to understand the disease epidemiology and support the prediction of clinical outcome of the disease. The aim of this study was to detect the genotypes and genotypic characters of clinical Mycobacterium tuberculosis (MTB) isolates from new and retreatment rifampicin-resistant patients using three different genotyping methods. Mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) typing was used to determine the diversity of 222 clinical isolates. Spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing were also used to investigate the genetic characters of 105 MTB strains. Among the 15 genotypes detected by MIRU-VNTR, Beijing strains were the most prevalent of all strains (54.8%); new cases (40.5%) and retreatment cases (69.4%), followed by EAI strain. Spoligotyping categorized the strains into 11 lineages and 13 orphans whereas 96 different IS6110 patterns were identified using RFLP method. The mode number of IS6110 was 18 and 20. Higher band numbers were found in Beijing genotype (p < 0.001). Clustering rates by spoligotyping, MIRU-VNTR and IS6110-RFLP typing were 0.714, 0.004 and 0.085, respectively. Discriminatory powers of spoligotyping, MIRU-VNTR typing and IS6110-RFLP typing were 0.637, 1.000 and 0.997, respectively. Dominant Beijing genotype in both new and retreatment cases denoting that prevailing tuberculosis in Myanmar changed from EAI to Beijing lineage.

Pre-treatment loss to follow-up and treatment delay among bacteriologically-confirmed tuberculosis patients diagnosed in Mandalay Region, Myanmar.

BACKGROUND: Pre-treatment loss to follow-up (PTLFU) among tuberculosis (TB) patients is a global public health problem, because such patients are highly infectious and experience high mortality. There is no published evidence on this issue from Myanmar. OBJECTIVE: To determine PTLFU and treatment delays (> 7 days duration between the date of diagnosis and starting anti-TB treatment) and their associated demographic, clinical, and health system-related factors among bacteriologically confirmed (sputum smear-positive and/or Xpert-positive) TB patients diagnosed in public health facilities of the Mandalay Region between January and June 2017. METHOD: This was a cohort study involving secondary analysis of routine programme data. Every bacteriologically confirmed TB patient in the laboratory register was tracked for at least 3 months in the treatment register. Patients neither found in the treatment register nor referred out for treatment were considered PTLFU. RESULTS: Of the 1365 bacteriologically confirmed patients diagnosed, 1051 (77%) started on anti-TB treatment, 200 (15.6%) were referred for treatment to health facilities outside the study area, and 114 (8.4%, 95% CI 7.0%-9.9%) did not initiate anti-TB treatment (PTLFU). PTLFU was significantly higher in those with TB/HIV co-infected (18%), sputum smear-negative but Xpert MTB-positive patients (31%), and patients diagnosed at a moderate- or high-volume facility (> 50 patients tested form TB during the study period) (~ 10%). Of the 940 patients with dates recorded, 46 (5%) had a treatment delay of more than 7 days. Patients aged 45-64 years had higher risk of treatment delay compared to those aged 15-44 years. About 97% of records did not have a phone number recorded. CONCLUSION: PTLFU and treatment delay were relatively low in the Mandalay Region. While this is reassuring, urgent steps must be taken to address those that are lost, which includes improving documentation of phone numbers to improve 'trackability', instituting proactive measures to trace patients lost in the care pathway, and introducing an indicator in the national tuberculosis programme (NTP) monthly report to monitor and review PTLFU. Patient subgroups with higher PTLFU should receive priority attention.