Molecular Epidemiology and Genetic Diversity of Multidrug-Resistant Mycobacterium tuberculosis Isolates in Bangladesh.

Although the number of multidrug-resistant (MDR) tuberculosis (TB) cases is high overall, a major gap exists in our understanding of the molecular characteristics and transmission dynamics of the MDR Mycobacterium tuberculosis isolates circulating in Bangladesh. The present study aims to characterize the MDR-TB isolates of Bangladesh and to investigate the mode of transmission. A total of 544 MDR-TB isolates were obtained from a nationwide drug-resistant TB surveillance study conducted between October 2011 and March 2017 covering all geographic divisions of Bangladesh. The isolates were characterized using TbD1 deletion analysis, spoligotyping, and mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing. Deletion analysis showed that 440 (80.9%) isolates were the modern type, while the remainder were the ancestral type. The largest circulating lineage was the Beijing type, comprising 208 isolates (38.2%), followed by T, EAI, and LAM with 93 (17.1%), 58 (10.7%), and 52 (9.5%) isolates, respectively. Combined MIRU-VNTR and spoligotyping analysis demonstrated that the majority of the clustered isolates were of the Beijing and T1 lineages. The overall rate of recent transmission was estimated at 33.8%. In conclusion, the MDR M. tuberculosis isolates circulating in Bangladesh are mostly of the modern virulent type. The Beijing and T lineages are the predominant types and most of the transmission of MDR-TB can be attributed to them. The findings also suggest that, along with the remarkable transmission, the emergence of MDR-TB in Bangladesh is largely due to acquired resistance. Rapid and accurate diagnosis and successful treatment will be crucial for controlling MDR-TB in Bangladesh. IMPORTANCE Multidrug-resistant TB is considered to be the major threat to tuberculosis control activities worldwide, including in Bangladesh. Despite the fact that the number of MDR-TB cases is high, a major gap exists in our understanding of the molecular epidemiology of the MDR-TB isolates in Bangladesh. In our study, we characterized and classified the MDR-TB isolates circulating in Bangladesh and investigated their mode of transmission. Our results demonstrated that the MDR M. tuberculosis isolates circulating in Bangladesh are mostly of the modern virulent type. The Beijing and T lineages are the predominant types and are implicated in the majority of MDR-TB transmission. Our findings reveal that, along with the remarkable transmission, the emergence of MDR-TB in Bangladesh is largely due to acquired resistance, which may be due to nonadherence to treatment or inadequate treatment of TB patients. Rapid diagnosis and adherence to an appropriate treatment regimen are therefore crucial to controlling MDR-TB in Bangladesh.

Nocardia infection causing non-healing surgical wounds: A case series from Bangladesh.

OBJECTIVE: Nocardia can be introduced accidentally causing non-healing surgical wounds. METHOD: From February 2017 to January 2021 samples from wounds were collected. Nocardia identification and susceptibility testing were carried out by standard procedure. RESULTS: Seventeen (35.4 %) Nocardia spp. and 20 other pathogens (41.7%) were recovered by culture. Drug susceptibility among Nocardia was >70% to amikacin, amoxicillin-clavulanic acid, levofloxacin, linezolid, and imipenem, 47% to cephalosporins and 41% to trimethoprim/sulfamethoxazole. CONCLUSIONS: Infections with Nocardia spp. should be considered in non-healing surgical wounds.

Diagnosis and management of latent tuberculosis infection in Asia: Review of current status and challenges.

Asia has the highest burden of tuberculosis (TB) and latent TB infection (LTBI) in the world. Optimizing the diagnosis and treatment of LTBI is one of the key strategies for achieving the WHO 'End TB' targets. We report the discussions from the Asia Latent TubERculosis (ALTER) expert panel meeting held in 2018 in Singapore. In this meeting, a group of 13 TB experts from Bangladesh, Cambodia, Hong Kong, India, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Taiwan, Thailand and Vietnam convened to review the literature, discuss the barriers and propose strategies to improve the management of LTBI in Asia. Strategies for the optimization of risk group prioritization, diagnosis, treatment, and research of LTBI are reported. The perspectives presented herein, may help national programs and professional societies of the respective countries enhance the adoption of the WHO guidelines, scale-up the implementation of national guidelines based on the regional needs, and provide optimal guidance to clinicians for the programmatic management of LTBI.

Quantitative drug-susceptibility in patients treated for multidrug-resistant tuberculosis in Bangladesh: implications for regimen choice.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) treatment in Bangladesh is empiric or based on qualitative drug-susceptibility testing (DST) by comparative growth in culture media with and without a single drug concentration. METHODS: Adult patients were enrolled throughout Bangladesh during the period of 2011-2013 at MDR-TB treatment initiation. Quantitative DST by minimum inhibitory concentration (MIC) testing for 12 first and second-line anti-TB drugs was compared to pretreatment clinical characteristics and treatment outcomes. MIC values at or one dilution lower than the resistance breakpoint used for qualitative DST were categorized as borderline susceptible, and MIC values one or two dilutions greater as borderline resistant. RESULTS: Seventy-four patients were enrolled with a mean age of 35 ± 15 years, and 51 (69%) were men. Of the rifampin isolates with MIC >1.0 µg/ml, 12 (19%) were fully susceptible or borderline susceptible to rifabutin (MIC ≤ 0.5 µg/ml). Amikacin was fully susceptible in 73 isolates (99%), but kanamycin in only 54 (75%) (p<0.001). Ofloxacin was borderline susceptible in 64%, and fully susceptible in only 14 (19%) compared to 60 (81%) of isolates fully susceptible for moxifloxacin (p<0.001). Kanamycin non-susceptibility and receipt of the WHO Category IV regimen trended with interim treatment failure: adjusted odd ratios respectively of 5.4 [95% CI 0.82-36.2] (p = 0.08) and 7.2 [0.64-80.7] (p = 0.11). CONCLUSIONS: Quantitative MIC testing could impact MDR-TB regimen choice in Bangladesh. Comparative trials of higher dose or later generation fluoroquinolone, within class change from kanamycin to amikacin, and inclusion of rifabutin appear warranted.

Multidrug-resistant tuberculosis in admitted patients at a tertiary referral hospital of Bangladesh.

BACKGROUND: This study was set out to investigate the magnitude, patterns and molecular characterization of drug-resistant Mycobacterium tuberculosis strains at a tertiary referral hospital in Bangladesh. METHODS: Pulmonary tuberculosis (TB) patients admitted at National Institute of Diseases of the Chest and Hospital from February 2002 to September 2005 with or without previous history of TB and/or other complications were randomly interviewed. Among 265 participants enrolled, M. tuberculosis isolates from 189 patients were finally tested for susceptibility to rifampicin (RMP), isoniazid (INH), ethambutol (ETM) and streptomycin (STM). Genotyping of M. tuberculosis was done using deletion analysis and spoligotyping. RESULTS: Eighty-eight percent (n = 167) of the patients had history of previous anti-TB treatment while the remaining 12% were new TB cases. Of the 189 isolates, 9% were fully susceptible to the first line anti-TB drugs and 73.5% were multi-drug resistant TB. Other susceptibility results showed 79.4%, 77.2%, 76.7% and 78.8% resistance to INH, RMP, ETM and STM respectively. Multi-drug resistance was significantly higher among the 130 (78%) patients with previous history of anti-tuberculosis treatment (95% confidence interval, p = 0.001). Among the 189 analyzed isolates, 69% were classified as "modern" M. tuberculosis strains (i.e. TbD1- strains, lacking the M. tuberculosis-deletion region TbD1), whereas the remaining 31% were found to belong to the "ancestal" TbD1+ M. tuberculosis lineages. One hundred and five different spoligotype patterns were identified in which 16 clusters contained 100 strains and 89 strains had unique pattern. Strains with a spoligotype characteristic for the "Beijing" cluster were predominant (19%) and most of these strains (75%) were multi-drug resistant (MDR). CONCLUSIONS: A high level of drug resistance observed among the re-treatment patients poses a threat of transmission of resistant strains to susceptible persons in the community. Proper counseling of patients and attention towards the completion of the anti-TB treatment is needed.

Pulmonary tuberculosis and drug resistance in Dhaka central jail, the largest prison in Bangladesh.

BACKGROUND: There are limited data on TB among prison inmates in Bangladesh. The aim of the study was to determine the prevalence of pulmonary tuberculosis (TB), its drug resistance and risk factors in Dhaka Central Jail, the largest prison in Bangladesh. METHODS: Cross sectional survey with, active screening of a total number of 11,001 inmates over a period of 2 years. Sputum samples from TB suspects were taken for acid- fast bacilli (AFB) microscopy, culture and drug susceptibility testing. RESULTS: Among 1,781 TB suspects 245 (13.8%) were positive for AFB on microscopy and/or culture. The prevalence rate of sputum- positive pulmonary TB was 2,227/100,000. Fifty three cases (21.6% of 245 cases) were AFB- negative on microscopy but were found positive on culture. Resistance to isoniazid, rifampicin, streptomycin and ethambutol was 11.4%, 0.8%, 22.4% and 6.5% respectively. No multidrug resistance was observed. The main risk factors of TB in prison were exposure to TB patients (adjusted odds ratio 3.16, 95% CI 2.36-4.21), previous imprisonment (1.86, 1.38-2.50), longer duration of stay in prison (17.5 months for TB cases; 1.004, 1.001-1.006) and low body mass index which is less than 18.5 kg/m(2) (5.37, 4.02-7.16). CONCLUSIONS: The study results revealed a very high prevalence of TB in the prison population in Dhaka Central Jail. Entry examinations and active symptom screening among inmates are important to control TB transmission inside the prison. Identifying undiagnosed smear-negative TB cases remains a challenge to combat this deadly disease in this difficult setting.