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Fulltext A study of primary drug resistance in pulmonary tuberculosis in west Malaysia 1984-1987

Jalleh RD, Kuppusamy I, Soshila R, Aziah AM, Faridza MY

Med J Malaysia, 1993 Jun;48(2):113-6.
PMID: 8350784

Eight hundred and fifty-six strains of Mycobacterium tuberculosis from previously untreated patients with pulmonary tuberculosis from various states in West Malaysia were studied during the period 1984 to 1987. All the strains were tested for in vitro susceptibility to the anti-tuberculosis drugs isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (ETB). One hundred and twenty-one of the isolates (14.18%) were resistant to 1 drug while 17 (1.97%) were resistant to 2 drugs. No strain was found to be resistant to more than 2 drugs. The prevalence of primary resistance to INH was 4.20%, SM was 7.59%, RMP was 0.95% and ETB was 1.44%. In 1.86% of isolates, resistance was noted to both INH and SM, while 0.11% were resistant to both RMP and ETB. There was no significant difference in distribution of resistant bacilli between the sexes (p > 0.01).

Matched MeSH terms: Mycobacterium tuberculosis/classification
Restriction fragment length polymorphism analysis of Mycobacterium tuberculosis isolated from countries in the western pacific region

Park YK, Bai GH, Kim SJ

J Clin Microbiol, 2000 Jan;38(1):191-7.
PMID: 10618086

A total of 422 Mycobacterium tuberculosis isolates from eight countries were subjected to IS6110 and IS1081 DNA fingerprinting by means of restriction fragment analysis to characterize M. tuberculosis strains from each country. Chinese, Mongolian, Hong Kong, Filipino, and Korean isolates had comparatively more copies of IS6110 (proportion with eight or more copies; 95% +/- 5%), while Thai, Malaysian, and Vietnamese isolates had fewer copies (proportion with eight or more copies, 60% +/- 4%). We found a number of novel IS1081 types in this study. One IS1081 type was present in 56% of Filipino isolates, had a specific 6.6-kb PvuII fragment in its IS6110 DNA fingerprint, and was termed the "Filipino family." The IS1081 types of Thai isolates had interposing characteristics between the characteristics of northeastern Asian and southeastern Asian IS1081 types. A 1.3-kb single-copy IS6110 fragment was found only in Vietnamese M. tuberculosis isolates. Although M. tuberculosis isolates from each country had comparatively similar characteristics depending on the classification factor, each country's isolates showed characteristic DNA fingerprints and differed slightly from the isolates from the other countries in either the mode number of IS6110 copies or the distribution of IS1081 types.

Matched MeSH terms: Mycobacterium tuberculosis/classification
Rapid detection of Mycobacterium tuberculosis in clinical samples by multiplex polymerase chain reaction (mPCR)

Tang TH, Ahmed SA, Musa M, Zainuddin ZF

World J Microbiol Biotechnol, 2013 Dec;29(12):2389-95.
PMID: 23807412 DOI: 10.1007/s11274-013-1407-0

Although the multi-copy and specific element IS6110 provides a good target for the detection of Mycobacterium tuberculosis complex by PCR techniques, the emergence of IS6110-negative strains suggested that false negative may occur if IS6110 alone is used as the target for detection. In this report, a multiplex polymerase chain reaction (mPCR) system was developed using primers derived from the insertion sequence IS6110 and an IS-like elements designated as B9 (GenBank accession no. U78639.1) to overcome the problem of detecting negative or low copy IS6110 containing strains of M. tuberculosis. The mPCR was evaluated using 346 clinical samples which included 283 sputum, 19 bronchial wash, 18 pleural fluid, 9 urine, 7 CSF, 6 pus, and 4 gastric lavage samples. Our results showed that the sensitivity (93.1 %) and specificity (89.6 %) of the mPCR system exceeds that of the conventional method of microscopy and culture. The mPCR assay provides an efficient strategy to detect and identify M. tuberculosis from clinical samples and enables prompt diagnosis when rapid identification of infecting mycobacteria is necessary.

Matched MeSH terms: Mycobacterium tuberculosis/classification
Detection and discrimination of Mycobacterium tuberculosis complex

Issa R, Mohd Hassan NA, Abdul H, Hashim SH, Seradja VH, Abdul Sani A

Diagn Microbiol Infect Dis, 2012 Jan;72(1):62-7.
PMID: 22078904 DOI: 10.1016/j.diagmicrobio.2011.09.021

A real-time quantitative polymerase chain reaction (qPCR) was developed for detection and discrimination of Mycobacterium tuberculosis (H37Rv and H37Ra) and M. bovis bacillus Calmette-Guérin (BCG) of the Mycobacterium tuberculosis complex (MTBC) from mycobacterial other than tuberculosis (MOTT). It was based on the melting curve (Tm) analysis of the gyrB gene using SYBR(®) Green I detection dye and the LightCycler 1.5 system. The optimal conditions for the assay were 0.25 μmol/L of primers with 3.1 mmol/L of MgCl(2) and 45 cycles of amplification. For M. tuberculosis (H37Rv and H37Ra) and M. bovis BCG of the MTBC, we detected the crossing points (Cp) at cycles of 16.96 ± 0.07, 18.02 ± 0.14, and 18.62 ± 0.09, respectively, while the Tm values were 90.19 ± 0.06 °C, 90.27 ± 0.09 °C, and 89.81 ± 0.04 °C, respectively. The assay was sensitive and rapid with a detection limit of 10 pg of the DNA template within 35 min. In this study, the Tm analysis of the qPCR assay was applied for the detection and discrimination of MTBC from MOTT.

Matched MeSH terms: Mycobacterium tuberculosis/classification*
Comparison of BACTEC MGIT 960 system and BACTEC 460 TB system for growth and detection of Mycobacteria from clinical specimens

Ganeswrie R, Chui CS, Balan S, Puthucheary SD

Malays J Pathol, 2004 Dec;26(2):99-103.
PMID: 16329561

This study was carried out to compare the performance of BACTEC MGIT 960 with the BACTEC 460 TB for growth and detection of Mycobacteria from human clinical specimens. The BACTEC MGIT 960 instrument is a fully automated system that utilizes MGIT tubes containing an oxygen sensor embedded in silicon at the bottom and filled with 7 mL of modified Middlebrook 7H9 broth. Identical samples were inoculated into the two automated systems and incubated for six weeks. Over a period of three months, 279 specimens were decontaminated and processed according to the standard CDC NALC/NaOH method, using the commercial MycoPrep kit. Forty-two specimens (15%) yielded Mycobacterium tuberculosis; 37 (88%) were detected by the fluorescent BACTEC MGIT 960 and 35 (83%) detected by the radiometric BACTEC 460 TB. Fifteen specimens (5%) yielded Mycobacterium Other Than Tuberculosis (MOTT); 10 (66%) were detected by BACTEC MGIT 960 and 11 (73%) detected by BACTEC 460 TB. The average time to detection and contamination rates and the average time to obtain results of antimicrobial susceptibility tests between the two systems were compared. The performance of the BACTEC MGIT 960 was comparable to the BACTEC 460 TB system which has been the "Gold Standard" for automated detection of TB. The former was more rapid, as sensitive and less labour intensive than the BACTEC 460. Our data demonstrates that the BACTEC MGIT 960 system is an accurate, automated and a non-radioactive alternative to the BACTEC 460 TB for the culture and susceptibility testing of M. tuberculosis.

Matched MeSH terms: Mycobacterium tuberculosis/classification
Fulltext Genomic epidemiology of tuberculosis in eastern Malaysia: insights for strengthening public health responses

Bainomugisa A, Meumann EM, Rajahram GS, Ong RT, Coin L, Paul DC, et al.

Microb Genom, 2021 05;7(5).
PMID: 33945455 DOI: 10.1099/mgen.0.000573

Tuberculosis is a leading public health priority in eastern Malaysia. Knowledge of the genomic epidemiology of tuberculosis can help tailor public health interventions. Our aims were to determine tuberculosis genomic epidemiology and characterize resistance mutations in the ethnically diverse city of Kota Kinabalu, Sabah, located at the nexus of Malaysia, Indonesia, Philippines and Brunei. We used an archive of prospectively collected Mycobacterium tuberculosis samples paired with epidemiological data. We collected sputum and demographic data from consecutive consenting outpatients with pulmonary tuberculosis at the largest tuberculosis clinic from 2012 to 2014, and selected samples from tuberculosis inpatients from the tertiary referral centre during 2012-2014 and 2016-2017. Two hundred and eight M. tuberculosis sequences were available for analysis, representing 8 % of cases notified during the study periods. Whole-genome phylogenetic analysis demonstrated that most strains were lineage 1 (195/208, 93.8 %), with the remainder being lineages 2 (8/208, 3.8 %) or 4 (5/208, 2.4 %). Lineages or sub-lineages were not associated with patient ethnicity. The lineage 1 strains were diverse, with sub-lineage 1.2.1 being dominant (192, 98 %). Lineage 1.2.1.3 isolates were geographically most widely distributed. The greatest diversity occurred in a border town sub-district. The time to the most recent common ancestor for the three major lineage 1.2.1 clades was estimated to be the year 1966 (95 % HPD 1948-1976). An association was found between failure of culture conversion by week 8 of treatment and infection with lineage 2 (4/6, 67 %) compared with lineage 1 strains (4/83, 5 %) (P<0.001), supporting evidence of greater virulence of lineage 2 strains. Eleven potential transmission clusters (SNP difference ≤12) were identified; at least five included people living in different sub-districts. Some linked cases spanned the whole 4-year study period. One cluster involved a multidrug-resistant tuberculosis strain matching a drug-susceptible strain from 3 years earlier. Drug resistance mutations were uncommon, but revealed one phenotype-genotype mismatch in a genotypically multidrug-resistant isolate, and rare nonsense mutations within the katG gene in two isolates. Consistent with the regionally mobile population, M. tuberculosis strains in Kota Kinabalu were diverse, although several lineage 1 strains dominated and were locally well established. Transmission clusters - uncommonly identified, likely attributable to incomplete sampling - showed clustering occurring across the community, not confined to households or sub-districts. The findings indicate that public health priorities should include active case finding and early institution of tuberculosis management in mobile populations, while there is a need to upscale effective contact investigation beyond households to include other contacts within social networks.

Matched MeSH terms: Mycobacterium tuberculosis/classification
Fulltext Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential

Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.

Sci Rep, 2014;4:4061.
PMID: 24515248 DOI: 10.1038/srep04061

Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.

Matched MeSH terms: Mycobacterium tuberculosis/classification
Convergence of tuberculosis and diabetes mellitus: time to individualise pharmaceutical care

Gnanasan S, Ting KN, Wong KT, Mohd Ali S, Muttalif AR, Anderson C

Int J Clin Pharm, 2011 Feb;33(1):44-52.
PMID: 21365392 DOI: 10.1007/s11096-010-9452-3

OBJECTIVE: To assess the feasibility of providing a pharmacist-led pharmaceutical care service to patients with tuberculosis and diabetes mellitus.
SETTING: The study was conducted at a tertiary hospital in the northern region of Peninsular Malaysia. Methods Action research methodology was used.
MAIN OUTCOME MEASURE: Pharmaceutical care issues.
RESULTS: The prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 15% (53/352). Out of 53 patients identified, 35 participated in the study. Patients' ages ranged between 29 and 73 years (mean of 52 ± 10 years). The male: female ratio was 1.7:1. Pharmaceutical care issues identified by pharmacists were nonadherence, uncontrolled diabetes mellitus, adverse drug reactions and individual patient's medication related problems. Pharmacists were able to intervene and resolve some of the pharmaceutical care issues.
CONCLUSION: Pharmacists played an important role in integrating the provision of care for tuberculosis and diabetes mellitus by providing individualised pharmaceutical care management. There still remains a need to address logistic barriers that impinged on the ability to conduct the pharmaceutical care service to its full potential.

Matched MeSH terms: Tuberculosis/classification
Fulltext Tuberculosis in Malaysia: predictors of treatment outcomes in a national registry

Liew SM, Khoo EM, Ho BK, Lee YK, Mimi O, Fazlina MY, et al.

Int J Tuberc Lung Dis, 2015 Jul;19(7):764-71.
PMID: 26056099 DOI: 10.5588/ijtld.14.0767

OBJECTIVES: To determine treatment outcomes and associated predictors of all patients registered in 2012 with the Malaysian National Tuberculosis (TB) Surveillance Registry.
METHODS: Sociodemographic and clinical data were analysed. Unfavourable outcomes included treatment failure, transferred out and lost to follow-up, treatment defaulters, those not evaluated and all-cause mortality.
RESULTS: In total, 21 582 patients were registered. The mean age was 42.36 ± 17.77 years, and 14.2% were non-Malaysians. The majority were new cases (93.6%). One fifth (21.5%) had unfavourable outcomes; of these, 46% died, 49% transferred out or defaulted and 1% failed treatment. Predictors of unfavourable outcomes were older age, male sex, foreign citizenship, lower education, no bacille Calmette-Guérin (BCG) vaccination scar, treatment in tertiary settings, smoking, previous anti-tuberculosis treatment, human immunodeficiency virus infection, not receiving directly observed treatment, advanced chest radiography findings, multidrug-resistant TB (MDR-TB) and extra-pulmonary TB. For all-cause mortality, predictors were similar except for rural dwelling and nationality (higher mortality among locals). Absence of BCG scar, previous treatment for TB and MDR-TB were not found to be predictors of all-cause mortality. Indigenous populations in East Malaysia had lower rates of unfavourable treatment outcomes.
CONCLUSIONS: One fifth of TB patients had unfavourable outcomes. Intervention strategies should target those at increased risk of unfavourable outcomes and all-cause mortality.

Matched MeSH terms: Tuberculosis/classification*