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  1. Tan JL, Simbun A, Chan KG, Ngeow YF
    Sci Data, 2020 05 05;7(1):135.
    PMID: 32371951 DOI: 10.1038/s41597-020-0475-x
    Mycobacterium tuberculosis (MTB) is commonly used as a model to study pathogenicity and multiple drug resistance in bacteria. These MTB characteristics are highly dependent on the evolution and phylogeography of the bacterium. In this paper, we describe 15 new genomes of multidrug-resistant MTB (MDRTB) from Malaysia. The assessments and annotations on the genome assemblies suggest that strain differences are due to lineages and horizontal gene transfer during the course of evolution. The genomes show mutations listed in current drug resistance databases and global MTB collections. This genome data will augment existing information available for comparative genomic studies to understand MTB drug resistance mechanisms and evolution.
    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology*
  2. Ahmad N, Javaid A, Sulaiman SA, Ming LC, Ahmad I, Khan AH
    Braz J Infect Dis, 2016;20(1):41-7.
    PMID: 26626164 DOI: 10.1016/j.bjid.2015.09.011
    BACKGROUND: Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan.

    OBJECTIVE: To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.

    METHODS: This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis.

    RESULTS: High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance.

    CONCLUSION: The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology*
  3. Noorizhab Fakhruzzaman MN, Abidin NZ, Aziz ZA, Lim WF, Richard JJ, Noorliza MN, et al.
    Int J Mycobacteriol, 2019 12 4;8(4):320-328.
    PMID: 31793500 DOI: 10.4103/ijmy.ijmy_144_19
    Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach.

    Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome.

    Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits.

    Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology*
  4. Rajendran M, Zaki RA, Aghamohammadi N
    Tuberculosis (Edinb), 2020 05;122:101925.
    PMID: 32275233 DOI: 10.1016/j.tube.2020.101925
    Multidrug-resistant tuberculosis (MDR-TB) is one of the causes of morbidity and mortality, among tuberculosis (TB) patients in Malaysia. The purpose of this study was to determine the contributing risk factors to the prevalence of (MDR-TB). Based on systematic review of the literatures, the prevalence of (MDR-TB) and associated risk factors in Malaysia were studied. A comprehensive search of Scopus, Science direct, PubMed, DOAJ, CINAHL Plus, MyJournal, BIREME, BMC Public Health, Medline, CAB, and WoS databases were done among the articles published from 31st January 2009 to 31st December 2018, by using medical subject heading (MeSH) key terms. In conducting this study, a total of 121 papers were reviewed and 23 research papers were chosen, because, they met the specific inclusion criteria. In this study, gender, age, marital status, ethnicity, homeless status, living in urban area and history of imprisonment were evaluated as demographic factors, while educational level and employment were evaluated as socioeconomic factors. Smoking, diabetes mellitus, drug abuse and alcohol consumption were evaluated as behavioral and co-morbidities factors. All the studies chosen as eligible to be included in this study were found to be significantly associated with the risk factors for the prevalence of (MDR-TB). It was also discovered that, lack of adequate knowledge among the community and (TB) patients might increase the progression of (MDR-TB) infection in Malaysia. Thus, carried out a systematic review provided a comprehensive assessment of the (MDR-TB) which might be useful for policy makers, health experts and researchers to implement appropriate strategies for (TB) infected population in Malaysia.
    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology
  5. Ahmad N, Khan AH, Syed Sulaiman SA, Javaid A
    Int J Mycobacteriol, 2015 09;4(3):258-9.
    PMID: 27649876 DOI: 10.1016/j.ijmyco.2015.05.012
    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology*
  6. Jaber AAS, Ibrahim B
    BMC Infect Dis, 2019 May 24;19(1):464.
    PMID: 31126246 DOI: 10.1186/s12879-019-4069-1
    BACKGROUND: The World Health Organization (WHO) has reported that Yemen has a high burden of drug resistance and a worrying shortage of implemented diagnostic methods and drug treatment regimens. Therefore, in this study, we evaluated the risk factors associated with multidrug-resistant tuberculosis (MDR-TB) and explored the poor TB management in Yemen.

    METHODS: Between January 2014 and December 2016, we enrolled 135 patients with MDR-TB from drug resistance programmes at four major TB centres in Yemen for this prospective study. After exclusion of 20 patients, treatment outcomes were reported for 115 patients who attended a series of follow-ups.

    RESULTS: A total of 115 patients with MDR-TB were analysed from the four main TB centres in Yemen. Most patients (35.2%) were from the Aden TB centre. A success rate of 77.4% was reported for TB treatment. Of the 115 patients, 69.6% were resistant to two drugs, 18.3% were resistant to three drugs, and 12.2% were resistant to four drugs. During the intensive phase of treatment, 19 patients (16.5%) reported one or more adverse events. A multivariate logistic regression analysis revealed that a baseline body weight of ≤40 kg [p = 0.016; adjusted odds ratio (AOR) = 25.09], comorbidity (p = 0.049; AOR = 4.73), baseline lung cavities (p = 0.004; AOR = 15.32), and positive culture at the end of the intensive phase (p = 0.009; AOR = 8.83) were associated with the unsuccessful treatment outcomes in drug-resistant TB patients.

    CONCLUSIONS: The success rate achieved after treatment was below the levels established by the WHO End TB Strategy (90%) and the United Nations Sustainable Development Goals (80%). Identification of risk factors associated with MDR-TB in Yemen is essential because it allows health workers to identify high-risk patients, especially in the absence of a second-line treatment or a laboratory diagnostic method. The Yemen National Tuberculosis Control Program should formulate new strategies for early detection of MDR-TB and invest in new programmes for MDR-TB management.

    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology
  7. Ikryannikova LN, Afanas'ev MV, Akopian TA, Il'ina EN, Kuz'min AV, Larionova EE, et al.
    J Microbiol Methods, 2007 Sep;70(3):395-405.
    PMID: 17602768
    A MALDI TOF MS based minisequencing method has been developed and applied for the analysis of rifampin (RIF)- and isoniazid (INH)-resistant M. tuberculosis strains. Eight genetic markers of RIF resistance-nucleotide polymorphisms located in RRDR of rpoB gene, and three of INH resistance including codon 315 of katG gene and -8 and -15 positions of the promoter region of fabG1-inhA operon were worked out. Based on the analysis of 100 M. tuberculosis strains collected from the Moscow region in 1997-2005 we deduced that 91% of RIF-resistant and 94% of INH-resistant strains can be identified using the technique suggested. The approach is rapid, reliable and allows to reveal the drug resistance of M. tuberculosis strains within 12 h after sample isolation.
    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology
  8. Javaid A, Ahmad N, Afridi AK, Basit A, Khan AH, Ahmad I, et al.
    Am J Trop Med Hyg, 2018 06;98(6):1629-1636.
    PMID: 29611497 DOI: 10.4269/ajtmh.17-0936
    To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.
    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology
  9. Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.
    Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
    PMID: 28225340 DOI: 10.5588/ijtld.16.0444
    BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.

    OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.

    METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.

    RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.

    CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

    Matched MeSH terms: Tuberculosis, Multidrug-Resistant/microbiology
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