Emergence of mixed infection of Beijing/Non-Beijing strains among multi-drug resistant Mycobacterium tuberculosis in Pakistan

Mustafa, S. E. S.; Javed, Hasnain; Hashmi, Jawairia; Jamil, Nazia; Tahir, Zarfishan; Akhtar, Abdul Majeed

doi:10.1007/s13205-016-0423-9

Cited by 11 publications

(12 citation statements)

References 27 publications

(27 reference statements)

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“…Of these, 22 patients were already known DM and due to taking medicine they had fasting blood sugar level <126 mg/dl at the time of data collection. The results of present study are similar to those of Amin et al that reported co-occurrence of TB and DM in 14% patients of Peshawar, Pakistan 6 . Similarly, another study of Pakistani population conducted by Jabbar et al in 2006 showed co-occurrence of TB and DM among 11.9% study participants 18 .…”

Section: Fig1 Overall Prevalence Of Diabetes Among Tb Patientssupporting

confidence: 92%

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Diabetes mellitus among tuberculosis patients: a cross sectional study from Pakistan

Tahir¹,

Ahmad²,

Akhtar

et al. 2017

Afr H. Sci.

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Background: The co-occurrence of diabetes mellitus (DM) and tuberculosis (TB) is largely associated with high frequency of morbidity. Objective: To determine the prevalence of DM among TB patients and describe the socio-demographic and behavioral factors associated with TB-DM co-occurrence . Methods: We enrolled 500 TB patients from September, 2014 to August 2015 at four major public sector hospitals of Lahore, Pakistan. A questionnaire was used to collect information regarding associated socio-demographic and behavioral factors of the patients. We monitored the fasting blood sugar of each patient by using a semi automated clinical chemistry analyzer followed by an HbA1c level check of all hyperglycemic patients. Results: The prevalence of TB-DM co-occurrence was 14.8%. The prevalence of TB-DM was higher (62.2%) among males. The >57 year age group had the highest proportion of patients (35.1%), with co-existent TB-DM. Most were illiterate (73.0%) and unemployed (48%). Moreover, among the 74 patients positive for TB-DM had a history of smoking. Age and education level were significantly associated with DM-TB while gender, occupation and smoking were not associated. Conclusion:The study revealed a 14.8% prevalence of DM among TB patients. This was associated with several socio-demographic factors, including age, unemployment, literacy and polluted environment. Thus, poor and unhealthy lifestyles were the factors associated with DM among immunologically compromised individuals due to TB. Keywords: Tuberculosis (TB), diabetes mellitus (DM), socio-demographic and behavioral factors.

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Section: Fig1 Overall Prevalence Of Diabetes Among Tb Patientssupporting

confidence: 92%

“…4 Therefore, it is essential to study the prevalence of both diseases in order to understand the factors associated with their co -occurrance. TB countries 6 . The World Health Organization (WHO) reported an estimated incindence of 275 cases per 100,000 persons and prevalence of 342 cases per 100,000 population 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Diabetes mellitus among tuberculosis patients: a cross sectional study from Pakistan

Tahir¹,

Ahmad²,

Akhtar

et al. 2017

Afr H. Sci.

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“…Multiplex PCR method was used to distinguish Beijing and non-Beijing genotypes as previously described 17 that region spanning genes Rv2816 to Rv2819 including part of Rv2820 is missing in Beijing genotype of M. tuberculosis strain. A set of primers BJ-F: 5ʹ-ACCGAGCTGATCAAACCCG -3ʹ and BJ-R: 5ʹ-ATGGCACGGCCGACCTGAATGAACC -3ʹ amplified the 239 bp PCR product containing regionspecific part of Rv2819 and part of Rv2820 in Beijing genotypes.…”

Section: Detection Of Beijing and Non-beijing Genotypesmentioning

confidence: 99%

<p>Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant <em>Mycobacterium tuberculosis</em> Clinical Isolates in Southern China</p>

Hameed¹,

Tan²,

Islam³

et al. 2020

IDR

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is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA + upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis. Methods: Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates. Results: Our data showed that among 448 M. tuberculosis clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drugresistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZA R isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncA-Rv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZA R. Compared with phenotypic data, 84.38% (227/269) PZA R strains with mutations in pncA + upstream region exhibited 83.64% sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48% (4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74% (2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C−114del) in upstream of pncA wt nullified the effect of A−11G mutation and induced positive PZase activity, divergent from five PZase negative A−11G PZA R mutants. Twenty-six PZA R strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms. Conclusion: Our study revealed that PZA R rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA + UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance.

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“…Furthermore, AMK, KAN and CAP resistance has been associated with mutations in the 16S rRNA gene ( rrs ), between nucleotide positions 1400 and 1500 particularly mutations in positions 1401, 1402 and 1484; up to 87% of KAN and AMK resistance worldwide is attributed to these mutations (especially a1401g) [11, 12]. Additionally, KAN and CAP resistance can also be mediated by mutations in the eis and tlyA genes, respectively.It is now well-documented that the frequencies of drug resistance conferring mutations described above vary between M. tuberculosis geno-groups and geographically [13, 14], which pose a significant challenge in the development of sequence-based diagnostic tools and their applicability without a thorough evaluation of their performance with respect to setting. Case in point is the MTBDR sl test which, although it is generally useful in detecting resistance to second-line anti-TB drugs, it has varying sensitivity especially in detecting FQ resistance [15].…”

Section: Introductionmentioning

confidence: 99%

Frequency and patterns of second-line resistance conferring mutations among MDR-TB isolates resistant to a second-line drug from eSwatini, Somalia and Uganda (2014–2016)

et al. 2019

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Background Pulmonary tuberculosis is a leading cause of morbidity and mortality in developing countries. Drug resistance, a huge problem in this contagious disease, is driven by point mutations in the Mycobacterium tuberculosis genome however, their frequencies vary geographically and this affects applicability of molecular diagnostics for rapid detection of resistance. Here, we report the frequency and patterns of mutations associated with resistance to second-line anti-TB drugs in multidrug-resistant (MDR) M. tuberculosis isolates from eSwatini, Somalia and Uganda that were resistant to a second-line anti-TB drug. Methods The quinolone resistance determining region (QRDR) of gyrA / gyrB genes and the drug resistance associated fragment of rrs gene from 80 isolates were sequenced and investigated for presence of drug resistance mutations. Of the 80 isolates, 40 were MDR, of which 28 (70%) were resistant to a second-line anti-TB injectable drug, 18 (45%) were levofloxacin resistant while 12 (30%) were extensively drug resistant (XDR). The remaining 40 isolates were susceptible to anti-TB drugs. MIRU-VNTR analysis was performed for M/XDR isolates. Results We successfully sub-cultured 38 of the 40 M/XDR isolates. The gyrA resistance mutations (Gly88Ala/Cys/Ala, Ala90Val, Ser91Pro, Asp94Gly/Asn) and gyrB resistance mutations (Asp500His, Asn538Asp) were detected in 72.2% (13/18) and 22.2% (4/18) of the MDR and levofloxacin resistant isolates, respectively. Overall, drug resistance mutations in gyrA / gyrB QRDRs occurred in 77.8% (14/18) of the MDR and levofloxacin resistant isolates. Furthermore, drug resistance mutations a1401g and g1484 t in rrs occurred in 64.3% (18/28) of the MDR isolates resistant to a second-line anti-TB injectable drug. Drug resistance mutations were not detected in drug susceptible isolates. Conclusions The frequency of resistance mutations to second-line anti-TB drugs in MDR-TB isolates resistant to second line anti-TB drugs from eSwatini, Somalia and Uganda is high, implying that rapid molecular tests are useful in detecting second-line anti-TB drug resistance in those countries. Relatedly, the frequency of fluoroquinolone resistance mutations in gyrB /QRDR is high relative to global estimates, and they occurred independently of gyrA /QRDR mutations implying that their absence in panels of molecular tests for detecting fluoroquinolone resistance may yield false negative results in our setting. Electronic supplementary material The online version of this article (10.1186/s12890-019-0891-x) ...

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Emergence of mixed infection of Beijing/Non-Beijing strains among multi-drug resistant Mycobacterium tuberculosis in Pakistan

Cited by 11 publications

References 27 publications

Diabetes mellitus among tuberculosis patients: a cross sectional study from Pakistan

Diabetes mellitus among tuberculosis patients: a cross sectional study from Pakistan

<p>Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant <em>Mycobacterium tuberculosis</em> Clinical Isolates in Southern China</p>

Frequency and patterns of second-line resistance conferring mutations among MDR-TB isolates resistant to a second-line drug from eSwatini, Somalia and Uganda (2014–2016)

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