scholarly journals Prevalence of Multi-Drug Resistant Mycobacterium Tuberculosis in Khyber Pakhtunkhwa – A High Tuberculosis Endemic Area of Pakistan

2020 ◽  
Vol 69 (2) ◽  
pp. 133-137 ◽  
Author(s):  
SAJID ALI ◽  
MUHAMMAD TAHIR KHAN ◽  
ANWAR SHEED KHAN ◽  
NOOR MOHAMMAD ◽  
MUHAMMAD MUMTAZ KHAN ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Large Scale ◽  
Simple Random Sampling ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Khyber Pakhtunkhwa ◽  
Mdr Tb

Anti-tuberculosis therapy involves the combination of drugs to hamper the growth of Mycobacterium tuberculosis (MTB). The emergence of multidrug-resistant tuberculosis (MDR-TB) is a global concern. Pakistan has been ranked 5th position in terms of a high burden of MDR-TB in the world. The aim of the current study was to investigate the prevalence of drug resistance in MTB in Khyber Pakhtunkhwa. Random samples were collected from 25 districts using the simple random sampling formula. All samples were processed in a biosafety level 3 laboratory for culture and drug susceptibility testing. Among 5759 presumptive tuberculosis (TB) cases, 1969 (34%) were positive. The proportion of TB was higher in females (39%) than males (29%), thus it represents a significant association between gender and tuberculosis (p < 0.05). People ages between 25 to 34 years were more likely to be infected with MTB (40%). Drug-resistant profile showed 97 (4.9%) patients were infected with MDR-TB. Streptomycin resistance was the highest and was observed in 173 (9%) isolates followed by isoniazid in 119 (6%) isolates. The lowest resistance was observed to pyrazinamide (3%). The prevalence of MDR-TB (10.4%) among patients that previously received anti-tuberculosis treatment is seemingly high. A large-scale drug resistance survey is required to evaluate the drug resistance for better management of tuberculosis.

scholarly journals Transmission patterns of rifampicin resistant Mycobacterium tuberculosis complex strains in Cameroon: a genomic epidemiological study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthias Merker ◽  
Nkongho F. Egbe ◽  
Yannick R. Ngangue ◽  
Comfort Vuchas ◽  
Thomas A. Kohl ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Prolonged Exposure ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
High Dose ◽  
Factors Affecting ◽  
Recent Transmission ◽  
Mdr Tb

Abstract Background Determining factors affecting the transmission of rifampicin (RR) and multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains under standardized tuberculosis (TB) treatment is key to control TB and prevent the evolution of drug resistance. Methods We combined bacterial whole genome sequencing (WGS) and epidemiological investigations for 37% (n = 195) of all RR/MDR-TB patients in Cameroon (2012–2015) to identify factors associated with recent transmission. Results Patients infected with a strain resistant to high-dose isoniazid, and ethambutol had 7.4 (95% CI 2.6–21.4), and 2.4 (95% CI 1.2–4.8) times increased odds of being in a WGS-cluster, a surrogate for recent transmission. Furthermore, age between 30 and 50 was positively correlated with recent transmission (adjusted OR 3.8, 95% CI 1.3–11.4). We found high drug-resistance proportions against three drugs used in the short standardized MDR-TB regimen in Cameroon, i.e. high-dose isoniazid (77.4%), ethambutol (56.9%), and pyrazinamide (43.1%). Virtually all strains were susceptible to fluoroquinolones, kanamycin, and clofazimine, and treatment outcomes were mostly favourable (87.5%). Conclusion Pre-existing resistance to high-dose isoniazid, and ethambutol is associated with recent transmission of RR/MDR strains in our study. A possible contributing factor for this observation is the absence of universal drug susceptibility testing in Cameroon, likely resulting in prolonged exposure of new RR/MDR-TB patients to sub-optimal or failing first-line drug regimens.

scholarly journals Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Daria N. Podlekareva ◽  
Dorte Bek Folkvardsen ◽  
Alena Skrahina ◽  
Anna Vassilenko ◽  
Aliaksandr Skrahin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Second Line ◽  
High Burden ◽  
Tb Treatment ◽  
Mdr Tb

Background. To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome. Methods. Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied. Results. Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up. Conclusions. We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients’ outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

scholarly journals Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

2019 ◽  
Vol 147 ◽  
Author(s):  
R. S. Salvato ◽  
S. Schiefelbein ◽  
R. B. Barcellos ◽  
B. M. Praetzel ◽  
I. S. Anusca ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Characterisation ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
High Burden ◽  
Brics Countries ◽  
Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

scholarly journals Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

2014 ◽  
Vol 53 (1) ◽  
pp. 131-135 ◽  
Author(s):  
Limei Zhu ◽  
Qiao Liu ◽  
Leonardo Martinez ◽  
Jinyan Shi ◽  
Cheng Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Value ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Standard Drug ◽  
Related Data ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

scholarly journals rpoB gene mutations in rifampin-resistant Mycobacterium tuberculosis isolates from rural areas of Zhejiang, China

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Mei-Chun Zeng ◽  
Qing-Jun Jia ◽  
Lei-Ming Tang
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rural Areas ◽  
Gene Mutations ◽  
Gene Sequencing ◽  
Rpob Gene ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Objective The aim was to analyze genetic mutations in the rpoB gene of rifampin-resistant Mycobacterium tuberculosis isolates (RIFR-MTB) from Zhejiang, China. Methods We prospectively analyzed RIFR-associated mutations in 13 rural areas of Zhejiang. Isolates were subjected to species identification, phenotype drug susceptibility testing (DST), DNA extraction, and rpoB gene sequencing. Results A total of 103 RIFR isolates were identified by DST (22 RIFR only, 14 poly-drug resistant, 49 multidrug resistant, 13 pre-extensively drug resistant [pre-XDR], and 5 extensively drug resistant [XDR]) from 2152 culture-positive sputum specimens. Gene sequencing of rpoB showed that the most frequent mutation was S450L (37.86%, 39/103); mutations P280L, E521K, and D595Y were outside the rifampicin resistance-determining region (RRDR) but may be associated with RIFR. Mutations associated with poly-drug resistant, pre-XDR, and XDR TB were mainly located at codon 445 or 450 in the RRDR. Conclusions The frequency of rpoB RRDR mutation in Zhejiang is high. Further studies are needed to clarify the relationships between RIFR and the TTC insertion at codon 433 in the RRDR and the P280L and D595Y mutations outside the RRDR.

scholarly journals Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Marie Demers ◽  
◽  
Soyeon Kim ◽  
Sara McCallum ◽  
Kathleen Eisenach ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sputum Sample ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Drug Susceptibility Testing ◽  
Study Entry ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Therapy Trial

Abstract Background Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

scholarly journals The epidemiological characteristics and profile of drug-resistant tuberculosis among children with tuberculosis in Sichuan, China, 2015-2018: A retrospective study

2020 ◽  
Author(s):  
Yuanhong Xu ◽  
Qingfeng Li ◽  
Ma Zhu ◽  
Xueqi Wu ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Clinical Information ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Epidemiological Characteristics

Abstract Background: The aim of this study was to investigate the epidemiological characteristics and profile of drug-resistant tuberculosis (DR-TB) among children with TB in Sichuan province of China.Methods: From January 2015 to December 2018, microbiological culture-confirmed child TB cases (aged<15 years old) were enrolled retrospectively. Epidemiological and clinical information from these cases, and the drug susceptibility testing (DST) results of the isolates were collected and analyzed.Results: Of 317 culture-confirmed child TB cases, 16.7% (53/317) were aged under 5 years old. 54.9% were Tibetans, and 31.9% had clear history of contact with TB patients. More than half (53.9%) weren’t vaccinated by Calmette–Guérin bacillus (BCG). 30% (n=95) were diagnosed as severe TB, and 92.4% (n=293) were new cases. The ratio of severe TB in BCG vaccinated group was significant lower than that observed in unvaccinated group (p<0.01). Significantly higher proportion of severe TB among Tibetans than Han child TB cases was observed in BCG unvaccinated group (p<0.01). The overall rate of DR-TB in this study was 24.3% (77/317) and 17 multidrug-resistant tuberculosis (MDR-TB) cases were identified with rate of MDR-TB at 5.4% (17/317). No XDR case was found. 13 out of 17 MDR-TB cases (76.4%) were Tibetan children. The ratio of any resistance to four first-line drugs identified were: INH, 15.5%; RIF, 9.1%; EMB, 0.6% and SM, 6.0%, respectively. More than half of MDR patterns were resistant to INH+RIF (9/17), followed by at least resistance to INH+RIF+SM (n=7). Conclusions: This was the first investigation on the epidemiological characteristics and profiles of DR-TB among child TB cases in Southwest of China. Our findings indicated a potentially high risk of TB infection to Tibetan children in the concentrated Tibetan communities of Sichuan.

scholarly journals EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR TB)

2019 ◽  
Vol 5 (2) ◽  
pp. 26
Author(s):  
Sarah Rahmayani Siregar
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Tuberculosis Programme ◽  
Mdr Tb ◽  
Directly Observed Treatment

Tuberkulosis adalah penyakit infeksi kronis menular yang masih merupakan masalah kesehatan masyarakat di dunia termasuk Indonesia. Tuberkulosis (TB) sebagian besar akan mengalami penyembuhan dengan pengobatan. Namun tidak semua penyakit TB sembuh dengan pengobatan. Hal ini disebabkan pengobatan dari TB yang belum terlaksana dengan baik sehingga dapat pula menyebabkan terjadinya resistensi terhadap Obat Anti Tuberkulosis (OAT), berupa Multidrug Resistant Tuberkulosis (MDR TB) dan Extensively Drug Resistant Tuberculosis (XDR TB). XDR TB adalah TB yang disebabkan oleh strain yang resistensi terhadap isoniazid dan rifampisin, disertai resisten terhadap salah satu fluorokuinolon dan salah satu dari tiga obat injeksi lini kedua (amikasin, kapreomisin atau kanamisin). XDR TB diperkenalkan tahun 2006 ketika terjadi epidemi yang sangat fatal di Afrika Selatan. XDR-TB dapat ditularkan melalui bakteri yang disebarkan oleh orang yang sudah terkena resistensi obat. Diagnosis XDR-TB ditegakkan dengan uji sensitiviti obat atau Drug Susceptibility Testing (DST), bukan sekedar berdasarkan gambaran foto toraks dan adanya faktor resiko yang ada pada seseorang. WHO telah merancang strategi Directly Observed Treatment Short Course (DOTS-Plus) untuk mengelola TB M/XDR di negara-negara miskin sumber daya. Revisi National Tuberculosis Programme (RNTCP) di bawah DOTS-Plus akan menggunakan rejimen pengobatan standar (STR) kategori IV, yang terdiri dari 6 obat (kanamisin, levofloxacin, etionamid, sikloserin, pirazinamid, dan etambutol) selama 6-9 bulan fase intensif dan 4 obat (levofloxacin, ethionamide, cycloserine, dan ethambutol) selama 18 bulan dari fase lanjutan. Penyembuhan tergantung pada tingkat resistensi obat, tingkat keparahan penyakit dan apakah sistem kekebalan pasien terganggu.

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