scholarly journals Resistance at No Cost: The Transmissibility and Potential for Disease Progression of Drug-ResistantM. Tuberculosis

2018 ◽  
Author(s):  
Mercedes C. Becerra ◽  
Chuan-Chin Huang ◽  
Leonid Lecca ◽  
Jaime Bayona ◽  
Carmen Contreras ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Pulmonary Tb ◽  
Genetic Fingerprint ◽  
Resistant Tuberculosis ◽  
Significant Difference ◽  
Mdr Tb ◽  
The Impact

AbstractBackgroundThe future trajectory of drug resistant tuberculosis strongly depends on the fitness costs of drug resistance mutations. Here, we measured the association of phenotypic drug resistance and the risk of TB infection and disease among household contacts (HHCs) of patients with pulmonary TB.MethodsWe evaluated 12767 HHCs of patients with drug sensitive and resistant pulmonary TB at baseline, two, six, and 12 months to ascertain infection status and to determine whether they developed tuberculosis disease. We also assessed the impact of drug resistance phenotype on the likelihood that a TB strain shared a genetic fingerprint with at least one other TB patient in the cohort.FindingsAmong 3339 TB patients for whom were DST available, 1274 (38%) had TB that was resistant to at least one drug and 478 (14⋅3%) had multi-drug resistant (MDR) TB, i.e. TB resistant to both INH and rifampicin. Compared to HHCs of drug sensitive TB patients, those exposed to a patient with MDR-TB had an 8% (95% CI: 4-13%) higher risk of infection by the end of follow up. We found no statistically significant difference in the relative hazard of incident TB disease among HHCs exposed to MDR-TB compared to DS-TB (Adjusted HR 1⋅28 [(95% CI: ⋅9-1⋅83]). Patients with MDR-TB were more likely to be part of a genetic cluster than were DS-TB patients.InterpretationClinical strains of MDR M. tuberculosis are neither less transmissible than drug sensitive strains nor less likely to cause disease. (ClinicalTrials.gov number,NCT00676754)FundingNational Institutes of Health: NIH/NIAID CETR U19AI109755StatementAll authors have seen the manuscript and approved the manuscript.

scholarly journals Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wan-mei Song ◽  
Jing Guo ◽  
Ting-ting Xu ◽  
Shi-jin Li ◽  
Jin-yue Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Normal Weight ◽  
Streptomycin Resistance ◽  
Drug Resistant ◽  
Newly Diagnosed ◽  
Clinical Predictors ◽  
Resistant Tuberculosis ◽  
Co Morbidity ◽  
Mdr Tb ◽  
The Impact

Abstract Background Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. Methods 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. Results Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726–0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049–1.730; adjusted OR (aOR) 1.31, 95% CI 1.017–1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002–2.566; aOR 1.639, 95% CI 1.02–2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061–3.577; aOR 2.113, 95% CI 1.141–3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013–2.14; aOR 1.483, 95% CI 1.017–2.164), P < 0.05. Conclusions The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

scholarly journals Trends, Characteristics and Treatment Outcomes of Patients with Drug-Resistant Tuberculosis in Uzbekistan: 2013–2018

2021 ◽  
Vol 18 (9) ◽  
pp. 4663
Author(s):  
Khasan Safaev ◽  
Nargiza Parpieva ◽  
Irina Liverko ◽  
Sharofiddin Yuldashev ◽  
Kostyantyn Dumchev ◽  
...  
Keyword(s):  
Risk Factors ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
National Level ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Loss To Follow Up ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013–2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016–2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.

scholarly journals Mycobaterial interspersed repetitive units-variable number of tandem repeats analysis and pattern of drug resistance in extended drug resistant (XDR) TB isolates from pulmonary tuberculosis patients in Bangladesh

2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir
Keyword(s):  
Drug Resistance ◽  
Molecular Typing ◽  
Tandem Repeats ◽  
Variable Number ◽  
Drug Resistant ◽  
Gyra Gene ◽  
Drug Resistant Tuberculosis ◽  
Tree Analysis ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation. Objective: This study was intended to observe the genotypes of XDR mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis. Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 multi drug resistant tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through line probe assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%)  XDR-TB isolates were typed and analysed. Results: Twenty four loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.60%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.20%), Haarlem two(18.20%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%)..  All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases. Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB. Bangladesh Med Res Counc Bull 2020; 46(1): 22-28

scholarly journals Socio-demographic Profile and Drug Sensitivity Pattern of Suspected Drug Resistant Tuberculosis among Patients in Regional Tuberculosis Reference Laboratory (R.T.R.L) of a Tertiary Hospital

2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Suspected Drug ◽  
Drug Resistant Tuberculosis ◽  
Demographic Profile ◽  
Resistant Tuberculosis ◽  
Sensitivity Pattern ◽  
Mdr Tb

Background: Drug resistant tuberculosis has been reported in all regions of the world. In this study we address the socio-demographic profile and drug sensitivity pattern as well as prevalence of drug resistance tuberculosis in a tertiary center (regional TB reference laboratory) in Bangladesh.Method: This Study was carried out in R.T.R.L. (Regional TB Reference Laboratory) in 250 bedded Chittagong General Hospital. Patients who were referred to R.T.R.L during the period July 2012 to July 2013 were included in the study. Total 100 patients with suspected drug resistant tuberculosis (TB) who had any one of 9 criteria of NTP (National Tuberculosis Control Programme) were selected consecutively. Gene xpert MTB/RIF (Rifampicin resistance) test for all sputum positive cases were performed. Sputum sample of Patients with positive microscopy for AFB or positive Xpert/MTB was sent for culture. The samples with positive sputum culture were sent for drug sensitivity test for 1st line anti- tubercular drug.Result: Among 100 patients 78 were male and 22 were female, majority of the patients (64) were between 15-45 years with poor socio economic condition (73%) and primarily educated. Analysis of our Study result showed that 18% of patients were mono-drug resistant. Among them 13% showed resistance to isoniazid (INH), 4% to streptomycin and only 2% to rifampicin. No patient was found resistant to pyrazinamide (PNZ) and 38% of patient with suspected drug – resistant TB was found to have no drug resistance. 18% of patient had multidrug resistant tuberculosis (MDR-TB) among which 56% were relapse cases (48% after cat -I, 8% after cat II), 24% were non – converter of cat –I, 12% belonged to failure of cat –I, 3% failure of cat –II, 2% return after default and others. 1% of patient had history of contact with MDR –TB patient.Conclusion: Drug-resistance tuberculosis especially MDR-TB, was higher in patients with previously incomplete anti-tuberculosis treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. For this reason proper counseling of patients and attention towards the completion of the anti-TB treatment are needed.J MEDICINE July 2017; 18 (2) : 62-67

scholarly journals Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals

2020 ◽  
Vol 75 (11) ◽  
pp. 3319-3326
Author(s):  
Benjamin Chimukangara ◽  
Jennifer Giandhari ◽  
Richard Lessells ◽  
Nonhlanhla Yende-Zuma ◽  
Benn Sartorius ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virological Failure ◽  
Statistical Significance ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
The Impact ◽  
Hiv 1 ◽  
Control Study

Abstract Objectives To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. Methods We conducted a case–control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs &lt;1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. Results We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8–18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6–4.3) compared with those without, P = 0.398. Conclusions Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions.

scholarly journals Evolution and Transmission Patterns of Extensively Drug-Resistant Tuberculosis in China

2014 ◽  
Vol 59 (2) ◽  
pp. 818-825 ◽  
Author(s):  
Feifei Wang ◽  
Lingyun Shao ◽  
Xiaoping Fan ◽  
Yaojie Shen ◽  
Ni Diao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Variable Number Tandem Repeat ◽  
Resistance Mutation ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTThe emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China. Eight drug resistance genes covering 7 drugs that define XDR-TB were amplified by PCR followed by DNA sequencing. Variable-number tandem repeat 16-locus (VNTR-16) genotyping and genotypic drug resistance profiles were used to determine the evolution or transmission patterns of XDR-TB strains. Our results indicated that the Beijing genotype was predominant (85/95 [89.5%]) in XDR-TB strains, and as many as 40.0% (38/95) of the isolates were distributed into 6 clusters based on VNTR-16 genotyping and drug resistance mutation profiles. All isolates of each cluster harbored as many as six identical resistance mutations in the drug resistance genesrpoB,katG,inhApromoter,embB,rpsL, andgidB. Among the nine cases with continuous isolates from multidrug-resistant (MDR) to XDR-TB, 4 cases represented acquired drug resistance, 4 cases were caused by transmission, and 1 case was due to exogenous superinfection. The XDR-TB epidemic in China is mainly caused by a high degree of clonal transmission, but evolution from MDR to XDR and even superinfection with a new XDR strain can also occur.

scholarly journals Drug resistance profile among multi-drug resistant tuberculosis patients at diagnosis and correlation with history of anti-tubercular treatment in a tertiary care center

2019 ◽  
Vol 6 (6) ◽  
pp. 1918
Author(s):  
Rahul Kumar ◽  
Rajiv Garg ◽  
Silpa Kshetrimayum ◽  
Amita Jain
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Drug Resistant ◽  
Second Line ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Primary Drug Resistance ◽  
Mdr Tb ◽  
History Of

Background: Drug Resistant Tuberculosis (DR-TB) is a major threat to the realization of the goal of a TB free world in the near future. It is important to study the reasons for the increasing number of such cases so that effective action can be taken to control this growing epidemic.Methods: Sputum from 36 patients diagnosed with acquired pulmonary Multidrug Resistant Tuberculosis (MDR-TB) were subjected to first- and second-line Drug Sensitivity Testing (DST) after liquid culture in mycobacterium growth Indicator Tube (MGIT). Primary MDR-TB cases were excluded. The relation of the drug sensitivity profile with the history of prior treatment taken was statistically analysed.Results: Majority of the patients had received appropriate treatment, and most had adhered to prescribed treatment. Among the 36 patients, 24(66.7%) were found to be Pre-Extensively Drug Resistant (Pre-XDR-TB) and 4(11.1%) were extensively drug resistant XDR-TB cases. Inappropriate prescription of fluoroquinolone (FQ) was found to be most common. Prior intake of any drug was not found to significantly affect subsequent resistance to that drug.Conclusions: Fluoroquinolone resistance is quite common in patients with DR-TB (66.7%). This study did not find the prior use of FQ or any other drug to significantly affect subsequent resistance to the drug. Primary drug resistance is thus a major concern. 11.1% patients were found to be XDR-TB cases. Hence DST for first- and second-line drugs should be done at the time of diagnosis to avoid failure of treatment with a predesigned regimen.

scholarly journals Molecular Detection of Drug-Resistant Mycobacterium tuberculosis in Sputum Specimens from the New and Previously Treated Tuberculosis Cases at the National Reference Chest Diseases Laboratory in Lusaka, Zambia

2021 ◽  
Vol 2 (4) ◽  
pp. 232-243
Author(s):  
DK Mumena ◽  
G Kwenda ◽  
CW Ngugi ◽  
AK Nyerere
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Polymerase Chain Reaction Amplification ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Health Issues ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Reaction Amplification ◽  
Previously Treated

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major public health issues globally. Zambia is highly burdened by TB and multi-drug resistant TB. In this study, sputum samples obtained from the new and previously treated cases of TB were examined for drug-resistant Mycobacterium tuberculosis (MTB). Methods: Sputum specimens were processed using the N-acetyl-L-cysteine-sodium hydroxide method, stained and examined using fluorescent technique and microscopy respectively. Mycobacterial DNA was extracted using the Genolyse kit, then subjected to multiplex polymerase chain reaction amplification and reverse hybridization. Drug-resistance and mutations in MTB genes were detected using the Genotype MTBDRplus VER 2.0 and MTBDRsl VER 2.0 assays. Results: A total of 329 MTB-positive sputum specimens, 102 from the new TB cases and 227 from previously treated TB cases, were analysed for drug-resistance. Among the new TB cases, 3.9% had Rifampicin (RIF) mono-resistance, 12.8% Isoniazid (INH) mono-resistance, and 17.7% had Multi-Drug Resistance (MDR). For the previously treated TB cases, 10.1% had RIF mono-resistance, 6.6% INH mono-resistance, 33.0% MDR, 1.8% poly-drug resistance, and 0.8% had pre-Extensively Drug-Resistance (pre-XDR). Mutations identified were rpoB (Ser531Leu, His526Asp, Asp516Val, His526Tyr, and Glu510His), katG (Ser315Thr 1 and Ser315Thr 2), InhA (Cys15Thr), gyrA (Ala90Val and Asp94Gly), and eis (Cys14Thr), each with a varying frequency. Conclusion: DR-TB is prevalent, especially MDR-TB, which is currently the most worrisome form of DR-TB and an emerging threat hampering efforts in the control of TB in Zambia. The early detection and effective treatment of TB cases are key in the control of DR-TB.

scholarly journals Efficacy and safety of regimen containing bedaquiline in children with drug-resistant tuberculosis

2021 ◽  
pp. 138-146
Author(s):  
V. A. Aksenova ◽  
N. I. Klevno ◽  
A. V. Kazakov ◽  
D. A. Kudlay ◽  
A. D. Pakhlavonova ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Efficacy And Safety ◽  
Duration Of Treatment ◽  
Drug Resistant Tuberculosis ◽  
Children And Adolescent ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Introduction. The treatment of children with multidrug-resistant and extensively drug-resistant tuberculosis (MDR / XDR-TB) is a difficult task due to many factors: the duration of treatment, the lack of drugs with children’s dosages, age restrictions (according to the drug instructions).Purpose of the study. To assess the efficacy and safety of regimen with the inclusion of bedaquiline in children and adolescent with respiratory tuberculosis with drug-resistant tuberculosis.Materials and methods. The study is prospective, cohort, non-comparative from the period 2017–2019. We included 24 patients aged 5 to 17 years with MDR-TB (established or suspected) began regimen containing bedaquiline for 24 weeks. The duration of observation of patients included in the study was 24 months.Results. We can state a sufficient level of safety of using the latter for 24 weeks: adverse events presumably associated directly with the intake of bedaquiline were noted in only 1 patient out of 24 (4.2%; 95% CI 0.7-20.3). The efficacy of a regimen containing bedaquiline in combination with other anti-tuberculosis reserve drugs is beyond doubt: positive clinical and radiological dynamics and cessation of bacterial excretion by the end of the 24-week course of treatment were noted in all patients included in the study. In the course of 2-year follow-up, no exacerbation of the tuberculous process was observed in any case. All patients achieved clinical cure of tuberculosis.Conclusion. Regimen containing bedaquiline for children aged 5–17 years with multidrug-resistant tuberculosis is effective and safe.

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