scholarly journals Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries

2018 ◽  
Author(s):  
Kathrin Zürcher ◽  
Marie Ballif ◽  
Lukas Fenner ◽  
Sonia Borrell ◽  
Peter M. Keller ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Hiv Status ◽  
Resistant Tuberculosis ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACTBackgroundDrug resistance and HIV co-infection are challenges for the global control of tuberculosis.MethodsWe collected Mycobacterium tuberculosis isolates from adult patients in Côte d’Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status.Findings634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases, corresponding to a sensitivity of 84.3% and a specificity of 90.8%. In patients with drug-resistant tuberculosis, discordant results were associated with increased mortality (risk ratio 1.81; 95% CI 1.07-3.07). In logistic regression, compared to adequately treated patients with pan-susceptible strains, the adjusted odds ratio for death was 4.23 (95% CI 2.16-8.29) for adequately treated patients with drug-resistant strains and 21.54 (95% CI 3.36-138.1) for inadequately treated patients with drug-resistant strains. HIV status was not associated with mortality.InterpretationUsing a reference laboratory standard, inaccurate DST leading to inappropriate treatment of drug-resistant tuberculosis, but not HIV infection, contributed to mortality.

scholarly journals Mortality of Drug-resistant Tuberculosis in High-burden Countries: Comparison of Routine Drug Susceptibility Testing with Whole-genome Sequencing

2020 ◽  
Author(s):  
Martina L. Reichmuth ◽  
Kathrin Zürcher ◽  
Marie Ballif ◽  
Chloé Loiseau ◽  
Sonia Borrell ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Hiv Status ◽  
High Burden

AbstractBackgroundDrug-resistant Mycobacterium tuberculosis (Mtb) strains threaten tuberculosis (TB) control. We compared data on drug resistance obtained at clinics in seven high TB burden countries during routine care with whole-genome sequencing (WGS) carried out centrally.MethodsWe collected pulmonary Mtb isolates and clinical data from adult TB patients in Africa, Latin America, and Asia, stratified by HIV status and drug resistance, from 2013 to 2016. Participating sites performed drug susceptibility testing (DST) locally, using routinely available methods. WGS was done using Illumina HiSeq 2500 at laboratories in the USA and Switzerland. We used TBprofiler to analyse the genomes. We used multivariable logistic regression adjusted for sex, age, HIV-status, history of TB, sputum positivity, and Mtb-lineage to analyse mortality.FindingsWe included 582 TB patients. The median age was 32 years (interquartile range: 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR-TB). The local DST results were discordant compared to WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with relatively high agreement (kappa 0.69 for isoniazid and 0.88 rifampicin). Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inadequate treatment according to WGS results and the World Health Organization treatment guidelines. The analysis of mortality was based on 530 patients; 63 patients (12%) died and 77 patients (15%) received inadequate treatment. Mortality ranged from 6% in patients with pan-susceptible Mtb (18/310) to 39% in patients with pre-XDR/XDR-TB (9/23). The adjusted odds ratio for mortality was 4.82 (95% CI 2.43-9.44) for under-treatment and 0.52 (95% CI 0.03-2.73) for over-treatment.InterpretationIn seven high-burden TB countries, we observed discrepancies between drug resistance patterns from local DST and WGS, which resulted in inadequate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information, which is required to improve the outcomes of drug-resistant TB in high burden settings. Our results support the WHO’s call for point-of-care tests based on WGS.

scholarly journals Drug Resistant Tuberculosis in the Northern Region of Zambia: A Retrospective Study

2021 ◽  
Vol 2 ◽  
Author(s):  
Ngula Monde ◽  
Mildred Zulu ◽  
Mathias Tembo ◽  
Ray Handema ◽  
Musso Munyeme ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Tuberculosis Patients ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis

BackgroundZambia like many countries in sub-Saharan Africa is affected with drug resistant tuberculosis. However, the drug resistant tuberculosis situation over the years has not been described in various regions of the country. Consequently, this study aims to determine the drug resistant tuberculosis burden in northern regions of Zambia over a four-year period based on data generated from a Regional Tuberculosis Reference Laboratory.MethodTwo hundred and thirty two (232) Tuberculosis Drug Susceptibility Testing results over a four-year period (2016-2019) were reviewed. Data was collected from tuberculosis registers and patient request forms and entered into a pre-tested standardized checklist and later entered in Excel Computer software. Double blinded checking was done by two independent data clerks to minimize duplication of cases. Cleaned data was then imported in R programme for analysis. Bivariant and descriptive statistics were performed and reported.ResultsOf 232 Drug Susceptibility Testing results, 90.9% were drug resistant TB while 9% were drug susceptible. Fifty three percent (53%) of these were multi-drug resistant Tuberculosis and 32% were confirmed as Rifampicin Mono-resistance. Only 1.7% of the Multi-drug resistant Tuberculosis patients were Pre-extensively drug-resistant Tuberculosis. Copperbelt province had the largest proportion (46.0%) of multi-drug resistant tuberculosis patients followed by Luapula (8.1%) and North-Western (4.7%) provinces. In new and previously treated patients, the proportion of Multi-drug resistant tuberculosis was 71.8% and 28.7% respectively. History of previous anti-tuberculosis treatment and treatment failure were associated with multi-drug resistance TB.Conclusion and RecommendationThis study has shown a small increase in the proportions of drug resistant tuberculosis cases over the four years under review with high rates being recorded on the Copperbelt Province. Previous treatment to first line TB treatment and treatment failure were associated with development of Multi-drug resistance. We therefore recommend strengthened routine laboratory surveillance and improved case management of multi-drug resistant tuberculosis patients in the region.

scholarly journals Speeding up the diagnosis of multidrug-resistant tuberculosis in a high-burden region with the use of a commercial line probe assay

2019 ◽  
Vol 45 (2) ◽  
Author(s):  
Angela Pires Brandao ◽  
Juliana Maira Watanabe Pinhata ◽  
Rosangela Siqueira Oliveira ◽  
Vera Maria Neder Galesi ◽  
Helio Hehl Caiaffa-Filho ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Reference Laboratory ◽  
Line Probe Assay ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Commercial Line ◽  
Probe Assay

ABSTRACT Objective: To evaluate the rapid diagnosis of multidrug-resistant tuberculosis, by using a commercial line probe assay for rifampicin and isoniazid detection (LPA-plus), in the routine workflow of a tuberculosis reference laboratory. Methods: The LPA-plus was prospectively evaluated on 341 isolates concurrently submitted to the automated liquid drug susceptibility testing system. Results: Among 303 phenotypically valid results, none was genotypically rifampicin false-susceptible (13/13; 100% sensitivity). Two rifampicin-susceptible isolates harboured rpoB mutations (288/290; 99.3% specificity) which, however, were non-resistance-conferring mutations. LPA-plus missed three isoniazid-resistant isolates (23/26; 88.5% sensitivity) and detected all isoniazid-susceptible isolates (277/277; 100% specificity). Among the 38 (11%) invalid phenotypic results, LPA-plus identified 31 rifampicin- and isoniazid-susceptible isolates, one isoniazid-resistant and six as non-Mycobacterium tuberculosis complex. Conclusions: LPA-plus showed excellent agreement (≥91%) and accuracy (≥99%). Implementing LPA-plus in our setting can speed up the diagnosis of multidrug-resistant tuberculosis, yield a significantly higher number of valid results than phenotypic drug susceptibility testing and provide further information on the drug-resistance level.

Activities of tubercular inflammation (on the morphological data) with different duration in the patients with drug-resistant pulmonary tuberculosis

2016 ◽  
Vol 10 (1) ◽  
pp. 0-0
Author(s):  
Елипашев ◽  
A. Elipashev ◽  
Никольский ◽  
V. Nikolskiy ◽  
Шпрыков ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Sensitivity ◽  
Morphological Data ◽  
Control Group ◽  
Drug Resistant ◽  
Specific Therapy ◽  
Resistant Tuberculosis ◽  
Number Of Patients ◽  
Resistant Strains ◽  
Drug Resistant Strains

The purpose of this research was to determine the dependence of the tubercular inflammation activity of varying duration of the disease and drug resistance. Morphological activity of inflammation in 161 patients with drug-resistant and 149 patients with retaining its high sensitivity was studied. Morphological assessment of the activity of specific changes in tuberculosis was carried out according to the B.M. Ariel classification (1998). It was revealed at morphologic study of resection material that the greatest activity of specific inflammation and its prevalence outside the main lesion was in the group of patients limited with drug resistance tuberculosis. It was noted the prevalence of IV-V degree of morphological activity of tubercular process in the study group by 3 times over the control group with disease duration of more than 1 year. Predominance of widespread active specific changes (IV degree) was determined in 2 times for the first educed patients of basic group with drug-resistant above a control group. This is due to increasing the number of patients with cavernous and fibro-cavernous tuberculosis.Thus, it is necessary to operate patients with drug-resistant tuberculosis as soon as possi-ble after adequate specific therapy and the presence of the signs of stabilization process, because as the full stabilization of tuberculosis process did not achieve according to the morphological study of surgical specimens in the preoperative period. Further specific therapy becomes futile due to the rise of drug resistance, the emer-gence of new drug-resistant strains of Mycobacterium tuberculosis.

scholarly journals Sensititre MycoTB Plate Compared to Bactec MGIT 960 for First- and Second-Line Antituberculosis Drug Susceptibility Testing in Tanzania: a Call To Operationalize MICs

2015 ◽  
Vol 59 (11) ◽  
pp. 7104-7108 ◽  
Author(s):  
Scott K. Heysell ◽  
Suporn Pholwat ◽  
Stellah G. Mpagama ◽  
Saumu J. Pazia ◽  
Happy Kumburu ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Acquired Resistance ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Second Line ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTMIC testing forMycobacterium tuberculosisis now commercially available. Drug susceptibility testing by the MycoTB MIC plate has not been directly compared to that by the Bactec MGIT 960. We describe a case of extensively drug-resistant tuberculosis (XDR-TB) in Tanzania where initial MIC testing may have prevented acquired resistance. From testing on archived isolates, the accuracy with the MycoTB plate was >90% for important first- and second-line drugs compared to that with the MGIT 960, and clinically useful quantitative interpretation was also provided.

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