scholarly journals Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Matthias Merker ◽  
Maxime Barbier ◽  
Helen Cox ◽  
Jean-Philippe Rasigade ◽  
Silke Feuerriegel ◽  
...  
Keyword(s):  
Soviet Union ◽  
Former Soviet Union ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Directly Observed Treatment ◽  
Bacterial Fitness ◽  
Resistance Rates

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear. We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR Mycobacterium tuberculosis complex isolates from Karakalpakstan, Uzbekistan (2001–2006). One clade (termed Central Asian outbreak, CAO) dating back to 1974 (95% HPD 1969–1982) subsequently acquired resistance mediating mutations to eight anti-TB drugs. Introduction of standardized WHO-endorsed directly observed treatment, short-course in Karakalpakstan in 1998 likely selected for CAO-strains, comprising 75% of sampled MDR-TB isolates in 2005/2006. CAO-isolates were also identified in a published cohort from Russia (2008–2010). Similarly, the presence of mutations supposed to compensate bacterial fitness deficits was associated with transmission success and higher drug resistance rates. The genetic make-up of these MDR-strains threatens the success of both empirical and standardized MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

scholarly journals Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

2018 ◽  
Author(s):  
Matthias Merker ◽  
Maxime Barbier ◽  
Helen Cox ◽  
Jean-Philippe Rasigade ◽  
Silke Feuerriegel ◽  
...  
Keyword(s):  
Soviet Union ◽  
Former Soviet Union ◽  
Multidrug Resistant ◽  
Transmission Networks ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Central Asian ◽  
Short Course ◽  
Mdr Tb ◽  
Directly Observed Treatment

AbstractBacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).One MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.The genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

scholarly journals Task-shifting directly observed treatment and multidrug-resistant tuberculosis injection administration to lay health workers: stakeholder perceptions in rural Eswatini

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ernest Peresu ◽  
J. Christo Heunis ◽  
N. Gladys Kigozi ◽  
Diana De Graeve
Keyword(s):  
Healthcare Workers ◽  
Health Workers ◽  
Multidrug Resistant ◽  
Task Shifting ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Key Stakeholders ◽  
Mdr Tb ◽  
Directly Observed Treatment

Abstract Background Eswatini is facing a critical shortage of human resources for health (HRH) and limited access to multidrug-resistant tuberculosis (MDR-TB) treatment in rural areas. This study assessed multiple stakeholders’ perceptions of task-shifting directly observed treatment (DOT) supervision and administration of intramuscular MDR-TB injections to lay health workers (LHWs). Methods A mixed methods study comprising a cross-sectional survey using a semi-structured questionnaire with community treatment supporters (CTSs) and a focus group discussion with key stakeholders including representatives from the Eswatini Ministry of Health (MOH), donor organisations, professional regulatory institutions, nursing academia, civil society and healthcare providers was conducted in May 2017. Descriptive statistics, thematic content analysis and data triangulation aided in the interpretation of results. Results A large majority of CTSs (n = 78; 95.1%) were female and 33 (40.2%) were older than 50 years. Most (n = 7; 70.0%) key stakeholders had over 10 years of work experience in policy-making, advocacy in the fields of HRH or day-to-day practice in MDR-TB management. Task-shifting of MDR-TB injection administration was implemented without national policy guidance and regulation. Stakeholders viewed the strategy to be driven by the prevailing shortage of professional frontline HRH and limited access to MDR-TB treatment. Task-shifting was perceived to improve medication adherence, and reduce stigma and transport-related MDR-TB treatment access barriers. Frontline healthcare workers and implementing donor partners fully supported task-shifting. Policy-makers and other stakeholders accepted task-shifting conditionally due to fears of poor standards of care related to perceived incompetence of CTSs. Appropriate compensation, adequate training and supervision, and non-financial incentives were suggested to retain CTSs. A holistic task-shifting policy and collaboration between the MOH, academia and nursing council in regulating the practice were recommended. Conclusions Stakeholders generally accepted the delegation of DOT supervision and administration of intramuscular MDR-TB injections to LHWs as a strategy to increase access to treatment, albeit with some apprehension. Findings from this study stress that task-shifting is not a panacea for HRH shortages, but a short-term solution that must form part of an overall simultaneous strategy to train, attract and retain adequate numbers of professional healthcare workers in Eswatini. To address some of the apprehension and ambivalence about expanding access to MDR-TB services through task-shifting, attention should be paid to important aspects such as competence-based training, certification and accreditation, adequate supportive on-the-job supervision, recognition, compensation, and expediting policy and regulatory support for LHWs.

scholarly journals Factors Associated with Multidrup-Resistant Tuberculosis

1970 ◽  
Vol 3 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Md Nurul Amin ◽  
Md Anisur Rahman ◽  
Meerjady Sabrina Flora ◽  
Md Abul Kalam Azad
Keyword(s):  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Tuberculosis Patients ◽  
Face To Face ◽  
Control Programs ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Directly Observed Treatment ◽  
Sputum Conversion

This case control study was conducted in selected centers of Dhaka City from March to July 2008 to determine the association of multidrug-resistant tuberculosis with the attributes related to treatment and socio-economic condition of tuberculosis patients. Sixty seven culture-proven multidrug-resistant tuberculosis cases and similar number of age and sex matched controls were selected purposively. Data were collected by face to face interview and documents' review, using a pre tested structured questionnaire and a checklist. Multidrug-resistance was found to be associated with occupation (p=0.001) and residential status (p=0.001) of the tuberculosis patients. Tuberculosis patients who did not remain under directly observed treatment were 3 times more likely to develop multidrugresistant tuberculosis (OR 3.21, 95%CI=1.59-6.52). Multidrug-resistance was associated with inadequacy of treatment (OR 2.56, 95%CI=2.03-3.23). Failure of sputum conversion at the end of 2 months of treatment was detected to be the best predictor of multidrug-resistant tuberculosis (OR 11.82, 95% CI=4.61-30.33), followed by treatment with non Directly Observed Treatment Short course regimen and high labor intensive occupations like agriculture, production and transport. The risk factors of multidrug-resistant tuberculosis warrant much improvement in the effective implementation of control programs. Ibrahim Med. Coll. J. 2009; 3(1): 29-33 Key wards: Tuberculosis, MDR TB.   doi: 10.3329/imcj.v3i1.2917   

scholarly journals Patient satisfaction with directly observed treatment and multidrug-resistant tuberculosis injection administration by lay health workers in rural Eswatini

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Ernest Peresu ◽  
Christo J Heunis ◽  
Gladys N Kigozi ◽  
Diana De Grave
Keyword(s):  
Patient Satisfaction ◽  
Multidrug Resistant ◽  
Task Shifting ◽  
Treatment Costs ◽  
Community Based ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Directly Observed Treatment ◽  
Adherence Counselling

Background: The human resources for health crisis in rural Eswatini led to a novel community-based multidrug-resistant tuberculosis (MDR-TB) treatment strategy based on task-shifting, that is delegation of directly observed treatment (DOT) and administration of MDR-TB injections, traditionally restricted to professional nurses, to lay community treatment supporters (CTSs).Aim: This study assessed the level of patient satisfaction with receiving community-based MDR-TB care from a CTS.Setting: The study was conducted at three MDR-TB-treating facilities in the mostly rural Shiselweni region.Methods: A cross-sectional survey of a purposive sample of 78 patients receiving DOT and intramuscular MDR-TB injections from CTSs was carried out in 2017. Descriptive statistics and regressions were calculated.Results: A high overall general patient satisfaction score for receiving community-based MDR-TB care from a CTS was observed. Adherence counselling, confidentiality, provider selection and treatment costs significantly (p 0.05) influenced satisfaction. A large majority (n = 62; 79.5%) of patients indicated that they would likely recommend their significant others to receive MDR-TB care from a CTS. Respondents identified the need to provide CTSs with adequate training, regular supervision and sufficient incentives and also to broaden the scope of their services.Conclusion: This study observed that task-shifting of DOT and MDR-TB injection administration to CTSs was supported from a patient perspective. However, adherence counselling, confidentiality, provider selection and treatment costs should be taken into account in community-based MDR-TB care programming. Further to the patients, community-based tuberculosis care could be enhanced by improving CTSs’ training, supervision and incentives, and broadening the scope of their services.

scholarly journals Analysis of Serial Multidrug-Resistant Tuberculosis Strains Causing Treatment Failure and Within-Host Evolution by Whole-Genome Sequencing

mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e00884-20
Author(s):  
Xinchang Chen ◽  
Guiqing He ◽  
Siran Lin ◽  
Shiyong Wang ◽  
Feng Sun ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Whole Genome ◽  
Second Line ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Host Evolution ◽  
Effective Drugs

ABSTRACTThe cure rate of multidrug-resistant tuberculosis (MDR-TB) is relatively low in China. The reasons for the treatment failure and within-host evolution during treatment have not been sufficiently studied. All MDR-TB patients receiving standard treatment from January 2014 to September 2016 at a designated TB Hospital in Zhejiang Province were retrospectively included and grouped according to their known treatment outcome. Clinical information was collected. Baseline strains of all patients and serial strains of treatment-failure patients were revived. Drug susceptibility tests (DSTs) of 14 drugs and single nucleotide polymorphism (SNP) analysis based on whole-genome sequencing (WGS) were performed. The genetic distance and within-host evolution were investigated based on SNPs. In total, 20 treatment failure patients and 74 patients who succeeded in treatment were included. The number of effective drugs for patients who failed treatment was no more than three. Eighteen (90.0%) treatment-failure patients were characterized by a continuous infection of the primary strain, of which 14 patients (77.8%) developed phenotypic or genotypic acquired drug resistance under ineffective treatment. Acquired resistance to amikacin and moxifloxacin (2.0 mg/ml) was detected most frequently, in 5 and 4 patients, respectively. The insufficient number of effective drugs in the combined treatment regimen was the main reason for MDR-TB treatment failure. The study emphasizes the importance of DST for second-line drugs when implementing the second-line drug regimen in MDR-TB patients. For patients with risk factors for MDR-TB, DST of second-line antituberculosis drugs should be performed at initiation of treatment. Second-line drugs should be selected based on the results of DST to avoid acquired resistance. WGS detects low-frequency resistance mutations and heterogeneous resistance with high sensitivity, which is of great significance for guiding clinical treatment and preventing acquired resistance.IMPORTANCE Few studies have focused on the reasons for the low cure rate of multidrug-resistant tuberculosis in China and within-host evolution during treatment, which is of great significance for improving clinical treatment regimens. Acquired resistance events were common during the ineffective treatment, among which resistance to amikacin and high-level moxifloxacin were the most common. The main reason for the treatment failure of MDR-TB patients was insufficient effective drugs, which may lead to higher levels of drug resistance in MDR-TB strains. Therefore, the study emphasizes the importance of DST in the development of second-line treatment regimen when there is a risk of MDR. By performing whole-genome sequencing of serial strains from patients with treatment failure, we found that WGS can detect low-frequency resistance mutations and heterogeneous resistance with high sensitivity. It is thus recommended to conduct drug susceptibility tests at the beginning of treatment and repeat the DST when the sputum bacteria remain positive.

scholarly journals Primary and acquired multidrug-resistant tuberculosis: Predictive factors for unfavorable treatment outcomes in Rio de Janeiro, 2000–2016

2020 ◽  
Vol 44 ◽  
pp. 1
Author(s):  
Marcela Bhering ◽  
Afrânio Kritski
Keyword(s):  
Rio De Janeiro ◽  
Acquired Resistance ◽  
Multidrug Resistant ◽  
Primary Resistance ◽  
Loss To Follow Up ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Janeiro State

Objective. To identify clinical and demographic factors associated with unfavorable treatment outcomes in patients with primary and acquired multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State. Methods. Retrospective cohort study using data on 2 269 MDR-TB cases in 2000–2016. Factors associated with unsuccessful, loss to follow-up, and death outcomes in patients with primary and acquired resistance were investigated with bivariate and multivariate regression. Results. Primary resistance was 14.7% among MDR-TB cases. The unfavorable outcomes proportion was 30.3% in the primary resistance group and 46.7% in the acquired resistance group. There were significant differences in demographic and clinical characteristics between the two groups. Proportionally, the group with primary resistance had more cases among women (46.4% vs. 33.5% in the acquired resistance group), Caucasians (47.3% and 34%), and those with ≥8 years of schooling (37.7% and 27.4%). Extensively drug-resistant TB patients had 12.2-fold higher odds of unsuccessful outcome than MDR-TB patients, and comorbidities had 2-fold higher odds in the primary resistance group. Extensively drug-resistant TB had 5.43-fold higher odds in the acquired MDR-TB group. Bilateral disease and <8 years of schooling were associated with unsuccessful outcome in both groups. Being an inmate had 8-fold higher odds of loss to follow-up in the primary resistance group. Culture conversion by the sixth month was a protective factor for all outcomes. Conclusions. Primary resistance cases of MDR-TB constitute a different transmission reservoir, which is related to other chronic diseases associated with higher acquisition of TB. The poor results observed in Rio de Janeiro State can contribute to increasing the transmission of primary MDR-TB, thus favoring drug resistance.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

PP581 Catastrophic Costs Of Multidrug-Resistant Tuberculosis: Estimation Based On The Cost Of Treatment In China

2020 ◽  
Vol 36 (S1) ◽  
pp. 43-43
Author(s):  
Lijun Shen ◽  
Shangshang Gu ◽  
Fan Zhang ◽  
Zhao Liu ◽  
Yuehua Liu
Keyword(s):  
Market Price ◽  
Multidrug Resistant ◽  
Policy Support ◽  
World Health ◽  
Chinese Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Affordability ◽  
The Cost

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.

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