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 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 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 Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Treatment Initiation ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb ◽  
The Impact

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.

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 Predicting the Outcomes of New Short-Course Regimens for Multidrug-Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modeling

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Tan N. Doan ◽  
Pengxing Cao ◽  
Theophilus I. Emeto ◽  
James M. McCaw ◽  
Emma S. McBryde
Keyword(s):  
Treatment Duration ◽  
Treatment Success ◽  
Empirical Evaluation ◽  
Multidrug Resistant ◽  
Pharmacodynamic Modeling ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb

ABSTRACT Short-course regimens for multidrug-resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug bedaquiline (BDQ) may have the potential to shorten MDR-TB treatment to less than 6 months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modeling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modeling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (4 months) while still maintaining a very high treatment success rate (100% for daily BDQ for 2 weeks, or 95% for daily BDQ for 1 week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes, then we anticipate clear cost savings and a subsequent improvement in the efficiency of national TB programs.

scholarly journals Improving access to contraception through integration of family planning services into a multidrug-resistant tuberculosis treatment programme

2019 ◽  
Vol 46 (2) ◽  
pp. 152-155
Author(s):  
Emily F Cornish ◽  
Jonathan Hudson ◽  
Ross Sayers ◽  
Marian Loveday
Keyword(s):  
Contraceptive Use ◽  
Multidrug Resistant ◽  
Treatment Programme ◽  
Post Intervention ◽  
Female Patients ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb

ObjectivesMultidrug-resistant tuberculosis (MDR-TB) is a global public health priority. The advent of the World Health Organisation’s Short Course regimen for MDR-TB, which halves treatment duration, has transformed outcomes and treatment acceptability for affected patients. Bedaquiline, a cornerstone of the Short Course regimen, has unknown teratogenicity and the WHO therefore recommends reliable contraception for all female MDR-TB patients in order to secure eligibility for bedaquiline. We were concerned that low contraceptive uptake among female patients in our rural South African MDR-TB treatment programme could jeopardise their access to bedaquiline. We therefore conducted a service delivery improvement project that aimed to audit contraceptive use in female MDR-TB patients, integrate family planning services into MDR-TB care, and increase the proportion of female patients eligible for bedaquiline therapy.MethodsContraceptive use and pregnancy rates were audited in all female patients aged 13–50 years initiated on our MDR-TB treatment programme in 2016. We then implemented an intervention consisting of procurement of depot-medroxyprogesterone acetate (DMPA) for the MDR-TB unit and training of specialist MDR-TB nurses in administration of DMPA. The audit cycle was repeated for all female patients aged 13–50 years initiated on the programme in January–October 2017 (post-intervention).ResultsThe proportion of women on injectable contraceptives by the time of MDR-TB treatment initiation increased significantly in the post-intervention cohort (77.4% vs 23.9%, p<0.0001).ConclusionBy integrating contraceptive services into our MDR-TB programme we significantly increased contraceptive uptake, protecting women from the obstetric risks associated with pregnancy during MDR-TB treatment and maximising their eligibility for bedaquiline therapy.

scholarly journals Efficacy of an Inexpensive Regimen Containing Pasiniazine for Multidrug-Resistant Tuberculosis with Low-concentration resistance to Isoniazid: a prospective cohort study in a high Tuberculosis burden area

2021 ◽  
Author(s):  
Wenwen Sun ◽  
Qin Tang ◽  
Jie Wang ◽  
Jinghui Yang ◽  
Fangyou Yu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Multidrug Resistant ◽  
Clinical Trial Registry ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Drug Sensitivity Test ◽  
Short Course ◽  
Mdr Tb

Abstract BackgroundTo verify the efficacy and safety of an inexpensive regimen for specific multidrug-resistant tuberculosis (MDR-TB) based on Minimum Inhibitory Concentration (MIC) Drug sensitivity test(DST), a prospective cohort study was conducted in China.MethodsMDR-TB cases were prospectively enrolled through a clinical access programmes with strict inclusion and exclusion criteria, given the regimen and followed up, observed the treatment outcome and adverse effects (AEs) .ResultsA total of 114 patients were enrolled into the study. The overall treatment favorable rate was 79.8% (91/114), among 91 cases with favorable treatment, 86(75.4%)cured and 5 (4.4%) completed treatment. 23 cases got unfavorable outcome including 10 8.8% (10/114) failures, 8.8%(10/114) losing follow up ,0.9%(1/114) withdrawing treatment due to intolerance to drugs and 1.8%(2/114 ) died,respectively. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p = 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients༈26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42) and no one was caused by Pa༈0%,0/114).ConclusionsThe regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population in China, especially for newly-treated patients, which could be expected to be developed into a short-course therapy.Clinical Trials Registration: China Clinical Trial Registry ChiCTR- OPC-16009380

scholarly journals A highly effective and inexpensive standardized treatment of multidrug- resistant tuberculosis: A muticenter prospective study in china

2021 ◽  
Author(s):  
Wenwen Sun ◽  
Zheyuan Wu ◽  
Zhou Ying ◽  
Xia Fan ◽  
Qin Tang ◽  
...  
Keyword(s):  
Prospective Study ◽  
Multidrug Resistant ◽  
Treatment Rate ◽  
Clinical Trial Registry ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Standardized Treatment ◽  
Mdr Tb ◽  
Multicenter Prospective Study

Abstract BackgroundTo verify the efficacy and safety of an inexpensive standardized treatment for multidrug-resistant tuberculosis (MDR-TB) based on minimum inhibitory concentration (MIC) drug sensitivity test(DST), a multicenter prospective study was conducted in eastern China.MethodsPatients diagnosed as MDR-TB with isoniazid resistance at low concentration and rifampicin resistance, second-line/injectable agents sensitive) were prospectively enrolled, given the regimen of Ak Mfx(Lfx)CsPtoPaZ for six months followed by 12 months of Mfx(Lfx)CsPtoPaZ and followed up for treatment outcomes and adverse events (AEs).ResultsA total of 114 patients were enrolled into the study. The overall rate of favorable treatment rate was 79.8% (91/114), among 91 cases with favorable treatment, 86(75.4%)cured and 5 (4.4%) completed treatment. 23 cases got unfavorable outcome including 10 8.8% (10/114) failures, 8.8% (10/114) losing follow up ,0.9%(1/114) withdrawing treatment due to intolerance to drugs and 1.8%(2/114 ) died. Treatment favorable rate was significantly higher in newly treated MDR-TB (91.7%, 33/36) than that in retreated MDR-TB (74.4%, 58/78, p = 0.03). The investigators recorded 42 AEs occurrences in 30 of 114 patients༈26.3%). Clinicians rated most AEs as mild or moderate (95.24%, 40/42) .ConclusionsThe regimen was proved to be effective, safe and inexpensive. It is suitable for specific drug resistant population, especially for newly-treated patients, which could be expected to be developed into a short-course regimen.Clinical Trials RegistrationChina Clinical Trial Registry ChiCTR- OPC-16009380

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