Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007–2011): Evidence leading to policy enhancement

Background. Multidrug-resistant tuberculosis (MDR-TB) has continued to be a challenge for tuberculosis (TB) control globally. Ethiopia is one of the countries with high MDR-TB burden. Objective. The main purpose of this study was to determine the prevalence of MDR-TB and associated factors in Ethiopia. Methods. A systematic review of the literatures on prevalence of MDR-TB and associated factors was conducted in the country. Results. In our electronic search, 546 citations were depicted. Among the total 546 citations described, a total of 22 articles met eligibility criteria and were included in the review article. According to our review, the prevalence of MDR-TB ranged from 0 to 46.3%. The average mean rate of MDR-TB in Ethiopia was found to be 12.6±15.9%. The overall prevalence of MDR-TB in all TB cases was estimated to be 1.4%. From a total of 3849 patients studied, 527 had MDR-TB. Previous exposure to antituberculosis treatment was the most commonly identified risk factor of MDR-TB in Ethiopia. Conclusion. Despite relative decline in incidence of MDR-TB, the distribution and prevalence of MDR-TB continued to be a serious challenge for TB control in Ethiopia. Previous exposure to antituberculosis treatment was also the most common risk factor for MDR-TB. Therefore, strong TB and MDR-TB treatment along with tight introduction of follow-up strategies should be applied for better TB control.

Download Full-text

Health System and Policy Perspectives of Multidrug-resistant Tuberculosis (MDR-TB) Control in India

Journal of Development Policy and Practice ◽

10.1177/2455133317740448 ◽

2017 ◽

Vol 3 (1) ◽

pp. 1-15

Author(s):

Janmejaya Samal

Keyword(s):

Decision Making ◽

Surveillance System ◽

Epidemiological Studies ◽

Multidrug Resistant ◽

Control Programme ◽

Tb Control ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The Right

Despite the lack of reliable information on multidrug-resistant tuberculosis (MDR-TB) epidemiology, research shows an increasing trend of MDR-TB incidence in India. Of several determinants attributable to the rising trend of MDR-TB, health systems and policy (HSP) determinants play a pivotal role. With this article, an attempt has been made to unravel the HSP challenges for the control of MDR-TB and recommend strategies to overcome that. Ten different strategies have been recommended in this article that includes operations research (OR), molecular epidemiological studies, drug susceptibility test (DST), surveillance system, advocacy communication and social mobilisation (ACSM), nutrition and livelihood support, contribution of private practitioners (PPs), human resources for health (HRH), social determinants of health and information systems. Methods of OR with the right technical expertise can help in decision-making and evaluation of the TB control programme. Molecular epidemiological studies further help identify the right strain and can help in institutionalising the right therapeutic regimen. Similarly, the DST allows extended treatment strategies, including second-line drugs. A proper surveillance system can enable the availability of the right information for public health decision-making. Communication enables and empowers the community in accessing health services and helps policymakers take informed decisions. Nutrition and livelihood support are essential in TB control as it mostly affects the poor and people in the productive age group. Further, tapping PPs is equally important as more than 50 per cent of TB patients visit them. Proper orientation of the PPs about the TB control programme is non-negotiable given these facts. The HRH issues are pertinent—staff members lack the required motivation owing to delay in payment of salaries and the lack of job promotion. The HRH form the backbone of any health system, as the mere presence of drugs, technologies and infrastructure do not suffice for the provision of healthcare. Attention on the neglected social determinants of health is required as well. Finally, all these suggestions need to be implemented in coordination with each other to bring down the scourge of MDR-TB in India.

Download Full-text

Multidrug-Resistant Tuberculosis (MDR-TB) Control Activities in Kano State, North West Nigeria: Progress so Far

TEXILA INTERNATIONAL JOURNAL OF PUBLIC HEALTH ◽

10.21522/tijph.2013.se.19.02.art002 ◽

2019 ◽

pp. 6-12

Author(s):

Musa K. Bawa

Keyword(s):

Multidrug Resistant ◽

North West ◽

Tb Control ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Download Full-text

Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02410-17 ◽

2018 ◽

Vol 62 (5) ◽

Cited By ~ 7

Author(s):

Agibothu Kupparam Hemanth Kumar ◽

Alok Kumar ◽

Thiruvengadam Kannan ◽

Rakesh Bhatia ◽

Dipti Agarwal ◽

...

Keyword(s):

High Performance ◽

Linear Regression Analysis ◽

Multidrug Resistant ◽

Control Programme ◽

Second Line ◽

Time Curve ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

The Government

ABSTRACTWe studied the pharmacokinetics of levofloxacin (LFX), pyrazinamide (PZA), ethionamide (ETH), and cycloserine (CS) in children with multidrug-resistant tuberculosis (MDR-TB) who were being treated according to the Revised National TB Control Programme (RNTCP) guidelines in India. This observational, pharmacokinetic study was conducted in 25 children with MDR-TB at the Sarojini Naidu Medical College, Agra, India, who were being treated with a 24-month daily regimen. Serial blood samples were collected after directly observed administration of drugs. Estimations of plasma LFX, PZA, ETH, and CS were undertaken according to validated methods by high-performance liquid chromatography. Adverse events were noted at 6 months of treatment. The peak concentration (Cmax) of LFX was significantly higher in female than male children (11.5 μg/ml versus 7.3 μg/ml;P= 0.017). Children below 12 years of age had significantly higher ETH exposure (area under the concentration-time curve from 0 to 8 h [AUC0–8]) than those above 12 years of age (17.5 μg/ml · h versus 9.4 μg/ml;P= 0.030). Multiple linear regression analysis showed significant influence of gender onCmaxof ETH and age onCmaxand AUC0–8of CS. This is the first and only study from India reporting on the pharmacokinetics of LFX, ETH, PZA, and CS in children with MDR-TB treated in the Government of India program. More studies on the safety and pharmacokinetics of second-line anti-TB drugs in children with MDR-TB from different settings are required.

Download Full-text

Treatment outcomes in multidrug-resistant tuberculosis according to pyrazinamide susceptibility

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0314 ◽

2020 ◽

Vol 24 (2) ◽

pp. 233-239

Author(s):

S. Park ◽

K-W. Jo ◽

T. S. Shim

Keyword(s):

Success Rate ◽

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Treatment Success Rate ◽

Aminosalicylic Acid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Effective Drugs

BACKGROUND: Pyrazinamide (PZA) is an important anti-tuberculosis drug for multidrug-resistant tuberculosis (MDR-TB). However, PZA has recently been demoted within the hierarchy of TB drugs used for MDR-TB.METHODS: We conducted a retrospective cohort study to investigate treatment outcomes for simple MDR-TB (susceptible to both second-line injectable drugs and fluoroquinolones) according to PZA susceptibility.RESULTS: Among 216 pulmonary MDR-TB patients included in the study, 68 (31.5%) were PZA-resistant (PZA-R). The mean age was 41.8 years, and 63.4% were male. Baseline characteristics such as comorbidity, previous TB history, acid-fast bacilli (AFB) smear positivity and cavitation were similar in PZA-susceptible (PZA-S) and PZA-R patients. The number of potentially effective drugs was slightly higher among PZA-S patients than among the PZA-R (5.1 vs. 4.8, respectively; P = 0.003). PZA was more frequently used in PZA-S patients (73.0%) than in the PZA-R (14.7%), while para-aminosalicylic acid was more frequently used in PZA-R than in PZA-S patients (76.5% vs. 50.7%). The treatment success rate was similar in PZA-S (77.7%) and PZA-R (75.0%) patients. PZA resistance was not associated with treatment success in multivariate analysis.CONCLUSIONS: PZA-resistant simple MDR-TB patients had the same treatment success rate as the PZA-susceptible group even without using novel anti-TB drugs.

Download Full-text

Treatment Outcomes and Adverse Drug Effects of Ethambutol, Cycloserine, and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00744-20 ◽

2020 ◽

Vol 65 (1) ◽

pp. e00744-20

Author(s):

Martha L. van der Walt ◽

Karen Shean ◽

Piet Becker ◽

Karen H. Keddy ◽

Joey Lancaster

Keyword(s):

Treatment Outcomes ◽

Adverse Drug Events ◽

Drug Effects ◽

Multidrug Resistant ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Default Rates ◽

Conversion Rates ◽

Mdr Tb ◽

Culture Conversion

ABSTRACTTreatment outcomes among multidrug-resistant tuberculosis (MDR-TB) patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen were compared, determining occurrence of serious adverse drug events (SADEs). Newly diagnosed adult MDR-TB patients were enrolled between 2000 and 2004, receiving a standardized multidrug regimen for 18 to 24 months, including ethambutol, cycloserine, or terizidone. Cycloserine and terizidone were recorded individually. SADEs and factors associated with culture conversion and unfavorable treatment outcomes (default, death, treatment failure) were determined. Of 858 patients, 435 (51%) received ethambutol, 278 (32%) received cycloserine, and 145 (17%) received terizidone. Demographic and baseline clinical data were comparable. Successful treatment occurred in 56%, significantly more in patients receiving cycloserine (60%) and terizidone (62%) than in those receiving ethambutol (52% [P = 0.03]). Defaults rates were 30% in ethambutol patients versus 15% and 11% for cycloserine and terizidone patients, respectively. Terizidone was associated with fewer unfavorable outcomes (adjusted odds ratio [AOR], 0.4; P = 0.008; 95% confidence interval [CI], 0.2 to 0.8). Patients receiving cycloserine were more likely to achieve culture conversion than those receiving ethambutol or terizidone (AOR, 2.2; P = 0.02; 95% CI, 1.12 to 4.38). Failure to convert increased the odds of unfavorable outcomes (AOR, 23.7; P < 0.001; 95% CI, 13 to 44). SADEs were reported in two patients receiving ethambutol, seven patients receiving cycloserine, and three receiving terizidone (P = 0.05). Ethambutol was associated with high culture conversion and default rates. Cycloserine achieved higher culture conversion rates than terizidone. Fewer patients on terizidone experienced SADEs, with lower default rates. The differences that we observed between cycloserine and terizidone require further elucidation.

Download Full-text

An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis

European Respiratory Journal ◽

10.1183/13993003.00803-2016 ◽

2017 ◽

Vol 49 (3) ◽

pp. 1600803 ◽

Cited By ~ 36

Author(s):

Mayara Lisboa Bastos ◽

Zhiyi Lan ◽

Dick Menzies

Keyword(s):

Systematic Review ◽

Treatment Outcomes ◽

Multidrug Resistant ◽

Current Evidence ◽

Aminosalicylic Acid ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

End Of Treatment ◽

Mdr Tb ◽

Culture Conversion

This systematic review aimed to update the current evidence for multidrug-resistant tuberculosis (MDR-TB) treatment.We searched for studies that reported treatment information and clinical characteristics for at least 25 patients with microbiologically confirmed pulmonary MDR-TB and either end of treatment outcomes, 6-month culture conversion or severe adverse events (SAEs). We assessed the association of these outcomes with patients' characteristics or treatment parameters. We identified 74 studies, including 17 494 participants.The pooled treatment success was 26% in extensively drug-resistant TB (XDR-TB) patients and 60% in MDR-TB patients. Treatment parameters such as number or duration and individual drugs were not associated with improved 6-month sputum culture conversion or end of treatment outcomes. However, MDR-TB patients that received individualised regimens had higher success than patients who received standardised regimens (64% versus 52%; p<0.0.01). When reports from 20 cohorts were pooled, proportions of SAE ranged from 0.5% attributed to ethambutol to 12.2% attributed to para-aminosalicylic acid. The lack of significant associations of treatment outcomes with specific drugs or regimens may reflect the limitations of pooling the data rather than a true lack of differences in efficacy of regimens or individual drugs.This analysis highlights the need for stronger evidence for treatment of MDR-TB from better-designed and reported studies.

Download Full-text

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Biomédica ◽

10.7705/biomedica.5072 ◽

2020 ◽

Vol 40 (4) ◽

pp. 616-625

Author(s):

Ángela Tobón ◽

Johana Rueda ◽

Diego H. Cáceres ◽

Gloria I. Mejía ◽

Elsa M. Zapata ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

Chronic Obstructive ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Poor Outcomes ◽

Lost To Follow Up

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses.Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Download Full-text

Effectiveness and Safety of Bedaquiline-containing Regimens for Treatment on Patients With Refractory Rifampicin/multidrug-resistant Tuberculosis: A Retrospective Cohort Study in East China

10.21203/rs.3.rs-833736/v1 ◽

2021 ◽

Author(s):

Shao-Jun Zhang ◽

Yan Yang ◽

Wen-Wen Sun ◽

Zhong-Shun Zhang ◽

He-ping Xiao ◽

...

Keyword(s):

Treatment Outcomes ◽

Treatment Success ◽

Multidrug Resistant ◽

East China ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Conversion Rates ◽

Mdr Tb ◽

Culture Conversion ◽

Closing Rate

Abstract Objective: To compare the effectiveness and safety of bedaquiline-containing and bedaquiline-free regimens for treatment of patients with refractory rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB).Methods: Patients with refractory RR/MDR-TB receiving bedaquiline-containing regimens (bedaquiline group, n=102) and bedaquiline-free regimens (non-bedaquiline group, n=100) were included in this retrospective historical control study across East China. The culture conversion, end-of-treatment outcomes, cavity closing rate, and adverse events (AEs) were compared between the two groups. Univariate and multivariate analyses were performed to identify independent predictors of treatment success and culture reversion.Results: The baseline characteristics of the patients were well balanced between the two groups. The culture conversion rates in the bedaquiline group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs. 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs. 65.0%) were all significantly higher than those in the non-bedaquiline group (all p<0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs. 8.0%, p=0.017) and month 12 (39.2% vs. 15.0%, p<0.001). Patients receiving bedaquiline-containing regimens had more treatment success than those receiving bedaquiline-free regimens (p<0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%). The use of bedaquiline was identified as an independent predictor of both treatment success (OR=7.356, 95% CI: 2.920–18.530, p<0.001) and culture reversion (OR=0.124, 95% CI: 0.035–0.452, p<0.001). AEs were similarly reported in 26.5% of patients in the bedaquiline group and 19.0% in the non-bedaquiline group (p=0.206).Conclusions: Bedaquiline-containing regimens resulted in better treatment outcomes and similar safety relative to bedaquiline-free regimens for patients with refractory pulmonary RR/MDR-TB.

Download Full-text

Treatment outcomes and antiretroviral uptake in Multidrug-Resistant Tuberculosis and HIV coinfected Patients in Sub Saharan Africa. A Systematic Review and Meta-Analysis

10.21203/rs.2.10131/v1 ◽

2019 ◽

Author(s):

Elvis Dzelamonyuy Chem ◽

Marie Claire Van Hout ◽

Vivian Hope

Keyword(s):

Treatment Outcomes ◽

Meta Analysis ◽

Multidrug Resistant ◽

Pooled Analysis ◽

Sub Saharan Africa ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb ◽

Sub Saharan ◽

Hiv Negative

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) in HIV endemic settings is a major threat to public health. MDR-TB is a substantial and underreported problem in Sub-Saharan Africa (SSA), with recognised cases projected to increase with advancement in diagnostic technology. There is paucity of review evidence on treatment outcomes and antiretroviral (ART) uptake among MDR-TB patients with HIV in SSA. To address this gap a review of treatment outcomes in HIV patients co-infected with MDR-TB in the SSA region was undertaken. Methods Three databases (Medline, Web of Science, CINHAL), Union on Lung Heath conference proceedings and grey literature were searched for publications between January 2004 and May 2018. Records were assessed for eligibility and data extracted. Random effect meta-analysis was conducted using STATA and Cochrane’s review manager. Results A total of 271 publications were identified of which nine fulfilled the inclusion criteria. Data was collected from 3,368 MDR-TB and HIV co-infected patients from four SSA countries; South Africa (6), Lesotho (1), Botswana (1) and Ethiopia (1). The most common outcome was cure (34.9% cured in the pooled analysis), this was followed by death (18.1% in pooled analysis). ART uptake was high, at 83% in the pooled analysis. Cure ranged from 22.2% to 57.7% among patients on ART and from 28.6% to 54.7% among those not on ART medication. MDR-TB and HIV coinfected patients were less likely to be successfully treated than HIV negative MDR-TB patients (Risk Ratio = 0.87, 95% CI 0.97, 0.96). Conclusion Treatment outcomes for MDR-TB and HIV coinfected patients do not vary widely from those reported globally. However, treatment success was lower among HIV positive MDR-TB patients compared to HIV negative MDR-TB patients. Prompt antiretroviral initiation and interventions to improve treatment adherence are necessary.

Download Full-text