Systematic review of therapeutic outcomes of multi-drug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and Human Immuno-deficiency Virus in low and middle-income countries: a study protocol

Abstract Background: Programs that integrated tuberculosis (TB) and Human Immunodeficiency Virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs.Methods: A systematic review of evidence from published observational and interventional studies will be performed. The evidence will be obtained by searching Medline, Embase, and Global Health electronic databases with date limits being March 2004 and December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using appropriate quality assessment tools. Analysis and synthesis of data on TB treatment outcomes will be performed using random-effects meta-analysis on STATA-15 software. Data on predictors of TB treatment outcomes will be analysed using thematic analysis and synthesised using a descriptive approach and where appropriate, random-effects meta-analysis will be performed to obtain pooled effect sizes. The confidence in cumulative quantitative and qualitative evidence will be assessed using the appropriate versions of the Grading of Recommendations, Assessment, Development and Evaluation approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal.Discussion: This study is expected to highlight the quality of integrated TB/HIV treatment programs and their potential to uphold successful MDR-TB treatment outcomes. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs.Systematic review registration: This review has been submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO)

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Systematic review of therapeutic outcomes of multi-drug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and Human Immuno-deficiency Virus in low and middle-income countries: a study protocol

10.21203/rs.2.18219/v3 ◽

2020 ◽

Author(s):

Benjamin Momo Kadia ◽

Desmond Aroke ◽

Kevin Pene Njefi ◽

Joel Noutakdie Tochie ◽

Frank-Leonel Tianyi ◽

...

Keyword(s):

Systematic Review ◽

Treatment Outcomes ◽

Meta Analysis ◽

Integrated Treatment ◽

Hiv Treatment ◽

Middle Income ◽

Resistant Tuberculosis ◽

Therapeutic Outcomes ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background: Programs that integrate tuberculosis (TB) and Human Immunodeficiency Virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs. Methods: A systematic review of quantitative evidence from observational cohort and case control studies will be performed. Medline, Embase, and Global Health electronic databases will be searched for relevant studies published from March 2004 to December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using quality assessment tools of the National Heart Lung and Blood Institute. Random-effects meta-analysis will be used to obtain summary estimates. Heterogeneity across studies will be assessed using the I 2 statistic. The confidence in the summary estimates will be rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal. Discussion: This study is expected to report the performance of integrated TB/HIV treatment programs as regards their potential to uphold successful MDR-TB treatment outcomes in LMICs. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs. Systematic review registration: This review has been registered with the International Prospective Register of Systematic Reviews and the reference ID is CRD42020159745

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Systematic review of therapeutic outcomes of multi-drug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and Human Immuno-deficiency Virus in low and middle-income countries: a study protocol

10.21203/rs.2.18219/v2 ◽

2020 ◽

Author(s):

Benjamin Momo Kadia ◽

Desmond Aroke ◽

Kevin Pene Njefi ◽

Joel Noutakdie Tochie ◽

Frank-Leonel Tianyi ◽

...

Keyword(s):

Systematic Review ◽

Treatment Outcomes ◽

Meta Analysis ◽

Integrated Treatment ◽

Hiv Treatment ◽

Middle Income ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

Abstract Background: Programs that integrated tuberculosis (TB) and Human Immunodeficiency Virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs. Methods: A systematic review of evidence from published observational and interventional studies will be performed. The evidence will be obtained by searching Medline, Embase, and Global Health electronic databases with date limits being March 2004 and December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using appropriate quality assessment tools. Analysis and synthesis of data on TB treatment outcomes will be performed using random-effects meta-analysis on STATA-15 software. Data on predictors of TB treatment outcomes will be analysed using thematic analysis and synthesised using a descriptive approach and where appropriate, random-effects meta-analysis will be performed to obtain pooled effect sizes. The confidence in cumulative quantitative and qualitative evidence will be assessed using the appropriate versions of the Grading of Recommendations, Assessment, Development and Evaluation approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal. Discussion: This study is expected to highlight the quality of integrated TB/HIV treatment programs and their potential to uphold successful MDR-TB treatment outcomes. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs. Systematic review registration: This review has been submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO)

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Systematic review of therapeutic outcomes of multidrug resistant tuberculosis and their predictors in adults receiving integrated treatment of tuberculosis and human immuno-deficiency virus in low- and middle-income countries: a study protocol

Systematic Reviews ◽

10.1186/s13643-020-01493-5 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Benjamin Momo Kadia ◽

Desmond Aroke ◽

Kevin Pene Njefi ◽

Joel Noutakdie Tochie ◽

Frank-Leonel Tianyi ◽

...

Keyword(s):

Systematic Review ◽

Treatment Outcomes ◽

Meta Analysis ◽

Integrated Treatment ◽

Hiv Treatment ◽

Middle Income ◽

Middle Income Countries ◽

Resistant Tuberculosis ◽

Therapeutic Outcomes ◽

Mdr Tb

Abstract Background Programs that integrate tuberculosis (TB) and human immunodeficiency virus (HIV) treatment aim to provide efficient treatment services and maximize successful treatment outcomes through the delivery of both TB and HIV treatment by one provider at the same time and location. However, multi-drug resistant tuberculosis (MDR-TB) is more difficult to treat as compared to drug-sensitive TB, and in low- and middle-income countries (LMICs), the potential of programs integrating TB/HIV treatment to sustain favourable MDR-TB treatment outcomes is poorly elucidated. The objective of this review is to perform a systematic collection, critical appraisal and synthesis of existing evidence on therapeutic outcomes of MDR-TB and their predictors among adults receiving integrated treatment for TB/HIV in LMICs. Methods A systematic review of quantitative evidence from observational cohort studies will be performed. MEDLINE, Embase, and Global Health electronic databases will be searched for relevant studies published from March 2004 to December 2019. Two investigators will independently screen the search output, review the eligible studies, and assess the quality of the eligible studies using quality assessment tools of the National Heart Lung and Blood Institute. Random-effects meta-analysis will be used to obtain summary estimates. Heterogeneity across studies will be assessed using the I2 statistic. The confidence in the summary estimates will be rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The final review will be reported following the guidelines of the Preferred Reporting System for Systematic Reviews and Meta-analysis, presented at scientific conferences and published in a peer-reviewed journal. Discussion This study is expected to report the performance of integrated TB/HIV treatment programs as regards their potential to uphold successful MDR-TB treatment outcomes in LMICs. Furthermore, the review will indicate patient-related and healthcare-related factors that should be addressed to improve on survival of patients with MDR-TB/HIV co-infection in LMICs. Systematic review registration This review has been registered with the International Prospective Register of Systematic Reviews and the reference ID is CRD42020159745

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Abstract #1036 Hypothyroidism Induced by Multi Drug Resistant Tuberculosis (MDR-TB) Treatment

Endocrine Practice ◽

10.1016/s1530-891x(20)47401-4 ◽

2018 ◽

Vol 24 ◽

pp. 236

Author(s):

Rulli Rosandi

Keyword(s):

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

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Effects of social protection on tuberculosis treatment outcomes in low or middle-income and in high-burden countries: systematic review and meta-analysis

Cadernos de Saúde Pública ◽

10.1590/0102-311x00153116 ◽

2018 ◽

Vol 34 (1) ◽

Cited By ~ 9

Author(s):

Kaio Vinicius Freitas de Andrade ◽

Joilda Silva Nery ◽

Ramon Andrade de Souza ◽

Susan Martins Pereira

Keyword(s):

Treatment Outcomes ◽

Social Protection ◽

Meta Analysis ◽

Treatment Success ◽

Qualitative Synthesis ◽

Middle Income ◽

High Burden ◽

Tb Treatment ◽

Protection Strategies ◽

Meta Analyses

Tuberculosis (TB) is a poverty infectious disease that affects millions of people worldwide. Evidences suggest that social protection strategies (SPS) can improve TB treatment outcomes. This study aimed to synthesize such evidences through systematic literature review and meta-analysis. We searched for studies conducted in low- or middle-income and in high TB-burden countries, published during 1995-2016. The review was performed by searching PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect and LILACS. We included only studies that investigated the effects of SPS on TB treatment outcomes. We retained 25 studies for qualitative synthesis. Meta-analyses were performed with 9 randomized controlled trials, including a total of 1,687 participants. Pooled results showed that SPS was associated with TB treatment success (RR = 1.09; 95%CI: 1.03-1.14), cure of TB patients (RR = 1.11; 95%CI: 1.01-1.22) and with reduction in risk of TB treatment default (RR = 0.63; 95%CI: 0.45-0.89). We did not detect effects of SPS on the outcomes treatment failure and death. These findings revealed that SPS might improve TB treatment outcomes in lower-middle-income economies or countries with high burden of this disease. However, the overall quality of evidences regarding these effect estimates is low and further well-conducted randomized studies are needed.

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Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0508 ◽

2020 ◽

Vol 24 (5) ◽

pp. 485-491

Author(s):

D. Butov ◽

C. Lange ◽

J. Heyckendorf ◽

I. Kalmykova ◽

T. Butova ◽

...

Keyword(s):

Treatment Outcomes ◽

Drug Susceptibility ◽

Multidrug Resistant ◽

Drug Susceptibility Testing ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Poor Treatment ◽

Mdr Tb ◽

Observational Cohort

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

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A systematic review and meta-analysis of the association between integrated tuberculosis and Human Immuno-deficiency Virus therapy and tuberculosis treatment outcomes among adults in sub-Saharan Africa

10.21203/rs.3.rs-21573/v1 ◽

2020 ◽

Author(s):

Benjamin Momo Kadia ◽

Noah Fongwen Takah ◽

Christian Akem Dimala ◽

Victoria Simms

Keyword(s):

Treatment Outcomes ◽

Meta Analysis ◽

Treatment Success ◽

Hiv Treatment ◽

Sub Saharan Africa ◽

P Value ◽

Human Immuno Deficiency Virus ◽

Tb Treatment ◽

All Cause Mortality ◽

Sub Saharan

Abstract Background: Despite the scale-up of programmes integrating treatment of tuberculosis (TB) and Human Immuno-deficiency Virus (HIV) in sub-Saharan Africa (SSA), TB treatment outcomes in TB/HIV co-infected patients in the region remain sub-optimal.Objective: To summarize the available evidence on the association between integrated TB/HIV treatment and TB treatment outcomes specifically, successful treatment and all-cause mortality in TB/HIV co-infected adults in SSA.Method: A systematic review of studies published between March 2004 and 10 July 2019 was performed. Seven electronic databases including Medline, Embase and Cochrane were searched to identify interventional and observational quantitative studies reporting on integrated TB/HIV treatment in SSA. Two investigators independently screened the search output, reviewed the eligible studies, and rated the quality of eligible studies using quality assessment tools of the National Heart Lung and Blood Institute. Pooled odds ratios (ORs) were derived using random-effects meta-analysis. Heterogeneity across studies was assessed using the I2 statistic. The confidence in the pooled ORs was rated using the GRADE. The final review was reported using the PRISMA.Results: Eleven studies including 4181 participants were retained. The studies were of moderate to good quality, with 10 being quasi-experimental and cohort. Pooling of relevant studies showed that the odds of treatment success with integration was 1.1 times (95% CI: 0.93-1.29; I2=74.5%; p-value for heterogeneity=0.001) the odds of treatment success without integration and the odds of mortality with integration was 1.27 (95% CI 1.02-1.59; I2=87.3%; p-value for heterogeneity<0.0001) times the odds of mortality without integration. On sensitivity analysis, the odds of mortality with integration decreased to 1.06 (95% CI: 0.83-1.34; I2=80.1%; p-value for heterogeneity<0.0001) times the odds of mortality without integration and there was strong evidence of an association between sample size variation and heterogeneity (p=0.01). Good quality studies (4/11) tended to support the effectiveness of integrated treatment in increasing successful outcomes and decreasing mortality. Certainty in the pooled ORs was low.Conclusion: Evidence on the effect of integrated TB/HIV treatment services on treatment success and all-cause mortality in TB/HIV co-infected patients in SSA is inconclusive but the few available good quality studies tend to favour the effectiveness of these services. More robust primary studies are warranted.

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Risk factors for poor treatment outcomes of 2,266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study

10.21203/rs.2.12034/v4 ◽

2020 ◽

Author(s):

Le Hong Van ◽

Phan Trieu Phu ◽

Dao Nguyen Vinh ◽

Vo Thanh Son ◽

Nguyen Thi Hanh ◽

...

Keyword(s):

Risk Factors ◽

Treatment Outcomes ◽

Multidrug Resistant ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Poor Treatment ◽

Mdr Tb ◽

History Of ◽

Poor Outcomes ◽

Poor Treatment Outcome

Abstract Background: Multidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam.Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment between 2011-2015 in HCMC. Treatment outcomes were available for 2,240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program.Results: Among 2,266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011-2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1kg/m2 of BMI for patients with BMI<21).Conclusion: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011-2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.

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Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda

African Health Sciences ◽

10.4314/ahs.v21i1.12 ◽

2021 ◽

Vol 21 (1) ◽

pp. 238-47

Author(s):

Charles Batte ◽

Martha S Namusobya ◽

Racheal Kirabo ◽

John Mukisa ◽

Susan Adakun ◽

...

Keyword(s):

Mulago Hospital ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Factors Associated ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb ◽

History Of ◽

Previously Treated

Background: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. Methods: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR- TB between January 2012 – May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sen- sitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. Results: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged be- tween 25 – 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prev- alence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. Conclusion: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DR- TB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients. Keywords: Non-adherence; multi-drug resistant tuberculosis; treatment.

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