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Microbes and Infection 2023The purpose of this research was to evaluate the effect of clofazimine on drug-resistant tuberculosis treatment outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this research was to evaluate the effect of clofazimine on drug-resistant tuberculosis treatment outcomes.
METHODS
A systematic search was conducted in the PubMed, Web of Science and EMBASE databases to identify eligible studies published up to July 10, 2021. The search terms were as follows: "clofazimine," "tuberculosis," "multidrug resistant tuberculosis" or "extensively drug resistant tuberculosis" and their synonyms or similar words. Two researchers independently screened the titles, abstracts, and full texts for inclusion. Meta-analysis was performed with Stata version 16.0 (Stata Corp., College Station, Texas, USA). Risk ratios (RRs) with 95% CIs were calculated to evaluate the treatment outcome.
RESULTS
Eight studies including 3219 participants were included in the meta-analysis. The meta-analysis found that the rates of treatment completion was higher in patients receiving clofazimine-containing regimens than in those not receiving clofazimine-containing regimens (RR: 1.185 (1.060-1.325), P = 0.003). Significant reduction in treatment failure (RR: 0.598 (0.473-0.756), P < 0.001) was found in the clofazimine treatment group. The subgroup analyses of randomized controlled trials (RCTs) found a higher rates of favorable outcomes, treatment completion and cure in the clofazimine group than in the control group (RR: 1.203 (1.029-1.407), P = 0.020; RR: 3.167 (2.043-4.908), P < 0.001; and RR: 1.251 (1.031-1.518), P = 0.023, respectively). Patients receiving clofazimine had a lower risk of treatment failure than those not receiving clofazimine (RR: 0.529 (0.454-0.616), P < 0.001). However, clofazimine treatment did not have a statistically significant effect on all-cause mortality in RCTs.
CONCLUSIONS
This study demonstrated that compared with patients who do not receive clofazimine, this drug has the potential to achieve a higher favorable outcome, treatment completion and cure rates, and a lower treatment failure risk among drug-resistant tuberculosis cases.
Topics: Humans; Antitubercular Agents; Clofazimine; Extensively Drug-Resistant Tuberculosis; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 35792202
DOI: 10.1016/j.micinf.2022.105020 -
The Journal of Infection Jul 2021Objectives estimate the prevalence of ototoxic hearing loss in drug-resistant tuberculosis (DR-TB) patients treated with aminoglycoside antibiotics via a systematic... (Meta-Analysis)
Meta-Analysis Review
Objectives estimate the prevalence of ototoxic hearing loss in drug-resistant tuberculosis (DR-TB) patients treated with aminoglycoside antibiotics via a systematic review and meta-analysis. Estimate the annual preventable cases of hearing loss in DR-TB patients and leverage findings to discuss primary, secondary and tertiary prevention. Methods studies published between 2005 and 2018 that reported prevalence of post-treatment hearing loss in DR-TB patients were included. We performed a random effects meta-analysis to determine pooled prevalence of ototoxic hearing loss overall and by medication type. Preventable hearing loss cases were estimated using World Health Organization (WHO) data on DR-TB treatment and prevalence determined by the meta-analysis. Results eighteen studies from 10 countries were included. Pooled prevalence of ototoxic hearing loss and the corresponding 95% confidence interval (CI) was 40.62% CI [32.77- 66.61%] for all drugs (kanamycin: 49.65% CI [32.77- 66.61%], amikacin: 38.93% CI [26.44-53.07%], capreomycin: 10.21% CI [4.33-22.21%]). Non-use of aminoglycosides may result in prevention of approximately 50,000 hearing loss cases annually. Conclusions aminoglycoside use results in high prevalence of ototoxic hearing loss. Widespread prevention of hearing loss can be achieved by following updated WHO guidelines for DR-TB treatment. When hearing loss cannot be avoided, secondary and tertiary prevention should be prioritized.
Topics: Aminoglycosides; Antitubercular Agents; Hearing Loss; Humans; Prevalence; Tuberculosis, Multidrug-Resistant
PubMed: 34015383
DOI: 10.1016/j.jinf.2021.05.010 -
International Journal of Infectious... Nov 2022We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because these, to the best of our knowledge, are sparsely available.
METHODS
Systematic review and meta-analysis.
RESULTS
A total of 14 studies were included, representing 4268 individuals in 14 of the 26 countries. Using a random-effects model meta-analysis, we observed a pooled success rate of 80.8% (95% confidence interval [CI] 56.0-93.3) for the Central African subgroup and 69.2% (95% CI 56.3-79.7) for the West African subgroup (P = 0.0522). The overall treatment success for all studies was 74.6% (95% CI 65.0-82.2). We found high heterogeneity among included studies (I = 96.1%). The estimated proportion of successfully treated individuals with MDR/rifampicin-resistant TB was considerably higher than the global estimate provided by the World Health Organization (59%), reaching the 2015 World Health Organization target of at least 75% treatment success for MDR-TB.
CONCLUSION
The use of shorter treatment regimens and the standardized treatment conditions, including directly observed therapy in these studies, could have contributed to a high treatment success. Yet, the available literature was not fully representative of the regions, possibly highlighting the sparse resources in many of these countries. The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022353163).
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Rifampin; Directly Observed Therapy; Treatment Outcome; Mycobacterium tuberculosis
PubMed: 36007688
DOI: 10.1016/j.ijid.2022.08.015 -
Frontiers in Public Health 2021Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different... (Meta-Analysis)
Meta-Analysis
Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally. We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed. We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5-4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively. The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.
Topics: Antitubercular Agents; Child; Extensively Drug-Resistant Tuberculosis; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 34490197
DOI: 10.3389/fpubh.2021.721817 -
Indian Journal of Ophthalmology Mar 2023The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating... (Review)
Review
The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating optic neuropathy in extended ethambutol use since 2010 and compared the outcome with a similar systematic review (1965-2010) by Ezer et al. Literature search was conducted in PubMed, Medline, EMBASE, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Main outcome measures were visual acuity, color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP). The JBI Critical Appraisal Checklists were used for quality assessment. Twelve studies were selected (out of 639 studies) for analysis of ethambutol optic neuropathy. Visual acuity improvement after stopping ethambutol was statistically significant. Similar improvement was not noted for other outcome measures. On comparing the results of this review with those by Ezer et al., significant improvement was noted in visual acuity, color vision, and visual field defects. Moreover, more patients reported increased optic nerve toxicity, color vision defects, and visual field defects in the present review. Hence, we conclude that the extended use of ethambutol beyond 2 months results in significant optic nerve toxicity. Further randomized controlled trials with different populations are needed to understand the magnitude of this issue.
Topics: Humans; Ethambutol; Evoked Potentials, Visual; Optic Nerve Diseases; Optic Nerve; Checklist; Rare Diseases
PubMed: 36872667
DOI: 10.4103/ijo.IJO_1920_22 -
PLoS Medicine Sep 2021Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes.
METHODS AND FINDINGS
We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications.
CONCLUSIONS
The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.
Topics: Anti-Retroviral Agents; Antitubercular Agents; Coinfection; Cost-Benefit Analysis; Drug Costs; HIV Infections; HIV Long-Term Survivors; Humans; Incidence; Models, Economic; Preventive Health Services; Risk Assessment; Risk Factors; Treatment Outcome; Tuberculosis
PubMed: 34520463
DOI: 10.1371/journal.pmed.1003712 -
Clinical Infectious Diseases : An... Nov 2021Although the incidence of tuberculosis is higher in men than in women, the relationship of sex with tuberculosis treatment outcomes has not been adequately studied. (Meta-Analysis)
Meta-Analysis
Male Sex Is Associated With Worse Microbiological and Clinical Outcomes Following Tuberculosis Treatment: A Retrospective Cohort Study, a Systematic Review of the Literature, and Meta-analysis.
BACKGROUND
Although the incidence of tuberculosis is higher in men than in women, the relationship of sex with tuberculosis treatment outcomes has not been adequately studied.
METHODS
We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex differences in clinical and microbiological outcomes in tuberculosis.
RESULTS
In our cohort of 2894 Taiwanese patients with drug-susceptible pulmonary tuberculosis (1975 male and 919 female), male patients had higher adjusted hazards of 9-month mortality due to all causes (hazard ratio, 1.43 [95% confidence interval (CI), 1.03-1.98]) and infections (1.70 [1.09-2.64]) and higher adjusted odds of 2-month sputum culture positivity (odds ratio [OR], 1.56 [95% CI, 1.05-2.33]) compared with female patients. Smear positivity at 2 months did not differ significantly (OR, 1.27 [95% CI, .71-2.27]) between the sexes. Among 7896 articles retrieved, 398 were included in our systematic review describing a total of 3 957 216 patients. The odds of all-cause mortality were higher in men than in women in the pooled unadjusted (OR, 1.26 [95% CI, 1.19-1.34]) and adjusted (1.31 [1.18-1.45]) analyses. Men had higher pooled odds of sputum culture (OR, 1.44 [95% CI, 1.14-1.81]) and sputum smear (1.58 [1.41-1.77]) positivity, both at the end of the intensive phase and on completion of treatment.
CONCLUSIONS
Our retrospective cohort showed that male patients with tuberculosis have higher 9-month all-cause and infection-related mortality, with higher 2-month sputum culture positivity after adjustment for confounding factors. In our meta-analysis, male patients showed higher all-cause and tuberculosis-related mortality and higher sputum culture and smear positivity rates during and after tuberculosis treatment.
Topics: Antitubercular Agents; Cohort Studies; Female; Humans; Male; Mycobacterium tuberculosis; Retrospective Studies; Sputum; Tuberculosis
PubMed: 34100919
DOI: 10.1093/cid/ciab527 -
AIDS Research and Therapy Nov 2021Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients' access to comprehensive... (Meta-Analysis)
Meta-Analysis
Barriers to and enablers of uptake of antiretroviral therapy in integrated HIV and tuberculosis treatment programmes in sub-Saharan Africa: a systematic review and meta-analysis.
INTRODUCTION
Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients' access to comprehensive treatment. However, several reports from sub-Saharan Africa (SSA) indicate suboptimal uptake of antiretroviral therapy (ART) even after integration of HIV and TB treatment. This study assessed ART uptake, its barriers and enablers in programmes integrating TB and HIV treatment in SSA.
METHOD
A systematic review was performed. Seven databases were searched for eligible quantitative, qualitative and mixed-methods studies published from March 2004 through July 2019. Random-effects meta-analysis was used to obtain pooled estimates of ART uptake. A thematic approach was used to analyse and synthesise data on barriers and enablers.
RESULTS
Of 5139 references identified, 27 were included in the review: 23/27 estimated ART uptake and 10/27 assessed barriers to and/or enablers of ART uptake. The pooled ART uptake was 53% (95% CI: 42, 63%) and between-study heterogeneity was high (I = 99.71%, p < 0.001). WHO guideline on collaborative TB/HIV activities and sample size were associated with heterogeneity. There were statistically significant subgroup effects with high heterogeneity after subgroup analyses by region, guideline on collaborative TB/HIV activities, study design, and sample size. The most frequently described socioeconomic and individual level barriers to ART uptake were stigma, low income, and younger age group. The most frequently reported health system-related barriers were limited staff capacity, shortages in medical supplies, lack of infrastructure, and poor adherence to or lack of treatment guidelines. Clinical barriers included intolerance to anti-TB drugs, fear of drug toxicity, and contraindications to antiretrovirals. Health system enablers included good management of the procurement, supply, and dispensation chain; convenience and accessibility of treatment services; and strong staff capacity. Availability of psychosocial support was the most frequently reported enabler of uptake at the community level.
CONCLUSIONS
In SSA, programmes integrating treatment of TB and HIV do not, in general, achieve high ART uptake but we observe a net improvement in uptake after WHO issued the 2012 guidelines on collaborative TB/HIV activities. The recurrence of specific modifiable system-level and patient-level factors in the literature reveals key intervention points to improve ART uptake in these programmes. Systematic review registration: CRD42019131933.
Topics: Anti-Retroviral Agents; Antitubercular Agents; HIV Infections; Humans; Social Stigma; Tuberculosis
PubMed: 34784918
DOI: 10.1186/s12981-021-00395-3 -
International Journal of... 2023Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline... (Review)
Review
BACKGROUND
Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline and/or delamanid have already shown promising outcomes in patients with DR-TB, increasing the rate of culture conversion and lowering TB-related mortality.
METHODS
We comprehensively searched and evaluated the effectiveness of individual regimens containing bedaquiline and delamanid on culture conversion and treatment success. We assessed for quality either observational or experimental studies.
RESULTS
We identified 14 studies that met the inclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart with 12 observational and 2 experimental studies. Of 1691 DR-TB patients enrolled in the included studies, 1407 of them concomitantly received regimens containing bedaquiline and delamanid. Overall multidrug resistant (MDR), preextensively drug resistant (XDR), and XDR-TB were seen in 21.4%, 44.1%, and 34.5%, respectively. Of 14 studies, 8 of them reported favorable outcomes including sputum culture conversion and cure rate at the end of treatment, meanwhile 6 studies only reported sputum culture conversion. Sputum culture conversion at the end of the 6 month was 63.6%-94.7% for observational studies, and 87.6%-95.0% for experimental studies. The favorable outcome at the end of treatment was 67.5%-91.4%. With high pre-XDR and XDR cases among DR-TB patients with limited treatment options, regimens containing bedaquiline and delamanid provide successful treatment.
CONCLUSION
In DR-TB patients receiving regimens containing bedaquiline and delamanid, favorable outcomes were high including sputum conversion and cure rate.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Diarylquinolines; Treatment Outcome
PubMed: 36926755
DOI: 10.4103/ijmy.ijmy_217_22 -
The Lancet. Microbe Nov 2021Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and...
BACKGROUND
Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and surveillance of drug resistance emergence. To facilitate molecular assay development, we aimed to identify genomic markers of bedaquiline resistance.
METHODS
In this systematic review and individual isolate analysis, we searched Europe PubMed Central and Scopus for studies published from the inception of each database until Oct 19, 2020, that assessed genotypic and phenotypic bedaquiline resistance in clinical or non-clinical isolates. All studies reporting on the assessment of variants in the four genes of interest (, , , and ) and phenotypic bedaquiline data in both clinical and non-clinical samples were included. We collated individual isolate data from eligible studies to assess the association between genomic variants with phenotypic bedaquiline resistance, using a standardised method endorsed by WHO. Risk of bias of the extracted data was independently assessed by two authors using the Quality Assessment of Diagnostic Accuracy Studies tool for clinical studies and Systematic Review Center for Laboratory Animal Experimentation tool for animal studies. The primary outcome was to identify mutations associated with resistance in four genes of interest (, , , and ); for each genomic variant, the odds ratio (OR), 95% CI, and p value were calculated to identify resistance markers associated with bedaquiline resistance. This study is registered with PROSPERO, CRD42020221498.
FINDINGS
Of 1367 studies identified, 41 published between 2007 and 2020 were eligible for inclusion. We extracted data on 1708 isolates: 1569 (91·9%) clinical isolates and 139 (8·1%) non-clinical isolates. We identified 237 unique variants in , 14 in , 28 in and 11 in . Most clinical isolates with a single variant reported in (229 [79%] of 287 variants), (14 [88%] of 16 variants), (32 [100%] of 32 variants), or (115 [98%] of 119 variants) were phenotypically susceptible to bedaquiline. Except for the 187G→C (OR ∞, [95% CI 13·28-∞]; p<0·0001) and 138_139insG (OR 6·91 [95% CI 1·16-47·38]; p=0·016) variants, phenotypic-genotypic associations were not significant (p≥0·05) for any single variant in , , and .
INTERPRETATION
Absence of clear genotypic-phenotypic associations for bedaquiline complicates the development of molecular drug susceptibility tests. A concerted global effort is urgently needed to assess the genotypic and phenotypic drug susceptibility of isolates, especially in patients who have received unsuccessful bedaquiline-containing regimens. Treatment regimens should be designed to prevent emergence of bedaquiline resistance and phenotypic drug susceptibility tests should be used to guide and monitor treatment.
FUNDING
Research Foundation Flanders, South African Medical Research Council, Department of Science and Innovation - National Research Foundation, National Institute of Health Institute of Allergy and Infectious Diseases, and Doris Duke Charitable Foundation.
Topics: Animals; Antitubercular Agents; Data Analysis; Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Multidrug-Resistant
PubMed: 34796339
DOI: 10.1016/s2666-5247(21)00175-0