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International Journal of Infectious... Aug 2014Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis.
METHODS
A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile.
RESULTS
This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009).
CONCLUSIONS
Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.
Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; CD4 Lymphocyte Count; Clinical Trials as Topic; Coinfection; Cyclopropanes; HIV Infections; Humans; Nevirapine; Rifampin; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24911886
DOI: 10.1016/j.ijid.2014.04.020 -
Bulletin of the World Health... Aug 2017To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches.
METHODS
We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization's portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses.
FINDINGS
Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01-1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38-1.13), for death RR: 1.01 (95% CI: 0.67-1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48-2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models.
CONCLUSION
Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings.
Topics: Antitubercular Agents; Delivery of Health Care; Health Expenditures; Humans; Medication Adherence; Tuberculosis, Multidrug-Resistant
PubMed: 28804170
DOI: 10.2471/BLT.17.193375 -
PloS One 2015Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.
METHODS
Systematic PubMed, Science Direct and Scopus searches for articles reporting phenotypic (liquid culture drug susceptibility testing or pyrazinamidase activity assays) and/or genotypic (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional summary estimates were obtained from random-effects meta-analysis, stratified by presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates were combined with regional WHO TB incidence estimates to determine the annual burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.
RESULTS
Pooled PZA resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases, 41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.
INTERPRETATION
PZA resistance is ubiquitous, with an estimated one in six incident TB cases and more than half of all MDR-TB cases resistant to PZA globally. The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics. These findings caution against relying on PZA in current and future TB drug regimens, especially in MDR-TB patients.
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Pyrazinamide; Tuberculosis, Multidrug-Resistant
PubMed: 26218737
DOI: 10.1371/journal.pone.0133869 -
Revista Espanola de Salud Publica Dec 2022There are different socioeconomic variables which determine tuberculosis's epidemiology, diagnosis and treatment. The objective of this paper was to analize these... (Review)
Review
OBJECTIVE
There are different socioeconomic variables which determine tuberculosis's epidemiology, diagnosis and treatment. The objective of this paper was to analize these effects in the last years in Spain.
METHODS
A systematic review was conducted. Screened studies were original articles written in English or Spanish and published between 2007 and 2020. Searching was performed in Pubmed and Web of Science databases. STROBE criteria were followed to analyze studies's quality, and studies included in the review had 15 points or more.
RESULTS
23 articles were selected, and were classified in different topics. Foreigners's proportion with tuberculosis changed in different autonomous communities between 10%-50%. There were diagnostic delay for this group compared to natives. This group had higher incidence of resistance to isoniazid, but without a clear increase in multidrug resistance. There were less adherence to tuberculosis's treatment in case of immigration, drug addiction, HIV coinfection, or lack of family support. Under-reporting of tuberculosis cases varied between 18%-28%, and it was higher in cases of social marginality, HIV coinfection, Spanish nationality or male sex. There were also other social risk groups in which the diagnostic approach to tuberculosis was relevant, such as in schools and health centers. Tuberculosis was one of the most frequent HIV associated diseases, although screening tests were not performed in almost 18%, depending on the concurrence of social risk factors.
CONCLUSIONS
Tuberculosis's incidence, diagnosis, and treatment are influenced by a lot of social and economic factors, which determine the approach to this disease.
Topics: Male; Humans; Delayed Diagnosis; Spain; Socioeconomic Factors; Tuberculosis; Isoniazid
PubMed: 36458439
DOI: No ID Found -
Annals of Clinical Microbiology and... Oct 2021Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycobacterium tuberculosis (MTB) is responsible for tuberculosis; that continues to be a public health threat across the globe. Furthermore, increasing heteroresistance (HR)-the presence of resistant and susceptible isolates among MTB strains- has been reported from around the world. This phenomenon can lead to full resistance development and treatment failure.
METHODS
We systematically searched the relevant studies in PubMed, Scopus, and Embase (Until October 21, 2020). The study outcomes revealed the weighted pooled prevalence of antibiotic HR in MTB isolates with subgroup analysis by year, quality of study, and heteroresistance detection method.
RESULTS
A total of 38 studies which had investigated MTB isolates were included in the meta-analysis. Geographically, the highest number of studies were reported from Asia (n = 24), followed by Africa (n = 5). Nineteen studies reported HR to isoniazid, with a weighted pooled prevalence of 5% (95% CI 0-12) among 11,761 MTB isolates. Also, there is no important trend for the subgroup analysis by the study period (2001-2014 vs 2015-2017 vs 2018-2020). HR to rifampin was reported in 17 studies, with a weighted pooled prevalence of 7% (95% CI 2-14) among 3782 MTB isolates. HR to fluoroquinolone and ethambutol were reported in 12 and 4 studies, respectively, with weighted pooled prevalence of 10% and 1% among 2153 and 1509 MTB isolates, correspondingly.
CONCLUSION
Based on our analysis, HR in MTB isolates with different frequency rate is present worldwide. Thus, the selection of appropriate and reliable methods for HR detection is crucial for TB eradication.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Isoniazid; Mycobacterium tuberculosis; Rifampin; Tuberculosis
PubMed: 34645463
DOI: 10.1186/s12941-021-00478-z -
Genes Oct 2022Objective: The Beijing strain of Mycobacterium tuberculosis (MTB) is controversially presented as the predominant genotype and is more drug resistant to rifampicin and... (Meta-Analysis)
Meta-Analysis Review
Comparison on Major Gene Mutations Related to Rifampicin and Isoniazid Resistance between Beijing and Non-Beijing Strains of : A Systematic Review and Bayesian Meta-Analysis.
Objective: The Beijing strain of Mycobacterium tuberculosis (MTB) is controversially presented as the predominant genotype and is more drug resistant to rifampicin and isoniazid compared to the non-Beijing strain. We aimed to compare the major gene mutations related to rifampicin and isoniazid drug resistance between Beijing and non-Beijing genotypes, and to extract the best evidence using the evidence-based methods for improving the service of TB control programs based on genetics of MTB. Method: Literature was searched in Google Scholar, PubMed and CNKI Database. Data analysis was conducted in R software. The conventional and Bayesian random-effects models were employed for meta-analysis, combining the examinations of publication bias and sensitivity. Results: Of the 8785 strains in the pooled studies, 5225 were identified as Beijing strains and 3560 as non-Beijing strains. The maximum and minimum strain sizes were 876 and 55, respectively. The mutations prevalence of rpoB, katG, inhA and oxyR-ahpC in Beijing strains was 52.40% (2738/5225), 57.88% (2781/4805), 12.75% (454/3562) and 6.26% (108/1724), respectively, and that in non-Beijing strains was 26.12% (930/3560), 28.65% (834/2911), 10.67% (157/1472) and 7.21% (33/458), separately. The pooled posterior value of OR for the mutations of rpoB was 2.72 ((95% confidence interval (CI): 1.90, 3.94) times higher in Beijing than in non-Beijing strains. That value for katG was 3.22 (95% CI: 2.12, 4.90) times. The estimate for inhA was 1.41 (95% CI: 0.97, 2.08) times higher in the non-Beijing than in Beijing strains. That for oxyR-ahpC was 1.46 (95% CI: 0.87, 2.48) times. The principal patterns of the variants for the mutations of the four genes were rpoB S531L, katG S315T, inhA-15C > T and oxyR-ahpC intergenic region. Conclusion: The mutations in rpoB and katG genes in Beijing are significantly more common than that in non-Beijing strains of MTB. We do not have sufficient evidence to support that the prevalence of mutations of inhA and oxyR-ahpC is higher in non-Beijing than in Beijing strains, which provides a reference basis for clinical medication selection.
Topics: Isoniazid; Mycobacterium tuberculosis; Rifampin; Antitubercular Agents; Bayes Theorem; Microbial Sensitivity Tests; Bacterial Proteins; Mutation; DNA, Intergenic
PubMed: 36292734
DOI: 10.3390/genes13101849 -
BMC Infectious Diseases Jun 2016In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In 2014 only 50 % of multidrug-resistant tuberculosis (MDR-TB) patients achieved a successful treatment outcome. With limited options for medical treatment, surgery has re-emerged as an adjuvant therapeutic strategy. We conducted a systematic review and meta-analysis to assess the evidence for the effect of surgery as an adjunct to chemotherapy on outcomes of adults treated for MDR-TB.
METHODS
Databases and grey literature sources were searched using terms incorporating surgery and MDR-TB. No language or publication type limits were applied. Articles published pre-1990, without a comparator group, or reporting <10 surgical participants were excluded. Two-stage sifting in duplicate was employed. Data on WHO-defined treatment outcomes were abstracted into a standardised database. Study-level risk of bias was evaluated using standardised tools. Outcome-level evidence quality was assessed using GRADE. Forest plots were generated, random effects meta-analysis conducted, and heterogeneity assessed using the I(2) statistic.
RESULTS
Of 1024 unique citations identified, 62 were selected for full-text review and 15 retained for inclusion. A further four articles were included after bibliography/citation searching, and one additional unpublished manuscript was identified, giving 20 articles for final inclusion. Six were meta-analyses/systematic reviews and 14 were primary research articles (observational studies). From the 14 primary research articles, a successful outcome (cured/treatment completed) was reported for 81.9 % (371/453) and 59.7 % (1197/2006) in the surgical and non-surgical group respectively, giving a summary odds ratio of 2.62 (95 % confidence interval 1.94-3.54). Loss to follow-up and treatment failure were lower in the surgery group (both p = 0.01). Overall GRADE quality of evidence for all outcomes considered was "very low".
CONCLUSIONS
This meta-analysis suggests that surgery as an adjunct to chemotherapy is associated with improved treatment outcomes in MDR-TB patients. However, inherent limitations in observational study design, insufficient reporting, and lack of adjustment for confounders, led to grading of the evidence as very low quality. Data on rationale for surgical referral, subsequent outcomes and resource-limited settings are scarce, precluding evidence-based recommendations on the suitability of surgery by patient characteristics or setting. It is hoped that highlighted methodological and reporting gaps will encourage improved design and reporting of future surgical studies for MDR-TB.
Topics: Antitubercular Agents; Humans; Odds Ratio; Pneumonectomy; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 27283524
DOI: 10.1186/s12879-016-1585-0 -
BMC Public Health Mar 2015Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prevalence of multidrug resistant tuberculosis (MDR-TB), defined as in vitro resistance to both rifampicin and isoniazid with or without resistance to other TB drugs, in sub-Saharan Africa (SSA) is reportedly low compared to other regions. These estimates are based on data reported to the World Health Organization (WHO) on drug resistance surveys, which may suffer from a reporting bias. We set out to evaluate the variation in prevalence of drug resistant tuberculosis (DR-TB) and its determinants across SSA countries among new and previously treated TB patients.
METHODS
The aim was to perform a systematic review and meta-analysis of DR-TB prevalence and associated risk factors in SSA. PubMed, EMBASE, Cochrane and bibliographies of DR-TB studies were searched. Surveys at national or sub-national level, with reported DR-TB prevalence (or sufficient data to calculate a prevalence) to isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and streptomycin (SM) conducted in SSA excluding the Republic of South Africa, published between 2003 and 2013 with no language restriction were considered. Two authors searched and reviewed the studies for eligibility and extracted the data in pre-defined forms. Forest plots of all prevalence estimates by resistance outcome were performed. Summary estimates were calculated using random effects models, when appropriate. Associations between any DR-TB and MDR-TB with potential risk factors were examined through subgroup analyses stratified by new and previously treated patients.
RESULTS
A total of 726 studies were identified, of which 27 articles fulfilled the inclusion criteria. Studies reported drug susceptibility testing (DST) results for a total of 13,465 new and 1,776 previously treated TB patients. Pooled estimate of any DR-TB prevalence among the new cases was 12.6% (95% CI 10.6-15.0) while for MDR-TB this was 1.5% (95% CI 1.0-2.3). Among previously treated patients, these were 27.2% (95% CI 21.4-33.8) and 10.3% (95% CI 5.8-17.4%), respectively. DR-TB (any and MDR-TB) did not vary significantly with respect to study characteristics.
CONCLUSIONS
The reported prevalence of DR-TB in SSA is low compared to WHO estimates. MDR-TB in this region does not seem to be driven by the high HIV prevalence rates.
Topics: Africa South of the Sahara; Antitubercular Agents; Bacteriological Techniques; Ethambutol; Humans; Isoniazid; Prevalence; Rifampin; Risk Factors; Streptomycin; Tuberculosis, Multidrug-Resistant; World Health Organization
PubMed: 25880829
DOI: 10.1186/s12889-015-1614-8 -
International Journal of Infectious... Sep 2020To assess poor treatment outcomes and their predictors among drug-resistant tuberculosis patients treated in Ethiopia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess poor treatment outcomes and their predictors among drug-resistant tuberculosis patients treated in Ethiopia.
METHODS
Data were searched from both electronic databases and other sources. From the whole search, 404 articles were reviewed and 17 articles that fulfilled the inclusion criteria were included in the analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed and Joanna Briggs Institute Critical Appraisal checklist was used for assessing the quality. Risk of bias was assessed using forest plot and Egger's regression test. Data were analyzed using STATA version 15 and Review Manager Software version 5.3.
RESULTS
The overall pooled proportion of poor treatment outcome and mortality was 17.86% and 15.13% respectively. The incidence density rate of poor treatment outcome and mortality was 10.41/1000 person-months and 9.28/1000 person-months respectively. Survival status and successful treatment outcomes were 76.97% and 63.82% respectively. HIV positivity, non-HIV comorbidities, clinical complications, extrapulmonary involvement, undernutrition, anemia, treatment delay, lower body weight, and older age were the predictors of poor treatment outcome.
CONCLUSION
Better survival and treatment success rates were noted in Ethiopia as compared to the global average. The majority of the poor treatment outcomes occurred within the intensive phase. Early initiation of anti-tuberculosis treatment would be important for successful treatment outcomes.
Topics: Adolescent; Adult; Antitubercular Agents; Ethiopia; Female; Humans; Male; Time-to-Treatment; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 32645375
DOI: 10.1016/j.ijid.2020.05.087 -
Clinical Microbiology and Infection :... Feb 2024Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk.
OBJECTIVES
To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB.
DATA SOURCES
EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions.
STUDY ELIGIBILITY CRITERIA
We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease.
PARTICIPANTS
Contacts of patients with MDR-TB.
INTERVENTIONS
TPT.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale was used.
METHODS OF DATA SYNTHESIS
Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed.
RESULTS
Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively.
DISCUSSION
TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Pyrazinamide; Levofloxacin; Drug-Related Side Effects and Adverse Reactions; Disease Progression
PubMed: 37741621
DOI: 10.1016/j.cmi.2023.09.015