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BMC Infectious Diseases Dec 2022Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB).
METHODS
We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays.
RESULTS
A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods.
CONCLUSIONS
Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.
Topics: Humans; Rifampin; Tuberculosis, Pulmonary; Mycobacterium tuberculosis; Delayed Diagnosis; Time-to-Treatment; Pathology, Molecular; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36517736
DOI: 10.1186/s12879-022-07855-9 -
Pharmacological Research Aug 2022We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice.
METHODS
We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality.
RESULTS
38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too.
CONCLUSIONS
Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.
Topics: Antitubercular Agents; Diarylquinolines; Extensively Drug-Resistant Tuberculosis; HIV Infections; Humans; Linezolid; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 35779814
DOI: 10.1016/j.phrs.2022.106336 -
PloS One 2022Cotrimoxazole and isoniazid preventive therapy (CPT, IPT) have been shown to be efficacious therapies for the prevention of opportunistic infections and tuberculosis...
Mixed methods systematic review and metasummary about barriers and facilitators for the implementation of cotrimoxazole and isoniazid-Preventive therapies for people living with HIV.
BACKGROUND
Cotrimoxazole and isoniazid preventive therapy (CPT, IPT) have been shown to be efficacious therapies for the prevention of opportunistic infections and tuberculosis (TB) among people living with human immunodeficiency virus (HIV). Despite governments' efforts to translate World Health Organization recommendations into practice, implementation remains challenging. This review aimed to explore and compare CPT and IPT with respect to similarities and differences of barriers identified across high TB/HIV burden countries. A secondary objective was to identify facilitators for implementing both preventive therapies.
METHODS
We searched MEDLINE, Web of Science and SCOPUS databases for peer-reviewed literature published before September 2020. We extracted and synthesized our findings using Maxqda software. We applied framework synthesis in conjunction with metasummary to compare both therapies with respect to similarities and differences of barriers identified across seven health system components (in line with the modified WHO's Framework for action). Protocol registration: PROSPERO (CRD42019137778).
FINDINGS
We identified four hundred and eighty-two papers, of which we included forty for review. Although most barrier themes were identical for both preventive therapies, we identified seven intervention-specific themes. Like for CPT, barriers identified for IPT were most frequently classified as 'service delivery-related barriers' and 'patient & community-related barriers'. 'Health provider-related barriers' played an important role for implementing IPT. Most facilitators identified referred to health system strengthening activities.
CONCLUSIONS
For researchers with limited working experience in high TB/HIV burden countries, this review can provide valuable insights about barriers that may arise at different levels of the health system. For policymakers in high TB/HIV burden countries, this review offers strategies for improving the delivery of IPT (or any newer therapy regimen) for the prevention of TB. Based on our findings, we suggest initial and continuous stakeholder involvement, focusing on the efficient use and reinforcement of existing resources for health.
Topics: Isoniazid
PubMed: 35231047
DOI: 10.1371/journal.pone.0251612 -
Computational Intelligence and... 2022Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate mofetil (MMF) have been carried out. This paper aimed to compare the efficacy and safety of MZR and MMF in immunosuppressive therapy of renal transplantation by meta-analysis.
METHODS
We searched randomized controlled trials (RCTs) comparing MZR versus MMF for renal transplantation in PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM). Articles were assessed for their risk of bias using the Cochrane Collaboration. Forest plots and funnel plots were also performed on the included articles.
RESULTS
A total of twelve studies with 1103 patients were selected in the analysis. No significant difference were observed between the MZR group and the MMF group for the rate of acute rejection (RR = 1.50, 95% CI 1.11 to 2.01, = 0.008), patient survival (RR = 1.01, 95% CI 0.99 to 1.03, = 0.56), graft survival (RR = 1.02, 95% CI 1.00 to 1.04, = 0.12), leucopenia (RR = 0.69, 95% CI 0.44 to 1.10, = 0.12), and liver damage (RR = 0.72, 95% CI 0.46 to 1.13, = 0.15). The MZR group was associated with a lower risk of gastrointestinal disorder (RR = 0.28, 95% CI 0.13 to 0.62, = 0.002) and cytomegalovirus infection (RR = 0.59, 95% CI 0.42 to 0.84, = 0.003) but had a higher risk of hyperuricemia (RR 1.79, 95% CI 1.17 to 2.75, = 0.007). No significant publication bias was observed among included studies. . MZR is similar to MMF in efficacy, and in terms of safety, MZR has a lower risk of gastrointestinal disorder and cytomegalovirus infection but a higher risk of hyperuricemia.
Topics: Cytomegalovirus Infections; Gastrointestinal Diseases; Humans; Hyperuricemia; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Ribonucleosides
PubMed: 35909831
DOI: 10.1155/2022/5717068 -
BMJ Global Health 2020The WHO End TB Strategy calls for a global reduction in the case fatality ratio (CFR) below 5%. India accounts for a third of global tuberculosis (TB) deaths. This... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The WHO End TB Strategy calls for a global reduction in the case fatality ratio (CFR) below 5%. India accounts for a third of global tuberculosis (TB) deaths. This systematic review estimated CFRs among Indian patients with TB both during and after treatment.
METHODS
We systematically searched Medline, Embase and Global Health for eligible studies published between 1 January 2006 and 8 January 2019, including both cohort studies and intervention study control arms that followed Indian patients with TB for fatality either during treatment or post-treatment. From relevant studies we extracted CFRs in addition to study demographics. Study quality was assessed using modified Scottish Intercollegiate Guidelines Network cohort criteria. Sufficiently homogenous studies were pooled using a random effect generalised linear mixed model. A meta-regression was performed to associate study characteristics with resulting CFRs.
RESULTS
218 relevant studies were identified, of which 211 provided treatment phase CFRs. Most patients (92.4%) were treated in the public sector. Quality concerns were identified in 74% of papers. We estimated a pooled treatment phase CFR of 5.16% (95% CI 4.20% to 6.34%) which fell to 3.78% (2.77% to 5.16%) when restricted to 52 high-quality studies. Treatment phase CFRs were higher for paediatric (n=27, 6.50% (2.65% to 10.36%)), drug-resistant (n=43, 14.06% (10.15% to 19.49%)) and HIV-infected (n=35, 10.91% (7.68% to 15.50%)) patients. Nineteen post-treatment CFR studies were too heterogeneous to pool except when restricting to three high-quality studies (2.69% (-0.79% to 6.18%)). Poor study quality (OR=2.27 (2.01 to 2.57)) and tertiary centres patients (OR=1.15 (1.03 to 1.28)) were significantly associated with increased treatment phase case fatality.
CONCLUSIONS
Case fatality is a critical measure of the quality of TB care. While India's treatment CFRs are in line with WHO targets, several key patient groups remain understudied and most studies suffer from methodological issues. Increased high-quality reporting on patient outcomes will help improve the evidence base on this topic.
Topics: Adolescent; Adult; Antitubercular Agents; Female; Humans; India; Male; Treatment Outcome; Tuberculosis; Young Adult
PubMed: 32133176
DOI: 10.1136/bmjgh-2019-002080 -
PloS One 2021Drug-resistant tuberculosis and extrapulmonary tuberculosis are the world major public health issues. Although some primary studies have been reported on the burden of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-resistant tuberculosis and extrapulmonary tuberculosis are the world major public health issues. Although some primary studies have been reported on the burden of drug-resistant tuberculosis in extrapulmonary tuberculosis patients in Ethiopia, there is no systematic review and meta-analysis that attempt to summarize the available literature. Thus, we aimed to estimates the prevalence of drug-resistance in extrapulmonary tuberculosis patients and summarize the risk factors associated with the occurrence of extrapulmonary tuberculosis in Ethiopia.
METHODS
We conducted a systematic review of the published primary studies on extrapulmonary drug-resistant tuberculosis in Ethiopia.
RESULTS
Eight observational studies were included in this review from different regions of Ethiopia. The overall pooled prevalence of rifampicin resistance was 6% (95% CI 0.03-0.10), while isoniazid resistance was 7% (95% CI 0.03-0.12). The pooled prevalence of multidrug-resistant tuberculosis was 4% (95% CI 0.01-0.07). Previous tuberculosis treatment history and male gender are frequently reported risk factors for developing drug-resistant tuberculosis in extrapulmonary tuberculosis patients.
CONCLUSION
The current review has identified a high proportion of resistance to rifampicin, isoniazid, and multidrug-resistant tuberculosis in patients with extrapulmonary tuberculosis in Ethiopia. Clinicians should request drug susceptibility testing for all patients with presumptive extrapulmonary tuberculosis to detect drug-resistance.
Topics: Ethiopia; Humans; Isoniazid; Prevalence; Rifampin; Risk Factors; Tuberculosis, Multidrug-Resistant
PubMed: 34624050
DOI: 10.1371/journal.pone.0258295 -
Journal of Global Antimicrobial... Sep 2021Globally, the incidence and mortality of tuberculosis (TB) are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward... (Meta-Analysis)
Meta-Analysis Review
Prevalence of drug resistance-conferring mutations associated with isoniazid- and rifampicin-resistant Mycobacterium tuberculosis in Ethiopia: a systematic review and meta-analysis.
OBJECTIVES
Globally, the incidence and mortality of tuberculosis (TB) are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward global TB control. Multiple rapid molecular diagnostic tests have recently been developed to detect genetic mutations in Mycobacterium tuberculosis (Mtb) known to confer drug resistance. However, their utility depends on the frequency and distribution of resistance-associated mutations in the pathogen population. This review aimed to assess the prevalence of gene mutations associated with rifampicin (RIF)- and isoniazid (INH)-resistant Mtb in Ethiopia.
METHODS
We searched the literature in PubMed/MEDLINE, Web of Science, Scopus and Cochrane Library. Data analysis was conducted in Stata 11.
RESULTS
Totally, 909 (95.8%) of 949 INH-resistant Mtb isolates had detectable gene mutations: 95.8% in katG315 and 5.9% in the inhA promoter region. Meta-analysis resulted in an estimated pooled prevalence of katGMUT1(S315T1) of 89.2% (95% CI 81.94-96.43%) and a pooled prevalence of inhAMUT1(C15T) of 77.5% (95% CI 57.84-97.13%). Moreover, 769 (90.8%) of 847 RIF-resistant strains had detectable rpoB gene mutations. Meta-analysis resulted in a pooled prevalence of rpoBMUT3(S531L) of 74.2% (95% CI 66.39-82.00%).
CONCLUSION
RIF-resistant Mtb were widespread, particularly those harbouring rpoB(S531L) mutation. Similarly, INH-resistant Mtb with katG(S315T1) and inhA(C15T) mutations were common. Tracking S531L, S315T1 and C15T mutations among RIF- and INH-resistant isolates, respectively, would be diagnostically and epidemiologically valuable. Rapid diagnosis of RIF- and INH-resistant Mtb would expedite modification of TB treatment regimens, and proper timely infection control interventions could reduce the risk of development and transmission of multidrug-resistant TB.
Topics: Drug Resistance; Ethiopia; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Prevalence; Rifampin; Tuberculosis, Multidrug-Resistant
PubMed: 34214698
DOI: 10.1016/j.jgar.2021.06.009 -
International Journal of Antimicrobial... May 2023A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant... (Review)
Review
A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant variability in measurements of bacterial load complicates data analysis in these trials. A systematic review and evaluation of methods for determination of EBA in pulmonary tuberculosis studies was undertaken. Bacterial load quantification biomarkers, reporting intervals, calculation methods, statistical testing, and handling of negative culture results were extracted. In total, 79 studies were identified in which EBA was determined. Colony-forming units on solid culture media and/or time-to-positivity in liquid media were the biomarkers used most often, reported in 72 (91%) and 34 (43%) studies, respectively. Twenty-two different reporting intervals were presented, and 12 different calculation methods for EBA were identified. Statistical testing for a significant EBA compared with no change was performed in 54 (68%) studies, and between-group testing was performed in 32 (41%) studies. Negative culture result handling was discussed in 34 (43%) studies. Notable variation was found in the analysis methods and reporting of EBA studies. A standardized and clearly reported analysis method, accounting for different levels of variability in the data, could aid the generalization of study results and facilitate comparison between drugs/regimens.
Topics: Humans; Mycobacterium tuberculosis; Time Factors; Tuberculosis, Pulmonary; Antitubercular Agents; Tuberculosis; Sputum
PubMed: 36893811
DOI: 10.1016/j.ijantimicag.2023.106775 -
International Journal of Antimicrobial... Jan 2024Adjunctive rifampicin for implant-associated infections is controversial. This study investigated the clinical outcomes of rifampicin combination therapy compared with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Adjunctive rifampicin for implant-associated infections is controversial. This study investigated the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating prosthetic joint infection (PJI) or prosthetic valve endocarditis (PVE) due to staphylococci and streptococci.
METHODS
A systematic search was performed from inception to 13 June 2022 in Embase, MEDLINE, Cochrane and Web of Science to investigate the clinical outcomes of rifampicin combination therapy compared with monotherapy in treating staphylococcal and streptococcal PJI or PVE. Randomised controlled trials (RCTs) and observational studies were included in the systematic review and meta-analysis.
RESULTS
Fourteen studies were included. A moderate quality of evidence was found in favour of rifampicin in patients with staphylococcal PJI who underwent a debridement, antibiotics and implant retention (DAIR) procedure [odds ratio = 2.49, 95% confidence interval (CI) 1.93-3.23]. Including the two RCTs only, adding rifampicin to the antibiotic regimen after DAIR was also in favour of rifampicin, but this was not statistically significant (risk ratio = 1.27, 95% CI 0.79-2.04; n = 126). Pooling data for patients with staphylococcal PJI who underwent a two-stage procedure showed that adding rifampicin was not associated with therapeutic success. Limited evidence was found for the use of rifampicin for PVE caused by staphylococci.
CONCLUSIONS
Adding rifampicin in the treatment of staphylococcal PJI treated by DAIR clearly increased the likelihood for therapeutic success. The clinical benefit of adjunctive rifampicin in the treatment of other staphylococci and streptococci implant-associated infections is still unclear.
Topics: Humans; Anti-Bacterial Agents; Arthritis, Infectious; Debridement; Prosthesis-Related Infections; Retrospective Studies; Rifampin; Staphylococcus; Streptococcus; Treatment Outcome
PubMed: 37875179
DOI: 10.1016/j.ijantimicag.2023.107015 -
International Journal of Infectious... Jun 2020Effective methods for diagnosing urogenital tuberculosis (UGTB) are important for its clinical management. Therefore, we undertook a systematic review to assess the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Effective methods for diagnosing urogenital tuberculosis (UGTB) are important for its clinical management. Therefore, we undertook a systematic review to assess the performance of the urine-based Xpert MTB/RIF assay for UGTB.
METHODS
PubMed, Embase, Web of Science, the Cochrane library, and Scopus were systematically searched up to July 30, 2019. A hierarchical summary receiver operating characteristic (HSROC) was applied to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and odds ratio (OR) for the diagnostic accuracy of the Xpert test.
RESULTS
Our search identified 858 unique articles from which 69 studies were selected for full-text revision, with 12 studies meeting the inclusion criteria. Eleven studies comprising 1202 samples compared Xpert with mycobacterial culture, while 924 samples from eight studies compared it with a composite reference standard (CRS). The values for pooled sensitivity, specificity, PLR, NLR, and OR were 0.89, 0.95, 20.1, 0.18, and 159.53, respectively, when compared with the mycobacterial culture. Likewise, when compared with a CRS, the respective pooled sensitivity, specificity, PLR, NLR, and OR values were 0.55, 0.99, 40.67, 0.43, and 166.17, thereby suggesting a high level of accuracy for diagnosing UGTB. A meta-regression and sub-group analysis of TB-burden countries, study design, decontamination, concentration, and reference standard could not explain the heterogeneity (p > 0.05) in the diagnostic efficiency.
CONCLUSIONS
Our results suggested that Xpert is a promising diagnostic tool for the diagnosis of UGTB via urine specimen.
Topics: Drug Resistance, Bacterial; Humans; Likelihood Functions; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Odds Ratio; ROC Curve; Rifampin; Sensitivity and Specificity; Tuberculosis, Urogenital; Urine
PubMed: 32194240
DOI: 10.1016/j.ijid.2020.03.023