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PloS One 2023The poor practice of tuberculosis infection control may increase the risk of transmission of tuberculosis in healthcare settings. Thus, this study aimed to determine the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The poor practice of tuberculosis infection control may increase the risk of transmission of tuberculosis in healthcare settings. Thus, this study aimed to determine the pooled magnitude of good tuberculosis infection control practice and associated factors among healthcare workers in Ethiopia.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guideline was followed for this review and meta-analysis. The electronic databases (Pub Med, Cochrane Library, Google scholar and grey literatures) were searched to retrieve articles by using keywords. The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument was used to assess the quality of studies. Heterogeneity was assessed using the I2 statistic. The meta-analysis with a 95% confidence interval using STATA 17 software was computed to present the pooled practice and odds ratio of the determinant factors. Publication bias was assessed visually by inspecting the funnel plot asymmetry and using statistical tests using the eggers and begs test.
RESULTS
Seven studies were included in this meta-analysis, with a total of 3256 health workers. The overall pooled magnitude of good tuberculosis infection control practice was 46.44% (95% CI: 34.21%, 58.67%). In subgroup analysis, the highest practice was in Addis Ababa 51.40% (95% CI: 47.40, 55.40%) and the lowest prevalence of tuberculosis infection control practice was in Amhara region 40.24% (95% CI: 15.46, 65.02%). Working in TB clinics (AOR; 7.42, 95% CI: 3.89, 14.13) and good TB related knowledge (AOR; 4.40, 95% CI: 1.76, 10.97) were the significant predictors of good TB infection control practice.
CONCLUSIONS
Only less than half of the health care workers had good practice of TB infection control. Working in TB clinics and having good TB related knowledge were statistically significant predictors of TB infection control practice. Periodic shifting of health care workers to work in TB clinics and an emphasis on TB infection control related skill based training was recommended to increase the TB infection control practice.
Topics: Humans; Ethiopia; Tuberculosis; Infection Control; Latent Tuberculosis; Health Personnel; Prevalence
PubMed: 38085729
DOI: 10.1371/journal.pone.0295555 -
Journal of Foot and Ankle Research Nov 2023Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy and its risk factors are scant impeding the development of targeted interventions to prevent and promote healing of ulcers. The aim of this review is to generate evidence on the prevalence of plantar ulcer and its risk factors in leprosy.
METHODS
Databases (Medline, Embase, Web of Science, CINAHL, BVS), conference abstracts and reference lists were searched for eligible studies. Studies were included that reported a point prevalence of plantar ulcer and/or its "risk factors" associated with development of ulcers (either causatively or predictively), including individual level, disease related and bio-mechanical factors. We followed PRISMA guidelines for this review. Random-effects meta-analysis was undertaken to estimate the pooled point prevalence of ulcers. Reported risk factors in included studies were narratively synthesised. This review is registered in PROSPERO: CRD42022316726.
RESULTS
Overall, 15 studies (8 for prevalence of ulcer and 7 for risk factors) met the inclusion criteria. The pooled point prevalence of ulcer was 34% (95% CIs: 21%, 46%) and 7% (95% CIs: 4%, 11%) among those with foot anaesthesia and among all people affected by leprosy, respectively. Risk factors for developing ulcers included: unable to feel 10 g of monofilament on sensory testing, pronated/hyper-pronated foot, foot with peak plantar pressure, foot with severe deformities, and those with lower education and the unemployed.
CONCLUSIONS
The prevalence of plantar ulceration in leprosy is as high as 34% among those with loss of sensation in the feet. However, the incidence and recurrence rates of ulceration are least reported. The inability to feel 10 g of monofilament appears to be a strong predictor of those at risk of developing ulcers. However, there is a paucity of evidence on identifying those at risk of developing plantar ulcers in leprosy. Prospective studies are needed to estimate the incidence of ulcers. Identifying individuals at risk of ulcers will help design targeted interventions to minimize risk factors, prevent ulcers and promote ulcer healing.
Topics: Humans; Foot Ulcer; Ulcer; Prevalence; Risk Factors; Leprosy
PubMed: 37953361
DOI: 10.1186/s13047-023-00674-4 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
Journal of Global Antimicrobial... Sep 2023The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline... (Meta-Analysis)
Meta-Analysis Review
Evaluation of genetic mutations associated with phenotypic resistance to fluoroquinolones, bedaquiline, and linezolid in clinical Mycobacterium tuberculosis: A systematic review and meta-analysis.
OBJECTIVES
The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs.
METHODS
We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association.
RESULTS
A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes.
CONCLUSION
The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.
Topics: Humans; Mycobacterium tuberculosis; Linezolid; Fluoroquinolones; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Levofloxacin; Phenotype
PubMed: 37172764
DOI: 10.1016/j.jgar.2023.05.001 -
Frontiers in Public Health 2023This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM).
METHODS
A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics.
RESULTS
A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity ( = 73.82, < 0.01; = 86.45, 95%CI: 79.64-93.27) and specificity ( = 95.34, < 0.01; = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all < 0.05).
CONCLUSION
Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.
Topics: Humans; Tuberculosis, Meningeal; Prospective Studies; Retrospective Studies; Lipopolysaccharides
PubMed: 37808998
DOI: 10.3389/fpubh.2023.1228134 -
The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
Scientific Reports Dec 2023Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer... (Meta-Analysis)
Meta-Analysis
Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13-89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.
Topics: Humans; Financial Stress; Tuberculosis, Multidrug-Resistant; Health Care Costs; Health Expenditures; Cost of Illness
PubMed: 38102144
DOI: 10.1038/s41598-023-47094-9 -
Clinical Microbiology and Infection :... Nov 2023Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI).
OBJECTIVES
To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI.
DATA SOURCES
PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023.
STUDY ELIGIBILITY CRITERIA
Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening.
PARTICIPANTS
Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON).
REFERENCE STANDARD
None.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale.
METHODS OF DATA SYNTHESIS
Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA.
RESULTS
Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I = 0%) and 2.94 (95% CI, 1.78-4.85; I = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I = 13%) and 2.67 (95% CI, 1.24-5.79; I = 23%), respectively.
DISCUSSION
Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.
Topics: Humans; Immunocompromised Host; Interferon-gamma Release Tests; Disease Progression; Latent Tuberculosis; Tuberculosis; Mass Screening
PubMed: 37422080
DOI: 10.1016/j.cmi.2023.07.003 -
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 -
PloS One 2023To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB.
METHODS
Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis.
RESULTS
Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome.
CONCLUSION
Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.
Topics: Humans; Isoniazid; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Treatment Outcome
PubMed: 37467275
DOI: 10.1371/journal.pone.0286194