A Systematic Review and Meta-Analysis of Tuberculous Preventative Therapy Adverse Events.

BACKGROUND: Tuberculosis preventative therapy (TPT) is a key part of the World Health Organization's (WHO) end tuberculosis (TB) strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and meta-analysis to estimate the incidence of AE and hepatotoxicity with various TPT regimens to help inform clinical decision making. METHODS: We searched MEDLINE, Cochrane, Health Star, and EMBASE from 1952 to April 2021 for studies reporting AE associated with TPT. Included studies reported AE stratified by regimen and provided the number of participants receiving each regimen. We used a random-effect model to meta-analyze the cumulative incidence of AE. RESULTS: We included 175 publications describing TPT-related AE in 277 cohorts. Among adults, the incidence of any AE, and hepatotoxicity leading to drug discontinuation was 3.7% and 1.1%, respectively, compared to 0.4% and 0.02%, respectively, in children. The highest incidence of any AE, and AE leading to drug discontinuation was with 3 months isoniazid and rifapentine (3HP), and the lowest was with 4 months rifampin (4R). 4R also had the lowest incidence of hepato-toxic AE and drug discontinuation due to hepato-toxic AE. 3HP also had a low incidence of hepato-toxic AE. CONCLUSIONS: Although our study was limited by variability in methods and quality of AE reporting in the studies reviewed, pediatric populations had a very low incidence of AE with all TPT regimens reviewed. In adults, compared to mono-H regimens all rifamycin-based regimens were safer, although 4R had the lowest incidence of TPT-related AE of all types and of hepatotoxicity.

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset. RESULTS: 5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%). CONCLUSION: Higher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests. STUDY REGISTRATION: PROSPERO CRD42020179452.

Active and latent tuberculosis in refugees and asylum seekers: a systematic review and meta-analysis.

BACKGROUND: In 2018, there were 70.8 million refugees, asylum seekers and persons displaced by wars and conflicts worldwide. Many of these individuals face a high risk for tuberculosis in their country of origin, which may be accentuated by adverse conditions endured during their journey. We summarised the prevalence of active and latent tuberculosis infection in refugees and asylum seekers through a systematic literature review and meta-analyses by country of origin and host continent. METHODS: Articles published in Medline, EMBASE, Web of Science and LILACS from January 2000 to August 2017 were searched for, without language restriction. Two independent authors performed the study selection, data extraction and quality assessment. Random effect models were used to estimate average measures of active and latent tuberculosis prevalence. Sub-group meta-analyses were performed according to country of origin and host continent. RESULTS: Sixty-seven out of 767 identified articles were included, of which 16 entered the meta-analyses. Average prevalence of active and latent tuberculosis was 1331 per 100 thousand inhabitants [95% confidence interval (CI) = 542-2384] and 37% (95% CI = 23-52%), respectively, both with high level of heterogeneity (variation in estimative attributable to heterogeneity [I2] = 98.2 and 99.8%). Prevalence varied more according to countries of origin than host continent. Ninety-one per cent of studies reported routine screening of recently arrived immigrants in the host country; two-thirds confirmed tuberculosis bacteriologically. Many studies failed to provide relevant information. CONCLUSION: Tuberculosis is a major health problem among refugees and asylum seekers and should be given special attention in any host continent. To protect this vulnerable population, ensuring access to healthcare for early detection for prevention and treatment of the disease is essential.

The mTST - An mHealth approach for training and quality assurance of tuberculin skin test administration and reading.

BACKGROUND: The Tuberculin Skin Test (TST) is a relatively simple test for detecting latent tuberculosis infection (LTBI) but requires regular quality assurance to ensure proper technique for administration and reading. The objective of this study was to estimate the accuracy and reproducibility of an mhealth approach (the mTST) to measure the size of swelling immediately following TST administration (TST injection bleb) and after 48-72 hours (TST induration). METHODS: Five non-clinical and one clinical reviewer measured the size of TST injection blebs, and TST indurations using smartphone acquired photos of sites of TST administration and readings in patients, or saline injections in volunteers. The reference standard was the onsite measurement (measured by an experienced TB nurse) of the actual TST injection bleb, or induration. Agreement of reviewers' measurements with the reference standard, as well as agreement within and between reviewers, was estimated using Cohen's kappa coefficient. RESULTS: Using the mTST method to assess bleb size in 64 photos of different TST injections, agreement between reviewers, and the reference standard was very good to excellent (κ ranged from 0.75 to 0.87), and within-reviewer reproducibility of readings was excellent (κ ranged from 0.86 to 0.96). Using the mTST method to assess TST induration in 72 photos, reviewers were able to detect no induration (<5mm) and induration of 15mm or greater with accuracy of 95% and 92% respectively, but accuracy was only 20% and 77% for reactions of 5-9mm and 10-14mm respectively. CONCLUSION: The mTST approach appears to be a reliable tool to assess TST administration. The mTST approach was accurate to read indurations of 0-4mm or 15+mm, but less accurate for reactions of 5-14mm. We believe the mTST approach could be useful for training and quality assurance in locations where on-site supervision is not possible.