Background We compared six new IGRAs (hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and T-SPOT.TB/T-Cell Select) with WHO-endorsed tests for tuberculosis infection (hereafter reference tests). Methods Data sources (2007/Jan/01-2021/Aug/18): Medline, EMBase, Web of Science, Cochrane Database of Systematic Reviews and manufacturers’ data. Study Selection: Cross-sectional and cohort studies comparing the diagnostic performance of index and reference tests. . Data synthesis: The primary outcomes of interest were the pooled differences in sensitivity and specificity between index and reference tests. The certainty of evidence (CoE) was summarized using the GRADE approach. Results Eighty-seven studies were included (44 evaluated the QFT-Plus, 4 QFT-Plus CLIA, 3 QIAreach, 26 TB-IGRA, 10 TB-Feron [1 assessing the QFT-Plus], and 1 T-SPOT.TB/T-Cell Select). Compared to the QFT-GIT, QFT Plus’s sensitivity was 0.1 percentage points lower (95% CI, -2.8, 2.6; CoE: moderate), and its specificity 0.9 percentage points lower (95% CI, -1.0, -0.9; CoE: moderate). Compared to the QFT-GIT, TB-IGRA’s sensitivity was 3.0 percentage points higher (95% CI, -0.2, 6.2; CoE: very low), and its specificity 2.6 percentage points lower (95% CI, -4.2, -1.0; CoE: low). Agreement between the QFT-Plus CLIA and QIAreach with QFT-Plus was excellent (pooled kappa statistics of 0.86 [95% CI, 0.78, 0.94; CoE: low]; and 0.96 [95% CI, 0.92, 1.00; CoE: low], respectively). The pooled kappa statistic comparing the TB-Feron and the QFT-Plus or QFT-GIT was 0.85 (95% CI, 0.79 to 0.92; CoE: low). Conclusions The QFT-plus and the TB-IGRA have very similar sensitivity and specificity as WHO-approved IGRAs.

Background Tuberculosis preventive therapy (TPT) is a key part of the WHO’s end TB strategy. However, the occurrence of potentially serious adverse events (AE) is a limitation of TPT regimens. We conducted a systemic review and metanalysis 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.

Background Despite progress in tuberculosis (TB) control globally, TB continues to be a leading cause of death from infectious diseases, claiming 1.2 million lives in 2018; 214,000 of these deaths were due to drug resistant strains. Of the estimated 10 million cases globally in 2018, 24% were in Africa, with Nigeria and South Africa making up most of these numbers. Nigeria ranks 6th in the world for TB burden, with an estimated 4.3% multi-drug resistance in new cases. However, the country had one of the lowest case detection rates, estimated at 24% of incident cases in 2018 - well below the WHO STOP TB target of 84%. This rate highlights the need to understand contextual issues influencing tuberculosis management in Nigeria. Our synthesis was aimed at synthesizing qualitative evidence on factors influencing TB care in Nigeria. Methods A three-stage thematic meta-synthesis of qualitative studies was used to identify barriers and facilitators to tuberculosis case finding and treatment in Nigeria. A purposive search of eleven databases was conducted. The date of publication was limited to 2006 to June 2020. We analyzed articles using a three-stage process, resulting in coding, descriptive subthemes and analytical themes. Results Our final synthesis of 10 articles resulted in several categories including community and family involvement, education and knowledge, attitudes and stigma, alternative care options, health system factors (including coverage and human resource), gender, and direct and indirect cost of care. These were grouped into three major themes: individual factors; interpersonal influences; and health system factors. Conclusion Case finding and treatment for TB in Nigeria currently depends more on individual patients presenting voluntarily to the hospital for care, necessitating an understanding of patient behaviors towards TB diagnosis and treatment. Our synthesis has identified several related factors that shape patients’ behavior towards TB management at individual, community and health system levels that can inform future interventions.