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Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease.Objectives: We investigated biosignatures with predictive ability for incident TB.Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated.Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-α variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events.Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Background: The worldwide prevalence of paternal perinatal anxiety (PPA) ranges between 3.4% and 25.0% antenatally, and 2.4% and 51.0% postnatally. Experiencing PPA can adversely impact the individual, partners, and infants. Research concerning PPA is lagging and fragmented compared to research for new mothers. Objectives: To establish the effectiveness of prevention or treatment interventions for PPA in adults identifying as male. Data sources: We completed searches of Medline, EMBASE, PsycINFO and Web of Science from inception to 2 December 2021, as well as hand searches of references from relevant papers. Search selection and data extraction: Randomised controlled trials delivering prevention or treatment interventions and reporting anxiety outcomes for new/expectant fathers in the perinatal mental health period were included. Our review follows the PRISMA reporting guidelines. One reviewer independently screened 5170 titles/abstracts; second reviewers screened 50%. Two reviewers independently screened full text, extracted data, and conducted risk of bias assessments. Synthesis: Cochrane's collaboration tool 2 was used to assess quality. Primarily results are synthesised narratively, a post-hoc sub-group analysis was completed on four studies using the same outcome measure. Main results: Twelve of the 5170 studies fulfilled the inclusion criteria. Studies used psychoeducational or practical skills interventions. Interventions mostly involved couple-dyads and three studies assessed PPA as a primary outcome. Included interventions were prevention-based; no treatment interventions were found. Father-only interventions consistently reported a significant reduction of PPA. Conclusions: Systematic searching yielded no treatment interventions, highlighting a substantial gap in the evidence base. Within a limited and heterogenous sample, no studies targeted diagnosed PPA. Evidence suggested father-focused interventions may be effective in preventing PPA, regardless of the intervention delivery mode or intervention content. However, consistency between study design and options within the field are lacking compared to interventions available for mothers. [ABSTRACT FROM AUTHOR]