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Background Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment. Methods and findings For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design where more than 10 participants were included was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. Conclusions This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. Trial registration Systematic review registration: PROSPERO 85226., Author(s): Claire J. Calderwood 1, James P. Wilson 1, Katherine L. Fielding 1, Rebecca C. Harris 1, Aaron S. Karat 1, Raoul Mansukhani 1, Jane Falconer 2, Malin Bergstrom 1, [...]

Background: India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. Methods: We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected baseline epidemiology to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025–2050 exploring uncertainty in product characteristics (vaccine efficacy, mechanism of effect, infection status required for vaccine efficacy, duration of protection) and implementation (achieved vaccine coverage and ages targeted). We estimated reductions in tuberculosis cases and deaths by each scenario compared to the no-new-vaccine baseline, as well as costs and cost-effectiveness from health-system and societal perspectives. Results: M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. Conclusions: M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially given the unknowns surrounding the mechanism of effect and infection status required for vaccine efficacy. Greater investment in vaccine development and delivery is needed to resolve these unknowns in vaccine product characteristics. [ABSTRACT FROM AUTHOR]

Aims: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE‐FLU trial recently found two electronic behavioural nudging letter strategies – a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 –effective in increasing influenza vaccination in Denmark. The aims of this pre‐specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off‐target effects on guideline‐directed medical therapy (GDMT) use. Methods and results: The nationwide NUDGE‐FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022–2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE‐FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain‐framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain‐framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use. Conclusions: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain‐framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed. Clinical Trial Registration: ClinicalTrials.gov NCT05542004. [ABSTRACT FROM AUTHOR]

Respiratory disease is a leading cause of deaths worldwide, and influenza and pneumococcal infections are major contributors. Certain groups, such as persons ≥ 65 years of age or with chronic [...]

A growing body of literature suggests important gender differences in the leadership of political institutions. It seems clear, for instance, that female legislators, especially legislative leaders, approach their jobs differently than do their male colleagues--and that these differences have an impact on the policy process. The exploration of gender differences in party organizations, however, is underdeveloped. This study, based on a telephone survey of 805 local party leaders, suggests that many hypotheses regarding gender-based differences cannot be supported by the data. Yet, important distinctions emerge. Specifically, women party leaders are much more likely to be found on the West Coast, to be older and more ideological, to oversee smaller budgets, and to have a more 'responsible' outlook than their male counterparts. This last point, that female party leaders are quite concerned about policy matters and the types of candidates party organizations should support, may have broad ramifications for the future of party politics in the United States. doi: 10.1300/J501v28n01_04 [Article copies available for a fee from The Haworth Document Delivery. Service: 1-800-HAWORTH. E-mail address: Website: [c] 2006 by The Haworth Press, Inc. All rights reserved.] KEYWORDS. Political parties--organization, political parties--leadership, political leadership--women, local politics, gender politics

The M72/AS01E tuberculosis vaccine showed 50% (95%CI: 2–74%) efficacy in a phase 2B trial in preventing active pulmonary tuberculosis disease, but potential cost-effectiveness of adolescent immunisation is unknown. We estimated the impact and cost-effectiveness of six scenarios of routine adolescent M72/AS01E-like vaccination in South Africa and India. All scenarios suggested an M72/AS01E-like vaccine would be highly (94–100%) cost-effective in South Africa compared to a cost-effectiveness threshold of $2480/disability-adjusted life-year (DALY) averted. For India, a prevention of disease vaccine, effective irrespective of recipient's M. tuberculosis infection status at time of administration, was also highly likely (92–100%) cost-effective at a threshold of $264/DALY averted; however, a prevention of disease vaccine, effective only if the recipient was already infected, had 0–6% probability of cost-effectiveness. In both settings, vaccinating 50% of 18 year-olds was similarly cost-effective to vaccinating 80% of 15 year-olds, and more cost-effective than vaccinating 80% of 10 year-olds. Vaccine trials should include adolescents to ensure vaccines can be delivered to this efficient-to-target population. The M72/AS01E tuberculosis vaccine has shown 50% efficacy in preventing pulmonary TB disease in infected 18–50 year olds. Here, the authors demonstrate that, in most scenarios modelled, vaccination of adolescents would also be cost effective in two high incidence settings, South Africa and India. [ABSTRACT FROM AUTHOR]