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A qualitative analysis of female sex workers' lived experiences with adherence to Pre-exposure Prophylaxis (PrEP) in Zimbabwe.
Get PDFBACKGROUND: Female sex workers (FSWs) are at an elevated risk of HIV infection with an eight-fold risk of HIV infection. In countries like Zimbabwe, FSWs have an HIV incidence of around 10.2%. With this elevated risk, the World Health Organization has prioritized Female sex workers (FSWS) for PrEP - an HIV prevention option taken as a daily pill during periods of risk but, FSWs continue to experience challenges with daily PrEP adherence due to daily dosing, related side effects, ARV stigma and low risk perception. This article presents the FSWs' lived experiences with PrEP adherence in Zimbabwe. METHODS: We purposively identified twenty FSWs and conducted individual interviews to understand FSW lived experiences with PrEP adherence. We applied Colaizzi's seven steps of phenomenological analysis to develop the themes. FINDINGS: Three main themes emerged, namely positive experiences with PrEP adherence, negative experiences with PrEP adherence and the meaning attached to PrEP adherence. The positive experiences theme had four sub-themes as, overcoming PrEP-related forgetfulness, overcoming mobility-related PrEP disruptions, overcoming COVID-19 pandemic-related PrEP experiences and overcoming PrEP-related side effects. The negative experiences theme had two sub-themes including, enduring GBV and stigma associated with PrEP use and, COVID-19-related disruptions to PrEP adherence. The third emerging them was on the meaning attached to PrEP adherence. This theme had one sub-theme on PrEP adherence as a survival strategy. CONCLUSION: Whilst FSWs reported both positive and negative experiences with PrEP adherence, it is important that FSWs used the meaning they attached to these experiences to take control of their lives and be more determined to use PrEP adherence for survival and protection from HIV. Based on these findings, we recommend close monitoring and support to promote adherence, minimize PrEP discontinuity and promote positive lived experiences with PrEP adherence
Effects of ambient temperature on under-five mortality: a nationwide space-time-stratified case-crossover study in Brazil
Get PDFBACKGROUND: Although climate change poses increasing risks to child health, particularly through temperature extremes, epidemiological evidence on its impact on child mortality is still limited. This study investigated the short-term effects of ambient temperatures (heat and cold) on under-five mortality in Brazil.
METHODS: We conducted a space-time-stratified case-crossover study across 5570 Brazilian municipalities from 2000 to 2019, using data from the Brazilian Mortality Information System and from the Brazilian Daily Weather Gridded Data (BR-DWGD). We estimated relative risks (RRs) and 95 % confidence intervals (CIs) using conditional quasi-Poisson regression models for extreme cold (1st percentile) and extreme heat (99th percentile) relative to the minimum mortality temperature (MMT), accounting for cumulative lag effects with DLNM stratified by region, age (neonatal, post-neonatal, and childhood), and specific causes of deaths.
FINDINGS: 1,061,229 under-five deaths were included, and the temperature-mortality relationship followed a U-shaped pattern. Compared to MMT, mortality risk was 1.95 (95 %CI: 1.66-2.30) times higher after extreme cold and 1.29 (95 %CI: 1.19-1.40) after extreme heat. Cold-related mortality was highest in the South (RR: 2.17, 95 %CI: 1.60-2.94), and heat-related mortality in the Northeast (RR: 2.02, 95 %CI: 1.60-2.94). Age-stratified analyses showed the highest vulnerability to cold in the post-neonatal period (RR: 4.64, 95 %CI: 3.47-6.22), while heat-related mortality increased with age, peaking in children aged 1-4 years (RR:1.85, 95 %CI: 1.49-2.29). Cause-specific analyses showed that both extreme cold and extreme heat were associated with higher mortality from diarrhoea and all infectious diseases, while respiratory mortality was associated only with heat. The associations were particularly strong for diarrhoeal causes.
INTERPRETATION: Extreme temperatures increase under-five mortality in Brazil, with risks varying by region, age, and cause of death. There is an urgent need for targeted interventions to adapt to and mitigate the impact of extreme temperatures on child health
Klebsiella pneumoniae emerging anti-immunology paradigms: from stealth to evasion.
Get PDFKlebsiella pneumoniae (KP) is a global threat to human health due to the isolation of multidrug-resistant strains. Despite advancements in understanding KP's population structure, antibiotic resistance mechanisms, and transmission patterns, a gap remains in how KP evades defenses, allowing the pathogen to flourish in tissues despite an activated immune system. KP infection biology has been shaped by the notion that the pathogen has evolved to shield from defenses more than actively suppress them. This review describes new paradigms of how KP exploits the coevolution with the innate immune system to hijack immune effectors and receptors to ablate signaling pathways and to counteract cell-intrinsic immunity, making apparent that KP can no longer be considered only as a stealth pathogen
Immunogenicity, safety, and efficacy of the vaccine H56:IC31 in reducing the rate of tuberculosis disease recurrence in HIV-negative adults successfully treated for drug-susceptible pulmonary tuberculosis: a double-blind, randomised, placebo-controlled, phase 2b trial
Get PDFBACKGROUND: People with tuberculosis who complete treatment remain at risk of recurrent disease. The vaccine H56:IC31 has been shown to be safe and immunogenic in phase 1 and 2 studies, but whether it can reduce the risk of tuberculosis recurrence is unknown.
METHODS: In a double-blind, randomised, placebo-controlled, phase 2b trial in South Africa (five clinical trial sites) and Tanzania (one clinical trial site), we enrolled participants aged 18-60 years, without HIV, who had completed more than 5 months (22 weeks) of treatment for drug-susceptible pulmonary tuberculosis. During trial screening (≤7 days after starting treatment), two sputum samples were obtained and frozen for later comparison to recurrent isolates by whole-genome sequencing (WGS). Eligible participants were randomly assigned (1:1; block size of four) to receive two intramuscular doses in the deltoid, 56 days apart, of H56:IC31 or placebo. After the first dose of H56:IC31 or placebo, participants were followed up until study day 421 (1 year after the second dose) and checked at each visit for tuberculosis signs and symptoms. If tuberculosis was suspected, two sputum samples were obtained: one sample was tested by automated molecular test (Xpert MTB/RIF Ultra) and sent for liquid culture; and the other sample was stored frozen for later analysis by whole-genome sequencing (WGS). At the last visit (day 421), two sputum samples were obtained from all sputum-productive participants, regardless of symptoms, to detect cases of asymptomatic tuberculosis. The primary endpoint was culture-confirmed recurrent pulmonary tuberculosis (due to relapse with the same strain, reinfection by a different strain, or indeterminate) occuring during the period starting at day 70 (14 days after the second dose) and ending on day 421 (1 year after the second dose). Vaccine efficacy against recurrent tuberculosis was derived from Cox proportional hazards models. Secondary endpoints included vaccine efficacy to prevent tuberculosis relapse or reinfection independently, as differentiated by WGS, and safety and immunogenicity outcomes (H56-specific CD4 T-cell responses and humoral anti-H56 IgG responses). Primary analysis of vaccine efficacy was based on modified intention-to-treat (mITT), in all randomly assigned participants except those with tuberculosis disease recurrence or who withdrew before day 70 (or 14 days after the second dose for those who received both doses). Safety was assessed in all randomly assigned participants who received at least one dose of vaccine or placebo. The trial was registered with ClinicalTrials.gov, NCT03512249, and is complete.
FINDINGS: 831 participants (mean age 34·7 years [SD 11·1]; 229 [28%] female and 602 [72%] male; 549 [66%] Black) were enrolled from Jan 31, 2019, to Jan 20, 2022; 415 participants were randomly assigned to receive H56:IC31 and 416 to receive placebo. Follow-up was completed by March 20, 2023 (mean follow-up duration 410·1 days [SD 82·8]). In the primary mITT analysis, recurrent tuberculosis occurred in 23 of 400 participants in the H56:IC31 group (12 relapses, eight reinfections, and three indeterminate); and in 14 of 406 in the placebo group (six relapses, seven reinfections, and one indeterminate). Vaccine efficacy for prevention of recurrence was -73·8% (95% CI -246·9 to 9·8; p=0·10). Vaccine efficacy for prevention of relapse was -116·1% (-522·2 to 16·3; p=0·11) and for prevention of reinfection was -21·1% (-245·3 to 56·5; p=0·71). 2 weeks after the planned second dose, H56:IC31 had significantly increased the frequencies of H56-specific CD4 T cells expressing interferon-γ, tumour necrosis factor, interleukin (IL)-2, or IL-17 in vaccinees (median percentage of CD4 T cells, 0·35% [IQR 0·19 to 0·57]) compared with placebo (0·11% [0·09 to 0·23]; p<0·0001). H56-specific IgG responses were significantly higher in H56:IC31 recipients (median arbitrary units per mL, 6·84 [IQR 1·64 to 32·8]) than in placebo recipients (1·94 [1·05 to 3·86]; p<0·0001). A greater proportion of H56:IC31 recipients had mild-to-moderate injection site reactions than placebo recipients (165 [40%] of 415 vs 78 [19%] of 416). No treatment-related serious adverse events were reported. Two participants who received H56:IC31 and six who received placebo died.
INTERPRETATION: Vaccination with H56:IC31 at treatment completion for pulmonary tuberculosis did not reduce the risk of recurrent disease. H56:IC31 was well tolerated and immunogenic but might have increased the risk of relapses by endogenous strains.
FUNDING: The European and Developing Countries Clinical Trials Partnership (EDCTP2) supported by the EU (grant number RIA2016V-1631, POR TB consortium). Additional funding to support completion of the trial was provided by the Statens Serum Institut, Aurum Institute, and the South African Tuberculosis Vaccine Initiative
The delivery of new tuberculosis vaccines to people living with HIV - when to vaccinate?
Get PDFBACKGROUND: Tuberculosis (TB) remains a major cause of morbidity and mortality in people living with HIV (PLHIV). New TB vaccines may help reduce this burden. There is limited data on the response to new TB vaccines in PLHIV and how this may vary with levels of immunosuppression and anti-retroviral therapy (ART). The potential interaction between vaccine efficacy and ART raises questions about the optimum timing of vaccination against TB in PLHIV. METHODS: Using a simple cumulative risk model, we compared the impact of different TB vaccination strategies for PLHIV. We compared the impact of vaccinating at linkage to HIV care, to the impact of vaccinating at ART initiation. We explored how the optimum timing of vaccination depends on characteristics of the vaccine and the ART program at an individual and population level. RESULTS: For an individual, the optimum timing of vaccination against TB is at ART initiation unless the time to ART initiation is more than 6 months or if the reduction in vaccine efficacy when given prior to ART is small. At a population level, the proportion of PLHIV who initiate ART is a key determinate of the optimum strategy. If ART uptake is low, it would be better to vaccinate at linkage to HIV care, even if vaccine efficacy in ART naïve individuals is less than 50% of efficacy in individuals on ART. CONCLUSIONS: Our results suggest that the optimum timing of new TB vaccination for PLHIV will depend on the relative efficacy of vaccination in ART-naïve individuals vs. individuals on ART, and the uptake and timing of ART initiation. If vaccine efficacy is lower among ART-naïve individuals, improvements in HIV programs may help maximize the impact of new TB vaccines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-025-11249-y
A genome-wide One Health study of Klebsiella pneumoniae in Norway reveals overlapping populations but few recent transmission events across reservoirs.
Get PDFBACKGROUND: Members of the Klebsiella pneumoniae species complex (KpSC) are opportunistic pathogens that cause severe and difficult-to-treat infections. KpSC are common in non-human niches, but the clinical relevance of these populations is disputed. METHODS: In this study, we analysed 3255 whole-genome sequenced isolates from human, animal and marine sources collected in Norway between 2001 and 2020. We used population genomics in a One Health context to assess the diversity of strains, genes and other clinically relevant genetic features within and between sources. We further explored niche-enriched traits using genome-wide association studies and investigated evidence of spillover and connectivity across the KpSC populations from the three niches. RESULTS: We found that the KpSC populations in different niches were distinct but overlapping. Overall, there was high genetic diversity both between and within sources, with nearly half (49%) of the genes in the accessory genome overlapping the ecological niches. Further, several sublineages (SLs) including SL17, SL35, SL37, SL45, SL107 and SL3010 were common across sources. There were few niche-enriched traits, except for aerobactin-encoding plasmids and the bacteriocin colicin a, which were associated with KpSC from animal sources. Human infection isolates showed the greatest connectivity with each other, followed by isolates from human carriage, pigs, and bivalves. Nearly 5% of human infection isolates had close relatives (≤22 substitutions) amongst animal and marine isolates, despite temporally and geographically distant sampling of these sources. There were limited but notable recent spillover events, including the movement of plasmids encoding the virulence locus iuc3 between pigs and humans. CONCLUSIONS: Our large One Health genomic study highlights that human-to-human transmission of KpSC is more common than transmission between ecological niches. Still, spillover of clinically relevant strains and genetic features between human and non-human sources does occur and should not be overlooked. Infection prevention measures are essential to limit transmission within human clinical settings and reduce infections. However, preventing transmission that leads to colonisation, e.g. from direct contact with animals or via the food chain, could also play an important role in reducing the KpSC disease burden
Ultra-fast MRI for dementia diagnosis and treatment eligibility: A prospective study.
Get PDFINTRODUCTION: Magnetic resonance imaging (MRI) is crucial for dementia diagnosis and a pre-requisite for amyloid-lowering therapies in Alzheimer's disease. Despite guidelines, many patients never undergo MRI due to limited scanner availability. Shorter scan times would reduce costs and patient burden. We developed and tested a fast MRI protocol incorporating highly accelerated sequences. METHODS: We compared blinded neuroradiologist assessments of a fast protocol with the standard-of-care protocol in a prospective real-world study. We estimated agreement coefficients to evaluate reliability. RESULTS: The fast protocol cut scan times by 63% and showed non-inferior reliability measures for diagnosis, visual scale ratings, and disease-modifying therapy eligibility assessment. Between scan-type, intra-rater reliability for diagnosis was greater than inter-rater reliability on the standard-of-care protocol (ratio of 1.37, 95% confidence interval: 1.21-1.58). DISCUSSION: This study proposed and applied a way of showing non-inferiority of a highly accelerated dementia protocol. Ultra-fast protocols could improve MRI access and patient equity and support the implementation of disease-modifying therapies. HIGHLIGHTS: The fast dementia protocol with four core sequences reduced acquisition time by 63%. The fast scan showed non-inferior reliability for diagnosis and visual ratings. Assessment for disease-modifying therapy eligibility was similar between scan types. Fast protocols may improve access to magnetic resonance imaging and diagnosis in dementia
Understanding associations between sexual identity change and the mental health of lesbian, gay, and bisexual adults in the United Kingdom through longitudinal survey.
Get PDFWhile the existence of poorer mental health among lesbian, gay and bisexual (LGB) populations is well-established, most research does not acknowledge sexual identity shifts when quantifying disparities. This study begins to fill this gap by examining associations between sexual identity change from 2011 to 2023 and current psychological wellbeing and mental health diagnoses self-reported between 2021 and 2023 in the United Kingdom. We utilized a nationally-representative sample of 25,141 respondents aged 16 and older who completed Understanding Society, a longitudinal household survey, in the 2021-2023 wave and responded to the sexual identity question in at least one wave. Using weighted linear and logistic regression, we examined associations between changes in reporting of sexual identity between heterosexual, LGB, and other identities and psychological distress and mental health diagnoses in Wave 13. Sexual identity change was associated (p < .05) with psychological distress and odds of reporting any mental health condition, depression, panic attacks, and anxiety, but not post-traumatic stress disorder. Changes towards LGB identities and consistently identifying as bisexual were significant predictors of poorer mental health across outcomes (increased distress range across groups:1.61-2.58, Adjusted Odds Ratio(AOR) range across items/groups:1.91-4.27). Those who changed from LGB to straight also had higher distress (1.65(95 % CI:0.40-2.91)) and odds of reporting any mental health diagnosis (AOR:1.99(1.34-2.96)) and depression (AOR:2.25(1.48-3.42)) than consistently-heterosexual respondents. Currently LGB-identifying groups, excluding those consistently reporting "other", also had higher odds of reporting any mental health condition (AOR range:1.90-3.71) and depression (AOR range:2.15-3.76). These insights can improve services to reduce mental health disparities among LGB populations
Highlights of the 14th International Bordetella Symposium.
No full textPertussis, or whooping cough, is a highly contagious and acute respiratory illness caused primarily by the gram-negative coccobacillus Bordetella pertussis. Despite near-universal vaccination, pertussis remains one of the least-controlled vaccine-preventable infectious diseases. Since 2023, pertussis incidence has been rising, and widespread pertussis outbreaks have resurged in many countries. In response to these emerging challenges, almost 300 experts from institutions across 24 countries convened at the 14th International Bordetella Symposium in Prague, Czech Republic, from 24 to 28 June 2024 to discuss pertussis epidemiology and research and strategies to mitigate the global pertussis burden. We present here the highlights of the symposium, comprising epidemiological and clinical aspects of Bordetella infections, results of clinical trials of pertussis vaccination in pregnant women and effectiveness of maternal vaccination in protecting newborn infants in Africa and Europe, the controlled human infection model (CHIM), and the latest insights into the biology, immunology, and pathogenesis of B. pertussis infection
A Hypothetical PM2.5 Intervention for the Risk of Hospitalization for Cardiovascular Diseases
Get PDFIMPORTANCE: There is limited direct evidence of the effects of policies regarding ambient particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) on the risk of hospitalization for cardiovascular diseases (CVD). This evidence is essential for estimating the benefits of meeting specific PM2.5 standards in the regulatory impact analysis.
OBJECTIVE: To estimate the association of strengthening ambient PM2.5 standards with the risk of hospitalization for major CVD outcomes.
DESIGN, SETTING, AND PARTICIPANTS: This population-based study used data from the UK Biobank cohort and followed up the participants from January 1, 2015, to December 31, 2019. All participants were 60 years or older and had no history of hospitalization with a primary diagnosis of a specific CVD at baseline. Data were analyzed from August 1, 2022, to August 25, 2025.
EXPOSURES: Annual mean PM2.5 exposure was assigned based on a 1 × 1-km2 resolution PM2.5 model linked to participants' residential locations.
MAIN OUTCOMES AND MEASURES: The main outcomes were the first hospitalization with a primary diagnosis of stroke, myocardial infarction, heart failure, or arrhythmia. Longitudinal targeted maximum likelihood estimation was used to estimate 5-year hospitalization risks under hypothetical PM2.5 interventions. RESULTS: Among the 502 133 UK Biobank participants recruited from 2006 to 2010 (273 158 [54.4%] female), 307 202 participants met the eligibility criteria for stroke, 304 212 for myocardial infarction, 310 100 for heart failure, and 302 255 for arrhythmia. The median age was 68.0 (IQR, 64.6-71.5) years for stroke, myocardial infarction, and arrhythmia, 68.0 (IQR, 64.7-71.5) years for heart failure, with female participants ranging from 54.4% to 55.0% across cohorts. Compared with no intervention on PM2.5, implementing a stricter ambient PM2.5 standard would reduce the absolute risk of hospitalization for major CVD. It was estimated that for the hypothetical PM2.5 intervention of reducing PM2.5 exposure by 5% if it is above the threshold of 9 µg/m3, the estimated 5-year risk difference of hospitalization for stroke was -2.26 per mille (95% CI, -8.97 to -20.64 per mille); for myocardial infarction, -8.64 per mille (95% CI, -9.16 to -6.38 per mille); for heart failure, -3.20 per mille (95% CI, -4.16 to -1.25 per mille); and for arrythmia, -4.16 per mille (95% CI, -12.70 to 12.93 per mille). For the hypothetical PM2.5 intervention of reducing PM2.5 exposure by 5% if it is above the threshold of 12 µg/m3, the estimated 5-year risk difference of hospitalization for stroke was -1.54 per mille (95% CI, -2.21 to 0.73 per mille). However, the reduction in risk for arrhythmia was not statistically significant (-2.06 per mille [95% CI, -4.79 to 3.12 per mille]).
CONCLUSIONS AND RELEVANCE: In this cohort study using data from the UK Biobank, the absolute risk reduction of hospitalization for stroke, myocardial infarction, heart failure, and arrhythmia due to hypothetical ambient PM2.5 interventions was quantified. The findings suggest the beneficial cardiovascular health impacts of further strengthening the current PM2.5 regulations in the United Kingdom