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Assessment of health risks from exposure to indoor volatile organic compounds in European educational buildings.
Get PDFVolatile organic compounds (VOCs) comprise an important group of indoor air pollutants, commonly found in building materials and consumer products. Due to their low boiling points, VOCs are prevalent in indoor environments, with concentrations in homes, schools, and offices often two to five times higher than outdoors. Chronic exposure to VOCs is linked to a range of adverse health outcomes, including respiratory, neurological, cardiovascular damage, and an increased cancer risk. Children and adolescents who spend a significant amount of time in educational buildings are particularly vulnerable to these effects. Therefore, this study aimed to estimate the related health risks to those in day care centres, schools, high-schools and universities across 17 member states of the European Union (EU) by utilizing a previously published dataset and collecting data on levels of 9 VOCs. Health risks were assessed using the World Health Organization's Indoor Air Quality Risk Calculator. Point of departure indices (PODIs) and cancer risks were calculated, with values above 1.0 and 10 cases/1 million population respectively indicating an increased health risk. Our results showed that formaldehyde exposure poses an increased risk of respiratory, neurological and carcinogenic effects in educational buildings in 14 of the countries studied. Additionally, neurological risks from exposure to benzene were above the limit in 4 EU countries. These findings indicate the need to reduce formaldehyde and benzene concentrations in European educational buildings to protect the health of the next generation
Characterising progression and regression patterns across the spectrum of tuberculosis: a multistate modelling approach.
Get PDFBACKGROUND: The conceptualisation of tuberculosis has undergone a paradigm shift from binary states to a spectrum, resulting in the International Consensus for Early TB (ICE-TB) framework. This study aimed to use data from a prospective, observational cohort study and multistate modelling to address the lack of contemporary data to quantify movement between ICE-TB states.
METHODS: ERASE-TB was a prospective, observational cohort study evaluating novel diagnostic tests for earlier detection of tuberculosis. Household contacts aged at least 10 years in Zimbabwe, Tanzania, and Mozambique were followed up 6-monthly for 12-24 months with comprehensive tuberculosis investigations at each visit. Those not diagnosed with prevalent tuberculosis, with state classification from at least two timepoints were included. ICE-TB states were defined by use of symptomatology, interferon gamma release assays, chest radiographs, and sputum microbiology. A Markov multistate model based on ICE-TB was applied with one initial state (Mycobacterium tuberculosis non-infection), two intermediate states (M tuberculosis infection and non-infectious disease [asymptomatic-symptomatic]), and one absorbing state (infectious disease [asymptomatic-symptomatic]). Transition probabilities were predicted.
FINDINGS: 1789 (84·8%) of 2109 recruited household contacts were included. At enrolment, most (1000 [55·9%]) did not have M tuberculosis infection; 674 (37·7%) had M tuberculosis infection, and 115 (6·5%) had non-infectious disease. 34 people developed infectious disease (23 asymptomatic, 11 symptomatic). In the multistate model, the transition probabilities of progressing from M tuberculosis non-infection to M tuberculosis infection and M tuberculosis infection to non-infectious disease were 13% and 3% by month 12. For those in non-infectious disease, the probabilities of regression and progression by month 12 were 85% and 13%, respectively.
INTERPRETATION: This study applied the ICE-TB framework to describe movement between states by use of contemporary, granular, longitudinal data. Although most people remained static over time, the non-infectious state was more dynamic, with most people regressing over time.
FUNDING: European and Developing Countries Clinical Trials Partnership
Whole genome sequencing to inform the epidemiology of Plasmodium falciparum malaria in the elimination setting of Malaysia.
Get PDFBackground: Imported malaria cases, driven by human migration and travel, pose a significant challenge to malaria elimination efforts. Genomic approaches have become essential for distinguishing between local transmission and imported infections. The state of Sarawak, Malaysia, provides a pertinent example of a malaria-eliminating setting under pressure from Plasmodium parasite importation.
Results: In this study, we analysed 21 Plasmodium falciparum isolates obtained from archived whole blood samples collected between 2008 and 2010 and compared them to 9,518 publicly available isolates from Central Africa (518), East Africa (849), Horn of Africa (25), Oceania (349), South America (75), South Asia (404) Southeast Asia (5,182) and West Africa (2,116). By applying nanopore sequencing and population genomic analyses, we found that most of the cases (n = 13/15) likely originated from endemic regions outside Malaysia, supported by patient travel histories and high multiplicity of infection levels. These findings and drug resistance profiles are consistent with the historical epidemiology of the suspected source regions. Notably, two cases showed genomic evidence of origins inconsistent with the patients’ reported travel histories, underscoring the limitations of traditional epidemiological methods. Identity-by-descent analysis revealed clustering in only two cases, indicating that the majority of infections were likely isolated introductions rather than evidence of sustained local transmission.
Conclusion: Overall, our results highlight the power of malaria genomics in discerning imported from locally acquired cases and emphasise its critical role in maintaining malaria elimination, particularly in regions situated along major migration and labour exchange corridors
Efficacy of ETVAX, a vaccine against enterotoxigenic Escherichia coli-positive diarrhoea in Gambian children: a double-blind, randomised, placebo-controlled, phase 2b trial.
Get PDFBACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes 75 million diarrhoea episodes with up to 42 000 deaths annually in children. To prevent ETEC in children, we aimed to evaluate the safety, immunogenicity, and efficacy of ETVAX, an oral, inactivated, whole-cell ETEC vaccine with toxoid and double-mutant heat-labile toxin adjuvant.
METHODS: In this phase 2b, double-blind, placebo-controlled trial, Gambian children aged 6-18 months were recruited from four enrolment centres and block-randomised (1:1) via a computer-generated sequence, stratified by enrolment centres, to receive ETVAX or placebo on days 1, 15, and 90. Parents, staff, investigators assessing outcomes, and investigators analysing the data were masked to group assignment. An immunogenicity subset was assessed for serum antibody responses to ETEC colonisation factors and heat-labile toxin. The primary safety endpoint was serious adverse events, assessed in all children who received at least one intervention dose. The primary efficacy endpoint was vaccine efficacy against moderate-to-severe ETEC-positive diarrhoea (MSD-ETEC), excluding co-infections with Cryptosporidium spp, norovirus genogroup II, rotavirus, or Shigella spp, assessed in the per-protocol population. Secondary endpoints included vaccine efficacy against MSD-ETEC regardless of copathogens and against moderate-to-severe diarrhoea (MSD) regardless of cause. Exploratory vaccine efficacy analyses were against MSD-ETEC excluding only enteroparasitic copathogens (Giardia lamblia and Cryptosporidium) and against MSD-ETEC regardless of copathogens when first dose was given before age 9 months. This trial was registered with the Pan African Clinical Trials Registry (PACTR20201081921856).
FINDINGS: Between Feb 22, 2021, and June 24, 2022, 5253 children were screened and 4936 (2499 [51%] girls, 2437 [49%] boys) were randomly assigned (2468 to ETVAX, 2468 to placebo). Serious adverse events occurred in 24 (1·0%) of 2474 in the vaccine group and 32 (1·3%) of 2462 in the placebo group, with none related to the investigational product. Immunogenicity was assessed in 122 children. ETVAX increased antibodies to colonisation factors (CFA/I, CS3) and heat-labile toxins. Vaccine efficacy was 26·6% (95% CI -58·3 to 66·0; p=0·43) for the primary endpoint, 48·2% (p=0·053) against MSD-ETEC regardless of copathogens, and 80·6% (p=0·0092) when excluding enteroparasitic copathogens. Vaccine efficacy against all MSD-ETEC reached 67·8% (p=0·026) when dosing started before age 9 months. Vaccine efficacy against MSD regardless of cause was 21·4% (p=0·032).
INTERPRETATION: ETVAX was safe and immunogenic. Although the primary endpoint was not met, the secondary and exploratory findings suggest ETVAX protects Gambian children against ETEC-positive MSD particularly when administered before age 9 months and when children were not co-infected with enteroparasites. ETVAX also showed a reduction in all-cause MSD. These results support advancing ETVAX to a pivotal phase 3 trial.
FUNDING: European & Developing Countries Clinical Trials Partnership
Association Between Antibiotic Use for Nongastrointestinal Infections and Inflammatory Bowel Disease Flare-Ups: A Self-Controlled Case Series Study.
No full textINTRODUCTION: Disruption of gut microbiota by antibiotic use has been linked to the development of inflammatory bowel disease (IBD). This study aimed to evaluate the association between antibiotic use for nongastrointestinal (GI) infections and the risk of IBD flare-ups, and to examine whether route of administration, antimicrobial spectrum, and antibiotic class modulate this risk.
METHODS: We conducted a self-controlled case series study using territory-wide electronic medical records from Hong Kong. Adults with IBD who experienced at least 1 flare-up and received at least 1 course of antibiotics for infections outside the GI tract between 2000 and 2024 were included, to reduce indication bias related to GI symptoms. Conditional Poisson regression models were used to estimate incidence rate ratios (IRRs) by comparing across predefined risk periods to the baseline period.
RESULTS: Among 810 patients, IBD flare incidence was elevated during the month preceding antibiotics (IRR 2.85), increased further during treatment (IRR 3.44), and peaked within 2 weeks after treatment (IRR 4.79), and returned to baseline levels within 6 months, vs baseline. Increased incidences were observed for oral antibiotics during and 2 weeks after treatment (IRRs 3.91 and 3.70), but not for injectable antibiotics (interaction P values <0.01). The IRRs for broad-spectrum antibiotics were higher than those for narrow-spectrum agents from 1 month before to 6 weeks after antibiotic use, vs baseline.
DISCUSSION: Antibiotic use for non-GI infections was associated with a short-term increase in IBD flare risk. Injectable or narrow-spectrum antibiotics may have a relatively smaller impact on potential IBD flare-ups
Association of disability and 12-year all-cause and cause-specific mortality: analyses from the Wellbeing of Older People cohort study in Uganda.
Get PDFINTRODUCTION: Disability is linked to poor health outcomes and increased mortality, yet evidence on this relationship in sub-Saharan Africa is limited. This study investigated the association between disability and all-cause and cause-specific mortality among older adults in Uganda. METHODS: The analysis was based on longitudinal data from the Wellbeing of Older People Study, an open cohort of individuals aged at least 50 years and followed over five data collection waves from 2009 to 2022. Disability was assessed using the WHO Disability Assessment Schedule 2.0. Mortality data were collected, supplemented by verbal autopsies. Gompertz regression models examined the association between disability severity and mortality, adjusting for sociodemographic, socioeconomic, health access and health risk factors. RESULTS: Among 938 participants followed up for a median of 8.0 years (interquartile range (IQR): 3.2-11.5), 153 deaths were recorded (mortality rate: 2.4 per 100 person-years). The age-sex-adjusted analyses showed that the hazard ratio (HR) was 3.88-fold higher (95% confidence interval (CI) 2.50 to 6.02; p value <0.001) among people with severe disability compared with none/mild disability. Adjusting for sociodemographic, economic, social support and health factors (health status, access and risk factors) somewhat attenuated the association (adjusted HR (aHR) 3.08, 95% CI 1.92 to 4.93; p value <0.001). This excess risk persisted across broadly categorised causes of death: HIV (aHR 8.96, 95% CI 2.52 to 31.83), communicable diseases excluding HIV (aHR 2.24, 95% CI 0.80 to 6.25), non-communicable diseases (aHR 2.29, 95% CI: 1.20 to 4.37) and indeterminate causes of death (aHR 6.89, 95% CI 1.63 to 29.1). Additionally, disability was associated with sociodemographic disadvantages, poor healthcare access and higher prevalence of health risk factors. CONCLUSIONS: Severe disability was strongly associated with elevated mortality risk among older Ugandans, underscoring the need for targeted interventions to improve health equity. Reducing mortality disparities might require addressing barriers to healthcare access, stronger social support and integrating disability-inclusive policies in achieving global health targets, including Universal Health Coverage
The benefits and risks of maternal RSV vaccination on mortality in South Africa: A modeling study.
Get PDFBACKGROUND: Maternal respiratory syncytial virus (RSV) vaccine, RSV prefusion F protein vaccine (RSVpreF (Abrysvo)), was found to be safe and efficacious in the MATISSE trial. However, post-hoc stratified analyses identified an excess of preterm births in the intervention arm in two upper-middle-income countries, most prominently in South Africa. This study weighs the potential benefits and risks in mortality associated with maternal RSV vaccination in South Africa, assuming the increased risk of preterm births observed in the trial was caused by vaccination. METHODS AND FINDINGS: We compared the estimated RSV-associated infant deaths averted by vaccination (benefits) and neonatal mortality potentially associated with vaccine-associated risk in preterm birth (risks) in South Africa. The benefit model estimated the South African RSV disease burden in 2011-2016 and waning vaccine protection during infancy. The risk model estimated excess neonatal mortality using gestational age (GA)-specific mortality data from the Drakenstein Child Health Study and the GA-specific birth distribution in South Africa in the MATISSE trial, but did not incorporate the mortality risk found in the MATISSE vaccine trial in which no excess deaths occurred. The benefit model estimated that vaccination would reduce RSV-associated infant deaths by 31 (95% credible interval (Crl): 27, 35) per 100,000 live births born to vaccinated mothers in South Africa. Using the number of infants born to mothers vaccinated at 24-36 GA weeks in the MATISSE trial, if the association in South Africa between vaccination and preterm birth is actually causal, the risk model suggested that neonatal deaths would increase by 44 (95%CrI: -43, 210), totaling 1.4 (95%CrI: -1.4, 6.9) excess neonatal deaths for every infant RSV death prevented. When this was changed to the number of infants born to mothers vaccinated at 27-36 GA weeks in the MATISSE trial, the predicted risks dropped and in 97% of the simulations the benefits outweighed the risks. The outcome was sensitive to the GA window that we used to determine which infants to include in the analysis. The study was limited by only considering mortality associated with RSV disease and preterm birth. CONCLUSIONS: If RSVpreF increases preterm birth risk, and if this increases neonatal mortality, then the benefit-risk analysis failed to show that the direct benefits of vaccination in reducing RSV-associated infant mortality would substantially outweigh the risks of preterm birth-associated neonatal mortality in South Africa with vaccination from 24 GA to 36 GA weeks. There was large uncertainty in the analyses due to small numbers of preterm births. With vaccination from 27 GA weeks, the benefit-risk analysis favored vaccination. RSVpreF vaccination has the potential to be safe and effective when used from the third trimester
The limits of promoting pleasure: Desiring-assemblages and HIV pre-exposure prophylaxis
Get PDFHIV pre-exposure prophylaxis (PrEP) is said to have transformed pleasure and sexual practices in myriad ways. This article draws on interviews with PrEP users in Australia who had paused, stopped, or switched PrEP use in order to explore the varied affects and experiences of PrEP in relation to different dosing strategies. Drawing on the concept of ‘desiring-assemblages’, we considered ‘what can a body with PrEP do?’. Our analysis affirms PrEP as transformative, enabling freedom through reduced or removed fear of HIV transmission. However, participant accounts also suggested that PrEP has been normalised as an ordinary part of sexual cultures, with some indicating that PrEP use was felt as obligatory or ambivalent. Daily and nondaily dosing also potentiated different flows of desire and connections, remaking what PrEP is and can be in participants’ lives in ways that trouble the idea that PrEP consistently facilitates pleasure. PrEP dosing was framed by discussion of changes to one’s sense of self and future priorities, and through ideas about freedom, pleasure, shame, safety, obligation, fitting in, waste, and potential. While PrEP is increasingly promoted through messaging linked to ‘pleasure’, instead of earlier discourses of ‘risk’, a pleasure-centric focus may delimit understandings of how PrEP can produce multiple sexual lives and practices, including the mundane aspects of sex and pleasure. To appeal to a range of potential PrEP users, health promotion should emphasise the different possibilities for PrEP – it’s potential for pleasure, its critical role in preventing HIV, and its normative mundanity
Disentangling Temporal Trends of Clade Ib Monkeypox Virus Transmission in Burundi.
Get PDFUtilizing mpox case data from Burundi between August 2024 and April 2025, we calibrated a mathematical model to quantify the temporal trends of clade Ib monkeypox virus transmission. The model outputs indicated a declining overall transmission trend. Children aged 0-4 and 5-9 years were estimated to be at higher risk of infection compared to older age groups, while sexual contact was inferred to contribute up to 50% of the overall transmission
Towards a shared vision for research on evidence-informed policy-making.
Get PDFThe World Health Organization (WHO) defines knowledge translation as the exchange, synthesis and effective com-
munication of reliable and relevant research results.(1) Also known as research utilization or knowledge mobilization,
knowledge translation is a transdisciplinary process that promotes sustained interaction between researchers and
users, tailoring information so that evidence-informed policy-making interventions are more widely adopted