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OBJECTIVES: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19. DESIGN: Phase III double blind randomised controlled trial. SETTING: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic. PARTICIPANTS: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG. INTERVENTION: Randomised 1:1 using a web-based procedure to receive a single 0.1mL intradermal dose of BCG-Denmark (BCG group, n=1999) or saline (placebo group, n=1989). MAIN OUTCOME MEASURES: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12-months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion). RESULTS: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6% to 24.5%) compared with the placebo group (19.6%; 95%CI 17.6% to 21.5%); adjusted difference +3.0 percentage points (95%CI 0.2% to 5.8%; p=0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95%CI 9.5% to 12.4%) compared with 9.6% in the placebo group (95%CI 8.3% to 11.1%); adjusted difference +1.3 percentage points (95%CI -0.7% to 3.3%, p=0.2). Breakthrough COVID-19 (post COVID-19 vaccination), and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95%CI 0.60 to 4.02, p=0.4) and two deaths due to COVID-19, both in the placebo group. CONCLUSIONS: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among health care workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.
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Humans have long relied on microbial communities to create products, produce energy, and treat waste. The microbiota residing within our bodies directly impacts our health, while the soil and rhizosphere microbiomes influence the productivity of our crops. However, the complexity and diversity of microbial communities make them challenging to study and difficult to develop into applications, as they often exhibit the emergence of unpredictable higher-order phenomena. Synthetic ecology aims at simplifying complexity by constituting synthetic or semi-natural microbial communities with reduced diversity that become easier to study and analyze. This strategy combines methodologies that simplify existing complex systems (top-down approach) or build the system from its constituent components (bottom-up approach). Simplified communities are studied to understand how interactions among populations shape the behavior of the community and to model and predict their response to external stimuli. By harnessing the potential of synthetic microbial communities through a multidisciplinary approach, we can advance knowledge of ecological concepts and address critical public health, agricultural, and environmental issues more effectively.
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Erwinia tracheiphila (Smith) is a recently emerged plant pathogen that causes severe economic losses in cucurbit crops in temperate Eastern North America. E. tracheiphila is xylem restricted, and virulence is thought to be related to Exopolysaccharides (EPS) and biofilm formation, which occlude the passage of sap in xylem vessels and causes systemic wilt. However, the role of EPS and biofilm formation, and their contribution to disease in relation to other virulence loci are unknown. Here, we use deletion mutants to explore the roles of EPS, Hrp Type III secretion system (Hrp T3SS) and Expansin in plant colonization and virulence. Then, we quantify the expression of the genes encoding these factors during infection. Our results show that Exopolysaccharides are essential for E. tracheiphila survival in host plants, while Hrp T3SS and Expansin are dispensable for survival but needed for systemic wilt symptom development. EPS and Hrp T3SS display contrasting expression patterns in the plant, reflecting their relevance in different stages of the infection. Finally, we show that expression of the eps and hrpT3SS operons is downregulated in mildly increased temperatures, suggesting a link between expression of these virulence factors and geographic restriction of E. tracheiphila to temperate regions. Our work highlights how E. tracheiphila virulence is a complex trait where several loci are coordinated during infection. These results further shed light into the relationship between virulence factors and the ecology of this pathosystem, which will be essential for developing sustainable management strategies for this emerging pathogen.
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Nowadays, epidemiological modeling is applied to a wide range of diseases, communicable and non-communicable, namely AIDS, Ebola, influenza, Dengue, Malaria, Zika. More recently, in the context of the last pandemic declared by the World Health Organization (WHO), several studies applied these models to SARS-CoV-2. Despite the increasing number of researches using spatial analysis, some constraints persist that prevent more complex modeling such as capturing local epidemiological dynamics or capturing the real patterns and dynamics. For example, the unavailability of: (i) epidemiological information such as the frequency with which it is made available; (ii) sociodemographic and environmental factors (e.g., population density and population mobility) at a finer scale which influence the evolution patterns of infectious diseases; or (iii) the number of cases information that is also very dependent on the degree of testing performed, often with severe territorial disparities and influenced by context factors. Moreover, the delay in case reporting and the lack of quality control in epidemiological information is responsible for biases in the data that lead to many results obtained being subject to the ecological fallacy, making it difficult to identify causal relationships. Other important methodological limitations are the control of spatiotemporal dependence, management of non-linearity, ergodicy, among others, which can impute inconsistencies to the results. In addition to these issues, social contact, is still difficult to quantify in order to be incorporated into modeling processes. This study aims to explore a modeling framework that can overcome some of these modeling methodological limitations to allow more accurate modeling of epidemiological diseases. Based on Geographic Information Systems (GIS) and spatial analysis, our model is developed to identify group of municipalities where population density (vulnerability) has a stronger relationship with incidence (hazard) and commuting movements (exposure). Specifically, our framework shows how to operate a model over data with no clear trend or seasonal pattern which is suitable for a short-term predicting (i.e., forecasting) of cases based on few determinants. Our tested models provide a good alternative for when explanatory data is few and the time component is not available, once they have shown a good fit and good short-term forecast ability.
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COVID-19 , SARS-CoV-2 , Análisis Espacio-Temporal , Humanos , COVID-19/epidemiología , Modelos Epidemiológicos , PandemiasRESUMEN
The lag phase is key in resuming bacterial growth, but it remains underexplored particularly in environmental bacteria. Here we use transcriptomics and 13C-labelled metabolomics to show that the lag phase of the model marine bacterium Phaeobacter inhibens is shortened by methylated compounds produced by the microalgal partner, Emiliania huxleyi. Methylated compounds are abundantly produced and released by microalgae, and we show that their methyl groups can be collected by bacteria and assimilated through the methionine cycle. Our findings underscore the significance of methyl groups as a limiting factor during the lag phase and highlight the adjustability of this growth phase. In addition, we show that methylated compounds, typical of photosynthetic organisms, prompt diverse reductions in lag times in bacteria associated with algae and plants, potentially favouring early growth in some bacteria. These findings suggest ways to accelerate bacterial growth and underscore the significance of studying bacteria within an environmental context.
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Haptophyta , Microalgas , Haptophyta/metabolismo , Haptophyta/crecimiento & desarrollo , Haptophyta/genética , Microalgas/metabolismo , Microalgas/crecimiento & desarrollo , Microalgas/genética , Metilación , Metabolómica , Bacteroidetes/genética , Bacteroidetes/crecimiento & desarrollo , Bacteroidetes/metabolismo , Metionina/metabolismo , Fotosíntesis , RhodobacteraceaeRESUMEN
Genioplasty is a common procedure in plastic surgery, with various alloplastic biomaterials utilized for chin augmentation. Despite their advantages, complications such as neuropraxia of the mental nerve can occur, leading to temporary or persistent sensory disturbances. This case report describes a 35-year-old female who sought correction of a small chin. Preoperative evaluation revealed a retrognathic profile, and the patient underwent genioplasty with high-density porous polyethylene implantation. Postoperatively, she experienced mild paresthesia, which improved over time. Neurosensory assessments, including mechanical and light touch tests, showed no abnormalities in A-beta and C fibers but decreased sensitivity in A-delta fibers. This case report emphasizes the importance of evaluating larger nerve fibers during postoperative assessments and the need for standardized testing methodologies to comprehensively assess nerve damage after genioplasty. Further research should explore strategies to standardize neurosensory assessment and optimize therapeutic interventions for nerve damage after genioplasty.
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Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.
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Marine ecosystems are influenced by phytoplankton aggregation, which affects processes like marine snow formation and harmful events such as marine mucilage outbreaks. Phytoplankton secrete exopolymers, creating an extracellular matrix (ECM) that promotes particle aggregation. This ECM attracts heterotrophic bacteria, providing a nutrient-rich and protective environment. In terrestrial environments, bacterial colonization near primary producers relies on attachment and the formation of multidimensional structures like biofilms. Bacteria were observed attaching and aggregating within algal-derived exopolymers, but it is unclear if bacteria produce an ECM that contributes to this colonization. This study, using Emiliania huxleyi algae and Phaeobacter inhibens bacteria in an environmentally relevant model system, reveals a shared algal-bacterial ECM scaffold that promotes algal-bacterial aggregation. Algal exudates play a pivotal role in promoting bacterial colonization, stimulating bacterial exopolysaccharide (EPS) production, and facilitating a joint ECM formation. A bacterial biosynthetic pathway responsible for producing a specific EPS contributing to bacterial ECM formation is identified. Genes from this pathway show increased expression in algal-rich environments. These findings highlight the underestimated role of bacteria in aggregate-mediated processes in marine environments, offering insights into algal-bacterial interactions and ECM formation, with implications for understanding and managing natural and perturbed aggregation events.
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Ecosistema , Fitoplancton , Fitoplancton/metabolismo , Fitoplancton/microbiología , Matriz Extracelular , Matriz Extracelular de Sustancias PoliméricasRESUMEN
Diabetes poses a substantial disease burden, prompting preventive interventions. Physical inactivity, a major risk factor for type 2 diabetes, can potentially be mitigated by enhancing area-level walkability. Despite this, limited population-based studies have investigated the link between walkability and objective diabetes measures. Our study aims to estimate the association between area-level walkability and individual glycated haemoglobin levels in the Portuguese adult population without the diagnosis of diabetes. Data from the 2011 census and an updated street map were obtained to construct a walkability index based on residential density, land-use mix, and street connectivity. Individual health data were sourced from The National Health Examination Survey (INSEF) 2015, a representative survey of the Portuguese adult population. Gamma regression was employed for estimation of the main associations, revealing that residing in moderately walkable areas significantly reduced average glycated haemoglobin levels (Exp(ß) = 0.906; 95% CI: 0.821, 0.999) compared to the least walkable areas. The association was less pronounced and not statistically significant for the third tertile of walkability (Exp(ß) = 0.919; 95% CI: 0.822, 1.028). Our findings highlight a nonlinear protective association between walkability and glycated haemoglobin, emphasizing the potential policy implications for urban planning, diabetes prevention, and health promotion.
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Planificación Ambiental , Hemoglobina Glucada , Caminata , Humanos , Portugal/epidemiología , Hemoglobina Glucada/análisis , Masculino , Femenino , Caminata/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Planificación Ambiental/estadística & datos numéricos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Anciano , Características de la Residencia/estadística & datos numéricos , Encuestas Epidemiológicas , Adulto JovenRESUMEN
The bacterial lag phase is a key period for resuming growth. Despite its significance, the lag phase remains underexplored, particularly in environmental bacteria. Here, we explore the lag phase of the model marine bacterium Phaeobacter inhibens when it transitions from starvation to growth with a microalgal partner. Utilizing transcriptomics and 13 C-labeled metabolomics, our study reveals that methylated compounds, which are abundantly produced by microalgae, shorten the bacterial lag phase. Our findings underscore the significance of methyl groups as a limiting factor during the lag phase and demonstrate that methyl groups can be harvested from algal compounds and assimilated through the methionine cycle. Furthermore, we show that methylated compounds, characteristic of photosynthetic organisms, induce variable reductions in lag times among bacteria associated with algae and plants. These findings highlight the adjustability of the bacterial lag phase and emphasize the importance of studying bacteria in an environmental context. One-Sentence Summary: Bacteria use algal compounds as a metabolic shortcut to transition from starvation to growth.
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Various novel platform technologies have been used for the development of COVID-19 vaccines. In this nested cohort study among healthcare workers in Australia and Brazil who received three different COVID-19-specific vaccines, we (a) evaluated the incidence of adverse events following immunization (AEFI); (b) compared AEFI by vaccine type, dose and country; (c) identified factors influencing the incidence of AEFI; and (d) assessed the association between reactogenicity and vaccine anti-spike IgG antibody responses. Of 1302 participants who received homologous 2-dose regimens of ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech) or CoronaVac (Sinovac), 1219 (94%) completed vaccine reaction questionnaires. Following the first vaccine dose, the incidence of any systemic reaction was higher in ChAdOx1-S recipients (374/806, 46%) compared with BNT162b2 (55/151, 36%; p = 0.02) or CoronaVac (26/262, 10%; p < 0.001) recipients. After the second vaccine dose, the incidence of any systemic reaction was higher in BNT162b2 recipients (66/151, 44%) compared with ChAdOx1-S (164/806, 20%; p < 0.001) or CoronaVac (23/262, 9%; p < 0.001) recipients. AEFI risk was higher in younger participants, females, participants in Australia, and varied by vaccine type and dose. Prior COVID-19 did not impact the risk of AEFI. Participants in Australia compared with Brazil reported a higher incidence of any local reaction (170/231, 74% vs 222/726, 31%, p < 0.001) and any systemic reaction (171/231, 74% vs 328/726, 45%, p < 0.001), regardless of vaccine type. Following a primary course of ChAdOx1-S or CoronaVac vaccination, participants who did not report AEFI seroconverted at a similar rate to those who reported local or systemic reactions. In conclusion, we found that the incidence of AEFI was influenced by participant age and COVID-19 vaccine type, and differed between participants in Australia and Brazil.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Vacunas contra la COVID-19/efectos adversos , Vacuna BNT162 , Estudios de Cohortes , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación/efectos adversos , ChAdOx1 nCoV-19RESUMEN
There is growing evidence that comprehensive and harmonized metadata are fundamental for effective public data reusability. However, it is often challenging to extract accurate metadata from public repositories. Of particular concern is the metagenomic data related to African individuals, which often omit important information about the particular features of these populations. As part of a collaborative consortium, H3ABioNet, we created a web portal, namely the African Human Microbiome Portal (AHMP), exclusively dedicated to metadata related to African human microbiome samples. Metadata were collected from various public repositories prior to cleaning, curation and harmonization according to a pre-established guideline and using ontology terms. These metadata sets can be accessed at https://microbiome.h3abionet.org/. This web portal is open access and offers an interactive visualization of 14 889 records from 70 bioprojects associated with 72 peer reviewed research articles. It also offers the ability to download harmonized metadata according to the user's applied filters. The AHMP thereby supports metadata search and retrieve operations, facilitating, thus, access to relevant studies linked to the African Human microbiome. Database URL: https://microbiome.h3abionet.org/.
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Metadatos , Microbiota , Humanos , Metagenoma , Bases de Datos Factuales , Metagenómica , Microbiota/genéticaRESUMEN
The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent1-7. With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8. We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations.
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ADN Antiguo , Emigración e Inmigración , Genética de Población , Lenguaje , Humanos , África Occidental , Conjuntos de Datos como Asunto , República Democrática del Congo , ADN Antiguo/análisis , Emigración e Inmigración/historia , Efecto Fundador , Flujo Génico/genética , Variación Genética/genética , Historia Antigua , Lenguaje/historia , Lingüística/historia , Zambia , Mapeo GeográficoRESUMEN
Introduction: We describe an outbreak of Serratia marcescens (S. marcescens) infection in the neonatal intensive care unit at Women's Hospital in Sinaloa, Mexico. Methods: In April 2021, an outbreak of S. marcescens infection was identified. A case was identified as any patient who tested positive for S. marcescens and showed signs of an infectious process. Results: S. marcescens was isolated from the blood cultures of 15 neonates with clinical signs of neonatal sepsis. Statistical analysis showed that all neonates had an invasive medical device. The problem was controlled after hospital hygiene and sanitation measures were strengthened. Conclusion: The study provides evidence of an outbreak of nosocomial bacteremia due to the cross-transmission of S. marcescens. The findings highlight the need for hospitals to implement strict hygiene measures, especially regarding hand washing, to prevent future outbreaks.
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Bacteria with antagonistic activity inhibit the growth of other bacteria through different mechanisms, including the production of antibiotics. As a result, these microorganisms are a prolific source of such compounds. However, searching for antibiotic-producing strains requires high-throughput techniques due to the vast diversity of microorganisms. Here, we screened and isolated bacteria with antagonistic activity against Escherichia coli expressing the green fluorescent protein (E. coli-GFP). We used microfluidics to co-encapsulate and co-culture single cells from different strains within picoliter gel beads and analyzed them using fluorescence-activated cell sorting (FACS). To test the methodology, we used three bacterial isolates obtained from Mexican maize, which exhibit high, moderate, or no antagonistic activity against E. coli-GFP, as determined previously using agar plate assays. Single cells from each strain were separately co-incubated into gel beads with E. coli-GFP. We monitored the development of the maize bacteria microcolonies and tracked the growth or inhibition of E. coli-GFP using bright-field and fluorescent microscopy. We correlated these images with distinctive light scatter and fluorescence signatures of each incubated bead type using FACS. This analysis enabled us to sort gel beads filled with an antagonistic strain, starting from a mixture of the three different types of maize bacteria and E. coli-GFP. Likewise, culturing the FACS-sorted beads on agar plates confirmed the isolation and recovery of the two antagonistic strains. In addition, enrichment assays demonstrated the methodology's effectiveness in isolating rare antibiotic-producer strains (0.01% abundance) present in a mixture of microorganisms. These results show that associating light side scatter and fluorescent flow cytometry signals with microscopy images provides valuable controls to establish successful high-throughput methods for sorting beads in which microbial interaction assays are performed.
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Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/metabolismo , Microfluídica , Agar/metabolismo , Bacterias , Citometría de Flujo/métodos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismoRESUMEN
Uropathogenic Escherichia coli (UPEC) is classified as the major causative agent of urinary tract infections (UTIs). UPEC virulence and antibiotic resistance can lead to complications in pregnant women and (or) newborns. Therefore, the aim of this study was to determine the etiological agents of UTIs, as well as to identify genes related to virulence factors in bacteria isolated from pregnant and nonpregnant women. A total of 4506 urine samples were collected from pregnant and nonpregnant women. Urine cultures were performed, and PCR was used to identify phylogroups and virulence-related genes. Antibiotic resistance profiles were determined. The incidence of UTIs was 6.9% (pregnant women, n = 206 and nonpregnant women, n = 57), and UPEC belonging to phylogroup A was the most prevalent. The presence of genes related to capsular protection, adhesins, iron acquisition, and serum protection in UPEC was associated with not being pregnant, while the presence of genes related to adhesins was associated with pregnancy. Bacteria isolated from nonpregnant women were more resistant to antibiotics; 36.5% were multidrug resistant, and 34.9% were extensively drug resistant. Finally, UTIs were associated with neonatal sepsis risk, particularly in pregnant women who underwent cesarean section while having a UTI caused by E. coli. In conclusion, UPEC isolated from nonpregnant women carried more virulence factors than those isolated from pregnant women, and maternal UTIs were associated with neonatal sepsis risk.
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Infecciones por Escherichia coli , Sepsis Neonatal , Infecciones Urinarias , Escherichia coli Uropatógena , Embarazo , Humanos , Femenino , Recién Nacido , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Virulencia/genética , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Sepsis Neonatal/tratamiento farmacológico , Cesárea , Farmacorresistencia Bacteriana/genética , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiología , Factores de Virulencia/genética , Escherichia coli Uropatógena/genéticaRESUMEN
Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2-8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27-2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32-0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69-3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26-0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3-2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.
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Ancient DNA studies reveal the genetic structure of Africa before the expansion of Bantu-speaking agriculturalists; however, the impact of now extinct hunter-gatherer and herder societies on the genetic makeup of present-day African groups remains elusive. Here, we uncover the genetic legacy of pre-Bantu populations from the Angolan Namib Desert, where we located small-scale groups associated with enigmatic forager traditions, as well as the last speakers of the Khoe-Kwadi family's Kwadi branch. By applying an ancestry decomposition approach to genome-wide data from these and other African populations, we reconstructed the fine-scale histories of contact emerging from the migration of Khoe-Kwadi-speaking pastoralists and identified a deeply divergent ancestry, which is exclusively shared between groups from the Angolan Namib and adjacent areas of Namibia. The unique genetic heritage of the Namib peoples shows how modern DNA research targeting understudied regions of high ethnolinguistic diversity can complement ancient DNA studies in probing the deep genetic structure of the African continent.
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Población Negra , ADN Antiguo , Humanos , Población Negra/genética , NamibiaRESUMEN
BACKGROUND: While the human oral microbiome is known to play an important role in systemic health, its average composition and diversity patterns are still poorly understood. To gain better insights into the general composition of the microbiome on a global scale, the characterization of microbiomes from a broad range of populations, including non-industrialized societies, is needed. Here, we used the portion of non-human reads obtained through an expanded exome capture sequencing approach to characterize the saliva microbiomes of 52 individuals from eight ethnolinguistically diverse southern African populations from Angola (Kuvale, Kwepe, Himba, Tjimba, Kwisi, Twa, !Xun) and Zimbabwe (Tshwa), including foragers, food-producers, and peripatetic groups (low-status communities who provide services to their dominant neighbors). RESULTS: Our results indicate that neither host genetics nor livelihood seem to influence the oral microbiome profile, with Neisseria, Streptococcus, Prevotella, Rothia, and Porphyromonas being the five most frequent genera in southern African groups, in line with what has been shown for other human populations. However, we found that some Tshwa and Twa individuals display an enrichment of pathogenic genera from the Enterobacteriaceae family (i.e. Enterobacter, Citrobacter, Salmonella) of the Proteobacteria phylum, probably reflecting deficient sanitation and poor health conditions associated with social marginalization. CONCLUSIONS: Taken together, our results suggest that socio-economic status, rather than ethnolinguistic affiliation or subsistence mode, is a key factor in shaping the salivary microbial profiles of human populations in southern Africa.
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Citrobacter , Microbiota , Humanos , Zimbabwe , Angola , África Austral , Microbiota/genéticaRESUMEN
Objective: This study aims to assess the active aging awareness of older adults in mainland Portugal and their levels of overall well-being and to identify social and health-related factors. Methods: A cross-sectional study was conducted with a representative sample of 613 older adults, aged 65 or older, who participated in the PROKnos - Knowing Social Prescribing needs of the elderly study in Portugal. The questionnaire consisted of the Active Ageing Awareness Questionnaire and the World Health Organization - Five Well-Being Index, as well as sociodemographic, economic, and health status questions. Correlation coefficients, t-tests for independent samples, and one-way ANOVA were used to explore potential associations between variables. Results: The active aging awareness levels were significantly higher for women (p = 0.031), and those who were younger (p = 0.011), more educated (p < 0.001), had a better financial situation (p < 0.001), and had better health (p < 0.001). The same pattern was found for well-being, except in relation to gender, as men had higher levels (p = 0.016). These variables were found to be correlated. Discussion: Even though active aging is an important strategy to implement, it is indispensable to consider the perceptions and conditions that need to be in place before that. This study reveals that several social and health-related factors are associated with well-being and active aging awareness, as well as the differences between groups that exist in mainland Portugal in relation to that. This emphasizes how vital it is to address social inequalities in active aging efforts, which are not necessarily uncovered when only considering actual active aging measures.