National Institute of Health Dr. Ricardo Jorge
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Vitex Genus as a Source of Antimicrobial Agents
No full textReviewThis article belongs to the Special Issue Medicinal Plants and Their Marker Compounds—Second Edition)Vitex L. is the largest genus of the Lamiaceae family, and most of its species are used in the traditional medicinal systems of different countries. A systematic review was conducted, according to the PRISMA methodology, to determine the potential of Vitex plants as sources of antimicrobial agents, resulting in 2610 scientific publications from which 141 articles were selected. Data analysis confirmed that Vitex species are used in traditional medicine for symptoms of possible infectious diseases. Conducted studies showed that these medicinal plants exhibited in vitro antimicrobial activity against Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Vitex agnus-castus L. and Vitex negundo L. have been the most studied species, not only against bacterial strains but also against fungi such as Aspergillus niger and Candida albicans, viruses such as HIV-1, and parasites such as Plasmodium falciparum. Natural products like agnucastoside, negundol, negundoside, and vitegnoside have been identified in Vitex extracts and their antimicrobial activity against a wide range of microbial strains has been determined. Negundoside showed significant antimicrobial activity against Staphylococcus aureus (MIC 12.5 µg/mL). Our results show that Vitex species are potential sources of new natural antimicrobial agents. However, further experimental studies need to be conducted.This research was funded by the Foundation for Science and Technology (FCT, Portugal) through national funds to iMed.ULisboa (UIDP/04138/2020 and UI/BD/153625/2022)
Comparison of the ABC and ACMG systems for variant classification
No full textThe ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as “maybe report” after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known
Impact of population aging on future temperature-related mortality at different global warming levels
No full textMCC Collaborative Research Network: Susana Pereira da Silva (Departamento de Epidemiologia, INSA)Older adults are generally amongst the most vulnerable to heat and cold. While temperature-related health impacts are projected to increase with global warming, the influence of population aging on these trends remains unclear. Here we show that at 1.5 °C, 2 °C, and 3 °C of global warming, heat-related mortality in 800 locations across 50 countries/areas will increase by 0.5%, 1.0%, and 2.5%, respectively; among which 1 in 5 to 1 in 4 heat-related deaths can be attributed to population aging. Despite a projected decrease in cold-related mortality due to progressive warming alone, population aging will mostly counteract this trend, leading to a net increase in cold-related mortality by 0.1%-0.4% at 1.5-3 °C global warming. Our findings indicate that population aging constitutes a crucial driver for future heat- and cold-related deaths, with increasing mortality burden for both heat and cold due to the aging population.This study reveals that population aging intensifies heat- and cold-related deaths, more so than climate change, in 50 countries. At 1.53 °C global warming, aging contributes to rising heat-related deaths, offsetting declines in cold related death.We acknowledge the World Climate Research Programme, which, through its Working Group on Coupled Modeling, coordinated and promoted CMIP6. We thank the climate modeling groups for producing and making available their model output, the Earth System Grid Federation (ESGF) for archiving the data and providing access, and the multiple funding agencies who support CMIP6 and ESGF. K.C. was supported by the Yale Planetary Solutions Project seed grant. A.G., A.S., and S.R. were supported by the European Union’s Horizon 2020 Project Exhaustion grant (820655). A.G. was also supported by the Medical Research Council UK grant (MR/V034162/1). J.M. received funding from the Fundação para a Ciência e a Tecnlogia Grant (SFRH/BPD/115112/2016). A.T. was supported by the MCIN/AEI/10.13039/501100011033 grant (CEX2018-000794-S). A.U. and J.K. were supported by the Czech Science Foundation (22-24920S). F.S. was supported by the Italian Ministry of University and Research (MUR), Department of Excellence project 2023-2027 ReDS ‘Rethinking Data Science’ - Department of Statistics, Computer Science and Applications - University of Florence. MNM. was supported by the European Commission (H2020-MSCA-IF-2020) under REA grant agreement no. 101022870. A.V.C. acknowledges the support of the Swiss National Foundation (TMSGI3_211626). V.H. received funding from the European Union’s Horizon 2020 research and innovation program (Marie Skłodowska-Curie Grant Agreement No.: 101032087)
Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023–January 2024
No full textErratum in: Vaccine. 2024 Oct 3;42(23):126089. https://doi.org/10.1016/j.vaccine.2024.06.056. Epub 2024 Jul 8.In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a testnegative case–control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26–53 %) overall, 48 % (95 % CI: 31–61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3–49 %) at 6–14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.This study has received funding from the European Centre for Disease Prevention and Control under framework contract ECDC/2021/ 019.info:eu-repo/semantics/publishedVersio
Genome-scale analysis of Mycobacterium avium complex isolates from Portugal reveals extensive genetic diversity
No full textOpportunist infections caused by nontuberculous mycobacteria (NTM) have emerged as a significant public health problem. Among these, species of the Mycobacterium avium complex (MAC) are the main responsible for the increase in the number of human disease cases. In order to address the current needs in the detection and surveillance of MAC disease cases, we evaluated different species classification methodologies (BLASTn-based marker-gene approach, Kraken v2, rMLST and MLST databases) and their congruence with a core-SNP phylogenetic approach, based on whole genome sequencing (WGS) data. For this purpose, we used a collection of 142 MAC isolates from Portuguese patients diagnosed between 2014 and 2022. The marker-gene approach (based on the rpoB, hsp65 and groEL genes), showed the best results, allowing the identification of the 142 MAC isolates to the species/subspecies level (M. avium subsp. hominissuis, M. intracellulare, M. intracellulare subsp. chimaera, M. intracellulare subsp. yongonense, M. marseillence and M. colombiense). Additionally, we performed drug susceptibility testing that confirmed clarithromycin efficacy as a first-line treatment for MAC disease, as 93 % of the Portuguese isolates were susceptible. Using a core-SNP approach we also performed an in-depth phylogenetic analysis within each identified species group, and despite the high genetic diversity within the MAC species, we were able to clearly distinguish all the species/subspecies and identify genetic clusters with epidemiological potential. We highlight not only the need for the standardization of an appropriate genotyping approach for species identification and management of MAC disease, but also a more robust large-scale WGS data analysis, in a One Health perspective, in order to identify potential routes of transmission.Highlights: - Genetic diversity of MAC isolates circulating in Portugal; - Multi-step approach to identify species and subspecies of MAC; - Core-SNP phylogenetic approach of PT MAC isolates; - Phylogenetic analysis of MAC isolates using single linkage hierarchical clustering.S. Carneiro was supported by the Portuguese Science and Technology Foundation (FCT) through grant 2020.08503.BD. This study was partially supported, by the Health Emergency Preparedness and Response (HERA) project (Grant/2021/PHF/23776) supported by the European Commission through the European Centre for Disease Control and Prevention and the project EU4H-2022-DGAMS-IBA-1 (https://www.insa.min-saude.pt/category/projectos/geneo/) supported by the European Union on behalf of EU4H programme
Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants
No full textNCD Risk Factor Collaboration (NCD-RisC) - INSA: Marta Barreto (Departamento de Epidemiologia)Erratum in: Lancet. 2025 Apr 5;405(10485):1146. doi: 10.1016/S0140-6736(25)00620-8.Background: Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories.
Methods: We used data from 1108 population-representative studies with 141 million participants aged 18 years and older with measurements of fasting glucose and glycated haemoglobin (HbA1c), and information on diabetes treatment. We defined diabetes as having a fasting plasma glucose (FPG) of 7·0 mmol/L or higher, having an HbA1c of 6·5% or higher, or taking medication for diabetes. We defined diabetes treatment as the proportion of people with diabetes who were taking medication for diabetes. We analysed the data in a Bayesian hierarchical meta-regression model to estimate diabetes prevalence and treatment.
Findings: In 2022, an estimated 828 million (95% credible interval [CrI] 757-908) adults (those aged 18 years and older) had diabetes, an increase of 630 million (554-713) from 1990. From 1990 to 2022, the age-standardised prevalence of diabetes increased in 131 countries for women and in 155 countries for men with a posterior probability of more than 0·80. The largest increases were in low-income and middle-income countries in southeast Asia (eg, Malaysia), south Asia (eg, Pakistan), the Middle East and north Africa (eg, Egypt), and Latin America and the Caribbean (eg, Jamaica, Trinidad and Tobago, and Costa Rica). Age-standardised prevalence neither increased nor decreased with a posterior probability of more than 0·80 in some countries in western and central Europe, sub-Saharan Africa, east Asia and the Pacific, Canada, and some Pacific island nations where prevalence was already high in 1990; it decreased with a posterior probability of more than 0·80 in women in Japan, Spain, and France, and in men in Nauru. The lowest prevalence in the world in 2022 was in western Europe and east Africa for both sexes, and in Japan and Canada for women, and the highest prevalence in the world in 2022 was in countries in Polynesia and Micronesia, some countries in the Caribbean and the Middle East and north Africa, as well as Pakistan and Malaysia. In 2022, 445 million (95% CrI 401-496) adults aged 30 years or older with diabetes did not receive treatment (59% of adults aged 30 years or older with diabetes), 3·5 times the number in 1990. From 1990 to 2022, diabetes treatment coverage increased in 118 countries for women and 98 countries for men with a posterior probability of more than 0·80. The largest improvement in treatment coverage was in some countries from central and western Europe and Latin America (Mexico, Colombia, Chile, and Costa Rica), Canada, South Korea, Russia, Seychelles, and Jordan. There was no increase in treatment coverage in most countries in sub-Saharan Africa; the Caribbean; Pacific island nations; and south, southeast, and central Asia. In 2022, age-standardised treatment coverage was lowest in countries in sub-Saharan Africa and south Asia, and treatment coverage was less than 10% in some African countries. Treatment coverage was 55% or higher in South Korea, many high-income western countries, and some countries in central and eastern Europe (eg, Poland, Czechia, and Russia), Latin America (eg, Costa Rica, Chile, and Mexico), and the Middle East and north Africa (eg, Jordan, Qatar, and Kuwait).
Interpretation: In most countries, especially in low-income and middle-income countries, diabetes treatment has not increased at all or has not increased sufficiently in comparison with the rise in prevalence. The burden of diabetes and untreated diabetes is increasingly borne by low-income and middle-income countries. The expansion of health insurance and primary health care should be accompanied with diabetes programmes that realign and resource health services to enhance the early detection and effective treatment of diabetes.UK Medical Research Council, UK Research and Innovation (Research England), and US Centers for Disease Control and Prevention
Study around the Barroso mine (Portugal): Baseline levels of lithium for assessing future exposure and risks from Li mining activity
No full textThe energetic green transition is increasing the demand for lithium (Li) exploitation. However, the Li supply faces challenges like limited reserves and environmental concerns. This pioneer study aims to characterize the Li concentrations in the region around the Barroso mine, in Portugal, by collecting and analyzing samples of cabbage, potato, drinking and irrigation water and soil from two nearby sites, and performing a preliminary exposure and risk assessment of local populations. Li levels ranged between 20 and 589 μg/kg in cabbages (n = 23), 2.3–21 μg/kg in potatoes (n =21), 1.1–5.9 μg/L in drinking water (n =10), 1.1–15 μg/L in irrigation water (n =23) and 35–121 mg/kg in soils (n =23). Significant differences in Li content between sampling sites were observed only for cabbage samples. The risk assessment revealed that none of the participants exceeded the provisional reference dose (p-RfD) (2 μg/kg bw/day), with a hazard quotient (HQ) <1, suggesting no health concerns for the population. It is expected that the studied area will be affected by the future expansion of the mine concession, thus this pioneer study is crucial for future research as it establishes a initial database for evaluating the potential impact of mining activity on the environment and the population’s exposure to Li.Highlights: - New database of Li levels in the Barroso mine area; - Evaluation of cabbage, potato, water (drinking and irrigation), and soil samples; - Significant differences observed in cabbage samples between sampling sites; - Risk assessment indicated acceptable human exposure levels to Li (THQ<1); - Baseline for Li studies following the mining expansion in the Barroso mine.This work is financed by national funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., within the scope of the project EXPL/CTA-AMB/0977/2021 AMB/0977/2021(http://doi.org/10.54499/EXPL/CTA-AMB/0977/2021). Strategic projects UIDB/04292/2020 (https://doi.org/10.54499/UIDB/04292/2020 and UIDP/04292/2020 (https://doi.org/10.54499/UIDP/04292/2020 granted to MARE - Marine and Environmental Sciences Centre, and the project LA/P/0069/2020 (https://doi.org/10.54499/LA/P/0069/2020 granted to the Associate Laboratory ARNET - Aquatic Research Network and project UIDB/04028/2020 granted to CERENA (Centro de Recursos Naturais e Ambiente)info:eu-repo/semantics/publishedVersio
Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study
No full textEuropean Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (EAS FHSC) - INSA: Mafalda Bourbon.Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.
Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression.
Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55-98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04-117·73]) than in those in the lowest risk category (aged 18-38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57-38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67-104·02) for those with obesity in the highest risk category and OR 20·07 (12·73-31·65) for those without obesity.
Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population.Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron
Resistome, Virulome, and Clonal Variation in Methicillin-Resistant (MRSA) in Healthy Swine Populations: A Cross-Sectional Study
No full text(This article belongs to the Section Animal Genetics and Genomics)This cross-sectional study investigates the methicillin-resistant (MRSA): its prevalence, antimicrobial resistance, and molecular characteristics in healthy swine populations in central Portugal. A total of 213 samples were collected from pigs on twelve farms, and MRSA prevalence was assessed using selective agar plates and confirmed via molecular methods. Antimicrobial susceptibility testing and whole genome sequencing (WGS) were performed to characterize resistance profiles and genetic determinants. Among the 107 MRSA-positive samples (83.1% prevalence), fattening pigs and breeding sows exhibited notably high carriage rates. The genome of 20 isolates revealed the predominance of the ST398 clonal complex, with diverse types identified. Antimicrobial susceptibility testing demonstrated resistance to multiple antimicrobial agents, including penicillin, cefoxitin, and tetracycline. WGS analysis identified a diverse array of resistance genes, highlighting the genetic basis of antimicrobial resistance. Moreover, virulence gene profiling revealed the presence of genes associated with pathogenicity. These findings underscore the significant prevalence of MRSA in swine populations and emphasize the need for enhanced surveillance and control measures to mitigate zoonotic transmission risks. Implementation of prudent antimicrobial use practices and targeted intervention strategies is essential to reducing MRSA prevalence and safeguarding public health. Continued research efforts are warranted to elucidate transmission dynamics and virulence potential, ultimately ensuring food safety and public health protection.This work received support and help from FCT/MCTES (LA/P/0008/2020 DOI 10.54499/LA/P/0008/2020, UIDP/50006/2020 DOI 10.54499/UIDP/50006/2020, and UIDB/50006/2020 DOI 10.54499/UIDB/50006/2020)
Mosquito (Diptera: Culicidae) Fauna of a Zoological Park in an Urban Setting: Analysis of Culex pipiens s.l. and Their Biotypes
No full text(This article belongs to the Special Issue Insect Vectors of Human and Zoonotic Diseases)Simple Summary: Mosquitoes are known for being a nuisance but also as important vectors of disease agents that affect not only humans but also animals. Zoological gardens are special places where humans and animals are found in close proximity, and where mosquitoes can also find the conditions required for their life cycle. This can be especially true for zoos located in urban areas. In this study, we characterized, for the first time, the mosquito fauna of Lisbon Zoo, and we found a low mosquito density and diversity. We found an average of 2.4 mosquitos per trap/night, and five different species were identified. The most common species was the northern house mosquito, Culex pipiens, with sympatric occurrence of the two biotypes and their hybrids in most collections. Mosquitoes were present year-round, with activity detected in winter months, in which mosquitoes usually diapause. This co-occurrence and activity during winter can have implications in terms of disease transmission, namely, flavivirus, which can affect both animals and humans.Abstract: Mosquito-borne diseases (MBDs) are important emerging diseases that affect humans and animals. Zoological parks can work as early warning systems for the occurrence of MBDs. In this study, we characterized the mosquito fauna captured inside Lisbon Zoo from May 2018 to November 2019. An average of 2.4 mosquitos per trap/night were captured. Five mosquito species potentially causing MBDs, including Culex pipiens biotypes, were found in the zoo. The sympatric occurrence of Culex pipiens biotypes represents a risk factor for the epizootic transmission of West Nile virus and Usutu virus. The mosquito occurrence followed the expected seasonality, with the maximum densities during summer months. However, mosquito activity was detected in winter months in low numbers. The minimum temperature and the relative humidity (RH) on the day of capture showed a positive effect on Culex pipiens abundance. Contrary, the RH the week before capture and the average precipitation the week of capture had a negative effect. No invasive species were identified, nor have flaviviruses been detected in the mosquitoes. The implementation of biosecurity measures regarding the hygiene of the premises and the strict control of all the animals entering the zoo can justify the low prevalence of mosquitoes and the absence of flavivirus-infected mosquitoes.This research was funded by FCT—Fundação para a Ciência e a Tecnologia, I.P., through the project grants UIDB/00276/2020 (CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisboa, Portugal), and LA/P/0059/2020 (AL4AnimalS—Laboratório Associado para Ciência Animal e Veterinária). The author Sara Madeira was supported by an FCT Ph.D. fellowship SFRH/BD/117431/2016.info:eu-repo/semantics/publishedVersio