National Institute of Health Dr. Ricardo Jorge
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Vaccine effectiveness against influenza hospitalisation in adults during the 2022/2023 mixed season of influenza A(H1N1)pdm09, A(H3N2) and B circulation, Europe: VEBIS SARI VE hospital network
No full textWe conducted a multicentre hospital-based test-negative case–control study to measure vaccine effectiveness (VE) against PCR-confirmed influenza in adult patients with severe acute respiratory infection (SARI) during the 2022/2023 influenza season in Europe. Among 5547 SARI patients ≥18 years, 2963 (53%) were vaccinated against influenza. Overall VE against influenza A(H1N1)pdm09 was 11% (95% CI: −23–36); 20% (95% CI: −4–39) against A(H3N2) and 56% (95% CI: 22–75) against B. During the 2022/2023 season, while VE against hospitalisation with influenza B was >55%, it was ≤20% for influenza A subtypes. While influenza vaccination should be a priority for future seasons, improved vaccines against influenza are needed.European Centre for Disease Prevention and Control, Grant/Award Number:ECDC/2021/12924info:eu-repo/semantics/publishedVersio
Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm Insights
No full textListeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses.This work was supported by the projects UIDB/00772/2020 (Doi:10.54499/UIDB/00772/2020), funded by the Portuguese Foundation for Science and Technology (FCT).info:eu-repo/semantics/publishedVersio
Influenza vaccine effectiveness in Europe: Results from the 2022–2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study
No full textThe VEBIS study team includes: Portugal - Verónica Gomez, Irina Kislaya, Ana Paula Rodrigues, Ausenda Machado (Departamento de Epidemiologia, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa); Daniela Dias, Licínia Gomes, Raquel Guiomar, Camila Henriques, Miguel Lança, Aryse Melo, Nuno Verdasca (Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa).Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study.
Materials and methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression.
Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation.
Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2).This study received funding from the European Centre for Disease Prevention and Control (ECDC) under the framework contract Vaccine Effectiveness, Burden and Impact Studies (VEBIS) of COVID-19 and Influenza ECDC/2021/019.info:eu-repo/semantics/publishedVersio
The Impact of Various Types of Cooking on the Fate of Hg and Se in Predatory Fish Species
No full textThis study addresses the effect of various cooking approaches on total Hg (HgT) and total Se (SeT) contents in three predatory fish species. For this purpose, samples of swordfish, dogfish, and tuna from regular French (fish) markets were cooked by boiling, steaming, grilling, and frying, respectively. The levels of HgT and SeT in raw and cooked samples were determined by inductively coupled plasma-mass spectrometry. The data showed a significant increase in HgT and SeT levels between raw and cooked samples (33% of the samples for SeT and 67% for HgT) due to the water loss during the cooking. High intra-species variation related to HgT and SeT levels was found. Considering the level of exposure to HgT through fish consumption and taking also into account the possible protective effect of Se (expressed here via the Se/Hg molar ratio), the safest cooking approach corresponds to grilled swordfish, fried tuna, and steamed dogfish, which show Se/Hg molar ratios of (1.0 ± 0.5), (4.3 ± 4.2), and (1.0 ± 0.6), respectively.This study is a contribution to a Ph.D. research project (MERSEL-FISH), which was funded by ANSES (France) and INSA (Portugal)
Long COVID is not the same for everyone: a hierarchical cluster analysis of Long COVID symptoms 9 and 12 months after SARS-CoV-2 test
No full textErratum for: BMC Infect Dis. 2024 Sep 19;24(1):1001.https://doi.org/10.1186/s12879-024-10086-9Background: Identifying symptom clusters in Long COVID is necessary for developing effective therapies for this diverse condition and improving the quality of life of those affected by this heterogeneous condition. In this study, we aimed to identify and compare symptom clusters at 9 and 12 months after a SARS-CoV-2 positive test and describe each cluster regarding factors at infection.
Methods: This is a cross-sectional study with individuals randomly selected from the Portuguese National System of Epidemiological Surveillance (SINAVE) database. Individuals who had a positive RT-PCR SARS-CoV-2 test in August 2022 were contacted to participate in a telephonic interview approximately 9 and 12 months after the test. A hierarchical clustering analysis was performed, using Euclidean distance and Ward's linkage. Clustering was performed in the 35 symptoms reported 9 and 12 months after the SARS-CoV-2 positive test and characterised considering age, sex, pre-existing health conditions and symptoms at time of SARS-CoV-2 infection.
Results: 552 individuals were included at 9 months and 458 at 12 months. The median age was 52 years (IQR: 40-64 years) and 59% were female. Hypertension and high cholesterol were the most frequently reported pre-existing health conditions. Memory loss, fatigue or weakness and joint pain were the most frequent symptoms reported 9 and 12 months after the positive test. Four clusters were identified at both times: no or minor symptoms; multi-symptoms; joint pain; and neurocognitive-related symptoms. Clusters remained similar in both times, but, within the neurocognitive cluster, memory loss and concentration issues increased in frequency at 12 months. Multi-symptoms cluster had older people, more females and more pre-existing health conditions at 9 months. However, at 12 months, older people and those with more pre-existing health conditions were in joint pain cluster.
Conclusions: Our results suggest that Long COVID is not the same for everyone. In our study, clusters remained similar at 9 and 12 months, except for a slight variation in the frequency of symptoms that composed each cluster. Understanding Long COVID clusters might help identify treatments for this condition. However, further validation of the observed clusters and analysis of its risk factors is needed.This work was supported by the Foundation for Science and Technology (FCT) through a PhD research scholarship [2020.09525.BD] granted under the Call DOCTORATES 4 COVID-19; Comprehensive Health Research Center [UIDP/04923/2020]; and FCT (reference: CEECINST/00049/2021/CP2817/CT0001 and DOI: https://doi.org/10.54499/CEECINST/00049/2021/CP2817/CT0001). This study is sponsored by Pfizer (grant code #68639655; URL: https://www.pfizer.pt/).info:eu-repo/semantics/publishedVersio
Purinergic exposure induces epigenomic and transcriptomic-mediated preconditioning resembling epilepsy-associated microglial states
No full textMicroglia play a crucial role in a range of neuropathologies through exacerbated activation. Microglial inflammatory responses can be influenced by prior exposures to noxious stimuli, like increased levels of extracellular adenosine and ATP. These are characteristic of brain insults like epileptic seizures and could potentially shape subsequent responses through epigenetic regulation. We investigated DNA methylation and expression changes in human microglia-like cells differentiated from monocytes following ATP-mediated preconditioning. We demonstrate that microglia-like cells display homeostatic microglial features, shown by surface markers, transcriptome, and DNA methylome. After exposure to ATP, TLR-mediated activation leads to an exacerbated pro-inflammatory response. These changes are accompanied by methylation and transcriptional reprogramming associated with enhanced immune-related functions. The reprogramming associated with ATP-mediated preconditioning leads to profiles found in microglial subsets linked to epilepsy. Purine-driven microglia immune preconditioning drives epigenetic and transcriptional changes that could contribute to altered functions of microglia during seizure development and progression.Highlights: - Microglia-like cells replicate microglial transcriptome and DNA methylome; - Purinergic preconditioning promotes enhanced pro-inflammatory response; - Methylation and transcription of inflammatory genes are altered by ATP pre-exposure; - ATP-related expression changes mimic microglial population expanded in epilepsy.E.B. is funded by the Spanish Ministry of Science and Innovation (MICINN) [PID2020117212RB-I00; AEI/10.13039/501100011033]. R.M-F. is funded by an FCT (Fundação para a Ciência e Tecnologia) fellowship (SFRH/BD/137900/2018). UMIB is funded by FCT Portugal (UIDB/00215/2020 and UIDP/00215/2020), and ITR (LA/P/006/2020)
Flavouring group evaluation 420 (FGE.420): Hesperetin dihydrochalcone
No full textThe EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of hesperetin dihydrochalcone [FL-no: 16.137] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance is structurally related to the group of flavonoids evaluated in FGE.32 and is the aglycone of neohesperidine dihydrochalcone. Based on the data provided for [FL-no: 16.137], the Panel considered that a read-across between hesperetin dihydrochalcone and the substances in FGE.32 is not needed. Nevertheless, the flavonoids evaluated in FGE.32 were considered in a cumulative exposure assessment. The information provided on the manufacturing process, the composition and the stability of [FL-no: 16.137] was considered sufficient. The Panel concluded that there is no concern with respect to genotoxicity. No absorption, distribution, metabolism and excretion (ADME) studies on [FL-no: 16.137] were provided, but studies investigating the ADME of neohesperidine dihydrochalcone were submitted. The Panel noted that [FL-no: 16.137] has the same fate in the organism, as that of neohesperidine dihydrochalcone and considered that [FL-no: 16.137] can be anticipated to be metabolised to innocuous products only. In a prenatal developmental toxicity study, no maternal or foetal toxicity was observed. In a 90-day toxicity study, indications were obtained that the substance affects thyroid hormone levels at all doses tested (100-1000 mg/kg bw per day). Since these changes were not accompanied by apical findings indicative of hypothyroidism, the Panel considered these hormonal effects as not adverse. Using 1000 mg/kg bodyweight (bw) per day as reference point, adequate margins of exposure were calculated for adults and children, when considering the chronic added portions exposure technique (APET) dietary exposure estimates. Cumulative chronic exposure estimates to [FL-no: 16.137] and the four structurally related substances evaluated in FGE.32 do not raise a safety concern. The use of [FL-no: 16.137] as food flavouring, under the proposed conditions of use, does not raise a safety concern
Estimated number of lives directly saved by COVID-19 vaccination programmes in the WHO European Region from December, 2020, to March, 2023: a retrospective surveillance study
No full textBackground: By March, 2023, 54 countries, areas, and territories (hereafter CAT) in the WHO European Region had reported more than 2·2 million COVID-19-related deaths to the WHO Regional Office for Europe. Here, we estimated how many lives were directly saved by vaccinating adults in the WHO European Region from December, 2020, to March, 2023.
Methods: In this retrospective surveillance study, we estimated the number of lives directly saved by age group, vaccine dose, and circulating variant-of-concern (VOC) period, regionally and nationally, using weekly data on COVID-19 mortality and infection, COVID-19 vaccination uptake, and SARS-CoV-2 virus characterisations by lineage downloaded from The European Surveillance System on June 11, 2023, as well as vaccine effectiveness data from the literature. We included data for six age groups (25-49 years, 50-59 years, ≥60 years, 60-69 years, 70-79 years, and ≥80 years). To be included in the analysis, CAT needed to have reported both COVID-19 vaccination and mortality data for at least one of the four older age groups. Only CAT that reported weekly data for both COVID-19 vaccination and mortality by age group for 90% of study weeks or more in the full study period were included. We calculated the percentage reduction in the number of expected and reported deaths.
Findings: Between December, 2020, and March, 2023, in 34 of 54 CAT included in the analysis, COVID-19 vaccines reduced deaths by 59% overall (CAT range 17-82%), representing approximately 1·6 million lives saved (range 1·5-1·7 million) in those aged 25 years or older: 96% of lives saved were aged 60 years or older and 52% were aged 80 years or older; first boosters saved 51% of lives, and 60% were saved during the Omicron period.
Interpretation: Over nearly 2·5 years, most lives saved by COVID-19 vaccination were in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among the most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures.Research in context: - Evidence before this study:
Since it was first identified in late December, 2019, COVID-19 has caused disproportionately high mortality rates in older adults (aged ≥60 years). With the rapid development, licensing, and availability of novel COVID-19 vaccines, immunisation campaigns across the WHO European Region started in late 2020 and March, 2021, initially targeting the most vulnerable and exposed populations, including older adults, people with comorbidities, and health-care professionals. We searched PubMed, without language restrictions, for articles published between Dec 1, 2020, and July 31, 2024, using the search terms “(impact COVID-19 vaccin*)” NOT “(cancer)” NOT “(tb)” NOT “(tuberculosis)” NOT “(childhood immunization)” NOT “(liver)” NOT “(diabetes)” NOT “(ebola)”. 82 identified studies have estimated the number of lives saved by COVID-19 vaccination, both at national level (n=71) and multi-country level (n=11), in the earlier stages of the COVID-19 pandemic. However, only one country-level study assessed the number of lives saved beyond January, 2022, when the Omicron variant of concern (VOC) circulated, a period when vaccination coverage was high in many countries, areas, and territories (CAT), but SARS-CoV-2 transmission was at its highest.
- Added value of this study: To our knowledge, this is the first retrospective surveillance study to quantify the impact of COVID-19 vaccination in adults, according to age group and variant, for the entire pandemic period across multiple countries. We calculated the numbers of lives saved by age group, vaccine dose, and period of circulation of VOC, across diverse settings, using real-world data reported for 34 CAT in the WHO European Region between December, 2020, to April, 2023. For this period, we estimated that COVID-19 vaccination programmes were associated with an overall 59% reduction (CAT range 17–82%) in the number of deaths among people aged 25 years or older, representing over 1·6 million lives saved (range 1·5–1·7 million). The first booster saved the most lives (51% of all lives saved). Those aged 60 years or older accounted for 96% of the total lives saved whereas people aged 80 years or older represented 52% of the total lives saved, and 60% of all lives were saved during the Omicron period.
- Implications of all the available evidence:
Our results reinforce the importance of up-to-date COVID-19 vaccination, particularly among older age groups. Communication campaigns supporting COVID-19 vaccination should stress the value of COVID-19 vaccination in saving lives to ensure that vulnerable groups are up to date with vaccination ahead of periods of potential increased transmission.This work was supported by a US Centers for Disease Control and Prevention cooperative agreement (grant number 6 NU511P000936–02–020)
Gene content, phage cycle regulation model and prophage inactivation disclosed by prophage genomics in the Helicobacter pylori Genome Project
No full textHpGP Research Network Collaborators: Mónica Oleastro, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, PortugalProphages can have major clinical implications through their ability to change pathogenic bacterial traits. There is limited understanding of the prophage role in ecological, evolutionary, adaptive processes and pathogenicity of Helicobacter pylori, a widespread bacterium causally associated with gastric cancer. Inferring the exact prophage genomic location and completeness requires complete genomes. The international Helicobacter pylori Genome Project (HpGP) dataset comprises 1011 H. pylori complete clinical genomes enriched with epigenetic data. We thoroughly evaluated the H. pylori prophage genomic content in the HpGP dataset. We investigated population evolutionary dynamics through phylogenetic and pangenome analyses. Additionally, we identified genome rearrangements and assessed the impact of prophage presence on bacterial gene disruption and methylome. We found that 29.5% (298) of the HpGP genomes contain prophages, of which only 32.2% (96) were complete, minimizing the burden of prophage carriage. The prevalence of H. pylori prophage sequences was variable by geography and ancestry, but not by disease status of the human host. Prophage insertion occasionally results in gene disruption that can change the global bacterial epigenome. Gene function prediction allowed the development of the first model for lysogenic-lytic cycle regulation in H. pylori. We have disclosed new prophage inactivation mechanisms that appear to occur by genome rearrangement, merger with other mobile elements, and pseudogene accumulation. Our analysis provides a comprehensive framework for H. pylori prophage biological and genomics, offering insights into lysogeny regulation and bacterial adaptation to prophages.Intramural Research Program from the US National Cancer Institute (NCI), National Institutes of Health (NIH)
FCT: PTDC/BTM-TEC/3238/2020 and CPCA-IAC/AV/478719/2022, FCT projects UIDB/04138/ 2020, UIDP/04138/2020, and UIDB/04046/202
Air pollution mixture complexity and its effect on PM2.5-related mortality: A multicountry time-series study in 264 cities
No full textMCC Collaborative Research Network - INSA: Susana das Neves Pereira da Silva (Department of Epidemiology, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal); Joana Madureira (Department of Environmental Health, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal)Background: Fine particulate matter (PM2.5) occurs within a mixture of other pollutant gases that interact and impact its composition and toxicity. To characterize the local toxicity of PM2.5, it is useful to have an index that accounts for the whole pollutant mix, including gaseous pollutants. We consider a recently proposed pollutant mixture complexity index (PMCI) to evaluate to which extent it relates to PM2.5 toxicity.
Methods: The PMCI is constructed as an index spanning seven different pollutants, relative to the PM2.5 levels. We consider a standard two-stage analysis using data from 264 cities in the Northern Hemisphere. The first stage estimates the city-specific relative risks between daily PM2.5 and all-cause mortality, which are then pooled into a second-stage meta-regression model with which we estimate the effect modification from the PMCI.
Results: We estimate a relative excess risk of 1.0042 (95% confidence interval: 1.0023, 1.0061) for an interquartile range increase (from 1.09 to 1.95) of the PMCI. The PMCI predicts a substantial part of within-country relative risk heterogeneity with much less between-country heterogeneity explained. The Akaike information criterion and Bayesian information criterion of the main model are lower than those of alternative meta-regression models considering the oxidative capacity of PM2.5 or its composition.
Conclusions: The PMCI represents an efficient and simple predictor of local PM2.5-related mortality, providing evidence that PM2.5 toxicity depends on the surrounding gaseous pollutant mix. With the advent of remote sensing for pollutants, the PMCI can provide a useful index to track air quality.What this study adds: This study assesses to which extent the complexity of the air pollutant mix, including several gaseous pollutants, can explain differential mortality risks of PM2.5. It shows that this index can represent an efficient summary of the toxicity of PM2.5, especially when comparing cities within the same country.Supported by Environments and Health Signature Initiative of the Canadian Institutes for Health Research