Repositório Científico do Instituto Nacional de Saúde
Entradas recentes
GLP-1 receptor agonists for obesity: eligibility across 99 countries
Publication . Yoo, Sang Gune K.; Teufel, Felix; Theilmann, Michaela; Si, Yajuan; Toure, Elhadji A.; Aryal, Krishna; Bärnighausen, Till; Bait, Abdul; Barreto, Marta; Bovet, Pascal; Brant, Luisa C.C.; Cuschieri, Sarah; Damasceno, Albertino; Farzadfar, Farshad; Fawwad, Asher; Geldsetzer, Pascal; Hambleton, Ian R.; Houehanou, Corine; Howitt, Christina; J Rgensen, Jutta; González-Rivas, Juan P.; Labadarios, Demetre; Marcus, Maja; Martins, João; Mwalim, Omar; Nieto-Martínez, Ramfis; Odili, Augustine N.; Orazumbekova, Binur; Perman, Gastón; Quesnel-Crooks, Sarah; Moghaddam, Sahar Saeedi; Sewpal, Ronel; Sousa-Uva, Mafalda; Sulola, Mubarak A.; Venkataraman, Kavita; Vollmer, Sebastian; Xueling, Sim; Atun, Rifat; Banegas, José R.; Franco, Juan V. A.; Arnott, Clare; Chandiwana, Nomathemba; Huffman, Mark D.; Davies, Justine; Ali, Mohammed K.; Flood, David; Manne-Goehler, Jennifer
We analysed pooled, individual participant data from nationally representative, cross-sectional household health surveys conducted in 99 countries between 2008 and 2021 (appendix pp 2–67). Our sample comprised non-pregnant individuals aged 25–64 years with an available diabetes biomarker, blood pressure measurement, and BMI measurement, as well as complete data on hypertension and diabetes diagnoses (appendix pp 69–75). Eligibility for GLP-1 receptor agonists was determined by applying the inclusion criteria from key randomised clinical trials.3,4 Individuals were defined as eligible for GLP-1 receptor agonists for weight management if they had a BMI of 30 kg/m2 or more or a BMI of 27 kg/m2 or more with hypertension or diabetes, or both—two common weight-related comorbidities. Hypertension was defined based on measured blood pressure and diabetes was defined based on glycaemic markers (HbA1c and plasma glucose). We did not consider other obesity-related comorbidities, such as obstructive sleep apnoea or cardiovascular disease, because data were not consistently available across surveys. For countries in the south, east, and southeast Asian region, we adjusted the eligibility to a BMI of 28 kg/m2 or more or a BMI of 24 kg/m2 or more with hypertension or diabetes, or both, in line with regionally based clinical trials.6 All statistical analyses included sampling weights that we rescaled in proportion to the countries’ population sizes. This study was deemed exempt from regulation by the institutional review board at the University of Michigan (Ann Arbor, MI, USA; HUM00201307).
Vaccine effectiveness against medically attended, laboratory-confirmed influenza in the I-MOVE primary care network in Europe, VEBIS project, 2024/25
Publication . Lucaccioni, Héloïse; Pozo, Francisco; Pérez-Gimeno, Gloria; Dürrwald, Ralf; Uras, Marina; Domegan, Lisa; Oroszi, Beatrix; Meijer, Adam; Trobajo-Sanmartín, Camino; Ujvari, Dorina; Rodrigues, Ana Paula; Mlinarić, Ivan; Lazar, Mihaela; Rivas Wagner, Eva; Erdwiens, Annika; Enouf, Vincent; McKenna, Adele; Túri, Gergő; de Lange, Marit; Martínez-Baz, Iván; Latorre-Margalef, Neus; Guiomar, Raquel; Kurečić Filipovic, Sanja; Dinu, Sorin; Mokoroa, Olatz; Tolksdorf, Kristin; Masse, Shirley; Bennett, Charlene; Kristóf, Katalin; Hooiveld, Mariette; Castilla, Jesús; Santos Almeida, João; Višekruna Vučina, Vesna; Popescu, Rodica; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther
Background: We conducted a multicenter test-negative study to estimate vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza in primary care, Europe, 2024/25.
Research design and methods: Specimens were collected from patients with acute respiratory infection. All or a random sample of viruses were sequenced. VE was (1-odds ratio) × 100, adjusted for confounders.
Results: We included 7275 cases and 17,516 controls (weeks 40-2024-18-2025). The overall VE was 46% (95% CI: 40-52), lowest in adults ≥65 years at 28% (95% CI: 12-42). VE against influenza A(H1N1)pdm09 was 30% (95% CI: 19-40); ranging 16-34% by age and vaccination target group. Most (88%) circulating clades were 5a.2a, distinct from the vaccine clade. VE was 28% (95% CI: 7-45) against 5a.2a (C.1.9), and 6% (95% CI: -62-45) against the vaccine-matched clade 5a.2a.1 (D). VE against influenza A(H3N2) was 38% (95% CI: 26-49); ranging 20-66% by age and target group. Circulating viruses belonged to the vaccine clade 2a.3a.1, with 88% subclade (J.2). VE against influenza B was 76% (95% CI: 69-81); ranging 70-80% by age and target group; all viruses belonged to the vaccine clade V1A.3a.2, with diverse subclades.
Conclusions: Influenza vaccination protected approximately one in two vaccinated individuals against medically attended infection in primary care in Europe, 2024/25, varying by (sub)type and age.
When disinfection fails: Biocide tolerance as a driver of campylobacter persistence and resistance
Publication . Fonseca, Inês M.; Martins, Inês; Oleastro, Mónica; Ferreira, Susana
Campylobacter spp. constitutes a significant global public health hazard as it is a leading cause of reported foodborne diseases. Human infection is predominantly acquired through the ingestion of contaminated food, unpasteurized milk and untreated water, prompting the widespread implementation of chemical disinfection across several sectors, from healthcare, domestic environments, and food-processing to animal husbandry. While these biocidal agents encompass multiples classes with different modes of action and efficacy, growing evidence suggests that their extensive and repeated use may unintentionally promote bacterial persistence, tolerance and adaptive responses. Although biocide resistance has been documented in several foodborne pathogens, data on biocide tolerance in Campylobacter spp. remain limited. Available studies report variable degrees of reduced susceptibility to commonly used biocides among isolates originating from poultry production, food-processing environments, and water systems. Importantly, while biocide-induced adaptive responses in Campylobacter spp. may potentially overlap with antimicrobial resistance mechanisms, the extent to which these agents drive co-selection, persistence, or dissemination requires further elucidation. Evidence remains limited on the effects of long-term and repeated exposure under realistic processing conditions, the interplay between stress-induced gene regulation and stable genetic changes, and the contribution of mobile genetic elements, biofilm formation, and microbial communities in shaping antimicrobial resistance evolution. In light of the global health burden imposed by campylobacteriosis and the rising challenge of antimicrobial-resistant Campylobacter, this review brings together current evidence on the role of biocides in shaping bacterial survival, adaptation, and resistance mechanisms.
Bioaccumulation and elimination kinetics of metals and polycyclic aromatic hydrocarbons in Hermetia illucens larvae: Implications for risk mitigation of selected contaminants in insect farming
Publication . Mostafaie, Amid; Silva, Patricia V.; Prodana, Marija; Silva, Ana Rita R.; Pinto, José N.; Duarte, Regina M.B.O.; Alvito, Paula; Coelho, Inês; Rego, Andreia; Lopes, Iva G.; Brooks, Bryan W.; Loureiro, Susana; Cardoso, Diogo N.
Rapidly expanding insect farming industries worldwide are raising concerns about introducing contaminants into food chains. One of the dominant species in this new bioindustry, the black soldier fly (Hermetia illucens), offers diverse benefits ranging from protein production to waste management, biofuel, and pharmaceutical applications. Recent studies have highlighted the ability of insects to accumulate metals; however, knowledge of their ability to eliminate contaminants is needed. Similarly, information regarding the accumulation of polycyclic aromatic hydrocarbons (PAHs) is lacking. This study aimed to understand how H. illucens larvae accumulate and eliminate metals and PAHs from contaminated substrates. We performed two-phase bioaccumulation experiments followed by toxicokinetic modelling to estimate uptake and elimination rate constants and half-lives in H. illucens. During the uptake phase, insects were exposed for five days to contaminated substrates at EU maximum feed concentrations: 2 mg kg−1 for As and Cd, 10 mg kg−1 for Pb, and 12.5 μg kg−1 for each of four PAHs (benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, chrysene). In the second phase, insects were exposed to non-contaminated substrates for five days to evaluate elimination. Results showed metal accumulation with kinetic bioaccumulation factors of 4.26, 1.16, and 1.31 for Cd, As, and Pb, respectively. A one-day depuration reduced As and Pb below regulatory thresholds; Cd required three days. Minimal to no accumulation was observed for B[a]P and B[b]F, with higher uptake for B[a]A. PAH half-lives were under one day. These findings, from controlled experiments with limited contaminants, support incorporating a depuration phase for risk mitigation in H. illucens waste-to-protein systems.
A single amino acid substitution in CspA increases germination sensitivity and broadens bile salt germinant specificity in clostridioides difficile spores
Publication . Roseiro, Isabel; Nunes, Alexandra; Martins, Diogo; Alves, Frederico; Persson, Søren; Henriques, Adriano O.; Oleastro, Mónica; Serrano, Mónica
Once regarded primarily as a healthcare-associated pathogen, Clostridioides difficile has increasingly been reported as a cause of community-acquired infection, raising questions about the contribution of animal and environmental reservoirs to persistence and transmission. Ribotype 033 (RT033) is predominantly associated with animal and environmental reservoirs, yet key traits underlying its ecology are poorly defined. Here we show that RT033 strains produce spores with enhanced germination sensitivity and expanded germinant specificity, enabling germination at low concentrations of bile-salts and in response to bile-salts that are typically inhibitory, including those more typical of animal hosts. Genetic analysis identified a single amino acid substitution (R1036I) in CspA, a component of the CspBAC germination apparatus, as the determinant of this phenotype. Expression of the RT033 cspBAC operon in a laboratory strain was sufficient to confer increased sensitivity and expanded bile-salt responsiveness. The R1036I substitution disrupts a conserved salt bridge at the CspA:CspC interface while not causing major destabilisation of the complex in the absence or presence of germinants and co-germinants. Together, our findings reveal a naturally occurring rewiring of bile-salt sensing in spores of RT033 strains that likely reflects adaptation to animal-associated bile-acid environments and may influence persistence, transmission, and zoonotic potential of this lineage.