National Institute of Health Dr. Ricardo Jorge
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Hazard characterization of the mycotoxins enniatins and beauvericin to identify data gaps and improve risk assessment for human health
No full textEnniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.The European Partnership for the Assessment of Risks from Chemicals (PARC) has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014 and has received co-funding of the authors’ institutions. Funding Open Access funding enabled and organized by Projekt DEAL. HORIZON EUROPE Framework Programme 101057014.
https://doi.org/10.13039/100018693
Porphyrias – National Reference Laboratory Implementation for Biochemical and Molecular Diagnosis
No full textRelatório REVIVE 2024 - Culicídeos, Ixodídeos e Flebótomos: Rede de Vigilância de Vetores
No full textO programa REVIVE resulta da colaboração entre instituições do Ministério da Saúde (Direção-Geral da Saúde, Administrações Regionais de Saúde, Direções Regionais de Saúde e INSA).Relatório REVIVE - Rede de Vigilância de Vetores relativo às atividades desenvolvidas em 2024, que apresenta os resultados da vigilância de culicídeos, ixodídeos e flebótomos. O programa REVIVE visa monitorizar a atividade de artrópodes hematófagos, caracterizar as espécies e sua ocorrência sazonal, e identificar agentes patogénicos importantes em saúde pública.
Das atividades apresentadas no presente relatório, destaca-se o seguinte:
REVIVE – Culicídeos:
- Participaram as cinco Regiões de Saúde e a Direção Regional de Saúde da Madeira, entidades que realizaram colheitas de mosquitos em 241 concelhos de Portugal;
- No total foram identificados 38522 mosquitos de 18 espécies, assim como 65802 ovos de espécies invasoras. Nas amostras em que foi pesquisada a presença de flavivírus e alfavírus patogénicos para o Homem, os resultados foram negativos;
- O mosquito invasor Aedes aegypti está presente na Região Autónoma da Madeira desde 2005. Outra espécie de mosquitos invasor, Aedes albopictus, foi identificado, pela primeira vez, na região Norte de Portugal em 2017, no Algarve em 2018, no Alentejo em 2022, na região de Lisboa em 2023 e na região Centro em 2024. Estas espécies são vetoras de vírus como dengue, Zika e chikungunya, e têm vindo a aumentar a sua distribuição geográfica nestas regiões. Aedes albopictus foi identificado em 20 concelhos do país em 2024;
- No âmbito do REVIVE – Culicídeos foi feita a vigilância em cinco aeroportos internacionais, dois aeródromos, catorze portos e dez outros pontos de entrada de acordo com o Regulamento Sanitário Internacional.
REVIVE – Ixodídeos
- Participaram as cinco Regiões de Saúde e a Direção Regional de Saúde da Madeira, entidades que realizaram colheitas de carraças em 218 concelhos;
- No total foram identificadas 4797 carraças. Para além de 12 espécies de Ixodidae já anteriormente identificadas em Portugal, foram identificados exemplares exóticos de Argasidae que foram classificados como Argas e Ornithodoros spp.;
- Nas 1378 carraças utilizadas na pesquisa de Borreliae Rickettsia, em 6,7% e 22,7% respetivamente, foi detetado DNA destes agentes. Nem todas as espécies detetadas são patogénicas para o Homem.
- Em 2024 destaca-se assim a deteção de quatro espécies de Borreliae quatro espécies de Rickettsia, já associadas a casos de doença no Homem em Portugal: afzelii, B. garinii, B. lusitaniae e B. valaisiana, agentes etiológicos da borreliose de Lyme; R. conorii agente da febre escaro-nodular; R. monacensis e R. raoultii sem denominação da doença e R. slovaca, agente responsável de TIBOLA. A pesquisa do vírus da febre hemorrágica Crimeia-Congo (CCHFV) foi realizada em 124 exemplares de carraças do género Hyalomma com resultados negativos.
REVIVE – Flebótomos
- Participaram as cinco Regiões de Saúde, com colheitas realizadas em 50 concelhos;
- No total foram colhidos 1046 flebótomos, tendo sido identificados exemplares pertencentes às espécies Phlebotomus ariasi, Ph. perniciosus, Ph. Sergente e Sergentomyia minuta;
- Nos 616 flebótomos pesquisados para a presença de flebovírus e de Leismania spp. foi detetada a presença de Leishmania infantum num pool
Wolbachia Screening in Aedes aegypti and Culex pipiens Mosquitoes from Madeira Island, Portugal
No full text(This article belongs to the Section Medical and Livestock Entomology)Simple Summary: Mosquitoes can spread serious diseases like dengue and West Nile virus. On Madeira Island, two mosquito species—Aedes aegypti and Culex pipiens—are present and may pose a risk to public health. Scientists are exploring new ways to control these mosquitoes using a natural bacterium called Wolbachia, which can reduce a mosquito’s ability to transmit viruses and even lower mosquito populations. However, for these methods to work, it is important to know first if the mosquitoes in the area already carry this bacterium. In this study, we tested Ae. aegypti and Cx. pipiens from Madeira for Wolbachia. Wolbachia was absent in all 100 Ae. aegypti tested but present in all 40 Cx. pipiens. We also found that the Wolbachia in Cx. pipiens belonged to a group commonly seen in other parts of the world. These results are important because they help us understand which mosquito control strategies might work in Madeira. Specifically, if scientists want to use Wolbachia to control Ae. aegypti on the island, they would need to introduce it artificially. This information can help improve public health efforts and reduce the risk of mosquito-borne diseases in the region.Abstract: Mosquito-borne diseases such as dengue and West Nile virus pose serious public health risks. On Madeira Island, the presence of the mosquito species Aedes aegypti (Linnaeus, 1762) and Culex pipiens (Linnaeus, 1758) raises concerns about local transmission. In this study, we tested 100 Ae. aegypti and 40 Cx. pipiens mosquitoes collected exclusively in the municipality of Funchal, Madeira Island, to assess the presence and diversity of Wolbachia, a naturally occurring bacterium known to reduce mosquitos' ability to transmit viruses. Molecular identification confirmed that all Cx. pipiens specimens belonged to the molestus biotype, with three individuals identified as hybrids between molestus and pipiens biotypes. This is the first evidence of such hybrids in Madeira. Wolbachia was not detected in any of the Ae. aegypti samples. In contrast, all Cx. pipiens mosquitoes were positive, showing a 100% prevalence. Genetic characterization placed these infections within the wPip clade, supergroup B, sequence type 9. These findings provide key baseline data to inform future mosquito control strategies on the island. As Ae. aegypti showed no natural Wolbachia infection, introducing Wolbachia-infected mosquitoes may be necessary to implement such biocontrol approaches in Madeira.This work was funded by the European Innovation Council and SMEs Executive Agency (EISMEA), project MOBVEC-Mobile Bio-Lab to support the first response in Arbovirus outbreaks, reference HORIZON-EIC-2022-PATHFINDEROPEN-01, with the grant agreement number 101099283; and PhD fellowships funded by Fundação para a Ciência e a Tecnologia (FCT), references: 2023.05286.BD and 2022.13476.BDANA.Acknowledgments to the Interactive Technologies Institute/Larsys, funded by FCT projects 10.54499/LA/P/0083/2020, 10.54499/UIDP/50009/2020 and 10.54499/UIDB/50009/2020
Mapping susceptibility to air pollution and its association with birth defects: a tool for public health intervention
No full textEpidemiological studies evaluating the relation of environmental air pollution (AP) and birth defect (BD) are relevant to public health. Some limitations on these studies may derive from multiple factors contributing to the spatial variation of AP. This study aimed to integrate multifactorial AP indicators into an index and explore its application in a case-control study conducted in Portugal between 2016 and 2021. Spatial multicriteria analysis was employed to identify areas susceptible to AP. Variables included: (i) Euclidean distance to industrial units; (ii) kernel estimation of industrial units density; (iii) land occupation; (iv) Euclidean distance to main roads; and (v) areas conductive to radiation fog formation. Variables were classified into high, moderate, and low susceptibility. An AP susceptibility map was generated using the weighted linear combination method, with the analytic hierarchy process assigning weights to the variables. Georeferenced BD cases and controls were overlaid with environmental exposure variables and the AP index. Three AP susceptibility areas were identified: consolidated urban, peri-urban area, and a residential–industrial area. In areas of high susceptibility, 47 cases (29%) and 65 controls (31%) were observed; and in areas of low susceptibility 25 cases (15%) and 21 controls (10%) were observed. The development of the AP susceptibility map has been demonstrated to be a valuable tool for identifying patterns, generating hypotheses regarding the potential environmental exposure of NB to AP agents during pregnancy.
When integrated into more complex analyses, these findings may contribute to assess the potential risk factors that play a major role in BD.Key points: - A case-control study was conducted to investigate the association between birth defects and maternal environmental exposure during pregnancy; - Spatial multicriteria analysis methodology was applied using geographic information system software; Five environmental factors were considered, each contributing to the emission and concentration of air pollutants in varying degrees: distance from polluting economic activities, density of polluting economic activities per square kilometer, distance to major road traffic, land use type and areas conducive to radiation fog formation; - A spatial index of air pollution susceptibility was generated; - Spatial analysis methodologies can be valuable tools for public health intervention
Twenty years of expanded newborn screening for metabolic diseases in Portugal (2004-2024)
No full textDengue and Oropouche virus co-infection in a traveller from Cuba to Portugal
No full textIn 2024, unprecedented outbreaks of dengue and Oropouche were reported in the Americas. We describe a documented co-infection with dengue and Oropouche viruses in a 35-year-old traveller from Cuba detected in Portugal. RT-PCR and next-generation sequencing confirmed both viruses. Our findings highlight the need for multiplex arboviral diagnostics in travellers from regions with concurrent outbreaks.This work was supported by DURABLE “Research Network against Epidemics” project co-funded by The European Commission Union under the EU4Health Programme (EU4H) [101102733 to V.B.]. This work was also supported by the European Union project “Sustainable use and integration of enhanced infrastructure into routine genome-based surveillance and outbreak investigation activities in Portugal”—GENEO [101113460 to J.P.G.] on behalf of the EU4H programme [EU4H-2022-DGA-MS-IBA-01-02]. This work was partially supported by the Portuguese Foundation for Science and Technology [FCT/MCTES UIB/00211/2020—DOI 10.54499/UIDB/00211; FCT/MCTES UIP/00211/2020—DOI 10.54499/UIDP/00211 to L.Z.Z.] and by the Wellcome Trust Dengue and Zika Immunology and Genomics Multi-CountryNetwork (DeZi Network) [316633/Z/24/Z to L.Z.Z and N.R.F.]
Department of Human Genetics of INSA, a pioneer in the molecular characterization of inherited bleeding and thrombotic disorders in the Portuguese population
No full textMulti-Network approach to predict new proteins involved in NMD
No full textThe mechanism of nonsense-mediated decay (NMD) selectively degrades mRNAs carrying a premature translation-termination codon and regulates the abundance of a large number of physiological mRNAs that encode full-length proteins. Although this complex process has been extensively studied along the years, the interactions and connectivity among NMD players is not completely understood. Additionally, some NMD mechanistical aspects suggest missing roles that can be played by proteins still not reported as involved in this pathway.
To tackle this hypothesis, we developed a bioinformatic network-based approach to predict new proteins involved in NMD. Our approach consists in performing several queries to different types of publicly available data, in order to explore the ability of proteins to bridge related processes, while integrating data regarding protein-protein interactions, co-expression and co-regulation.
We found that known NMD-factors have physical, regulatory and co-expression interaction signatures with related processes (mRNA translation, mRNA splicing, mRNA degradation and mRNA transport), which can be used to distinguish them from other proteins. We computed a scoring algorithm to rank NMD-neighbors according to the similarity to these signatures, generating a list of NMD candidates, that we aim to validate experimentally. Interestingly, some candidates were recently studied in NMD context and showed promising results. Furthermore, a cross-validation analysis indicated the robustness of the predictions provided by our method.
On the road to developing a tool to apply this approach to other biological processes, we observed good cross-validations results for other RNA-related processes, suggesting this method’s usefulness in the RNA research area.Partially supported by UID/MULTI/04046/2019 center grant from FCT to BioISI.
Gonçalo Nogueira is recipient of a fellowship from BioSys PhD programme (PD/BD/130959/2017) from FCT.info:eu-repo/semantics/publishedVersio
Genotipagem de isolados de Aspergillus fumigatus de origem clínica e ambiental
No full textDissertação de Mestrado em Microbiologia Aplicada, apresentada à Faculdade de Ciências da Universidade de Lisboa, 2022.Dissertação de Mestrado defendida em janeiro 2023O trabalho apresentado nesta Dissertação de Mestrado foi
realizado no Instituto Nacional de Saúde Doutor Ricardo Jorge
sob a orientação direta da Doutora Raquel Sabino. A Professora Doutora Margarida Barata foi a orientadora interna da Faculdade de Ciências da Universidade de Lisboa.Aspergillus fumigatus é um fungo sapróbio, ubíquo no ambiente, com crescente importância clínica para a saúde humana, pois é responsável por provocar, entre outras patologias, infeções invasivas graves, especialmente em indivíduos imunocomprometidos.
Dada a elevada taxa de mortalidade associada às infeções relacionadas com este fungo, bem como a emergência de um grave problema de resistência aos antifúngicos triazóis utilizados como primeira linha de tratamento nestas, torna-se importante perceber a sua dinâmica no ambiente e no organismo humano. Além disso, o aparecimento de novos grupos de risco aos quais a infeção está associada, tem vindo a levantar também uma crescente preocupação no que toca aos critérios para diagnóstico e tratamento da doença, que ainda representam um desafio.
O conhecimento da epidemiologia do fungo permite uma melhor perceção das suas interações com o ambiente e com o Homem, tornando esta área de elevada importância no contexto da relevância crescente de Aspergillus fumigatus na clínica.
No presente estudo, foi utilizada uma técnica robusta de genotipagem, específica para Aspergillus fumigatus sensu stricto, o ensaio STRAf, que permite distinguir diferentes estirpes desta espécie, através da amplificação de loci específicos numa reação de amplificação multiplex com primers marcados com fluorescência.
Com o ensaio realizado foi possível comprovar a grande variabilidade genética de Aspergillus fumigatus, tendo-se observado 85 genótipos de entre os 100 isolados viáveis analisados. Foi também possível perceber a interação entre alguns dos isolados em estudo. A técnica revelou, como esperado, um elevado poder discriminatório (0,9820) o que confirma a sua utilidade em futuros estudos epidemiológicos de grande escala, essenciais para melhor entender como abordar a problemática crescente que este fungo tem representado.Aspergillus fumigatus is a saprophytic fungus, ubiquitous in the environment, with increasing clinical relevance for human health. This fungus is responsible for causing, among other pathologies, severe invasive infections, particularly in immunocompromised individuals. Given the high mortality rate associated with these infections, as well as the emergence of a serious problem of resistance to triazole antifungals, used as the first line of treatment in Aspergillus infections, it is important to comprehend its dynamics in the environment and in the human body. In addition, the emergence of new risk groups to which the infection is associated, is also raising growing concerns about the criteria for diagnosis and treatment of the disease, which still poses a challenge. Understanding the epidemiology of the fungus allows a better perception of its interactions with the environment and with humans, which makes epidemiology, an area of great importance in the context of the growing relevance of Aspergillus fumigatus in human health. In the present study, a robust genotyping technique, specific to Aspergillus fumigatus sensu stricto, the STRAf assay, was used. The assay allows the distinction of different strains of this species, through amplification of specific loci in a multiplex amplification reaction with fluorescent-labeled primers. With the assay performed, it was possible to verify the great genetic variability of Aspergillus fumigatus, and 85 genotypes were observed, among the 100 viable isolates analyzed. It was also possible to perceive the interaction between some of the isolates under study. The technique revealed, as expected, a high discriminatory power (0,9820) which confirms its usefulness in future large-scale epidemiological studies, essential to better understand how to approach the growing problem that A. fumigatus is becoming.N/