Repositório Científico do Instituto Nacional de Saúde
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Predicted no effect concentrations of antifungals for wastewater management and agricultural use
Publication . Gil, D.; José, S.; Ascenso, A.; Babič, M. Novak; Segal, E.; Meletiadis, J.; Gangneux, J.P.; Weiskerger, C.J.; Solo-Gabriele, H.M.; Valério, E.; Brandão, J.
Antifungal resistance is an on-growing public health concern due to the difficulty in managing or treating medical conditions that often favour fatal fungal infections. The changing climate and globalisation, which increase fungal persistence and propagation, adds to that concern. Wastewater disposal is one potential source to the environment as antifungals are released into it. Considering that most fungal infections originate from the environment and considering the One Health principle, introducing antifungals through wastewater effluents has the potential to promote the emergence and dissemination of antifungal resistance. The objective of this study was to generate knowledge that can assist regulating the release of antifungals in the environment by quantifying predicted no-effect concentrations (PNECs) that would not promote antifungal resistance. For this purpose, a systematic review was performed to consolidate information on antifungals released to the environment and respective concentrations. The systematic literature review followed Preferred Reporting Items for Systematic literature reviews and Meta Analyses extension for Scoping Reviews (PRISMA-SLR). The analysis of 122 reviewed articles using this approach showed high concentrations and dispersion of antifungals in water, wastewater or soil. This highlights their potential dispersion in the environment, thus increasing the potential of fungal antimicrobial resistance. Due to the lack of PNEC values using fungi as model organisms in this review, PNECs for 17 antifungals were calculated using as model, as it is done for clinical purposes. We consider that the antifungal PNECs calculated and consolidated from the literature can be used to prioritise them for regulation and to determine acceptable levels in wastewater effluents.
Trends in delivery hospitalizations and the impact of ICD-9-CM to ICD-10-CM-PCS transition in Portugal between 2010 and 2018
Publication . Camarinha, Catarina de Paraíso; Oliveira, Maria Miguel Gomes; Elias, Cecília; Nobre, Miguel de Araújo; Nicolau, Leonor Bacelar Costa; Furtado, Cristina; Costa, Andreia Silva da; Nogueira, Paulo Jorge da Silva
Background: Hospital discharge data are essential for maternal health surveillance, clinical research, and healthcare resource allocation. In 2017, Portuguese hospitals transitioned from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, 10th edition, Clinical Modification and Procedure Coding System (ICD-10-CM/PCS), impacting the recording of delivery hospitalizations. This study examines trends in delivery hospitalizations from 2010 to 2018 and assesses the impact of the ICD-10-CM/PCS transition.
Methods: We conducted a register-based observational cross-sectional analysis using data from the National Hospital Discharge Database, covering delivery hospitalizations in public hospitals from January 1, 2010, to December 31, 2018. Delivery episodes were identified using diagnosis codes, normal delivery codes, diagnosis-related group (DRG) codes, and procedure codes. Statistical analyses included descriptive statistics, interrupted time series with segmented regression, and Prophet forecasting models to evaluate trends and the impact of the coding transition.
Results: A total of 673,978 delivery hospitalizations were recorded. The transition from ICD-9-CM to ICD-10-CM/PCS in 2017 had minimal overall impact on delivery trends. DRG codes consistently identified the majority of delivery episodes, with outcome of delivery codes and selected procedure codes showing varying trends. An increase in episodes identified by normal delivery codes and a significant decrease in episodes identified by procedure codes was observed immediately after the ICD-10 transition (p < 0.001). The Prophet model indicated improved forecast accuracy for procedure codes when including the ICD-10 transition variable.
Conclusion: The transition to ICD-10-CM/PCS had a limited impact on overall delivery hospitalization trends but significantly affected procedure coding. These findings underscore the importance of considering coding system changes in healthcare data analyses. Further research should incorporate private hospital data and continuously monitor coding practices to ensure reliable health data for research and policy-making.
SCCS Opinion on Benzophenone-1 (CAS No. 131-56-6, EC No. 205-029-4)
Publication . Scientific Committee on Consumer Safety (SCCS)
Conclusion of the opinion: (1) In light of the data provided and taking under consideration the concerns related to potential endocrine disrupting properties of Benzophenone-1, does the SCCS consider Benzophenone-1 safe when used as a light stabilizer in cosmetic products up to a maximum concentration of 2%?
Having considered the data provided (including two new mutagenicity/genotoxicity studies submitted to ECHA as part of the REACH registration dossier), and the concerns relating to genotoxicity and potential endocrine disrupting properties, the SCCS considers Benzophenone-1 not safe when used as a light stabiliser in cosmetic products for the following reasons:
The available data indicate genotoxicity potential of Benzophenone-1.
The evidence assessed by the SCCS also shows that Benzophenone-1 is an endocrine-active substance due to clear demonstration of estrogenic activity and weak anti-androgenic activity both in vitro and in vivo, and potential activity against thyroid modality in vitro.
A new (2023) OECD TG 422 study relating to ED effects submitted to ECHA as part of the REACH registration dossier has not been assessed by the SCCS at this stage because of the remaining concerns over genotoxicity of Benzophenone-1. The SCCS will be ready to assess the evidence in support of the safe use of Benzophenone-1 in cosmetic products when received in a new mandate.
(2) Alternatively, what is according to the SCCS the maximum concentration considered safe for use of Benzophenone-1 in cosmetic products?
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(3) Does the SCCS have any further scientific concerns with regard to the use of Benzophenone-1 in cosmetic products?
The SCCS mandate does not address environmental aspects. Therefore, this assessment has not covered the safety of BP-1 for the environment.
Vigilância Laboratorial da Tuberculose em Portugal: relatório 2025
Publication . Laboratório Nacional de Referência de Micobactérias
Relatório de Vigilância Laboratorial da Tuberculose em Portugal referente ao ano de 2025, elaborado pelo Laboratório Nacional de Referência de Micobactérias (LNR-TB) do Departamento de Doenças Infeciosas do INSA.
O documento apresenta a análise da vigilância molecular das estirpes do complexo Mycobacterium tuberculosis (MTC), com base em dados acumulados desde 2020, incluindo a caracterização genómica e a identificação de relações filogenéticas relevantes para a deteção de cadeias de transmissão.
Na sequência da implementação de metodologias baseadas em sequenciação do genoma total (WGS), o LNR-TB consolidou a sua capacidade para realizar, de forma sistemática, a caracterização genómica das estirpes de MTC. Esta abordagem permite a previsão do perfil de suscetibilidade aos antibacilares, incluindo de primeira linha, com elevado grau de fiabilidade, bem como a identificação precoce de eventos de transmissão. A utilização do WGS constitui, assim, uma ferramenta central para apoiar a decisão clínica e reforçar a resposta das Autoridades de Saúde, em linha com as recomendações europeias para países de baixa incidência de tuberculose.
A vigilância laboratorial das micobactérias foi ainda alargada, incluindo de forma continuada a monitorização de Mycobacterium leprae, já integrada desde 2023, e, pela primeira vez, a caracterização de casos de micobactérias não tuberculosas (MNT), refletindo a crescente relevância destas infeções no contexto clínico e epidemiológico.
Dos resultados apresentados no relatório, destacam-se os seguintes pontos:
- A confirmação bacteriológica da tuberculose mantém-se essencial para a monitorização da doença e para a determinação do perfil de suscetibilidade aos antibacilares, devendo ser sempre complementada com exames laboratoriais adequados;
- Os casos de tuberculose resistente à rifampicina ou multirresistente (TB-RR/MR) mantêm-se em vigilância, com variações anuais que justificam acompanhamento contínuo;
- A distribuição geográfica dos casos evidencia maior concentração nas regiões de Lisboa e Vale do Tejo e do Norte, à semelhança do observado em anos anteriores;
- A análise genómica permitiu identificar múltiplos clusters moleculares, incluindo cadeias de transmissão com persistência temporal, reforçando a importância da vigilância molecular contínua;
- Desde 2023, que se confirmam anualmente casos de infeção por Mycobacterium leprae, todos com enquadramento epidemiológico compatível, evidenciando a importância da capacidade diagnóstica instalada;
- A inclusão da vigilância das micobactérias não tuberculosas (MNT) constitui um avanço relevante, permitindo uma abordagem mais abrangente das infeções por micobactérias em Portugal;
- Em alinhamento com as mais recentes recomendações europeias, nomeadamente do European Reference Laboratory Network for Tuberculosis (ERLTB-Net), está em curso a transição para a utilização sistemática da sequenciação do genoma total (WGS) em todos os isolados de Mycobacterium tuberculosis, com o objetivo de substituir progressivamente os testes fenotípicos de suscetibilidade aos antibacilares de primeira linha. Esta abordagem permitirá uma resposta diagnóstica mais rápida, integrada e preditiva, reforçando a eficiência do sistema e a qualidade da informação disponibilizada a clínicos e autoridades de saúde.
Este relatório reforça o papel do INSA enquanto laboratório nacional de referência, evidenciando a importância da integração de ferramentas genómicas na vigilância laboratorial e no apoio à decisão clínica e em saúde pública.
Development of a multiplex PCR for tiled amplicon sequencing of highly variable Human Cytomegalovirus (HCMV) genomic regions
Publication . Carrasqueira, Patrícia; Ferreira, Rita; Lopo, Sílvia; Chasqueira, Maria de Jesus; Borges, Vítor; Paixão, Paulo; Gomes, João Paulo
Human cytomegalovirus (HCMV) possesses a ~236 kb genome and exhibits genetic diversity mostly concentrated in discrete hypervariable regions, such as envelope glycoprotein genes like UL55 (gB), UL73 (gN), and UL75 (gH), and recombination occurs frequently. Despite numerous efforts to associate viral polymorphisms and intra-patient population diversity with enhanced viral fitness, clinical outcomes, and latency, correlations remains inconclusive. Therefore, in this study a multiplex tiling PCR assay was developed, for the simultaneous sequencing of multiple hypervariable HCMV genomic regions, aiming for a comprehensive characterization of viral population variability and dynamics.
To take advantage of the vast potential of targeted next-generation sequencing (tNGS), a 2-pool primer scheme (51 amplicons) for multiplex tiling PCR was designed, taking into account the genetic diversity of 358 HCMV genome sequences available at NCBI Virus (https://www.ncbi.nlm.nih.gov/labs/virus). The novel multiplex targets seven independent genomic regions, encompassing 14 polymorphic loci of interest (UL33, UL55, UL73–UL75, UL100, UL115, UL128–UL131A, and UL144–UL147A). Protocol optimization and performance assays were conducted using Illumina NGS and subsequent bioinformatics analysis with the online platform INSaFLU-TELEVIR (https://insaflu.insa.pt/).
Preliminary results of the application of the novel multiplex tNGS assay to clinical samples (n = 11) from different matrices (urine, BALF, plasma, placenta) collected between 2020 and 2024 demonstrated its high potential, with successful amplification and sequencing of all amplicons in all samples with a Ct value ≤25. The assay also proved effective in sequencing highly polymorphic regions and detecting mixed infections. We anticipate that this innovative approach will open new avenues for characterizing circulating HCMV diversity and investigating whether viral population diversity and specific genetic profiles correlate with clinical outcomes, ultimately supporting earlier interventions and improved management of HCMV infections (e.g. congenital infections).