Repositório Científico do Instituto Nacional de Saúde
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The potential bias introduced into COVID-19 vaccine effectiveness studies at primary care level due to the availability of SARS-CoV-2 tests in the general population
Publication . Lanièce Delaunay, Charlotte; Nunes, Baltazar; Monge, Susana; de Lange, Marit; Túri, Gergő; Machado, Ausenda; Latorre-Margalef, Neus; Mlinarić, Ivan; Lazar, Mihaela; Botella Rocamora, Paloma; Erdwiens, Annika; Sève, Noémie; Domegan, Lisa; Martínez-Baz, Iván; Hooiveld, Mariëtte; Oroszi, Beatrix; Guiomar, Raquel; Sperk, Maike; Kurečić Filipović, Sanja; Pascu, Catalina; Linares Dopido, Juan Antonio; Dürrwald, Ralf; Rameix-Welti, Marie-Anne; McKenna, Adele; Castilla, Jesús; van Hagen, Cheyenne; Knol, Mirjam; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther; VEBIS Primary Care Vaccine Effectiveness Group
Background: With SARS-CoV-2 self-tests, persons with acute respiratory infections (ARI) can know their COVID-19 status. This may alter their decision to consult a general practitioner (GP), potentially biasing COVID-19 vaccine effectiveness (VE) studies. We explore bias mechanisms, simulate magnitude, and verify control methods.
Methods: We used directed acyclic graphs (DAGs) to illustrate the bias mechanisms. Based on the European primary care VEBIS multicentre test-negative design (TND) study, we simulated populations with varying true VE (20%-60%), proportions of persons with ARI self-testing (10%-30%), effect of COVID-19 vaccination on self-testing (1.5-2.5), and effect of self-test result on GP consultation (0.5-2). We performed 5000 runs per scenario, estimating VE among those consulting a GP. We calculated bias as true VE minus mean simulated VE, unadjusted and adjusted for self-testing, using logistic regression.
Results: DAGs suggested collider stratification bias if vaccination had an effect on self-testing and if self-test results affected GP consultation. Bias was -12% to 18% at 20% true VE, with the most extreme associations and 30% self-testing. With 60% true VE and 10%-20% self-testing, bias was lower. Bias was higher (-18% to 45%) if both positive and negative self-test results affected GP consultation. Adjusting for self-testing removed the bias.
Conclusions: Self-testing may bias COVID-19 VE TND studies in primary care if self-testing is high, particularly with low VE. We recommend primary care TND VE studies collect self-testing information to eliminate potential bias. Observational studies are needed to understand the relationship between vaccination, self-testing, and GP consultation, in these studies' source population.
Description and comparison of national surveillance systems and response measures for Aedes-borne diseases in France, Italy and Portugal: a benchmarking study, 2023
Publication . Fotakis, Emmanouil Alexandros; Grau-Pujol, Berta; Kelly, David; Leite, Pedro Pinto; Martins, João Vieira; Alves, Maria João; Di Luca, Marco; Venturi, Giulietta; Ferraro, Federica; Franke, Florian; Pietin, Clément; Calba, Clémentine; Charles, Tanja; Riccardo, Flavia; Vasconcelos, Paula; Ramalli, Lauriane
Background: Regions of southern Europe are increasingly colonised by Aedes albopictus, with incidence of autochthonous dengue cases rising in recent years.AimWe describe and compare Aedes-borne disease (dengue, chikungunya and Zika) incidence from 2017 to 2023, and the surveillance systems and response measures operating in France, Italy and Portugal in 2023, to improve surveillance, prevention, preparedness and response in Europe.MethodsWe performed a benchmarking analysis to systematically capture the systems used in each country. We collected data from key-informant interviews, national guidelines, reports and scientific literature using a standardised questionnaire adapted from the European Centre for Disease Prevention and Control framework.ResultsAll three countries have an integrated surveillance system for Aedes-borne diseases and share similarities in surveillance type, geographic coverage and case definitions. Differences entail mainly event-based and active surveillance activities. Geographic coverage of vector surveillance is national in France and Portugal but regional in Italy. In response to autochthonous transmission, all countries implement/foresee active case-finding and blood safety protocols, while France and Italy strongly rely on vector control. Upon vector detection in non-colonised areas, the three countries implement ad hoc entomological surveillance and vector control.ConclusionsSurveillance systems and response measures in France, Italy and Portugal are broadly similar, with variations reflecting differences in healthcare system organisation (centralised in Portugal and France, regionalised in Italy), Ae. albopictus distribution and local transmission of Aedes-borne diseases. Risk-based surveillance, considering the national and cross-border epidemiological and entomological situations, can strengthen preparedness and early warning for Aedes-borne diseases in Europe.
Relative effectiveness of the second booster COVID-19 vaccines against laboratory confirmed SARS-CoV-2 infection in healthcare workers: VEBIS HCW VE cohort study (1 October 2022-2 May 2023)
Publication . Savulescu, Camelia; Prats-Uribe, Albert; Brolin, Kim; Uusküla, Anneli; Bergin, Colm; Fleming, Catherine; Zvirbulis, Viesturs; Zavadska, Dace; Szułdrzyński, Konstanty; Gaio, Vânia; Popescu, Corneliu Petru; Craiu, Mihai; Cisneros, Maria; Latorre-Millán, Miriam; Lohur, Liis; McGrath, Jonathan; Ferguson, Lauren; Abolina, Ilze; Gravele, Dagne; Machado, Ausenda; Florescu, Simin Aysel; Lazar, Mihaela; Subirats, Pilar; Clusa Cuesta, Laura; Sui, Jacklyn; Kenny, Claire; Krievins, Dainis; Barzdina, Elza Anna; Melo, Aryse; Kosa, Alma Gabriela; Miron, Victor Daniel; Muñoz-Almagro, Carmen; Milagro, Ana María; Bacci, Sabrina; Kramarz, Piotr; Nardone, Anthony; VEBIS HCW Study Group
Introduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs.
Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023. We estimated rVE of the second versus first COVID-19 vaccine booster dose against SARS-CoV-2 infection, overall, by time since second booster and restricted to the bivalent vaccines only. Using Cox regression, we calculated the rVE as (1-hazard ratio)*100, adjusting for hospital, age, sex, prior SARS-CoV-2 infection and at least one underlying condition.
Results: Among the 979 included HCWs eligible for a second booster vaccination, 392 (40 %) received it and 192 (20 %) presented an infection during the study period. The rVE of the second versus first booster dose was -5 % (95 %CI: -46; 25) overall, 3 % (-46; 36) in the 7-89 days after receiving the second booster dose. The rVE was 11 % (-43; 45) when restricted to the use of bivalent vaccines only.
Conclusion: The bivalent COVID-19 could have reduced the risk of SARS-CoV-2 infection among HCWs by 11 %. However, we note the limitation of imprecise rVE estimates due to the proportion of monovalent vaccine used in the study, the small sample size and the study being conducted during the predominant circulation of XBB.1.5 sub-lineage. COVID-19 vaccine effectiveness studies in HCWs can provide important evidence to inform the optimal timing and the use of updated COVID-19 vaccines.
Prevalence of T. rubrum and T. interdigitale Exhibiting High MICs to Terbinafine in Clinical Samples Analyzed in the Portuguese Mycology Reference Laboratory
Publication . Schirmer, Helena; Henriques, Camila; Simões, Helena; Veríssimo, Cristina; Sabino, Raquel
Cutaneous fungal infections represent a significant burden worldwide with a high impact on public health. Accurate identification of dermatophyte species causing these infections is vital for an appropriate treatment. Terbinafine is the primary agent against Trichophyton species due to its clinical efficacy; however, cases of elevated minimum inhibitory concentration (MIC) have been reported, raising clinical and epidemiological concerns. Herein, we aimed to detect Trichophyton rubrum and Trichophyton interdigitale isolates collected from clinical samples with terbinafine-high MICs (TRB-hMIC). A total of 168 isolates, recovered from 2017 to 2023, were identified as T. rubrum complex (140/83.4%) or T. interdigitale (28/16.7%) and further screened regarding their terbinafine susceptibility. Four isolates with capacity to grow in terbinafine media were detected by screening, and these and a further sixteen random isolates were submitted to the broth microdilution method. This methodology confirmed the four (2.4%) isolates as TRB-hMIC. One T. rubrum and three T. interdigitale showed a minimum inhibitory concentration (MIC) higher than 1 mg/L. Partial sequencing of the SQLE gene identified point mutations in T. rubrum (Phe397Iso) and in one T. interdigitale (Phe397Leu) isolate. Notably, in the other two T. interdigitale isolates with TRB-hMIC, no point mutations in the SQLE gene were identified. In conclusion, TRB-hMIC isolates (T. rubrum and T. interdigitale) were identified in clinical samples analyzed in Portugal, as antifungal susceptibility testing is a crucial routine for identifying treatment failures and also for epidemiological purposes aiming to monitor the dynamics of terbinafine resistance.
SOLARIS project: a portable 3D-printed bioaerosol sampler for environmental bacterial collection
Publication . Dobroes Fonseca, Pedro Henrique; Duarte, Filipe Miguel Borgas Henriques; Alves, Frederico Silva de Sousa; Borges, Jose Alberto de Jesus; Cardoso, Susana Isabel Pinheiro; Silverio, Vania Cristina Henriques; Antunes, Wilson David Talhao
Bioaerosols, a subset of aerosols released from the biosphere, can carry pathogens, and include particles with diameters from nanometres to a few micrometres. They can remain suspended indoors and travel significant distances. Bioaerosol studies play a vital role in public health, as bioaerosols are an effective route for human and animal pathogen transmission, especially in animal production and handling facilities, which are considered hotspots for the emergence of zoonotic pathogens. The 'One Health' approach, which interconnects human, animal and environmental health, underscores the need for robust biomonitoring and biosurveillance systems. We introduce the SOLARIS project, a novel bioaerosol sampler manufactured through three-dimensional printing with a biocompatible material. Our sampler is compact, portable and uses a liquid collection medium, increasing bioefficiency. Our sampler's laboratory testing demonstrated the successful separation of viable bacteria from artificially generated bioaerosols. Collected samples were found suitable for downstream analysis methods such as culturing, mass spectrometry, molecular detection and electron microscopy. A field trial at a swine facility was performed, in which spores were successfully collected from bioaerosols and identified using microbiological and molecular methods, reinforcing our sampler's utility and emphasizing the significance of incorporating aerosol samples in research studies within the One Health approach.