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Background: European epidemic intelligence (EI) systems receive vast amounts of information and data on disease outbreaks and potential health threats. The quantity and variety of available data sources for EI, as well as the available methods to manage and analyse these data sources, are constantly increasing. Our aim was to identify the difficulties encountered in this context and which innovations, according to EI practitioners, could improve the detection, monitoring and analysis of disease outbreaks and the emergence of new pathogens., Methods: We conducted a qualitative study to identify the need for innovation expressed by 33 EI practitioners of national public health and animal health agencies in five European countries and at the European Centre for Disease Prevention and Control (ECDC). We adopted a stepwise approach to identify the EI stakeholders, to understand the problems they faced concerning their EI activities, and to validate and further define with practitioners the problems to address and the most adapted solutions to their work conditions. We characterized their EI activities, professional logics, and desired changes in their activities using NvivoⓇ software., Results: Our analysis highlights that EI practitioners wished to collectively review their EI strategy to enhance their preparedness for emerging infectious diseases, adapt their routines to manage an increasing amount of data and have methodological support for cross-sectoral analysis. Practitioners were in demand of timely, validated and standardized data acquisition processes by text mining of various sources; better validated dataflows respecting the data protection rules; and more interoperable data with homogeneous quality levels and standardized covariate sets for epidemiological assessments of national EI. The set of solutions identified to facilitate risk detection and risk assessment included visualization, text mining, and predefined analytical tools combined with methodological guidance. Practitioners also highlighted their preference for partial rather than full automation of analyses to maintain control over the data and inputs and to adapt parameters to versatile objectives and characteristics., Conclusions: The study showed that the set of solutions needed by practitioners had to be based on holistic and integrated approaches for monitoring zoonosis and antimicrobial resistance and on harmonization between agencies and sectors while maintaining flexibility in the choice of tools and methods. The technical requirements should be defined in detail by iterative exchanges with EI practitioners and decision-makers., (© 2024. The Author(s).)

Background: The natural transmission cycle of tick-borne encephalitis (TBE) virus is enhanced by complex interactions between ticks and key hosts strongly connected to habitat characteristics. The diversity of wildlife host species and their relative abundance is known to affect transmission of tick-borne diseases. Therefore, in the current context of global biodiversity loss, we explored the relationship between habitat richness and the pattern of human TBE cases in Europe to assess biodiversity's role in disease risk mitigation., Methods: We assessed human TBE case distribution across 879 European regions using official epidemiological data reported to The European Surveillance System (TESSy) between 2017 and 2021 from 15 countries. We explored the relationship between TBE presence and the habitat richness index (HRI 1 ) by means of binomial regression. We validated our findings at local scale using data collected between 2017 and 2021 in 227 municipalities located in Trento and Belluno provinces, two known TBE foci in northern Italy., Findings: Our results showed a significant parabolic effect of HRI on the probability of presence of human TBE cases in the European regions included in our dataset, and a significant, negative effect of HRI on the local presence of TBE in northern Italy. At both spatial scales, TBE risk decreases in areas with higher values of HRI., Interpretation: To our knowledge, no efforts have yet been made to explore the relationship between biodiversity and TBE risk, probably due to the scarcity of high-resolution, large-scale data about the abundance or density of critical host species. Hence, in this study we considered habitat richness as proxy for vertebrate host diversity. The results suggest that in highly diverse habitats TBE risk decreases. Hence, biodiversity loss could enhance TBE risk for both humans and wildlife. This association is relevant to support the hypothesis that the maintenance of highly diverse ecosystems mitigates disease risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

During the pandemic outdoor activities were encouraged to mitigate transmission risk while providing safe spaces for social interactions. Human behaviour, which may favour or disfavour, contact rates between questing ticks and humans, is a key factor impacting tick-borne encephalitis (TBE) incidence. We analyzed annual and weekly TBE cases in Finland, Norway and Sweden from 2010 to 2021 to assess trend, seasonality, and discuss changes in human tick exposure imposed by COVID-19. We compared the pre-pandemic incidence (2010-2019) with the pandemic incidence (2020-2021) by fitting a generalized linear model (GLM) to incidence data. Pre-pandemic incidence was 1.0, 0.29 and 2.8 for Finland, Norway and Sweden, respectively, compared to incidence of 2.2, 1.0 and 3.9 during the pandemic years. However, there was an increasing trend for all countries across the whole study period. Therefore, we predicted the number of cases in 2020/2021 based on a model fitted to the annual cases in 2010-2019. The incidences during the pandemic were 1.3 times higher for Finland, 1.7 times higher for Norway and no difference for Sweden. When social restrictions were enforced to curb the spread of SARS-CoV-2 there were profound changes in outdoor recreational behavior. Future consideration of public health interventions that promote outdoor activities may increase exposure to vector-borne diseases., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

BackgroundTick-borne encephalitis (TBE) is a disease which can lead to severe neurological symptoms, caused by the TBE virus (TBEV). The natural transmission cycle occurs in foci and involves ticks as vectors and several key hosts that act as reservoirs and amplifiers of the infection spread. Recently, the incidence of TBE in Europe has been rising in both endemic and new regions.AimIn this study we want to provide comprehensive understanding of the main ecological and environmental factors that affect TBE spread across Europe.MethodsWe searched available literature on covariates linked with the circulation of TBEV in Europe. We then assessed the best predictors for TBE incidence in 11 European countries by means of statistical regression, using data on human infections provided by the European Surveillance System (TESSy), averaged between 2017 and 2021.ResultsWe retrieved data from 62 full-text articles and identified 31 different covariates associated with TBE occurrence. Finally, we selected eight variables from the best model, including factors linked to vegetation cover, climate, and the presence of tick hosts.DiscussionThe existing literature is heterogeneous, both in study design and covariate types. Here, we summarised and statistically validated the covariates affecting the variability of TBEV across Europe. The analysis of the factors enhancing disease emergence is a fundamental step towards the identification of potential hotspots of viral circulation. Hence, our results can support modelling efforts to estimate the risk of TBEV infections and help decision-makers implement surveillance and prevention campaigns.

Ticks are amongst the most important zoonotic disease vectors affecting human and animal health worldwide. Tick-borne diseases (TBDs) are rapidly expanding geographically and in incidence, most notably in temperate regions of Europe where ticks are considered the principal zoonotic vector of Public Health relevance, as well as a major health and economic preoccupation in agriculture and equine industries. Tick-borne pathogen (TBP) transmission is contingent on complex, interlinked vector-pathogen-host dynamics, environmental and ecological conditions and human behavior. Tackling TBD therefore requires a better understanding of the interconnected social and ecological variables (i.e., the social-ecological system) that favor disease (re)-emergence. The One Health paradigm recognizes the interdependence of human, animal and environmental health and proposes an integrated approach to manage TBD. However, One Health interventions are limited by significant gaps in our understanding of the complex, systemic nature of TBD risk, in addition to a lack of effective, universally accepted and environmentally conscious tick control measures. Today individual prevention gestures are the most effective strategy to manage TBDs in humans and animals, making local communities important actors in TBD detection, prevention and management. Yet, how they engage and collaborate within a multi-actor TBD network has not yet been explored. Here, we argue that transdisciplinary collaborations that go beyond research, political and medical stakeholders, and extend to local community actors can aid in identifying relevant social-ecological risk indicators key for informing multi-level TBD detection, prevention and management measures. This article proposes a transdisciplinary social-ecological systems framework, based on participatory research approaches, to better understand the necessary conditions for local actor engagement to improve TBD risk. We conclude with perspectives for implementing this methodological framework in a case study in the south of France (Occitanie region), where multi-actor collaborations are mobilized to stimulate multi-actor collective action and identify relevant social-ecological indicators of TBD risk., Competing Interests: None., (© 2023 The Authors. Published by Elsevier B.V.)

We present the findings from the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) Member Survey conducted in October to December 2021. The EAN consists of field epidemiologists (EPIET) and public health microbiologists (European Public Health Microbiology Training Programme (EUPHEM)) who stay connected after their 2-year fellowship. This active alumni network provides opportunities for career development, mentorship, knowledge exchange and sharing of best practices for community members, affiliated professionals and public health organisations in Europe. Overall, 281 of 732 members participated in the survey. Of the 192 European fellowship alumni respondents, 173 (90%) indicated that skills and competencies acquired during their fellowship improved performance in their role compared with their abilities before the fellowship. Reported skills and competencies that could be further strengthened included data management/analysis, communication, mathematical modelling and leadership/team management. The EAN Member Survey provides valuable feedback to the EAN, as well as the fellowship programme offices at the European Centre for Disease Prevention and Control (ECDC) and affiliated field epidemiology programmes. The COVID-19 pandemic was a stark reminder of how essential cross-border collaborations are for continued European health security. Maintaining and increasing the professional, well-trained workforce remains crucial for optimal response to infectious diseases and protection of public health.

Epidemic Intelligence (EI) encompasses all activities related to early identification, verification, analysis, assessment, and investigation of health threats. It integrates an indicator-based (IBS) component using systematically collected surveillance data, and an event-based component (EBS), using non-official, non-verified, non-structured data from multiple sources. We described current EI practices in Europe by conducting a survey of national Public Health (PH) and Animal Health (AH) agencies. We included generic questions on the structure, mandate and scope of the institute, on the existence and coordination of EI activities, followed by a section where respondents provided a description of EI activities for three diseases out of seven disease models. Out of 81 gatekeeper agencies from 41 countries contacted, 34 agencies (42%) from 26 (63%) different countries responded, out of which, 32 conducted EI activities. Less than half (15/32; 47%) had teams dedicated to EI activities and 56% (18/34) had Standard Operating Procedures (SOPs) in place. On a national level, a combination of IBS and EBS was the most common data source. Most respondents monitored the epidemiological situation in bordering countries, the rest of Europe and the world. EI systems were heterogeneous across countries and diseases. National IBS activities strongly relied on mandatory laboratory-based surveillance systems. The collection, analysis and interpretation of IBS information was performed manually for most disease models. Depending on the disease, some respondents did not have any EBS activity. Most respondents conducted signal assessment manually through expert review. Cross-sectoral collaboration was heterogeneous. More than half of the responding institutes collaborated on various levels (data sharing, communication, etc.) with neighbouring countries and/or international structures, across most disease models. Our findings emphasise a notable engagement in EI activities across PH and AH institutes of Europe, but opportunities exist for better integration, standardisation, and automatization of these efforts. A strong reliance on traditional IBS and laboratory-based surveillance systems, emphasises the key role of in-country laboratories networks. EI activities may benefit particularly from investments in cross-border collaboration, the development of methods that can automatise signal assessment in both IBS and EBS data, as well as further investments in the collection of EBS data beyond scientific literature and mainstream media., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The COVID-19 pandemic has shown the need for better global governance of pandemic prevention, preparedness, and response (PPR) and has emphasised the importance of organised knowledge production and uptake. In this Health Policy, we assess the potential values and risks of establishing an Intergovernmental Panel for One Health (IPOH). Similar to the Intergovernmental Panel on Climate Change, an IPOH would facilitate knowledge uptake in policy making via a multisectoral approach, and hence support the addressing of infectious disease emergence and re-emergence at the human-animal-environment interface. The potential benefits to pandemic PPR include a clear, unified, and authoritative voice from the scientific community, support to help donors and institutions to prioritise their investments, evidence-based policies for implementation, and guidance on defragmenting the global health system. Potential risks include a scope not encompassing all pandemic origins, unclear efficacy in fostering knowledge uptake by policy makers, potentially inadequate speed in facilitating response efforts, and coordination challenges among an already dense set of stakeholders. We recommend weighing these factors when designing institutional reforms for a more effective global health system., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies after hantavirus infection, together with the observation that PUUV infects B cells, motivated us to study the risk of lymphoid malignancies after PUUV infection., Methods: We linked data from the Finnish Cancer Registry and National Infectious Diseases Register for 2009-2019. We used a time-dependent Cox regression model to evaluate the hazard of the lymphoid malignancies grouped according to the HAEMACARE classification., Results: We identified 68 cases of lymphoid malignancies after PUUV infection among 16,075 PUUV-infected individuals during 61,114,826 person-years of observation. A total of 10 cases occurred within 3-<12 months and 38 within 1-<5 years after PUUV infection, and the risk of lymphoid malignancies increased with hazard ratios (HRs) of 2.0 (95% confidence interval [CI], 1.1-3.7) and 1.6 (95% CI, 1.2-2.3), respectively. The group of mature B cell neoplasms showed an increased risk 3-<12 months and 1-<5 years after PUUV infection, HR 2.2 (95% CI, 1.2-4.3) and HR 1.8 (95% CI, 1.3-2.5), respectively., Conclusion: PUUV infection is associated with lymphoid malignancies in the Finnish population, supporting the earlier studies. Further research is required to understand the pathophysiological mechanisms behind this association., Competing Interests: Declaration of competing interest TD works in Monitoring Outbreaks for Disease surveillance in a data science context (MOOD)/Horizon 2020 project, for which funding is received from the Finnish Institute for Health and Welfare and is a member of the executive board of MOOD Horizon 20202. TD also works on a project for vector-borne diseases and climate change in Finland (VECLIMIT), for which funding is received by the Finnish Institute for Health and Welfare from the Academy of Finland. JS owns stocks in a company (Genmab) that is involved in lymphoma drug development. EK reports a grant paid for their institution from the Finnish Society of Sciences and Letters for PUUV research outside of the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Long-term care facilities (LTCF) residents are at high risk for severe coronavirus disease 2019 (COVID-19), and therefore, COVID-19 vaccinations were prioritized for residents and personnel in Finland at the beginning of 2021., Methods: We investigated COVID-19 outbreaks in two LTCFs, where residents were once or twice vaccinated. After the outbreaks we measured immunoglobulin G (IgG) antibodies to severe acute respiratory syndrome coronavirus 2 spike glycoprotein, neutralizing antibody (NAb) titers, and cell-mediated immunity markers from residents and healthcare workers (HCWs)., Results: In LTFC-1, the outbreak was caused by an Alpha variant (B.1.1.7) and the attack rate (AR) among once vaccinated residents was 23%. In LTCF-2 the outbreak was caused by a Beta variant (B.1.351). Its AR was 47% although all residents had received their second dose 1 month before the outbreak. We observed that vaccination had induced lower IgG concentrations, NAb titers and cell-mediated immune responses in residents compared to HCWs. Only 1/8 residents had NAb to the Beta variant after two vaccine doses., Conclusions: The vaccinated elderly remain susceptible to breakthrough infections caused by Alpha and Beta variants. The weaker vaccine response in the elderly needs to be addressed in vaccination protocols, while new variants capable of evading vaccine-induced immunity continue to emerge., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for "Unity-aligned" First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases; 16 provided by Unity Studies collaborators) were retained in the systematic review; 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%-71%; I 2  = 99.7%); I 2 values remained >99% in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses., (© 2022 World Health Organization; licensed by John Wiley & Sons Ltd. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.

Background: Household transmission studies offer the opportunity to assess both secondary attack rate (SAR) and persistence of SARS-CoV-2 antibodies over time., Methods: In Spring 2020, we invited confirmed COVID-19 cases and their household members to four visits, where we collected nasopharyngeal and serum samples over 28 days after index case onset. We calculated SAR based on the presence of SARS-CoV-2 neutralizing antibodies (NAb) and assessed the persistence of NAb and IgG antibodies (Ab) against SARS-CoV-2 spike glycoprotein and nucleoprotein., Results: SAR was 45% (39/87), including 35 symptomatic secondary cases. During the initial 28-day follow-up, 62% (80/129) of participants developed NAb. Of those that seroconverted, 90% (63/70), 85% (63/74), and 78% (45/58) still had NAb to early B-lineage SARS-CoV-2 3, 6, and 12 months after the onset of the index case. Anti-spike IgG Ab persisted in 100% (69/69), 97% (72/74), and 93% (55/59) of seroconverted participants after 3, 6, and 12 months, while anti-nucleoprotein IgG Ab levels waned faster, persisting in 99% (68/69), 78% (58/74), and 55% (39/71) of participants, respectively., Conclusion: Following detection of a COVID-19 case in a household, other members had a high risk of becoming infected. NAb to early B-lineage SARS-CoV-2 persisted for at least a year in most cases., Competing Interests: The Finnish Institute for Health and Welfare had received research funding for studies not related to COVID-19 from GlaxoSmithKline Vaccines (NE, CV, AP, and MM as investigators), Pfizer (AP), and Sanofi Pasteur (AP). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dub, Solastie, Hagberg, Liedes, Nohynek, Haveri, Virta, Vara, Lasander, Ekström, Österlund, Lind, Valtonen, Hemmilä, Ikonen, Lukkarinen, Palmu and Melin.)

BackgroundIn Finland, surveillance of tularaemia relies on laboratory-confirmed case notifications to the National infectious Diseases Register (NIDR).AimThe aim of the study was to assess the suitability and usefulness of clinical surveillance as an addition to laboratory notification to improve tularaemia surveillance in Finland.MethodsWe retrieved NIDR tularaemia surveillance and primary healthcare data on clinically diagnosed tularaemia cases in Finland between 2013 and 2019. We compared incidences, demographic distributions and seasonal trends between the two data sources.ResultsThe median annual incidence was 0.6 (range: 0.1-12.7) and 0.8 (range: 0.6-7.2) per 100,000 for NIDR notifications and primary healthcare notifications, respectively. Cases reported to NIDR were slightly older than cases reported to primary healthcare (median: 53 years vs 50 years, p = 0.04), but had similar sex distribution. Seasonal peaks differed between systems, both in magnitude and in timing. On average, primary healthcare notifications peaked 3 weeks before NIDR. However, peaks in NIDR were more pronounced, for example in 2017, monthly incidence per 100,000 of NIDR notifications peaked at 12.7 cases in September, while primary healthcare notifications peaked at 7.2 (1.8 ratio) in August.ConclusionsClinically diagnosed cases provide a valuable additional data source for surveillance of tularaemia in Finland. A primary healthcare-based system would allow for earlier detection of increasing incidences and thereby for early warning of outbreaks. This is crucial in order to implement targeted control and prevention measures as early as possible.

Validation and standardization of accurate serological assays are crucial for the surveillance of the coronavirus disease 2019 (COVID-19) pandemic and population immunity. We describe the analytical and clinical performance of an in-house fluorescent multiplex immunoassay (FMIA) for simultaneous quantification of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein and spike glycoprotein. Furthermore, we calibrated IgG-FMIA against World Health Organization (WHO) International Standard and compared FMIA results to an in-house enzyme immunoassay (EIA) and a microneutralization test (MNT). We also compared the MNT results of two laboratories. IgG-FMIA displayed 100% specificity and sensitivity for samples collected 13 to 150 days post-onset of symptoms (DPO). For IgA- and IgM-FMIA, 100% specificity and sensitivity were obtained for a shorter time window (13 to 36 and 13 to 28 DPO for IgA- and IgM-FMIA, respectively). FMIA and EIA results displayed moderate to strong correlation, but FMIA was overall more specific and sensitive. IgG-FMIA identified 100% of samples with neutralizing antibodies (NAbs). Anti-spike IgG concentrations correlated strongly (ρ = 0.77 to 0.84, P <  2.2 × 10 -16 ) with NAb titers, and the two laboratories' NAb titers displayed a very strong correlation (ρ = 0.95, P <  2.2 × 10 -16 ). Our results indicate good correlation and concordance of antibody concentrations measured with different types of in-house SARS-CoV-2 antibody assays. Calibration against the WHO international standard did not, however, improve the comparability of FMIA and EIA results. IMPORTANCE SARS-CoV-2 serological assays with excellent clinical performance are essential for reliable estimation of the persistence of immunity after infection or vaccination. In this paper we present a thoroughly validated SARS-CoV-2 serological assay with excellent clinical performance and good comparability to neutralizing antibody titers. Neutralization tests are still considered the gold standard for SARS-CoV-2 serological assays, but our assay can identify samples with neutralizing antibodies with 100% sensitivity and 96% specificity without the need for laborious and slow biosafety level 3 (BSL-3) facility-requiring analyses.

The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis is reverse transcription (RT)-PCR from a nasopharyngeal swab specimen (NPS). Its collection involves close contact between patients and health care workers, requiring a significant amount of workforce and putting them at risk of infection. We evaluated self-collection of alternative specimens and compared their sensitivity and cycle threshold ( C T ) values to those of NPS. We visited acute coronavirus disease 2019 (COVID-19) outpatients to collect concomitant NPS and gargle specimens and had patients self-collect gargle and either sputum or spit specimens the next morning. We included 40 patients and collected 40 concomitant NPS and gargle specimens, as well as 40 gargle, 22 spit, and 16 sputum specimens the next day (2 patients could not produce sputum). All specimens were as sensitive as NPS. Gargle specimens had a sensitivity of 0.97 (95% confidence interval [CI], 0.92 to 1.00), whether collected concomitantly with NPS or the next morning. Next-morning spit and sputum specimens showed sensitivities of 1.00 (95% CI, 1.00 to 1.00) and 0.94 (95% CI, 0.87 to 1.00]), respectively. The gargle specimens had significantly higher mean C T values of 29.89 (standard deviation [SD], 4.63; P < 0.001) and 29.25 (SD, 3.99; P < 0.001) when collected concomitantly and the next morning, respectively, compared to NPS (22.07 [SD, 4.63]). C T values obtained with spit (23.51 [SD, 4.57]; P = 0.11) and sputum (25.82 [SD, 9.21]; P = 0.28) specimens were close to those of NPS. All alternative specimen collection methods were as sensitive as NPS, but spit collection appeared more promising, with a low C T value and ease of collection. Our findings warrant further investigation. IMPORTANCE Control of the COVID-19 pandemic relies heavily on a test-trace-isolate strategy. The most commonly used specimen for diagnosis of SARS-CoV-2 infection is a nasopharyngeal swab. However, this method is quite uncomfortable for the patient, requires specific equipment (nose swabs and containers), and requires close proximity to health care workers, putting them at risk of infection. Developing alternative sampling strategies could decrease the burden for health care workers, help overcome potential shortages of equipment, and improve acceptability of testing by reducing patient discomfort.

We update our previous insights into COVID-19 vaccine acceptance and hesitancy in Finland. Vaccine acceptance increased from 64% (November/December 2020) to 74% (April 2021). However, there was a group of participants that were preferring to wait to get vaccinated ranging from 6% of over-64-years-olds to 29% of under-30-years-olds. The previously identified enablers convenience (below-50-years-olds), worry about severe disease and protection for oneself (above-50-years-olds) were no longer significantly associated with increased vaccine acceptance. Understanding barriers and enablers behind vaccine acceptance is decisive in ensuring a successful implementation of COVID-19 vaccination programs, which will be key to ending the pandemic.

Even when receiving combination antiretroviral therapy, women living with HIV are at high risk of human papillomavirus (HPV) infection and/or cervical lesions, including cancer. Using data from the PapilloV prospective cohort, we evaluated the prevalence of high-risk HPV (HR-HPV) infections after cervical lesion treatment and investigated factors associated with their carriage. Women were followed up for three years with annual Pap smear and HPV genotyping. We offered treatment to women presenting either a Pap smear with high-grade squamous intraepithelial lesion or higher, and/or a biopsy showing cervical intraepithelial neoplasia II or III. We compared the prevalence of HR-HPV infection at the time of first treatment indication and at the end of follow-up among women who received treatment and those who did not. Overall, 46 women had treatment indication. HR-HPV prevalence significantly decreased from 67% to 27% ( p value = 0.001) in the 30 women who received treatment, while it did not significantly decrease (from 56% to 38%) in the 16 women who did not ( p value = 0.257). Due to lack of statistical power, the 40% relative difference in HR-HPV carriage between treated and untreated women was not significant. In women living with HIV, the treatment of a cervical lesion may be beneficial for clearing HR-HPV infections.

Pogosta disease is a mosquito-borne infection, caused by Sindbis virus (SINV), which causes epidemics of febrile rash and arthritis in Northern Europe and South Africa. Resident grouse and migratory birds play a significant role as amplifying hosts and various mosquito species, including Aedes cinereus , Culex pipiens , Cx. torrentium and Culiseta morsitans are documented vectors. As specific treatments are not available for SINV infections, and joint symptoms may persist, the public health burden is considerable in endemic areas. To predict the environmental suitability for SINV infections in Finland, we applied a suite of geospatial and statistical modeling techniques to disease occurrence data. Using an ensemble approach, we first produced environmental suitability maps for potential SINV vectors in Finland. These suitability maps were then combined with grouse densities and environmental data to identify the influential determinants for SINV infections and to predict the risk of Pogosta disease in Finnish municipalities. Our predictions suggest that both the environmental suitability for vectors and the high risk of Pogosta disease are focused in geographically restricted areas. This provides evidence that the presence of both SINV vector species and grouse densities can predict the occurrence of the disease. The results support material for public-health officials when determining area-specific recommendations and deliver information to health care personnel to raise awareness of the disease among physicians.

Background: The COVID-19 pandemic has intensely changed the everyday lives of people worldwide. This study explores the forms and outcomes of coronavirus and COVID-19-related social stigma and the experiences of people who were home quarantined or isolated in Finland during the spring 2020. The findings of this study can be used to improve support for those quarantined or isolated and to develop strategies to reduce the stigma associated with coronavirus and COVID-19., Methods: The study is based on qualitative one-to-one interviews with households with at least two members and at least one PCR confirmed COVID-19 case. Recruitment took place via website or SMS messages sent to PCR confirmed cases in the capital area of Helsinki. Sampling was based on maximum variation to acquire different types of respondents. The framework of health stigma was used to develop question guides and analyze stigma. Quarantine and isolation experiences were explored through open-ended questions. The analysis was based on thematic analysis., Results: The study included 64 participants from 24 households. Perceived stigma among respondents was driven by fear and blame for infection, and it manifested in various ways leading to a reluctance to disclose their coronavirus status to others. Self-stigma developed from conflicting information and advice about coronavirus and COVID-19 led to difficulties interacting with others outside of the house and reluctance to meet people after quarantine and isolation. Quarantine and isolation experiences included uncertainty, health concerns, and boredom. Communication with others in similar situations was perceived vital, whereas discussions with family members about worries and fears related to coronavirus and COVID-19 was not preferred., Conclusions: This study shed light on the lives of those quarantined or isolated at home and provided a set of operational recommendations to minimize coronavirus and COVID-19-associated stigma and to reduce challenges faced by those in quarantine or isolation., Competing Interests: No authors have no competing interest.

Objectives: We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19., Design: Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020., Primary Measure: Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections., Results: We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous., Conclusion: Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Healthcare workers (HCWs) are at increased risk of both exposure and transmission of infectious disease. Two European Union (EU) directives state that health services are responsible for assessing their employees' potential exposure to infectious diseases and offering immunisation free of charge. We assessed current policy for immunisation of HCWs and the availability of vaccine coverage data in the Nordic countries by surveying national vaccination experts in Denmark, Finland, Iceland, Norway and Sweden, as well as Swedish county medical officers (CMOs). All national experts and 17 of 21 Swedish CMOs responded. All EU countries had transposed the European directives into national law, while Norway and Iceland had similar national legislation. Recommendations or guidelines were issued in Denmark, Finland, Iceland, Norway and 15 of 17 responding Swedish counties. The range of diseases covered differed by countries and Swedish counties. HCW vaccine coverage data were not systematically collected; incomplete estimates were only available for Finland and two Swedish counties. In conclusion, recommendations or guidelines exist in the Nordic countries, but their impact cannot be assessed, as vaccine uptake among HCWs is not currently measured. Systematic collection of data is a necessary step towards improving HCW immunisation policy and practice in the Nordic countries.

Tick-borne encephalitis (TBE) is an endemic infection of public health importance in Finland. We investigated the effect of ecologic factors on 2007-2017 TBE trends. We obtained domestic TBE case data from the National Infectious Diseases Register, weather data from the US National Oceanic and Atmospheric Administration, and data from the Natural Resources Institute in Finland on mammals killed by hunters yearly in game management areas. We performed a mixed-effects time-series analysis with time lags on weather and animal parameters, adding a random effect to game management areas. During 2007-2017, a total of 395/460 (86%) domestic TBE cases were reported with known place of exposure and date of sampling. Overall, TBE incidence increased yearly by 15%. After adjusting for the density of other animals and minimum temperatures, we found thatTBE incidence was positively associated with white-tailed deer density. Variation in host animal density should be considered when assessing TBE risks and designing interventions.

Background: People who inject drugs (PWID) are the most exposed to hepatitis C virus (HCV). In Thailand, drug use is highly criminalized, and harm reduction services are scarce. This study estimates risky injection practices and assesses the proportion of HCV awareness and screening in the PWID population in Northern Thailand., Methods: We used respondent-driven sampling (RDS) to recruit PWID in Chiang Mai Province. Social and behavioural data were collected through face-to-face interviews at an addiction treatment facility. Weighted population estimates were calculated to limit biases related to the non-random sampling method. Univariate and multivariate analyses were performed to study factors associated with HCV awareness and screening., Results: One hundred seventy-one PWID were recruited between April 2016 and January 2017. Median age was 33 (Interquartile range: 26-40) years, 12.2% were women, and 49.4% belonged to a minority ethnic group. Among participants, 76.8% injected heroin, 20.7% methadone, and 20.7% methamphetamine. We estimate that 22.1% [95% CI: 15.7-28.6] of the population had shared needles in the last 6 months and that 32.0% [95% CI: 23.6-40.4] had shared injection material. Only 26.6% [95% CI: 17.6-35.6] had heard of HCV. Factors independently associated with knowledge of HCV included belonging to a harm reduction organization (adjusted odds ratio (aOR) = 5.5 [95% CI: 2.0-15.3]) and voluntary participation in a drug rehabilitation programme (aOR = 4.3 [95% CI: 1.3-13.9]), while Lahu ethnicity was negatively associated (aOR = 0.3 [95% CI: 0.1-0.9]). We estimate that 5% of the PWID population were screened for HCV; the only factor independently associated with being screened was membership of a harm reduction organization (aOR = 5.7 [95% CI: 1.6-19.9])., Conclusion: Our study reveals that the PWID population is poorly informed and rarely screened for HCV, despite widespread risky injection practices. A public health approach aimed at reducing the incidence of HCV should target the PWID population and combine harm reduction measures with information and destigmatization campaigns. Civil society organizations working with PWID are a major asset for the success of such an approach, based on their current positive interventions promoting awareness of and screening for HCV.

The numbers of reported human tick-borne encephalitis (TBE) cases in Europe have increased in several endemic regions (including Finland) in recent decades, indicative of an increasing threat to public health. As such, it is important to identify the regions at risk and the most influential factors associated with TBE distributions, particularly in understudied regions. This study aimed to identify the risk areas of TBE transmission in two different datasets based on human TBE disease cases from 2007 to 2011 (n = 86) and 2012-2017 (n  = 244). We also examined which factors best explain the presence of human TBE cases. We used ensemble modelling to determine the relationship of TBE occurrence with environmental, ecological, and anthropogenic factors in Finland. Geospatial data including these variables were acquired from several open data sources and satellite and aerial imagery and, were processed in GIS software. Biomod2, an ensemble platform designed for species distribution modelling, was used to generate ensemble models in R. The proportion of built-up areas, field, forest, and snow-covered land in November, people working in the primary sector, human population density, mean precipitation in April and July, and densities of European hares, white-tailed deer, and raccoon dogs best estimated distribution of human TBE disease cases in the two datasets. Random forest and generalized boosted regression models performed with a very good to excellent predictive power (ROC = 0.89-0.96) in both time periods. Based on the predictive maps, high-risk areas for TBE transmission were located in the coastal regions in Southern and Western Finland (including the Åland Islands), several municipalities in Central and Eastern Finland, and coastal municipalities in Southern Lapland. To explore potential changes in TBE distributions in future climate, we used bioclimatic factors with current and future climate forecast data to reveal possible future hotspot areas. Based on the future forecasts, a slightly wider geographical extent of TBE risk was introduced in the Åland Islands and Southern, Western and Northern Finland, even though the risk itself was not increased. Our results are the first steps towards TBE-risk area mapping in current and future climate in Finland., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)

We report an outbreak of invasive pneumococcal disease and pneumococcal pneumonia among shipyard workers, in Turku, Southwest Finland. In total, 31 confirmed and six probable cases were identified between 3 May and 28 November 2019. Streptococcus pneumoniae serotypes 12F, 4 and 8 were isolated from blood cultures of 25 cases. Occupational hygiene measures and vaccination of ca 4,000 workers are underway to control the outbreak at the shipyard.

Background: Snakebite has only recently been recognized as a neglected tropical disease by the WHO. Knowledge regarding snakebites and its care is poor both at the population level, and at the health care staff level. The goal of this study was to describe the level of knowledge and clinical practice regarding snakebite among health care staff from Cameroon., Methods: A two-day training dedicated to snakebite and its care was organized in 2015 in Yaoundé, capital city of Cameroon. A total of 98 health care staff from all over Cameroon attended the training. Prior to and after the training, an evaluation quantified the attendees' level of knowledge. Pre- and post-training evaluations were compared to assess knowledge improvement., Results: Overall, prior to the training knowledge regarding snakebite and care was poor, and wrong beliefs that "pierre noire" or tourniquet were useful in case of snakebite were common. Knowledge was statistically improved after the training., Conclusion: Trainings dedicated to all type of health care staff towards snakebite to improve care are needed, this training must take into consideration the context and the targeted population., Competing Interests: The following institutions/pharmaceutical Companies also contributed for the smooth running of the training: the Centre for Research on Filariasis & other tropical Diseases (CRfilMT), The Research Foundation for Tropical Disease and Environment – Buea (REFOTDE), the Laboratoire National Veterinaire du Cameroun (LANAVET), the Multilateral Initiative on Malaria in Africa (MIM), the FAIRMED, the Centre Pasteur du Cameroun (CPC), INOSAN BioPharma and VINS Bioproducts Limited. These companies had no input in content or in the decision to publish these findings. The authors have declared that no competing interests exist.

Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.

The spread of Zika virus in the Americas has been associated with a surge in Guillain-Barré syndrome (GBS) cases. Given the severity of GBS, territories affected by Zika virus need to plan health-care resources to manage GBS patients. To inform such planning in Martinique, we analyzed Zika virus surveillance and GBS data from Martinique in real time with a modeling framework that captured dynamics of the Zika virus epidemic, the risk of GBS in Zika virus-infected persons, and the clinical management of GBS cases. We compared our estimates with those from the 2013-2014 Zika virus epidemic in French Polynesia. We were able to predict just a few weeks into the epidemic that, due to lower transmission potential and lower probability of developing GBS following infection in Martinique, the total number of GBS cases in Martinique would be substantially lower than suggested by simple extrapolations from French Polynesia. We correctly predicted that 8 intensive-care beds and 7 ventilators would be sufficient to treat GBS cases. This study showcased the contribution of modeling to inform local health-care planning during an outbreak. Timely studies that estimate the proportion of infected persons that seek care are needed to improve the predictive power of such approaches., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Congenital Zika virus infection is associated with severe brain anomalies and impaired function. To determine outcomes, we followed 2 affected children for ≈30 months. For 1 who was symptomatic at birth, transient hepatitis developed. However, neurodevelopment for both children was age appropriate.

Objectives: To analyse episiotomy and perineal tears rates in Burgundy after French National College of Obstetricians and Gynecologists (CNGOF) guidelines in 2005., Materials and Method: Multicenter retrospective study, between 2003-2005 (period 1) et 2012-2014 (period 2), conducted on singletons vaginal deliveries, in cephalic presentation from 37 weeks. We compared the episiotomy rate (ER), and perineal lesions in normal deliveries (ND) and instrumental deliveries (ID) between the two periods., Results: A total of 74,268 women were included. The overall ER significantly decreased from 35.8 to 16.7% (P<0.01), without increasing third degree perineal tears (0.73% vs. 0.66%) or fourth degree (0.14% vs 0.14%). First degree perineal tears rose (42.1% vs 17.6%, P<0.001), second degree decreased (13.5% vs 20.5%, P<0.001). ER decreased whatever the level of motherhood, healthcare ward, vaginal delivery type, or the instrument used., Conclusion: Our study found a strong impact in Burgundy of the French guidelines for the practice of restrictive episiotomy for both ND and for ID without increasing sphincter tears and in decreasing spontaneous morbidity., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified., Methods: We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk., Findings: The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62-70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0-8) per 10,000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34-191) per 10,000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data., Interpretation: Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus., Funding: Labex-IBEID, NIH-MIDAS, AXA Research fund, EU-PREDEMICS., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome., Methods: In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays., Findings: 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively)., Interpretation: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome., Funding: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Although several face-to-face programs are dedicated to informal caregivers of persons with dementia, they are not always accessible to overburdened or isolated caregivers. Based on a face-to-face intervention program, we adapted and designed a Web-based fully automated psychoeducational program (called Diapason) inspired by a cognitive approach., Objective: This study aimed to evaluate through a pilot unblinded randomized controlled trial the efficacy and acceptability of a Web-based psychoeducational program for informal caregivers of persons with Alzheimer's disease (PWAD) based on a mixed methods research design., Methods: We recruited and randomized offline 49 informal caregivers of a PWAD in a day care center in Paris, France. They either received the Web-based intervention and usual care for 3 months (experimental group, n=25) or only usual care (control group, n=24). Caregivers' perceived stress (PSS-14, primary outcome), self-efficacy, burden, perceived health status, and depression (secondary outcomes) were measured during 3 face-to-face on-site visits: at baseline, at the end of the program (month 3), and after follow-up (month 6). Additionally, semistructured interviews were conducted with experimental group caregivers at month 6 and examined with thematic analysis., Results: Intention-to-treat analysis did not show significant differences in self-perceived stress between the experimental and control groups (P=.98). The experimental group significantly improved their knowledge of the illness (d=.79, P=.008) from baseline to month 3. Of the 25 participants allocated to the experimental group, 17 (71%) finished the protocol and entirely viewed at least 10 of 12 online sessions. On average, participants used the website 19.72 times (SD 12.88) and were connected for 262.20 minutes (SD 270.74). The results of the satisfaction questionnaire showed that most participants considered the program to be useful (95%, 19/20), clear (100%, 20/20), and comprehensive (85%, 17/20). Significant correlations were found between relationship and caregivers' program opinion (P=.01). Thus, positive opinions were provided by husbands and sons (3/3), whereas qualified opinions were primarily reported by daughters (8/11). Female spouses expressed negative (2/3) or neutral opinions (1/3). Caregivers expected more dynamic content and further interaction with staff and peers., Conclusions: In this study, quantitative results were inconclusive owing to small sample size. Qualitative results indicated/showed little acceptance of the program and high expectations from caregivers. Caregivers did not rule out their interest in this kind of intervention provided that it met their needs. More dynamic, personalized, and social interventions are desirable. Our recruitment issues pointed out the necessity of in-depth studies about caregivers' help-seeking behaviors and readiness factors., Trial Registration: Clinicaltrials.gov NCT01430286; http://clinicaltrials.gov/ct2/show/NCT01430286 (Archived by WebCite at http://www.webcitation/6KxHaRspL).