Citizen involvement in COVID-19 contact tracing with digital tools: a qualitative study to explore citizens' perspectives and needs.

BACKGROUND: Contact tracing (CT) is a key strategy when dealing with outbreaks of infectious diseases such as COVID-19. The scale of the COVID-19 pandemic has often left public health professionals (PHPs), who are responsible for the execution of CT, unable to keep up with the rapid and largescale spread of the virus. To enhance or support its execution, and potentially lower the workload for PHPs, citizens may be more actively involved in CT-tasks that are commonly executed by PHPs (referred to as 'self-led CT'). There is limited insight into citizens' perspectives on and needs for self-led CT for COVID-19. This study aims to explore the perspectives and needs of Dutch citizens on taking more responsibilities in the execution of CT for COVID-19, potentially through the use of digital tools. METHODS: An exploratory qualitative study was performed, in which online semi-structured interviews were conducted. Questions were based on the Reasoned Action Approach and Health Belief Model. Interviews were audio-recorded and transcribed verbatim. A thematic analysis was conducted to identify citizens' perspectives and needs to participate in self-led CT. RESULTS: We conducted 27 interviews with Dutch citizens. Seven main themes were identified from the interviews: 1) 'Citizens' perspectives on self-led CT are influenced by prior experiences with regular CT', 2) 'Citizens' felt responsibilities and the perceived responsibilities of the PHS in CT shape their perspectives on self-led CT', 3) 'Anticipated impacts of self-led CT on the CT-process', 4) 'Citizens' attitude towards the application of self-led CT depends on their own perceived skills and the willingness and skills of others', 5) 'Shame and social stigma may hamper participation in self-led CT', 6) 'Concerns about privacy and data security: a barrier for self-led CT', and 7) 'Citizens' perspectives and anticipated needs for the implementation and application of self-led CT in practice'. CONCLUSIONS: Most interviewees hold a positive attitude towards self-led CT and using digital tools for this purpose. However, their intention for self-led CT may depend on various factors, such as prior experiences with regular CT, and their perceived self-efficacy to participate. Perspectives and needs of citizens should be considered for the future implementation of self-led CT in practice.

Dutch public health professionals' perspectives and needs regarding citizen involvement in COVID-19 contact tracing through digital support tools: an exploratory qualitative study.

BACKGROUND: Contact tracing (CT) is an important, but resource-intensive tool to control outbreaks of communicable diseases. Under pandemic circumstances, public health services may not have sufficient resources at their disposal to effectively facilitate CT. This may be addressed by giving cases and their contact persons more autonomy and responsibility in the execution of CT by public health professionals, through digital contact tracing support tools (DCTS-tools). However, the application of this approach has not yet been systematically investigated from the perspective of public health practice. Therefore, we investigated public health professionals' perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools. METHODS: Between October 2020 and February 2021, we conducted online semi-structured interviews (N = 17) with Dutch public health professionals to explore their perspectives and needs regarding the involvement of cases and contact persons in CT for COVID-19 through DCTS-tools, in the contact identification, notification, and monitoring stages of the CT-process. Interviews were audio recorded and transcribed verbatim. A thematic analysis was performed. RESULTS: Four main themes related to Dutch public health professionals' perspectives and needs regarding involving cases and contact persons in CT for COVID-19 through DCTS-tools emerged from the data: 'Distinct characteristics of CT with DCTS-tools'; 'Anticipated benefits and challenges of CT for COVID-19 with DCTS- tools'; 'Circumstances in CT for COVID-19 that permit or constrain the application of DCTS-tools'; and 'Public health professionals' needs regarding the development and application of DCTS-tools for CT'. Public health professionals seem to have a positive attitude towards involving cases and contact persons through DCTS-tools. Public health professionals' (positive) attitudes seem conditional on the circumstances under which CT is performed, and the fulfilment of their needs in the development and application of DCTS-tools. CONCLUSIONS: Dutch public health professionals seem positive towards involving cases and contact persons in CT for COVID-19 through DCTS-tools. Through adequate implementation of DCTS-tools in the CT-process, anticipated challenges can be overcome. Future research should investigate the perspectives and needs of cases and contact persons regarding DCTS-tools, and the application of DCTS-tools in practice.

Impact of inter-hospital transfers on the prevalence of resistant pathogens in a hospital-community system.

The spread of resistant bacteria in hospitals is an increasing problem worldwide. Transfers of patients, who may be colonized with resistant bacteria, are considered to be an important driver of promoting resistance. Even though transmission rates within a hospital are often low, readmissions of patients who were colonized during an earlier hospital stay lead to repeated introductions of resistant bacteria into hospitals. We developed a mathematical model that combines a deterministic model for within-hospital spread of pathogens, discharge to the community and readmission, with a hospital-community network simulation of patient transfers between hospitals. Model parameters used to create the hospital-community network are obtained from two health insurance datasets from Germany. For parameter values representing transmission of resistant Enterobacteriaceae, we compute estimates for the single admission reproduction numbers RA and the basic reproduction numbers R0 per hospital-community pair. We simulate the spread of colonization through the network of hospitals, and investigate how increasing connectedness of hospitals through the network influences the prevalence in the hospital-community pairs. We find that the prevalence in hospitals is determined by their RA and R0 values. Increasing transfer rates between network nodes tend to lower the overall prevalence in the network by diluting the high prevalence of hospitals with high R0 to hospitals where persistent spread is not possible. We conclude that hospitals with high reproduction numbers represent a continuous source of risk for importing resistant pathogens for hospitals with otherwise low levels of transmission. Moreover, high risk hospital-community nodes act as reservoirs of pathogens in a densely connected network.

The incidence of symptomatic infection with influenza virus in the Netherlands 2011/2012 through 2016/2017, estimated using Bayesian evidence synthesis.

Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7-9.0) for season 2011/2012, 36.7 (95% UI: 31.2-42.8) for 2012/2013, 9.1 (95% UI: 6.3-12.9) for 2013/2014, 41.1 (95% UI: 35.0-47.7) for 2014/2015, 39.4 (95% UI: 33.4-46.1) for 2015/2016 and 27.8 (95% UI: 22.7-33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation - with appropriately quantified uncertainty - of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.

Waning and boosting: on the dynamics of immune status.

The aim is to describe the distribution of immune status (as captured by antibody level) on the basis of a within-host submodel for continuous waning and occasional boosting. Inspired by Feller's fundamental work and the more recent delay equation formulation of models for the dynamics of physiologically structured populations, we derive, for given force of infection, a linear renewal equation. The solution is obtained by generation expansion, with the generation number corresponding to the number of times the individual became infected. Our main result provides a precise characterization of the stable distribution of immune status.

Development of prediction models for upper and lower respiratory and gastrointestinal tract infections using social network parameters in middle-aged and older persons -The Maastricht Study.

The ability to predict upper respiratory infections (URI), lower respiratory infections (LRI), and gastrointestinal tract infections (GI) in independently living older persons would greatly benefit population and individual health. Social network parameters have so far not been included in prediction models. Data were obtained from The Maastricht Study, a population-based cohort study (N = 3074, mean age (±s.d.) 59.8 ± 8.3, 48.8% women). We used multivariable logistic regression analysis to develop prediction models for self-reported symptomatic URI, LRI, and GI (past 2 months). We determined performance of the models by quantifying measures of discriminative ability and calibration. Overall, 953 individuals (31.0%) reported URI, 349 (11.4%) LRI, and 380 (12.4%) GI. The area under the curve was 64.7% (95% confidence interval (CI) 62.6-66.8%) for URI, 71.1% (95% CI 68.4-73.8) for LRI, and 64.2% (95% CI 61.3-67.1%) for GI. All models had good calibration (based on visual inspection of calibration plot, and Hosmer-Lemeshow goodness-of-fit test). Social network parameters were strong predictors for URI, LRI, and GI. Using social network parameters in prediction models for URI, LRI, and GI seems highly promising. Such parameters may be used as potential determinants that can be addressed in a practical intervention in older persons, or in a predictive tool to compute an individual's probability of infections.

Use of a Dose-Response Model to Study Temporal Trends in Spatial Exposure to Coxiella burnetii: Analysis of a Multiyear Outbreak of Q Fever.

The Netherlands underwent a large Q fever outbreak between 2007 and 2009. In this paper, we study spatial and temporal Coxiella burnetii exposure trends during this large outbreak as well as validate outcomes against other published studies and provide evidence to support hypotheses on the causes of the outbreak. To achieve this, we develop a framework using a dose-response model to translate acute Q fever case incidence into exposure estimates. More specifically, we incorporate a geostatistical model that accounts for spatial and temporal correlation of exposure estimates from a human Q fever dose-response model to quantify exposure trends during the outbreak. The 2051 cases, with the corresponding age, gender and residential addresses, reside in the region with the highest attack rates during the outbreak in the Netherlands between 2006 and 2009. We conclude that the multiyear outbreak in the Netherlands is caused by sustained release of infectious bacteria from the same sources, which suggests that earlier implementation of interventions may have prevented many of the cases. The model predicts the risk of infection and acute symptomatic Q fever from multiple exposure sources during a multiple-year outbreak providing a robust, evidence-based methodology to support decision-making and intervention design.

Linking the seroresponse to infection to within-host heterogeneity in antibody production.

A recently published model for the serum antibody response to infection appeared well suited for use in statistical analyses of longitudinal serological data. The published model assumed exponential decay with fixed rates for pathogen and serum antibody kinetics, ignoring any within-host heterogeneity in the seroresponse. A bi-exponential model shows that there is rapid initial decay followed by a prolonged period of persistent low serum antibody concentrations. We propose a small modification of the decay model that greatly increases its flexibility by allowing for non-exponential antibody decay. The modified model produces power functions that may be interpreted as a mixture of exponential decay curves, with a mixing distribution representing the relative contribution of many centres of antibody production to the serum antibody concentration. Fitting the power function decay model to observed longitudinal data for pertussis shows improved goodness of fit compared to the exponential decay model, with estimates for the shape parameter (r=2.2; 95% CI (1.7-2.8)) that differ from exponential shape (r=1). The power function decay model predicts more persistent antibody concentrations in the long term (symptomatic threshold reached >30 years after infection) which, when used in biomarker studies, will lead to lower estimates of seroconversion rates compared to exponential antibody decay.

Estimating the risk of dengue transmission from Dutch blood donors travelling to Suriname and the Dutch Caribbean.

BACKGROUND: The risk of dengue transmitted by travellers is known. Methods to estimate the transmission by transfusion (TT) risk from blood donors travelling to risk areas are available, for instance, the European Up-Front Risk Assessment Tool (EUFRAT). This study aimed to validate the estimated risk from travelling donors obtained from EUFRAT. METHODS: Surveillance data on notified dengue cases in Suriname and the Dutch Caribbean islands (Aruba, Curaçao, St. Maarten, Bonaire, St. Eustatius and Saba) in 2001-2011 was used to calculate local incidence rates. Information on travel and donation behaviour of Dutch donors was collected. With the EUFRAT model, the TT risks from Dutch travelling donors were calculated. Model estimates were compared with the number of infections in Dutch travellers found by laboratory tests in the Netherlands. RESULTS: The expected cumulative number of donors becoming infected during travels to Suriname and the Dutch Caribbean from 2001 to 2011 was estimated at 5 (95% CI, 2-11) and 86 (45-179), respectively. The infection risk inferred from the laboratory-based study was 19 (9-61) and 28 (14-92). Given the independence of the data sources, these estimates are remarkably close. The model estimated that 0·02 (0·001-0·06) and 0·40 (0·01-1·4) recipients would have been infected by these travelling donors. CONCLUSIONS: The EUFRAT model provided an estimate close to actual observed number of dengue infections. The dengue TT risk among Dutch travelling donors can be estimated using basic transmission, travel and donation information. The TT risk from Dutch donors travelling to Suriname and the Dutch Caribbean is small.

Use of DALYs in economic analyses on interventions for infectious diseases: a systematic review.

A systematic literature review was performed on full economic evaluations of infectious disease interventions using disability-adjusted life years (DALY) as outcome measure. The search was limited to the period between 1994 and September 2011 and conducted in Medline, SciSearch and EMBASE databases. We included 154 studies, mostly targeting HIV/AIDS and malaria with most conducted for African countries (40%) and <10% in high-income countries. Third-payer perspective was applied in 29% of the studies, 25% used the societal perspective and 12% used both. Only 16% of the studies took indirect effects (i.e. herd immunity) of interventions into account. Intervention, direct healthcare and indirect non-healthcare costs were taken into account in respectively 100%, 81% and 36% of the studies. The majority of the studies followed the Global Burden of Disease method for DALY estimations, but most studies deviated from WHO cost-effectiveness guidelines. Better adherence to freely accessible guidelines will improve generalizability between full economic evaluations.

A two-phase within-host model for immune response and its application to serological profiles of pertussis.

We present a simple phenomenological within-host model describing both the interaction between a pathogen and the immune system and the waning of immunity after clearing of the pathogen. We implement the model into a Bayesian hierarchical framework to estimate its parameters for pertussis using Markov chain Monte Carlo methods. We show that the model captures some essential features of the kinetics of titers of IgG against pertussis toxin. We identify a threshold antibody level that separates a large increase in antibody level upon infection from a small increase and accordingly might be interpreted as a threshold separating clinical from subclinical infections. We contrast predictions of the model with observations reported in the literature and based on independent data and find a remarkable correspondence.

Benefits of hepatitis C virus treatment: a balance of preventing onward transmission and re-infection.

By treating HCV-infected injecting drug users (IDUs), we may prevent infections to other IDUs. Curing preferentially individuals who most often share injecting equipment has the advantage of preventing more infections. However, such high risk behavior IDUs are also more likely to become re-infected. We have created a model that can inform us about most efficient HCV treatment policy; the expected benefits per treatment of one HCV-infected IDU are calculated, defined as a decrease in the number of chronic HCV infections. This includes the probability that the cured IDU remains uninfected, and the number of new infections prevented both directly and indirectly in further infection generations. We explore analytically how these benefits depend on the syringe sharing frequency of the cured IDU. We find that whom to best cure is determined by the prevalence of HCV contamination among exchanged syringes within the IDU population. Treating lowest risk IDUs is most beneficial above a certain prevalence of contamination, since the term for re-infection dominates the equation in this domain. At lower prevalence treating highest risk IDUs is most beneficial, since here the term for prevention dominates. In a much simplified model the threshold between domains is found at exactly 50% HCV prevalence. The threshold value is lowered when taking HCV induced mortality or increased infectiousness during an acute stage of infection into account. It is increased when taking into account treatment duration, or when HCV-treatment is combined with intervention that reduces the syringe sharing rate of the cured IDU.

The disease burden of hepatitis B, influenza, measles and salmonellosis in Germany: first results of the burden of communicable diseases in Europe study.

Setting priorities in the field of infectious diseases requires evidence-based and robust baseline estimates of disease burden. Therefore, the European Centre for Disease Prevention and Control initiated the Burden of Communicable Diseases in Europe (BCoDE) project. The project uses an incidence- and pathogen-based approach to measure the impact of both acute illness and sequelae of infectious diseases expressed in disability-adjusted life years (DALYs). This study presents first estimates of disease burden for four pathogens in Germany. The number of reported incident cases adjusted for underestimation served as model input. For the study period 2005-2007, the average disease burden was estimated at 33 116 DALYs/year for influenza virus, 19 115 DALYs/year for Salmonella spp., 8708 DALYs/year for hepatitis B virus and 740 DALYs/year for measles virus. This methodology highlights the importance of sequelae, particularly for hepatitis B and salmonellosis, because if omitted, the burden would have been underestimated by 98% and 56%, respectively.

Comparing the impact of two concurrent infectious disease outbreaks on The Netherlands population, 2009, using disability-adjusted life years.

In 2009 two notable outbreaks, Q fever and the novel influenza A(H1N1)pdm09, occurred in The Netherlands. Using a composite health measure, disability-adjusted life years (DALYs), the outbreaks were quantified and compared. DALYs were calculated using standardized methodology incorporating age- and sex-stratified data in a disease progression model; years lost due to disability and years of life lost were computed by outcome. Nationally, influenza A(H1N1)pdm09 caused more DALYs (24 484) than Q fever (5797). However, Q fever was 8·28 times more severe [497 DALYs/1000 symptomatic cases (DP1SC)] than A(H1N1)pdm09 (60 DP1SC). The A(H1N1)pdm09 burden is largely due to mortality while the Q fever burden is due primarily to long-term sequelae. Intervention prioritization for influenza should support patients in a critical condition while for Q fever it should target immediate containment and support for patients with long-term sequelae. Burden estimates provide guidance for focusing intervention options during outbreaks of infectious diseases.

Estimating the long-term effects of HPV vaccination in Germany.

In Germany, vaccination against the most oncogenic HPV types 16/18 is recommended by the Standing Committee on Vaccination (STIKO) for 12-17 year old girls since March 2007. We developed a dynamic mathematical model for the natural history and transmission of HPV infections to estimate the impact of vaccination on incidence and mortality of cervical cancer and its pre-stages, and on anogenital warts. We focused on an extensive model calibration to epidemiologic data for all stages of the natural history model as well as on a detailed implementation of cervical cancer screening modalities in Germany. Our model predicts first a substantial reduction of cervical cancer incidence and mortality over the next 30 years, which is mainly attributable to an increase in screening participation in the 1990s and not to HPV vaccination, followed by a further reduction attributable to vaccination. Over the next 100 years, HPV vaccination will prevent approximately 37% of cervical cancer cases even if vaccination coverage is only 50% (as currently observed in Germany). Consideration of cross-protection results in a further reduction of approximately 7% of all cervical cancer cases for the bivalent and about 5% for the quadrivalent vaccine in our model. Vaccination of boys was only reasonable if moderate to high vaccination coverage in girls was not achieved. Strategies should be implemented in Germany to increase HPV vaccination coverage among girls thereby making better use of the demonstrated benefits of the vaccine.

Time-course of antibody responses against Coxiella burnetii following acute Q fever.

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.

Dynamic concurrent partnership networks incorporating demography.

We introduce a population model that incorporates From a mathematical point of view we deal with continuous-time Markov chains at the individual level, with the interaction between individuals captured by a global variable describing opportunities for new partnerships. We show that for large time a stationary distribution is attained and we deduce various statistical features of that distribution, with particular attention for concurrency, i.e. the overlap in time of multiple partnerships of one and the same individual. Our ultimate motivation is to model the spread of sexually transmitted infections in the population, for which the present paper serves as a prelude.

The burden of 2009 pandemic influenza A(H1N1) in the Netherlands.

BACKGROUND: The disease burden of the 2009 influenza pandemic has been debated but reliable estimates are lacking. To guide future policy and control, these estimates are necessary. This study uses burden of disease measurements to assess the contribution of the pandemic influenza A(H1N1) virus to the overall burden of disease in the Netherlands. METHODS: The burden of disease caused by 2009 pandemic influenza was estimated by calculating Disability Adjusted Life Years (DALY), a composite measure that combines incidence, sequelae and mortality associated with a disease, taking duration and severity into account. Available influenza surveillance data sources (primary care sentinel surveillance, notification data on hospitalizations and deaths and death registries) were used. Besides a baseline scenario, five alternative scenarios were used to assess effects of changing values of input parameters. RESULTS: The baseline scenario showed a loss of 5800 DALY for the Netherlands (35 DALY per 100 000 population). This corresponds to 0.13% of the estimated annual disease burden in the Netherlands and is comparable to the estimated disease burden of seasonal influenza, despite a different age distribution in incidence and mortality of the pandemic compared to seasonal influenza. CONCLUSIONS: This disease burden estimate confirmed that, although there was a higher mortality observed among young people, the 2009 pandemic was overall a mild influenza epidemic. The disease burden of this pandemic was comparable to the burden of seasonal influenza in the Netherlands.

[Effects of ageing on infectious disease]. / Effecten van vergrijzing op infectieziekten.

Expectations are that 25% of the Dutch population will be aged 65 years or older in 2050 whilst in 2008 this proportion was only 15%. As a consequence the annual absolute number of new cases of specific infectious diseases will increase. Elderly people often have less clear symptoms of infection, making it harder for clinicians to recognize the disease. Morbidity and mortality caused by infections increase with age. Ageing will possibly cause an increase in levels of antibiotic resistance. There will be more elderly people in hospitals and nursing homes, where more antibiotics are used. This development will come in addition to other developments in the field of antibiotic resistance. There will be more elderly people with chronic HIV and viral hepatitis B and C infection and their complications because patients who are presently infected with those pathogens are ageing. Policy makers should more often consider introducing vaccination of older age groups against certain infectious diseases.

Kinetics of the IgG antibody response to pertussis toxin after infection with B. pertussis.

We aimed to provide a quantitative description of decay in pertussis antibody levels to aid in finding a serological estimate of the incidence of pertussis. The serum IgG response against pertussis toxin was studied in a group of clinically diagnosed patients. Individual records consisted of repeated serum IgG measurements at irregular intervals for up to 10 years post diagnosis. These data were analysed with a nonlinear regression model taking into account censoring at upper and lower threshold levels, measurement errors, and individual variation in the shape and magnitude of the immune response. There was considerable variation between individual responses, both in strength (amplitude) and duration (shape). The inverse model relating IgG levels to time from infection (diagnosis) can be applied to cross-sectional IgG data to generate distributions of times from infection, which may be used to calculate infection rates and their variation, in populations sampled for cross-sectional IgG data.