Risk factors associated with the incidence of self-reported COVID-19-like illness: data from a web-based syndromic surveillance system in the Netherlands.

During the first wave of the severe acute respiratory syndrome-coronavirus-2 epidemic in the Netherlands, notifications consisted mostly of patients with relatively severe disease. To enable real-time monitoring of the incidence of mild coronavirus disease 2019 (COVID-19) - for which medical consultation might not be required - the Infectieradar web-based syndromic surveillance system was launched in mid-March 2020. Our aim was to quantify associations between Infectieradar participant characteristics and the incidence of self-reported COVID-19-like illness. Recruitment for this cohort study was via a web announcement. After registering, participants completed weekly questionnaires, reporting the occurrence of a set of symptoms. The incidence rate of COVID-19-like illness was estimated and multivariable Poisson regression used to estimate the relative risks associated with sociodemographic variables, lifestyle factors and pre-existing medical conditions. Between 17 March and 24 May 2020, 25 663 active participants were identified, who reported 7060 episodes of COVID-19-like illness over 131 404 person-weeks of follow-up. The incidence rate declined over the analysis period, consistent with the decline in notified cases. Male sex, age 65+ years and higher education were associated with a significantly lower COVID-19-like illness incidence rate (adjusted rate ratios (RRs) of 0.80 (95% CI 0.76-0.84), 0.77 (0.70-0.85), 0.84 (0.80-0.88), respectively) and the baseline characteristics ever-smoker, asthma, allergies, diabetes, chronic lung disease, cardiovascular disease and children in the household were associated with a higher incidence (RRs of 1.11 (1.04-1.19) to 1.69 (1.50-1.90)). Web-based syndromic surveillance has proven useful for monitoring the temporal trends in, and risk factors associated with, the incidence of mild disease. Increased relative risks observed for several patient factors could reflect a combination of exposure risk, susceptibility to infection and propensity to report symptoms.

Visual tools to assess the plausibility of algorithm-identified infectious disease clusters: an application to mumps data from the Netherlands dating from January 2009 to June 2016.

IntroductionWith growing amounts of data available, identification of clusters of persons linked to each other by transmission of an infectious disease increasingly relies on automated algorithms. We propose cluster finding to be a two-step process: first, possible transmission clusters are identified using a cluster algorithm, second, the plausibility that the identified clusters represent genuine transmission clusters is evaluated.AimTo introduce visual tools to assess automatically identified clusters.MethodsWe developed tools to visualise: (i) clusters found in dimensions of time, geographical location and genetic data; (ii) nested sub-clusters within identified clusters; (iii) intra-cluster pairwise dissimilarities per dimension; (iv) intra-cluster correlation between dimensions. We applied our tools to notified mumps cases in the Netherlands with available disease onset date (January 2009 - June 2016), geographical information (location of residence), and pathogen sequence data (n = 112). We compared identified clusters to clusters reported by the Netherlands Early Warning Committee (NEWC).ResultsWe identified five mumps clusters. Three clusters were considered plausible. One was questionable because, in phylogenetic analysis, genetic sequences related to it segregated in two groups. One was implausible with no smaller nested clusters, high intra-cluster dissimilarities on all dimensions, and low intra-cluster correlation between dimensions. The NEWC reports concurred with our findings: the plausible/questionable clusters corresponded to reported outbreaks; the implausible cluster did not.ConclusionOur tools for assessing automatically identified clusters allow outbreak investigators to rapidly spot plausible transmission clusters for mumps and other human-to-human transmissible diseases. This fast information processing potentially reduces workload.

Real-time Estimation of Epidemiologic Parameters from Contact Tracing Data During an Emerging Infectious Disease Outbreak.

BACKGROUND: Contact tracing can provide accurate information on relevant parameters of an ongoing emerging infectious disease outbreak. This is crucial to investigators seeking to control such an outbreak. However, crude contact tracing data are difficult to interpret and methods for analyzing these data are scarce. We present a method to estimate and visualize key outbreak parameters from contact tracing information in real time by taking into account data censoring. METHODS/RESULTS: Exposure type-specific attack rates and the reproduction number R(t) are estimated from contact tracing data by using maximum likelihood estimation to account for censored data. The attack rates reflect, in the context of contact tracing, the specificity of the contact definition; a higher value indicates relatively efficient contact tracing. The evolution of R(t) over time provides information regarding the effectiveness of interventions. To allow a real-time overview of the outbreak, the attack rates and the evolution of R(t) over time are visualized together with the case-contact network and epicurve. We applied the method to a well-documented smallpox outbreak in The Netherlands to demonstrate the added value. CONCLUSION: Our method facilitates the analysis of contact tracing information by quickly turning it into accessible information, helping outbreak investigators to make real-time decisions to more effectively and efficiently control infectious disease outbreaks.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

Echovirus type 6 transmission clusters and the role of environmental surveillance in early warning, the Netherlands, 2007 to 2016.

BackgroundIn the Netherlands, echovirus type 6 (E6) is identified through clinical and environmental enterovirus surveillance (CEVS and EEVS). AimWe aimed to identify E6 transmission clusters and to assess the role of EEVS in surveillance and early warning of E6. MethodsWe included all E6 strains from CEVS and EEVS from 2007 through 2016. CEVS samples were from patients with enterovirus illness. EEVS samples came from sewage water at pre-specified sampling points. E6 strains were defined by partial VP1 sequence, month and 4-digit postcode. Phylogenetic E6 clusters were detected using pairwise genetic distances. We identified transmission clusters using a combined pairwise distance in time, place and phylogeny dimensions. ResultsE6 was identified in 157 of 3,506 CEVS clinical episodes and 92 of 1,067 EEVS samples. Increased E6 circulation was observed in 2009 and from 2014 onwards. Eight phylogenetic clusters were identified; five included both CEVS and EEVS strains. Among these, identification in EEVS did not consistently precede CEVS. One phylogenetic cluster was dominant until 2014, but genetic diversity increased thereafter. Of 14 identified transmission clusters, six included both EEVS and CEVS; in two of them, EEVS identification preceded CEVS identification. Transmission clusters were consistent with phylogenetic clusters, and with previous outbreak reports. ConclusionAlgorithms using combined time-place-phylogeny data allowed identification of clusters not detected by any of these variables alone. EEVS identified strains circulating in the population, but EEVS samples did not systematically precede clinical case surveillance, limiting EEVS usefulness for early warning in a context where E6 is endemic.

Dot map cartograms for detection of infectious disease outbreaks: an application to Q fever, the Netherlands and pertussis, Germany.

Geographical mapping of infectious diseases is an important tool for detecting and characterising outbreaks. Two common mapping methods, dot maps and incidence maps, have important shortcomings. The former does not represent population density and can compromise case privacy, and the latter relies on pre-defined administrative boundaries. We propose a method that overcomes these limitations: dot map cartograms. These create a point pattern of cases while reshaping spatial units, such that spatial area becomes proportional to population size. We compared these dot map cartograms with standard dot maps and incidence maps on four criteria, using two example datasets. Dot map cartograms were able to illustrate both incidence and absolute numbers of cases (criterion 1): they revealed potential source locations (Q fever, the Netherlands) and clusters with high incidence (pertussis, Germany). Unlike incidence maps, they were insensitive to choices regarding spatial scale (criterion 2). Dot map cartograms ensured the privacy of cases (criterion 3) by spatial distortion; however, this occurred at the expense of recognition of locations (criterion 4). We demonstrate that dot map cartograms are a valuable method for detection and visualisation of infectious disease outbreaks, which facilitates informed and appropriate actions by public health professionals, to investigate and control outbreaks.

Chlamydia test results were associated with sexual risk behavior change among participants of the Chlamydia screening implementation in The Netherlands.

OBJECTIVE: To examine the effect of a laboratory-confirmed Chlamydia trachomatis (Ct) test result on subsequent sexual risk behavior in a large population-based screening program. METHODS: The study population consisted of 16- to 29-year-old participants of the Chlamydia Screening Implementation who completed Ct testing and questionnaires in 2 or more rounds. The influence of a Ct test result on sexual behavior was analyzed by generalized estimating equation models, in which the Ct test result of the previous round was the independent variable and 1 of the 8 sexual risk behavior indicators was the dependent variable, adjusted for covariates. RESULTS: Of 48,910 Chlamydia Screening Implementation participants with completed questionnaires and test results, 14.1% (n = 6802) and 2.6% (n = 1272) completed 2 and 3 rounds, respectively, and were included in this study. Analysis showed that Ct positives less often reported to "never" use condoms with a casual partner (%change pretest/posttest = -5.7% [-10.3 to -0.9]), whereas Ct negatives less often reported to "always" use condoms with a casual partner (-4.6% [-6.4 to -2.8]; odds ratio [95% confidence interval], 1.75 [1.09 to 2.80]). Ct positives also had more sexual partners in the subsequent round than did participants with a Ct-negative test result (relative risk [95% confidence interval], 1.14 [1.01 to 1.29]). CONCLUSIONS: Ct test results were associated with subsequent sexual risk behavior. In general, Ct positives were more likely to change their behavior after a Ct test result in a more positive and protective direction than Ct negatives, who were more likely to change their behavior toward more risky behavior. Effects over time after a Ct test should be investigated further, especially in the Ct negatives.

Adhering to a national surgical care bundle reduces the risk of surgical site infections.

BACKGROUND: In 2008, a bundle of care to prevent Surgical Site Infections (SSIs) was introduced in the Netherlands. The bundle consisted of four elements: antibiotic prophylaxis according to local guidelines, no hair removal, normothermia and 'hygiene discipline' in the operating room (i.e. number of door movements). Dutch hospitals were advised to implement the bundle and to measure the outcome. This study's goal was to assess how effective the bundle was in reducing SSI risk. METHODS: Hospitals assessed whether their staff complied with each of the bundle elements and voluntary reported compliance data to the national SSI surveillance network (PREZIES). From PREZIES data, we selected data from 2009 to 2014 relating to 13 types of surgical procedures. We excluded surgeries with missing (non)compliance data, and calculated for each remaining surgery with reported (non)compliance data the level of compliance with the bundle (that is, being compliant with 0, 1, 2, 3, or 4 of the elements). Subsequently, we used this level of compliance to assess the effect of bundle compliance on the SSI risk, using multilevel logistic regression techniques. RESULTS: 217 489 surgeries were included, of which 62 486 surgeries (29%) had complete bundle reporting. Within this group, the SSI risk was significantly lower for surgeries with complete bundle compliance compared to surgeries with lower compliance levels. Odds ratios ranged from 0.63 to 0.86 (risk reduction of 14% to 37%), while a 13% risk reduction was demonstrated for each point increase in compliance-level. Sensitivity analysis indicated that due to analysing reported bundles only, we probably underestimated the total effect of implementing the bundle. CONCLUSIONS: This study demonstrated that adhering to a surgical care bundle significantly reduced the risk of SSIs. Reporting of and compliance with the bundle compliance can, however, still be improved. Therefore an even greater effect might be achieved.

Ongoing transmission of hepatitis B virus in rural parts of the Netherlands, 2009-2013.

BACKGROUND: Reported acute hepatitis B incidence in the Netherlands reached its nadir in 2013. However, regional signals about increased number of hepatitis B cases raised the question how hepatitis B incidence was distributed over the country. In this study, regional differences in hepatitis B epidemiology were investigated using epidemiological and molecular data. METHODS: Acute hepatitis B virus (HBV) infections, reported between 2009-2013, were included. If serum was available, a fragment of S and C gene of the HBV was amplified and sequenced. Regional differences in incidence were studied by geographical mapping of cases and cluster analysis. Regional differences in transmission were studied by constructing regional maximum parsimony trees based on the C gene to assess genetic clustering of cases. RESULTS: Between 2009 and 2013, 881 cases were notified, of which respectively 431 and 400 cases had serum available for S and C gene sequencing. Geographical mapping of notified cases revealed that incidences in rural border areas of the Netherlands were highest. Cluster analysis identified two significant clusters (p<0.000) in the South-western and North-eastern regions. Genetic cluster analysis showed that rural border areas had relatively large clusters of cases with indistinguishable sequences, while other regions showed more single introductions. CONCLUSION: This study showed that regional differences in HBV epidemiology were present in the Netherlands. Rural border regions showed higher incidences and more ongoing transmission, mainly among MSM, than the more urban inland areas. Therefore, preventive measures should be enhanced in these regions.