GGD Hart voor Brabant

Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.

Since the steady rise in human cases which started in 2007, Q fever has become a major public health problem in the Netherlands with 2,357 human cases notified in the year 2009. Ongoing research confirms that abortion waves on dairy goat farms are the primary source of infection for humans, primarily affecting people living close (under 5 km) to such a dairy goat farm. To reverse the trend of the last three years, drastic measures have been implemented, including the large-scale culling of pregnant goats on infected farms.

We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most affected were men, smokers and persons aged 40–60 years. Pneumonia was the most common clinical presentation (62% in 2007 and 2008). Only 3.2% of the patients were working in the agriculture sector and 0.5% in the meat-processing industry including abattoirs. Dairy goat farms with Coxiella burnetii-induced abortion waves were mainly located in the same area where human cases occurred. Airborne transmission of contaminated dust particles from commercial dairy goat farms in densely populated areas has probably caused this epidemic. In 2010, there was a sharp decline in the number of notified cases following the implementation of control measures on dairy goat and sheep farms such as vaccination, hygiene measures and culling of pregnant animals on infected farms. In combination with a rise in the human population with antibodies against C. burnetii, these have most likely ended the outbreak. Development of chronic Q fever in infected patients remains an important problem for years to come.

BACKGROUND: Long-term fatigue with detrimental effects on daily functioning often occurs following acute Q-fever. Following the 2007-2010 Q-fever outbreak in the Netherlands with over 4000 notified cases, the emphasis on long-term consequences of Q-fever increased. The aim of this study was to provide an overview of all relevant available literature, and to identify knowledge gaps regarding the definition, diagnosis, background, description, aetiology, prevention, therapy, and prognosis, of fatigue following acute Q-fever. DESIGN: A systematic review was conducted through searching Pubmed, Embase, and PsycInfo for relevant literature up to 26th May 2015. References of included articles were hand searched for additional documents, and included articles were quality assessed. RESULTS: Fifty-seven articles were included and four documents classified as grey literature. The quality of most studies was low. The studies suggest that although most patients recover from fatigue within 6-12 months after acute Q-fever, approximately 20% remain chronically fatigued. Several names are used indicating fatigue following acute Q-fever, of which Q-fever fatigue syndrome (QFS) is most customary. Although QFS is described to occur frequently in many countries, a uniform definition is lacking. The studies report major health and work-related consequences, and is frequently accompanied by nonspecific complaints. There is no consensus with regard to aetiology, prevention, treatment, and prognosis. CONCLUSIONS: Long-term fatigue following acute Q-fever, generally referred to as QFS, has major health-related consequences. However, information on aetiology, prevention, treatment, and prognosis of QFS is underrepresented in the international literature. In order to facilitate comparison of findings, and as platform for future studies, a uniform definition and diagnostic work-up and uniform measurement tools for QFS are proposed.

A Q fever outbreak occurred in the southeast of The Netherlands in spring and summer 2007. Risk factors for the acquisition of a recent Coxiella burnetii infection were studied. In total, 696 inhabitants in the cluster area were invited to complete a questionnaire and provide a blood sample for serological testing of IgG and IgM phases I and II antibodies against C. burnetii, in order to recruit seronegative controls for a case-control study. Questionnaires were also sent to 35 previously identified clinical cases. Limited environmental sampling focused on two goat farms in the area. Living in the east of the cluster area, in which a positive goat farm, cattle and small ruminants were situated, smoking and contact with agricultural products were associated with a recent infection. Information leaflets were distributed on a large scale to ruminant farms, including hygiene measures to reduce the risk of spread between animals and to humans.

The Netherlands is again facing a sharp increase in Q fever notifications, after the unprecedented outbreaks of 2007 and 2008. The most affected province of Noord Brabant has a high density of large dairy goat farms, and farms with abortion waves have been incriminated. Mandatory vaccination of small ruminants has started and should have an effect in 2010. A large multidisciplinary research portfolio is expected to generate better knowledge about transmission and additional control measures.

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infections (68/126) in minks and farm workers (>50% of farms) were detected, with limited community spread. Three of five initial introductions of SARS-CoV-2 led to subsequent spread between mink farms until November 2020. Viruses belonging to the largest cluster acquired an amino acid substitution in the receptor binding domain of the Spike protein (position 486), evolved faster and spread longer and more widely. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combining genetic information with epidemiological information when investigating outbreaks at the animal-human interface.

Q fever is a worldwide zoonosis caused by the bacterium Coxiella burnetii which is common in a wide range of wild and domestic animals. Cattle and small ruminants, in particular sheep and goats, have been associated with large human outbreaks. Humans become infected primarily by inhaling aerosols that are contaminated by C. burnetii. Most infections remain asymptomatic but in about 40% lead to a febrile disease, pneumonia and/or hepatitis. Chronic infections, mainly endocarditis, are observed in 3 to 5% of cases, with an increased risk for pregnant women and persons with heart valve disorders or impaired immunity. Q fever in pregnancy, whether symptomatic or asymptomatic, may also result in adverse pregnancy outcomes [1]. Q fever in humans is a notifiable disease in The Netherlands. The notification criteria for a confirmed case of acute Q fever are clinical symptoms consistent with Q fever and a positive serology defined by immunofluoresence assay (IFA) test or a C. burnetii complement fixation test [2]. Also clinical patients diagnosed by PCR are considered as confirmed cases. Between 1997 and 2006, Q fever was notified rarely with an average of 11 (range 5-16) cases annually [3]. In 2007, we reported in this journal the first community outbreak of Q fever in the south of The Netherlands [4].

Control of norovirus outbreaks relies on enhanced hygiene measures, such as handwashing, surface cleaning, using disposable paper towels, and using separate toilets for sick and well persons. However, little is known about their effectiveness in limiting further spread of norovirus infections. We analyzed norovirus outbreaks in 7 camps at an international scouting jamboree in the Netherlands during 2004. Implementation of hygiene measures coincided with an 84.8% (95% predictive interval 81.2%-86.6%) reduction in reproduction number. This reduction was unexpectedly large but still below the reduction needed to contain a norovirus outbreak. Even more stringent control measures are required to break the chain of transmission of norovirus.

The decomposition process of human remains can be used to estimate the post-mortem interval (PMI), but decomposition varies due to many factors. Temperature is believed to be the most important and can be connected to decomposition by using the accumulated degree days (ADD). The aim of this research was to develop a decomposition scoring method and to develop a formula to estimate the PMI by using the developed decomposition scoring method and ADD. A decomposition scoring method and a Book of Reference (visual resource) were made. Ninety-one cases were used to develop a method to estimate the PMI. The photographs were scored using the decomposition scoring method. The temperature data was provided by the Royal Netherlands Meteorological Institute. The PMI was estimated using the total decomposition score (TDS) and using the TDS and ADD. The latter required an additional step, namely to calculate the ADD from the finding date back until the predicted day of death. The developed decomposition scoring method had a high interrater reliability. The TDS significantly estimates the PMI (R 2 = 0.67 and 0.80 for indoor and outdoor bodies, respectively). When using the ADD, the R 2 decreased to 0.66 and 0.56. The developed decomposition scoring method is a practical method to measure decomposition for human remains found on land. The PMI can be estimated using this method, but caution is advised in cases with a long PMI. The ADD does not account for all the heat present in a decomposing remain and is therefore a possible bias.

Effective infection control measures during norovirus outbreaks are urgently needed in places where vulnerable individuals gather. In the present study, the effect of a number of measures was investigated in daily practice. Forty-nine Dutch nursing homes were monitored prospectively for norovirus outbreaks during two winter seasons. A total of 37 norovirus outbreaks were registered. Control measures were most effective when implemented within 3 days after onset of disease of the first patient. Measures targeted at reduced transmission between persons, via aerosols, and via contaminated surfaces reduced illness in staff and in residents. Reducing illness in staff results in fewer costs for sick leave and substitution of staff and less disruption in the care of residents. The effect of control measures on outbreak duration was limited. This is the first intervention study examining the effect of control measures. Further research is needed to extend and refine the conclusions.

Abstract The zoonotic origin of the SARS-CoV-2 pandemic is still unknown. Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation of outbreaks on 16 mink farms and humans living or working on these farms, using whole genome sequencing. We conclude that the virus was initially introduced from humans and has evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. At the moment, despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, there is ongoing transmission between mink farms with three big transmission clusters with unknown modes of transmission. We also describe the first animal to human transmissions of SARS-CoV-2 in mink farms. One sentence summary SARS-CoV-2 transmission on mink farms.

Large outbreaks of Q fever in the Netherlands from 2007 to 2009 were monitored using notification data of acute clinical Q fever. However, the notification system provides no information on infections that remain subclinical or for which no medical attention is sought. The present study was carried out immediately after the peak of the 2009 outbreak to estimate the ratio between Coxiella burnetii infections and Q fever notifications. In 23 postcode areas in the high-incidence area, notification rates were compared with seroconversion rates in blood donors from whom serial samples were available. This resulted in a ratio of one Q fever notification to 12.6 incident infections of C. burnetii. This ratio is time and place specific and is based on a small number of seroconversions, but is the best available factor for estimating the total number of infections. In addition, as subclinical C. burnetii infection may lead to chronic Q fever, the ratio can be used to estimate the expected number of chronic Q fever patients in the coming years and as input for cost–benefit analyses of screening options.

The duration and level of virus excretion in blood and faeces of patients with hepatitis A virus (HAV) infection were studied in relation to levels of alanine aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood and faeces were collected from 27 patients with acute hepatitis A (median age: 33 years) for a maximum of 26 weeks. Single blood donations from 55 other patients with acute HAV (median age: 32 years) were also used. Virus loads were quantified by competitive nested RT-PCR. HAV was excreted in faeces for a median period of 81 days after disease onset, with 50% of patients still excreting high levels at Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was detected, but not quantifiable, for a median period of 42 days. In the first 10 days of illness, higher ALT levels were correlated with higher viraemia levels. Comparison of patients infected with genotype 1a with those infected with type 1b did not differ significantly in terms of the duration of HAV excretion or jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first month, perhaps making patients infectious for a longer period than assumed currently. Blood banks should be aware that viraemia may be present for more than 1 month, and genotype did not affect the duration of virus excretion or jaundice.

BACKGROUND: In the Netherlands, from 2007 to 2009, 3,522 Q-fever cases were notified from three outbreaks. These are the largest documented outbreaks in the world. Previous studies suggest that symptoms can persist for a long period of time, resulting in a reduced quality of life (QoL). The aim of this study was to qualify and quantify the health status of Q-fever patients after long-term follow-up. METHODS: 870 Q-fever patients of the 2007 and 2008 outbreaks were mailed a questionnaire 12 to 26 months after the onset of illness. We assessed demographic data and measured health status with the Nijmegen Clinical Screening Instrument (NCSI). The NCSI consists of three main domains of functional impairment, symptoms and QoL that are divided into eight sub-domains. The NCSI scores of Q-fever patients older than 50 years (N=277) were compared with patients younger than 50 years (N=238) and with norm data from healthy individuals (N=65) and patients with chronic obstructive pulmonary disease (N=128). RESULTS: The response rate was 65.7%. After applying exclusion criteria 515 Q-fever patients were included in this study. The long-term health status of two thirds of Q-fever patients (both younger and older than 50 years) was severely affected for at least one sub-domain. Patients scores were most severely affected on the sub-domains general QoL (44.9%) and fatigue (43.5%). Hospitalisation in the acute phase was significantly related to long-term behavioural impairment (OR 2.8, CI 1.5-5.1), poor health related QoL (OR 2.3,CI 1.5-4.0) and subjective symptoms (OR 1.9, CI 1.1-3.6). Lung or heart disease, depression and arthritis significantly affected the long-term health status of Q-fever patients. CONCLUSIONS: Q-fever patients presented 12 to 26 months after the onset of illness severe -clinically relevant- subjective symptoms, functional impairment and impaired QoL. All measured sub-domains of the health status were impaired. Hospitalisation and co-morbidity were predictors for worse scores. Our data emphasise that more attention is needed not only to prevent exposure to Q-fever but also for the prevention and treatment of the long-term consequences of this zoönosis.

PURPOSE: In 2007, a large goat-farming-associated Q fever outbreak occurred in the Netherlands. Data on the clinical outcome of Dutch Q fever patients are lacking. The current advocated follow-up strategy includes serological follow-up to detect evolution to chronic disease and cardiac screening at baseline to identify and prophylactically treat Q fever patients in case of valvulopathy. However, serological follow-up using commercially available tests is complicated by the lack of validated cut-off values. Furthermore, cardiac screening in the setting of a large outbreak has not been implemented previously. Therefore, we report here the clinical outcome, serological follow-up and cardiac screening data of the Q fever patients of the current ongoing outbreak. METHODS: The implementation of a protocol including clinical and serological follow-up at baseline and 3, 6 and 12 months after acute Q fever and screening echocardiography at baseline. RESULTS: Eighty-five patients with acute Q fever were identified (male 62%, female 38%). An aspecific, flu-like illness was the most common clinical presentation. Persistent symptoms after acute Q fever were reported by 59% of patients at 6 months and 30% at 12 months follow-up. We observed a typical serological response to Coxiella burnetii infection in both anti-phase I and anti-phase II IgG antibodies, with an increase in antibody titres up to 3 months and a subsequent decrease in the following 9 months. Screening echocardiography was available for 66 (78%) out of 85 Q fever patients. Cardiac valvulopathy was present in 39 (59%) patients. None of the 85 patients developed chronic Q fever. CONCLUSIONS: Clinical, serological and echocardiographic data of the current ongoing Dutch Q fever outbreak cohort are presented. Screening echocardiography is no longer part of the standard work-up of Q fever patients in the Netherlands.

OBJECTIVE: The objective of this study was to determine to which degree travelers who received pretravel advice at a travel clinic have protected or unprotected sexual contact with a new partner and what factors influence this behavior. METHOD: An anonymous questionnaire was sent to travelers who came to a pretravel clinic between June 1 and August 31, 2005. Risk factors for casual travel sex and predictors of protected sex were studied in a multivariate model. RESULTS: A total of 1,907 travelers were included (response rate 55%) in the study. Only 4.7% of the respondents had sexual contact with a new partner, and 63.1% of these new partners were from the country of destination. Of those who had casual travel sex, 52.4% did not expect this (women 75%), 30.9% did not always use condoms, and 41% were not protected against hepatitis B. Independent risk factors for casual travel sex were traveling without steady partner (OR 14.4), expecting casual travel sex (OR 9.2), having casual sexual contacts in the home country (OR 2.4), non-tourist journeys (OR 2.2), being male (OR 2.1), the fact that the information on sexually transmitted infections (STI) had been read (OR 2.0), and traveling to South and Central America (OR 2.0). Taking condoms along (OR 5.4) and reading the information on STI (OR 3.3) were identified as independent predictors of protected sex. CONCLUSIONS: Travelers have substantial sexual risk behavior. Casual sex is usually not expected, and the most important predictor is traveling without a steady partner. We would advice every client of a travel clinic who will travel without a steady partner to read the STI information, to take condoms along, and to be vaccinated against hepatitis B.

From 2007 to 2009, the Netherlands faced large seasonal outbreaks of Q fever, in which infected dairy goat farms were identified as the primary sources. Veterinary measures including vaccination of goats and sheep and culling of pregnant animals on infected farms seem to have brought the Q fever problem under control. However, the epidemic is expected to result in more cases of chronic Q fever among risk groups in the coming years. In the most affected area, in the south of the country, more than 12% of the population now have antibodies against Coxiella burnetii. Questions remain about the follow-up of acute Q fever patients, screening of groups at risk for chronic Q fever, screening of donors of blood and tissue, and human vaccination. There is a considerable ongoing research effort as well as enhanced veterinary and human surveillance.

UNLABELLED: Poor air quality in schools has been associated with adverse health effects. Indoor air quality can be improved by increasing ventilation. The objective of this study was to compare the effectiveness of different interventions to improve ventilation behavior in primary schools. We used indoor CO(2) concentrations as an indicator. In 81 classes of 20 Dutch primary schools, we applied three different interventions: (i) a class-specific ventilation advice; (ii) the advice combined with a CO(2) warning device and (iii) the advice combined with a teaching package. The effectiveness of the interventions was tested directly after intervention and 6 weeks after intervention by measuring the CO(2) concentrations and comparison with a control group (iv). Before intervention, the CO(2) concentration exceeded 1000 ppm for 64% of the school day. The class-specific ventilation advice without further support appeared an ineffective tool to improve ventilation behavior. The advice in combination with a CO(2) warning device or the teaching package proved effective tools and resulted in lower indoor CO(2) concentrations when compared with the control group. Ventilation was significantly improved, but CO(2) concentrations still exceeded 1000 ppm for more than 40% of the school day. Hence, until ventilation facilities are upgraded, the CO(2) warning device and the teaching package are useful low-cost tools. PRACTICAL IMPLICATIONS: To improve ventilation behavior and indoor air quality in schools, CO(2) warning device and teaching package combined with a class-specific ventilation advice, are effective tools, while giving the ventilation advice solely, is not effective. Although ventilation is significantly improved through behavioral change, the ventilation rate is still insufficient to maintain good air quality during the full school day. Therefore, the improvement of the ventilation facilities is recommended. Hence, until ventilation facilities in schools are upgraded, the CO(2) warning device and the teaching package are useful low-cost tools to improve current indoor air quality.

OBJECTIVE: To estimate, using routinely available data, the predictive values of tuberculin testing with 2TU RT23 for detection of latent tuberculosis infection (LTBI) in the Dutch population as a basis for recommendations on cut-off values at various levels of infection prevalence. DESIGN: Smoothed distributions of TST reactions among 312 tuberculosis patients and 2848 healthy non-BCG-vaccinated persons were used to estimate the sensitivity and specificity at various cut-off values. RESULTS: Sensitivity was 98.9% at 5 mm, 95.4% at 10 mm and 79.8% at 15 mm cut-off. Specificity with the corresponding cut-offs was 95.3%, 96.3% and 97.1% before and 98.0%, 98.8% and 99.6% after adjustment for presumed LTBI. At 10 mm, the positive predictive value (PPV) was > 75% if the infection prevalence in the tested population was at least 10%, but strongly declined with lower prevalences. For lower prevalences a cut-off of 15 mm was proposed, as this results in a higher PPV without greatly affecting the negative predictive value. CONCLUSION: Estimation of the predictive values of the TST from routine data can be useful for establishing cut-off values for detection of LTBI in different populations with different tuberculin preparations.