A prospective matched case-control study on the genomic epidemiology of colistin-resistant Enterobacterales from Dutch patients.

Background: Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing. Methods: A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant Escherichia coli or Klebsiella pneumoniae (COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including mcr genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of pmrAB, phoPQ, mgrB and crrB. Results: In total, 72 COLR-EK/COLS-EK pairs (75% E. coli and 25% K. pneumoniae) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained mcr-1 and two mcr-9. One isolate lost mcr-9 after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance. Conclusions: Colistin resistance is present but uncommon in the Netherlands and caused by the mcr gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.

Comparing national infectious disease surveillance systems: China and the Netherlands.

BACKGROUND: Risk assessment and early warning (RAEW) are essential components of any infectious disease surveillance system. In light of the International Health Regulations (IHR)(2005), this study compares the organisation of RAEW in China and the Netherlands. The respective approaches towards surveillance of arboviral disease and unexplained pneumonia were analysed to gain a better understanding of the RAEW mode of operation. This study may be used to explore options for further strengthening of global collaboration and timely detection and surveillance of infectious disease outbreaks. METHODS: A qualitative study design was used, combining data retrieved from the literature and from semi-structured interviews with Chinese (5 national-level and 6 provincial-level) and Dutch (5 national-level) experts. RESULTS: The results show that some differences exist such as in the use of automated electronic components of the early warning system in China ('CIDARS'), compared to a more limited automated component in the Netherlands ('barometer'). Moreover, RAEW units in the Netherlands focus exclusively on infectious diseases, while China has a broader 'all hazard' approach (including for example chemical incidents). In the Netherlands, veterinary specialists take part at the RAEW meetings, to enable a structured exchange/assessment of zoonotic signals. CONCLUSION: Despite these differences, the main conclusion is that for the two infections studied, the early warning system in China and the Netherlands are remarkably similar considering their large differences in infectious disease history, population size and geographical setting. Our main recommendations are continued emphasis on international corporation that requires insight into national infectious disease surveillance systems, the usage of a One Health approach in infectious disease surveillance, and further exploration/strengthening of a combined syndromic and laboratory surveillance system.

ECDC Round Table Report and ProMed-mail most useful international information sources for the Netherlands Early Warning Committee.

The Netherlands Early Warning Committee (NEWC) aims to identify infectious diseases causing a potential threat to Dutch public health. Threats are assessed and published as (information) alerts for public health experts. To identify threats from abroad, the NEWC screens 10 sources reporting disease outbreaks each week. To identify the sources essential for complete and timely reporting, we retrospectively analysed 178 international alerts published between 31 January 2013 and 30 January 2014. In addition, we asked the four NEWC coordinators about the required time to scan the information sources. We documented the date and source in which the signal was detected. The ECDC Round Table (RT) Report and ProMED-mail were the most complete and timely sources, reporting 140 of 178 (79%) and 121 of 178 (68%) threats respectively. The combination of both sources reported 169 (95%) of all threats in a timely manner. Adding any of the other sources resulted in minor increases in the total threats found, but considerable additional time investment per additional threat. Only three potential relevant threats (2%) would have been missed by only using the ECDC RT Report and ProMed-mail. We concluded that using only the ECDC RT Report and ProMed-mail to identify threats from abroad maintains a sensitive Early Warning System.

The economic burden of a Salmonella Thompson outbreak caused by smoked salmon in the Netherlands, 2012-2013.

Background: In 2012, the Netherlands experienced the most extensive food-related outbreak of Salmonella ever recorded. It was caused by smoked salmon contaminated with Salmonella Thompson during processing. In total, 1149 cases of salmonellosis were laboratory confirmed and reported to RIVM. Twenty percent of cases was hospitalised and four cases were reported to be fatal. The purpose of this study was to estimate total costs of the Salmonella Thompson outbreak. Methods: Data from a case-control study were used to estimate the cost-of-illness of reported cases (i.e. healthcare costs, patient costs and production losses). Outbreak control costs were estimated based on interviews with staff from health authorities. Using the Dutch foodborne disease burden and cost-of-illness model, we estimated the number of underestimated cases and the associated cost-of-illness. Results: The estimated number of cases, including reported and underestimated cases was 21 123. Adjusted for underestimation, the total cost-of-illness would be €6.8 million (95% CI €2.5-€16.7 million) with productivity losses being the main cost driver. Adding outbreak control costs, the total outbreak costs are estimated at €7.5 million. Conclusion: In the Netherlands, measures are taken to reduce salmonella concentrations in food, but detection of contamination during food processing remains difficult. As shown, Salmonella outbreaks have the potential for a relatively high disease and economic burden for society. Early warning and close cooperation between the industry, health authorities and laboratories is essential for rapid detection, control of outbreaks, and to reduce disease and economic burden.

Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections.

BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non-respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10-year time period (2003-2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.

To notify or not to notify: decision aid for policy makers on whether to make an infectious disease mandatorily notifiable.

Mandatory notification can be a useful tool to support infectious disease prevention and control. Guidelines are needed to help policymakers decide whether mandatory notification of an infectious disease is appropriate. We developed a decision aid, based on a range of criteria previously used in the Netherlands or in other regions to help decide whether to make a disease notifiable. Criteria were categorised as being effective, feasible and necessary with regard to the relevance of mandatory notification. Expert panels piloted the decision aid. Here we illustrate its use for three diseases (Vibrio vulnificus infection, chronic Q fever and dengue fever) for which mandatory notification was requested. For dengue fever, the expert panel advised mandatory notification; for V. vulnificus infection and chronic Q fever, the expert panel concluded that mandatory notification was not (yet) justified. Use of the decision aid led to a structured, transparent decision making process and a thorough assessment of the advantages and disadvantages of mandatory notification of these diseases. It also helped identify knowledge gaps that required further research before a decision could be made. We therefore recommend use of this aid for public health policy making.

[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.

[Changes in the duty of notification of infectious diseases via the Dutch Public Health Act]. / Veranderingen in de meldingsplicht voor infectieziekten door de Wet Publieke Gezondheid.

The Dutch Public Health Act, which came into force on 1 December 2008, replaces the existing laws concerning the combating of infectious diseases. Important changes have been incorporated in the new Public Health Act in comparison with the previous law on infectious diseases. Diseases which are probably infectious in nature and caused by as yet unknown pathogens are now notifiable, laboratories also have a nominal duty of notification and the list of notifiable diseases has been extended with 10 new infectious diseases. The provisions in the law comply with the International Health Regulations of the World Health Organization. The Centre for Infectious Disease Control Netherlands at the Dutch National Institute for Public Health and the Environment (RIVM) has issued a booklet for all Dutch physicians and laboratories providing background information on notifiable diseases. This can be useful in daily practice for helping to decide whether a disorder or cluster of infections is notifiable.

Calicivirus inactivation by nonionizing (253.7-nanometer-wavelength [UV]) and ionizing (gamma) radiation.

Noroviruses (previously Norwalk-like viruses) are the most common viral agents associated with food- and waterborne outbreaks of gastroenteritis. In the absence of culture methods for noroviruses, animal caliciviruses were used as model viruses to study inactivation by nonionizing (253.7-nm-wavelength [UV]) and ionizing (gamma) radiation. Here, we studied the respiratory feline calicivirus (FeCV) and the presumed enteric canine calicivirus (CaCV) and compared them with the well-studied bacteriophage MS2. When UV irradiation was used, a 3-log(10) reduction was observed at a fluence of 120 J/m(2) in the FeCV suspension and at a fluence of 200 J/m(2) for CaCV; for the more resistant phage MS2 there was a 3-log(10) reduction at a fluence of 650 J/m(2). Few or no differences were observed between levels of UV inactivation in high- and low-protein-content virus stocks. In contrast, ionizing radiation could readily inactivate MS2 in water, and there was a 3-log(10) reduction at a dose of 100 Gy, although this did not occur when the phage was diluted in high-protein-content stocks of CaCV or FeCV. The low-protein-content stocks showed 3-log(10) reductions at a dose of 500 Gy for FeCV and at a dose of 300 for CaCV. The inactivation rates for both caliciviruses with ionizing and nonionizing radiation were comparable but different from the inactivation rates for MS2. Although most FeCV and CaCV characteristics, such as overall particle and genome size and structure, are similar, the capsid sequences differ significantly, making it difficult to predict human norovirus inactivation. Adequate management of UV and gamma radiation processes for virus inactivation should limit public health risks.

Inactivation of caliciviruses.

The viruses most commonly associated with food- and waterborne outbreaks of gastroenteritis are the noroviruses. The lack of a culture method for noroviruses warrants the use of cultivable model viruses to gain more insight on their transmission routes and inactivation methods. We studied the inactivation of the reported enteric canine calicivirus no. 48 (CaCV) and the respiratory feline calicivirus F9 (FeCV) and correlated inactivation to reduction in PCR units of FeCV, CaCV, and a norovirus. Inactivation of suspended viruses was temperature and time dependent in the range from 0 to 100 degrees C. UV-B radiation from 0 to 150 mJ/cm(2) caused dose-dependent inactivation, with a 3 D (D = 1 log(10)) reduction in infectivity at 34 mJ/cm(2) for both viruses. Inactivation by 70% ethanol was inefficient, with only 3 D reduction after 30 min. Sodium hypochlorite solutions were only effective at >300 ppm. FeCV showed a higher stability at pH <3 and pH >7 than CaCV. For all treatments, detection of viral RNA underestimated the reduction in viral infectivity. Norovirus was never more sensitive than the animal caliciviruses and profoundly more resistant to low and high pH. Overall, both animal viruses showed similar inactivation profiles when exposed to heat or UV-B radiation or when incubated in ethanol or hypochlorite. The low stability of CaCV at low pH suggests that this is not a typical enteric (calici-) virus. The incomplete inactivation by ethanol and the high hypochlorite concentration needed for sufficient virus inactivation point to a concern for decontamination of fomites and surfaces contaminated with noroviruses and virus-safe water.

Immunoglobulin a as a serological marker for the (silent) circulation of poliovirus in an inactivated poliovirus-vaccinated population.

Poliovirus-specific immunoglobulin A (IgA) is detected after infection with wild-type virus or vaccination with live attenuated oral poliovirus (OPV) but not after vaccination with inactivated poliovirus (IPV). We examined whether the presence of IgA in serum can be used as a marker for poliovirus circulation in IPV-vaccinated populations in The Netherlands. In seronegative persons challenged with OPV, the sensitivity of this marker was 76%-86%. Results from a serosurvey showed a high seroprevalence (63%-73%) of IgA in the population born before vaccination was introduced in The Netherlands, which reflects natural exposure. The start of the vaccination program in 1957 corresponded to a reduction in the IgA seroprevalence in both vaccinated (2.1%-4.5%) and nonvaccinated groups (8.3%-11.7%). The presence of IgA-positive persons in the population could largely be explained by the occurrence of episodes of proven poliovirus circulation. We propose to use the detection of poliovirus-specific IgA as a tool to monitor virus circulation in IPV-vaccinated and nonvaccinated populations, to aid the poliovirus eradication process.