Laboratory methods for case finding in human psittacosis outbreaks: a systematic review.

Psittacosis outbreak investigations require rapid identification of cases in order to trace possible sources and perform public health risk assessments. In recent outbreaks in the Netherlands, such investigations were hampered by the non-specificity of laboratory testing methods to identify human Chlamydia psittaci infections

Estimation of acute and chronic Q fever incidence in children during a three-year outbreak in the Netherlands and a comparison with international literature

Background:  In the Dutch 2007-2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. Methods:  As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0-15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007-2009. Results:  In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. Conclusion:  In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice

Influenza vaccine effectiveness estimates in the Dutch population from 2003 to 2014:The test-negative design case-control study with different control groups

Information about influenza vaccine effectiveness (IVE) is important for vaccine strain selection and immunization policy decisions. The test-negative design (TND) case-control study is commonly used to obtain IVE estimates. However, the definition of the control patients may influence IVE estimates. We have conducted a TND study using the Dutch Sentinel Practices of NIVEL Primary Care Database which includes data from patients who consulted the General Practitioner (GP) for an episode of acute influenza-like illness (ILI) or acute respiratory infection (ARI) with known influenza vaccination status. Cases were patients tested positive for influenza virus. Controls were grouped into those who tested (1) negative for influenza virus (all influenza negative), (2) negative for influenza virus, but positive for respiratory syncytial virus, rhinovirus or enterovirus (non-influenza virus positive), and (3) negative for these four viruses (pan-negative). We estimated the IVE over all epidemic seasons from 2003/2004 through 2013/2014, pooled IVE for influenza vaccine partial/full matched and mismatched seasons and the individual seasons using generalized linear mixed-effect and multiple logistic regression models. The overall IVE adjusted for age, GP ILI/ARI diagnosis, chronic disease and respiratory allergy was 35% (95% CI: 15-48), 64% (95% CI: 49-75) and 21% (95% CI: -1 to 39) for all influenza negative, non-influenza virus positive and pan-negative controls, respectively. In both the main and subgroup analyses IVE estimates were the highest using non-influenza virus positive controls, likely due to limiting inclusion of controls without laboratory-confirmation of a virus causing the respiratory disease

Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivi resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. (aut. ref.

Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021-2022 I-MOVE primary care multicentre study

Background: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). Methods: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. Results: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. Discussion: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.This project has received funding from the European Centre for Disease Prevention and Control with in the framework contract ECDC/2018/029.S

Estimation of acute and chronic Q fever incidence in children during a three-year outbreak in the Netherlands and a comparison with international literature

Background:  In the Dutch 2007-2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. Methods:  As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0-15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007-2009. Results:  In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. Conclusion:  In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Chronic Q fever diagnosis—consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fe­ver Consensus Group and a set of diagnostic criteria pro­posed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cas­es of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative cri­teria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch lit­erature-based consensus guideline is more sensitive and easier to use in clinical practice

Temporal and spatial analysis of psittacosis in association with poultry farming in the Netherlands, 2000-2015

Background: Human psittacosis is a highly under diagnosed zoonotic disease, commonly linked to psittacine birds. Psittacosis in birds, also known as avian chlamydiosis, is endemic in poultry, but the risk for people living close to poultry farms is unknown. Therefore, our study aimed to explore the temporal and spatial patterns of human psittacosis infections and identify possible associations with poultry farming in the Netherlands. Methods: We analysed data on 700 human cases of psittacosis notified between 01-01-2000 and 01-09-2015. First, we studied the temporal behaviour of psittacosis notifications by applying wavelet analysis. Then, to identify possible spatial patterns, we applied spatial cluster analysis. Finally, we investigated the possible spatial association between psittacosis notifications and data on the Dutch poultry sector at municipality level using a multivariable model. Results: We found a large spatial cluster that covered a highly poultry-dense area but additional clusters were found in areas that had a low poultry density. There were marked geographical differences in the awareness of psittacosis and the amount and the type of laboratory diagnostics used for psittacosis, making it difficult to draw conclusions about the correlation between the large cluster and poultry density. The multivariable model showed that the presence of chicken processing plants and slaughter duck farms in a municipality was associated with a higher rate of human psittacosis notifications. The significance of the associations was influenced by the inclusion or exclusion of farm density in the model. Conclusions: Our temporal and spatial analyses showed weak associations between poultry-related variables and psittacosis notifications. Because of the low number of psittacosis notifications available for analysis, the power of our analysis was relative low. Because of the exploratory nature of this research, the associations found cannot be interpreted as evidence for airborne transmission of psittacosis from poultry to the general population. Further research is needed to determine the prevalence of C. psittaci in Dutch poultry. Also, efforts to promote PCR-based testing for C. psittaci and genotyping for source tracing are important to reduce the diagnostic deficit, and to provide better estimates of the human psittacosis burden, and the possible role of poultry

Mortality surveillance in the Netherlands: winter 2015/2016 of moderate severity

ObjectiveWeekly numbers of deaths are monitored to increase the capacityto deal with both expected and unusual (disease) events such aspandemic influenza, other infections and non-infectious incidents.The monitoring information can potentially be used to detect, trackand estimate the impact of an outbreak or incident on all-causemortality.IntroductionThe mortality monitoring system (initiated in 2009 during theinfluenza A(H1N1) pandemic) is a collaboration between the Centrefor Infectious Disease Control (CIb) and Statistics Netherlands.The system monitors nation-wide reported number of deaths(population size 2014: 16.8 million) from all causes, as cause ofdeath information is not available real-time. Data is received fromStatistics Netherlands by weekly emails.MethodsOnce a week the number of reported deaths is checked for excessabove expected levels at 2 different time-lags: within 1 and 2 weeksafter date of death (covering a median 43% and 96% of all deathsrespectively). A weekly email bulletin reporting the findings is sentto the Infectious Disease Early Warning Unit (at CIb) and a summaryof results is posted on the RIVM website (National Institute for PublicHealth and the Environment). Any known concurrent and possiblyrelated events are also reported. When excess deaths coincide withhot temperatures, the bulletin is sent to the Heat Plan Team (also atRIVM). Data are also sent to EuroMOMO which monitors excessmortality at a European level. For the Dutch system baselines andprediction limits are calculated using a 5 year historical period(updated each July). A serfling-like algorithm based on regressionanalysis is used to produce baselines which includes cyclical seasonaltrends (models based on historical data in which weeks with extremeunderreporting have been removed. Also periods with high excessmortality in winter and summer were removed so as not to influencethe baseline with previous outbreaks).ResultsIncreased mortality occurred during the entire influenza epidemicand up to three weeks thereafter (weeks 1-14 of 2016), except for adrop in week 7 (figure1). Excess mortality was primarily observedin persons 75 or older. Additionally, in several weeks mortality wasincreased in 65-74 year olds, (weeknr 4-6; peaking in week 4 with564 deaths, when 468 baseline deaths were predicted). Also, inweek 4, mortality in the 25-34 year-old age group was significantlyincreased (25 deaths, while 14 were expected as baseline). Cumulativeexcess mortality was estimated at 3,900 deaths occurring duringthe 11 weeks of the 2015/2016 influenza epidemic and at 6,085during the total winter season (44 weeks running from week 40 up toweek 20).ConclusionsIn terms of number of deaths during the winter season (weeks40-20) and during the influenza epidemic (weeks 1-11), the 2015/2016season in the Netherlands was of moderate severity compared with theprevious five years (and was of similar magnitude as the 2011/2012winter). Notable was the short three-week time span with a higherpeak in mortality in 65-74 year olds than has been observed in recentyears. Although the influenza epidemic reached its peak in week7, the mortality data showed a dip in week 7. The reason for thetemporary decrease is unknown but there was a partial overlap witha public holiday