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Surveillance data shows a geographical overlap between the early coronavirus disease 2019 (COVID-19) pandemic and the past Q fever epidemic (2007–2010) in the Netherlands. We investigated the relationship between past Q fever and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2020/2021, using a retrospective matched cohort study. In January 2021, former Q fever patients received a questionnaire on demographics, SARS-CoV-2 test results and related hospital/intensive care unit (ICU) admissions. SARS-CoV-2 incidence with 95% confidence intervals (CI) in former Q fever patients and standardised incidence ratios (SIR) to compare to the age-standardised SARS-CoV-2 incidence in the general regional population were calculated. Among 890 former Q fever patients (response rate: 68%), 66 had a PCR-confirmed SARS-CoV-2 infection. Of these, nine (14%) were hospitalised and two (3%) were admitted to ICU. From February to June 2020 the SARS-CoV-2 incidence was 1573/100 000 (95% CI 749–2397) in former Q fever patients and 695/100 000 in the general population (SIR 2.26; 95% CI 1.24–3.80). The incidence was not significantly higher from September 2020 to February 2021. We found no sufficient evidence for a difference in SARS-CoV-2 incidence or an increased severity in former Q fever patients vs. the general population during the period with widespread SARS-CoV-2 testing availability (September 2020–February 2021). This indicates that former Q fever patients do not have a higher risk of SARS-CoV-2 infection.

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.

Background This study aimed to determine short- and long-term physical and psychosocial impact of Coxiella burnetii infection in three distinct entities: Q-fever fatigue syndrome (QFS), chronic Q-fever, and patients with past acute Q-fever without QFS or chronic Q-fever. Methods Integrative data analysis was performed, combining original data from eight studies measuring quality of life (QoL), fatigue, physical and social functioning with identical validated questionnaires, from three months to eight years after onset infection. Linear trends in each outcome were compared between Q-fever groups using multilevel linear regression analyses to account for repeated measures within patients. Results Data included 3947 observations of 2313 individual patients (228 QFS, 135 chronic Q-fever and 1950 patients with past acute Q-fever). In the first years following infection, physical and psychosocial impact was highest among QFS patients, and remained high without significant improvements over time. In chronic Q-fever patients, QoL and physical functioning worsened significantly over time. Levels of fatigue and social participation in patients with past acute Q-fever improved significantly over time. Conclusion The impact differs greatly between the three Q-fever groups. It is important that physicians are aware of these differences, in order to provide relevant care for each patient group.

Infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are often preceded by asymptomatic carriage. Higher incidences in enteric infectious diseases during summer have been reported. Here, we assessed whether the presence of seasonality in intestinal ESBL-Escherichia coli/Klebsiella pneumoniae (ESBL-E/K) carriage in the general Dutch population exists. From 2014 to 2017, the faecal carriage of ESBL-E/K in healthy individuals was determined in three cross-sectional studies in the Netherlands, including 5985 subjects. Results were pooled to identify seasonal trends in prevalence (by month of sampling). Multivariate logistic regression analysis was used to calculate pooled odds ratios and 95% confidence intervals. Results were adjusted for age, sex, antibiotic use and travel. Overall prevalence of ESBL-E/K carriage was 4.3% (n = 260 ESBL-E/K-positive), with differences between months ranging from 2.6% to 7.4%. Compared to January, the monthly prevalence of ESBL-E carriage was highest in August (OR 1.88, 95% CI 1.02–3.49) and September (OR 2.25, 95% CI 1.30–3.89). The observed monthly differences in ESBL-E/K carriage rates suggest that there is seasonal variation in exposure to ESBL-E/K other than due to travelling and antibiotic use. This should be taken into account in designing future ESBL-E prevalence studies in temperate regions.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

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.

Genes involved in human immune response are well recognized to influence the clinical course of infection. The association of host genetics with susceptibility to and severity of clinical symptoms in acute Q fever was investigated. Single nucleotide polymorphisms (SNPs) in the IFNG (rs2430561/rs1861493), STAT1 (rs1914408), and VDR (rs2228570) genes were determined in 85 patients from the 2007 Dutch acute Q fever outbreak, and a symptom score was calculated. IFNG rs1861493 showed a significant association with the symptom score; IFNG rs2430561 showed a similar trend. These SNPs were then used to reproduce results in a 2009 outbreak population (n = 123). The median symptom score differed significantly in both populations: 2 versus 7. The significant association of IFNG rs1861493 with symptom score in the first population was not reproduced in the second population. We hypothesize that individuals in the second outbreak were exposed to a higher Coxiella burnetii dose compared to the first, which overruled the protection conferred by the A-allele of IFNG rs1861493 in the first population.

In this study, we comparedCoxiella burnetiiIgG phase I, IgG phase II, and IgM phase II detection among a commercially available enzyme-linked immunosorbent assay (ELISA) (Virion/Serion), an indirect fluorescent antibody test (IFAT) (Focus Diagnostics), and a complement fixation test (CFT) (Virion/Serion). For this, we used a unique collection of acute- and convalescent-phase sera from 126 patients with acute Q fever diagnosed by positiveCoxiella burnetiiPCR of blood. We were able to establish a reliable date of onset of disease, since DNA is detectable within 2 weeks after the start of symptoms. In acute samples, att= 0, IFAT demonstrated IgM phase II antibodies in significantly more sera than did ELISA (31.8% versus 19.7%), although the portion of solitary IgM phase II was equal for IFAT and for ELISA (18.2% and 16.7%, respectively). Twelve months after the diagnosis of acute Q fever, 83.5% and 62.2% of the sera were still positive for IgM phase II with IFAT and ELISA, respectively. At 12 months IFAT IgG phase II showed the slowest decline. Therefore, definitive serological evidence of acute Q fever cannot be based on a single serum sample in areas of epidemicity and should involve measurement of both IgM and IgG antibodies in paired serum. Based on IgG phase II antibody detection in paired samples (at 0 and 3 months) from 62 patients, IFAT confirmed more cases than ELISA and CFT, but the differences were not statically significant (100% for IFAT, 95.2% for ELISA, and 96.8% for CFT). This study demonstrated that the three serological tests are equally effective in diagnosing acute Q fever within 3 months of start of symptoms. In follow-up sera, more IgG antibodies were detected by IFAT than by ELISA or CFT, making IFAT more suitable for prevaccination screening programs.

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.

SUMMARYQ fever patients are often reported to experience a long-term impaired health status, including fatigue, which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a laboratory-confirmedCoxiella burnetiiinfection were not notified as acute Q fever because they did not fulfil the clinical criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis). Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193 non-notified Q fever patients. The most severely affected subdomain in both patient groups was ‘Fatigue’ (50·5% of the notified and 54·6% of the non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group. Our findings suggest that the magnitude of the 2007–2009 Q fever outbreak in The Netherlands was underestimated when only notified patients according to the European Union case definition are considered.

PCR is very effective in diagnosing acute Q fever in the early stages of infection, when bacterial DNA is present in the bloodstream but antibodies have not yet developed. The objective of this study was to further analyze the diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the qPCR assay were calculated for patients with negative qPCR results with a follow-up sample obtained within 14 days ( n = 305) and qPCR-positive patients with at least one follow-up sample ( n = 369). The correctness of the qPCR result was based on immunofluorescence assay results for samples submitted for qPCR and follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%, specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed serologic profiles indicative of chronic Q fever infection had significantly higher C. burnetii DNA loads during the acute phase than did patients who did not ( P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever and should be used in outbreak situations when the onset of symptoms is C. burnetii DNA loads during the acute phase, as this might be an indicator for the development of a serologic profile indicative of chronic infection.

Item does not contain fulltext BACKGROUND: Chronic Q-fever, a condition with high morbidity and mortality, may develop after an acute infection with Coxiella burnetii (acute Q-fever). Several strategies have been suggested for early detection of chronic Q-fever, focusing on follow-up of known acute Q-fever patients and detection of asymptomatic or unknown chronic infections. As there is no international standard or consensus, the aims of this study were to summarise the available literature and assess the evidence for different follow-up and screening strategies. DESIGN: We conducted a systematic review by searching PubMed and Embase. Twenty articles were included, of which fourteen only provided information on follow-up of known acute Q-fever cases, four presented data on identification of previously unknown C. burnetii infections, and two had information on both topics. RESULTS: The conversion rate of acute to chronic Q-fever ranged from 0 to 5.0%. Most studies advised serological follow-up of acute Q-fever patients, but without consistent advice on optimum timing and duration. The recommendation to use echocardiography for all acute Q-fever patients to detect valvular damage remains controversial. Screening of high-risk patients in an outbreak setting is advised by studies investigating such strategy. CONCLUSIONS: There is sufficient evidence to support serological follow-up of all known acute Q-fever patients at least once during the first year following the acute infection, and more frequently in patients with known risk factors for chronic disease, such as heart valve- or vascular prosthesis. Screening of risk groups should be considered in outbreaks of Q-fever.

Little is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response toCoxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P= 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.

Background From 2007 to 2009, the Netherlands experienced a major Q fever epidemic, with higher hospitalization rates than the 2–5% reported in the literature for acute Q fever pneumonia and hepatitis. We describe epidemiological and clinical features of hospitalized acute Q fever patients and compared patients presenting with Q fever pneumonia with patients admitted for other forms of community-acquired pneumonia (CAP). We also examined whether proximity to infected ruminant farms was a risk factor for hospitalization. Methods A retrospective cohort study was conducted for all patients diagnosed and hospitalized with acute Q fever between 2007 and 2009 in one general hospital situated in the high incidence area in the south of the Netherlands. Pneumonia severity scores (PSI and CURB-65) of acute Q fever pneumonia patients (defined as infiltrate on a chest x-ray) were compared with data from CAP patients. Hepatitis was defined as a >twofold the reference value for alanine aminotransferase and for bilirubin. Results Among the 183 hospitalized acute Q fever patients, 86.0% had pneumonia. Elevated liver enzymes (alanine aminotransferase) were found in 32.3% of patients, although hepatitis was not observed in any of them. The most frequent clinical signs upon presentation were fever, cough and dyspnoea. The median duration of admission was five days. Acute Q fever pneumonia patients were younger, had less co-morbidity, and lower PSI and CURB-65 scores than other CAP patients. Anecdotal information from attending physicians suggests that some patients were admitted because of severe subjective dyspnoea, which was not included in the scoring systems. Proximity to an infected ruminant farm was not associated with hospitalization. Conclusion Hospitalized Dutch acute Q fever patients mostly presented with fever and pneumonia. Patients with acute Q fever pneumonia were hospitalized despite low PSI and CURB-65 scores, presumably because subjective dyspnoea was not included in the scoring systems.