Exposure to tick-borne encephalitis virus among nature management workers in the Netherlands.

Tick-borne encephalitis virus (TBEV) has only recently been detected in the Netherlands. With still few autochthonous tick-borne encephalitis (TBE) patients, human exposure to TBEV is expected to be very low among the general population. We aimed to assess the exposure to TBEV among persons with an occupationally high risk of tick bites in the Netherlands. In our cross-sectional serological survey, employees and volunteers of nature management organizations provided a single blood sample and completed an online questionnaire in 2017. The sera were screened in the anti-TBEV IgG Enzyme-Linked Immunosorbent Assay (ELISA), after which a TBEV-specific virus neutralization test (VNT) was applied to confirm positive ELISA outcomes. Ten sera tested positive for IgG antibodies in the TBEV ELISA, among 556 participants who did not report vaccination against TBEV. Through confirmation in VNT, TBEV-specific IgG antibodies were detected among 0.5% (3/556, 95%CI 0.1%-1.6%). During the five years prior to the questionnaire, 87% reported tick bites. Half of the participants considered that most of their tick bites (75% to 100%) had been acquired while being at work. A very low seroprevalence of TBEV exposure was observed among these nature management workers, even though they report a six times higher exposure to tick bites, compared to our general population. Nonetheless, the emergence of TBEV in the Netherlands reaffirms the need for education and preventative measures against tick bites and tick-borne diseases.

First paediatric case of autochthonous tick-borne encephalitis in the Netherlands, 2018.

Since 2016, sporadic cases of autochthonous tick-borne encephalitis (TBE) have been encountered in the Netherlands, in two distinct geographic regions. We describe the first paediatric autochthonous case of TBE, in 2018, which was contracted outside these regions, suggesting that TBE is more widespread. Countrywide vigilance for new TBE cases remains necessary.

Chikungunya virus outbreak in Sint Maarten: Long-term arthralgia after a 15-month period.

BACKGROUND & OBJECTIVES: The first chikungunya (CHIK) epidemic in the Americas was reported in December 2013. Chikungunya virus (CHIKV) causes an acute febrile illness and is transmitted to humans by Aedes mosquitoes. Although earlier studies have described long-term clinical manifestations of CHIK patients infected with the East/Central/South African (ECSA) genotype, little is known about persistent manifestations in the Caribbean region, for which the Asian genotype is responsible. The objective of this study was to describe the presence of persisting clinical manifestations, specifically arthralgia, in CHIKV-infected patients on the Caribbean Island, Sint Maarten, 15 months after onset of the disease. METHODS: This retrospective cohort study included confirmed CHIK patients that were recorded by the participating general practitioners (GPs) during the chikungunya outbreak in 2014 in Sint Maarten. Between March and July 2015, 15 months after the onset of disease, patients were interviewed via telephone about the presence, duration and impact of clinical CHIKV manifestations. RESULTS: In total, 56 patients were interviewed (median age 47 yr), of which 30 (54%) were females. Out of the total interviewed patients, 52 (93%) reported arthralgia for the first three months after the disease onset, of which 23 (44%) patients reported to have persistent arthralgia, 15 months after the disease onset. Pain intensity of persistent arthralgia was perceived as mild in the majority of patients (n = 14; 60%), moderate in 7 (30%) patients and severe in 2 (9%) patients. During the acute phase of disease, most patients had to miss school or work (n = 39; 72%) due to clinical CHIKV manifestations and reported a negative impact on daily activities (n = 36; 57%). INTERPRETATION & CONCLUSION: Results suggested that persisting arthralgia is a frequent complication in CHIK patients included in the study. Future research on strain-specific clinical long-term manifestations and on their impact on daily life of patients, in the form of a comparative study between patients and controls, is recommended.

Editor's Choice--External Validation of Models Predicting Survival After Ruptured Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Prediction of survival after intervention for ruptured abdominal aortic aneurysms (RAAA) may support case mix comparison and tailor the prognosis for patients and relatives. The objective of this study was to assess the performance of four prediction models: the updated Glasgow Aneurysm Score (GAS), the Vancouver scoring system, the Edinburgh Ruptured Aneurysm Score (ERAS), and the Hardman index. DESIGN, MATERIALS, AND METHODS: This was a retrospective cohort study in 449 patients in ten hospitals with a RAAA (intervention between 2004 and 2011). The primary endpoint was combined 30 day or in hospital death.The accuracy of the prediction models was assessed for discrimination (area under the curve [AUC]). An AUC>0.70 was considered sufficiently accurate. In studies with sufficiently accurate discrimination, correspondence between the predicted and observed outcomes (i.e. calibration) was recalculated. RESULTS: The AUC of the updated GAS was 0.71 (95% confidence interval [CI] 0.66-0.76), of the Vancouver score was 0.72 (95% CI 0.67-0.77), and of the ERAS was 0.58 (95% CI 0.52-0.65). After recalibration, predictions by the updated GAS slightly overestimated the death rate, with a predicted death rate 60% versus observed death rate 54% (95% CI 44-64%). After recalibration, predictions by the Vancouver score considerably overestimated the death rate, with a predicted death rate 82% versus observed death rate 62% (95% CI 52-71%). Performance of the Hardman index could not be assessed on discrimination and calibration, because in 57% of patients electrocardiograms were missing. CONCLUSIONS: Concerning discrimination and calibration, the updated GAS most accurately predicted death after intervention for a RAAA. However, the updated GAS did not identify patients with a ≥95% predicted death rate, and therefore cannot reliably support the decision to withhold intervention.

The hanta hunting study: underdiagnosis of Puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the Netherlands, in 2010 and April to November 2011.

Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused by infection with a spirochete while HFRS is the result of an infection with certain hantaviruses. Both diseases are relatively rare in the Netherlands. Increased incidence of HFRS has been observed since 2007 in countries that border the Netherlands. Since a similar rise in incidence has not been registered in the Netherlands, we hypothesise that due to overlapping clinical manifestations, hantavirus infections may be confused with leptospirosis, leading to underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients with symptoms compatible with leptospirosis, but with a negative diagnosis, during 2010 and from April to November 2011. Sera were screened with pan-hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive) and IFA results were confirmed using focus reduction neutralisation tests (FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255) of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011 period. After FRNT confirmation, seven patients were classed as having acute Puumala virus infections. A review of hantavirus diagnostic requests revealed that at least three of the seven confirmed acute cases as well as seven probable acute cases of hantavirus infection were missed in the Netherlands during the study period.

Effect of regional cooperation on outcomes from ruptured abdominal aortic aneurysm.

BACKGROUND: Care for patients with a ruptured abdominal aortic aneurysm (rAAA) in the Amsterdam ambulance region (The Netherlands) was concentrated into vascular centres with a 24-h full emergency vascular service in cooperation with seven referring regional hospitals. Previous population-based survival after rAAA in the Netherlands was 46 (95 per cent confidence interval (c.i.) 43 to 49) per cent. It was hypothesized that regional cooperation would improve survival. METHODS: This was a prospective observational cohort study carried out simultaneously with the Amsterdam Acute Aneurysm Trial. Consecutive patients with an rAAA between 2004 and 2011 in all ten hospitals in the Amsterdam region were included. The primary outcome was 30-day survival after admission. Multivariable logistic regression, including age, sex, co-morbidity, intervention (endovascular or open repair), preoperative systolic blood pressure, cardiopulmonary resuscitation and year of intervention, was used to assess the influence of hospital setting on survival. RESULTS: Of 453 patients with rAAA from the Amsterdam ambulance region, 61 did not undergo intervention; 352 patients were treated surgically at a vascular centre and 40 at a referring hospital. The regional survival rate was 58.5 (95 per cent c.i. 53.9 to 62.9) per cent (265 of 453). After multivariable adjustment, patients treated at a vascular centre had a higher survival rate than patients treated surgically at a referring hospital (adjusted odds ratio 3.18, 95 per cent c.i. 1.43 to 7.04). CONCLUSION: After regional cooperation, overall survival of patients with an rAAA improved. Most patients were treated in a vascular centre and in these patients survival rates were optimal.

Outcomes after open repair for ruptured abdominal aortic aneurysms in patients with friendly versus hostile aortoiliac anatomy.

OBJECTIVES: In patients with a ruptured abdominal aortic aneurysm (RAAA), anatomic suitability for endovascular aneurysm repair (EVAR) depends on aortic neck and iliac artery characteristics. If the aortoiliac anatomy is unsuitable for EVAR ("hostile anatomy"), open repair (OR) is the next option. We hypothesized that the death rate for OR is higher in patients with hostile anatomy than in patients with friendly anatomy. METHODS: We conducted an observational cohort study in 279 consecutive patients with an RAAA treated with OR between 2004 and 2011. The primary endpoint was 30-day or in-hospital death. Aortoiliac anatomy (friendly vs. hostile) was determined prospectively by the vascular surgeon and the interventional radiologist treating the patient. A multivariable logistic regression analysis was done to assess the risk of dying in patients with hostile anatomy after adjustment for age, sex, comorbidity, and hemodynamic stability. RESULTS: Aortoiliac anatomy was friendly in 71 patients and hostile in 208 patients. Death rate was 38% (95% confidence interval (CI): 28 to 50%) in patients with friendly anatomy and 30% (95% CI: 24 to 37%) in patients with hostile anatomy (p = .23). After multivariable adjustment, the risk of dying was not higher in patients with hostile anatomy (adjusted odds ratio 0.744, 95% CI 0.394 to 1.404). CONCLUSION: The death rate after open repair for an RAAA is comparable in patients with friendly and hostile aortoiliac anatomy.

Cost-effectiveness and cost-utility of endovascular versus open repair of ruptured abdominal aortic aneurysm in the Amsterdam Acute Aneurysm Trial.

BACKGROUND: Minimally invasive endovascular aneurysm repair (EVAR) could be a surgical technique that improves outcome of patients with ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to analyse the cost-effectiveness and cost-utility of EVAR compared with standard open repair (OR) in the treatment of rAAA, with costs per 30-day and 6-month survivor as outcome parameters. METHODS: Resource use was determined from the Amsterdam Acute Aneurysm (AJAX) trial, a multicentre randomized trial comparing EVAR with OR in patients with rAAA. The analysis was performed from a provider perspective. All costs were calculated as if all patients had been treated in the same hospital (Onze Lieve Vrouwe Gasthuis, teaching hospital). RESULTS: A total of 116 patients were randomized. The 30-day mortality rate was 21 per cent after EVAR and 25 per cent for OR: absolute risk reduction (ARR) 4·4 (95 per cent confidence interval (c.i.) -11·0 to 19·7) per cent. At 6 months, the total mortality rate for EVAR was 28 per cent, compared with 31 per cent among those assigned to OR: ARR 2·4 (-14·2 to 19·0) per cent. The mean cost difference between EVAR and OR was €5306 (95 per cent c.i. -1854 to 12,659) at 30 days and €10,189 (-2477 to 24,506) at 6 months. The incremental cost-effectiveness ratio per prevented death was €120,591 at 30 days and €424,542 at 6 months. There was no significant difference in quality of life between EVAR and OR. Nor was EVAR superior regarding cost-utility. CONCLUSION: EVAR may be more effective for rAAA, but its increased costs mean that it is unaffordable based on current standards of societal willingness-to-pay for health gains.

Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm.

BACKGROUND: A substantial proportion of patients with a ruptured abdominal aortic aneurysm (rAAA) die outside hospital. The objective of this study was to estimate the total mortality, including prehospital deaths, of patients with rAAA. METHODS: This was a systematic review and meta-analysis following the MOOSE guidelines. The Embase, MEDLINE and Cochrane Library databases were searched. All population-based studies reporting both prehospital and in-hospital mortality in patients with rAAA were included. Studies were assessed for methodological quality and heterogeneity, and pooled estimates of mortality from rAAA were calculated using a random-effects model. RESULTS: From a total of 3667 studies, 24 retrospective cohort studies, published between 1977 and 2012, met the inclusion criteria. The quality of included studies varied, in particular the method of determining prehospital deaths from rAAA. The estimated pooled total mortality rate was 81 (95 per cent confidence interval 78 to 83) per cent. A decline in mortality was observed over time (P = 0·002); the pooled estimate of total mortality in high-quality studies before 1990 was 86 (83 to 89) per cent, compared with 74 (72 to 77) per cent since 1990. Some 32 (27 to 37) per cent of patients with rAAA died before reaching hospital. The in-hospital non-intervention rate was 40 (33 to 47) per cent, which also declined over the years. CONCLUSION: The pooled estimate of total mortality from rAAA is very high, although it has declined over the years. Most patients die outside hospital, and there is no surgical intervention in a considerable number of those who survive to reach hospital.

Seroprevalence of hepatitis E antibodies and risk profile of HEV seropositivity in The Netherlands, 2006-2007.

SHepatitis E virus (HEV) is now considered an endemic pathogen in industrialized countries, leading to acute and sometimes chronic hepatitis, mostly in vulnerable people. The endemic sources are unclear. A survey in The Netherlands in 2006-2007 showed a 1·9% seroprevalence of HEV antibodies measured by ELISA and confirmed by immunoblot in a nationwide sample. Overall, in 134/7072 (1·9%) seropositive individuals, older age (P<0·01), being male (P<0·01), working with patients (P=0·03), working with animals (P=0·07), recent diarrhoeal complaints (P=0·07) and adhering to a religion that considers pigs unclean (P<0·01) were independently associated with seropositivity in multivariate analysis. Sub-analysis of 59/4022 (1·5%) anti-HEV antibody-positive subjects with probable endemic exposure showed independent association with youngest household member being aged <5 years or between 19 and <65 years (P=0·05) in multivariate analysis. These findings may contribute to a better understanding of the sources of endemic HEV exposure, and also highlight the need for systematic epidemiological and serological evaluation of new cases.

Profiling of humoral immune responses to influenza viruses by using protein microarray.

The emergence of pandemic A(H1N1) 2009 influenza showed the importance of rapid assessment of the degree of immunity in the population, the rate of asymptomatic infection, the spread of infection in households, effects of control measures, and ability of candidate vaccines to produce a response in different age groups. A limitation lies in the available assay repertoire: reference standard methods for measuring antibodies to influenza virus are haemagglutination inhibition (HI) assays and virus neutralization tests. Both assays are difficult to standardize and may be too specific to assess possible partial humoral immunity from previous exposures. Here, we describe the use of antigen-microarrays to measure antibodies to HA1 antigens from seven recent and historical seasonal H1, H2 and H3 influenza viruses, the A(H1N1) 2009 pandemic influenza virus, and three avian influenza viruses. We assessed antibody profiles in 18 adult patients infected with A(H1N1) 2009 influenza virus during the recent pandemic, and 21 children sampled before and after the pandemic, against background reactivity observed in 122 persons sampled in 2008, a season dominated by seasonal A(H1N1) influenza virus. We show that subtype-specific and variant-specific antibody responses can be measured, confirming serological responses measured by HI. Comparison of profiles from persons with similar HI response showed that the magnitude and broadness of response to individual influenza subtype antigens differs greatly between individuals. Clinical and vaccination studies, but also exposure studies, should take these findings into consideration, as they may indicate some level of humoral immunity not measured by HI assays.

The application of an enzyme-linked immunosorbent assay or an immunofluorescent assay test leads to different estimates of seroprevalence of Coxiella burnetii in the population.

The diagnosis and epidemiological studies of Q fever depend on serology. Among the main methods employed are the enzyme-linked immunosorbent assay (ELISA) and the immunofluorescent assay test (IFAT). We show that two commercial assays representing the two methods with two different cut-off titres can lead to significant differences in diagnostic and seroprevalence estimates. This in turn emphasizes the need for a standardized gold method to compare the various assays; whether this standard is 'in-house' or commercially obtained.

Low seroprevalence of Q fever in The Netherlands prior to a series of large outbreaks.

The Netherlands has experienced large community outbreaks of Q fever since 2007. Sera and questionnaires containing epidemiological data from 5654 individuals were obtained in a nationwide seroprevalence survey used to evaluate the National Immunization Programme in 2006-2007. We tested these sera for IgG phase-2 antibodies against Coxiella burnetii with an ELISA to estimate the seroprevalence and to identify determinants for seropositivity before the Q fever outbreaks occurred. Overall seroprevalence was 1·5% [95% confidence interval (CI) 1·3-1·7]. Corrected for confirmation with immunofluorescence results in a subset, the estimated seroprevalence was 2·4%. Seropositivity ranged from 0·48% (95% CI 0·00-0·96) in the 0-4 years age group to 2·30% (95% CI 1·46-3·15) in the 60-79 years age group. Keeping ruminants, increasing age and being born in Turkey were independent risk factors for seropositivity. The low seroprevalence before the start of the outbreaks supports the hypothesis that The Netherlands has been confronted with a newly emerging Q fever problem since spring 2007.

Case report: tick-borne encephalitis in two Dutch travellers returning from Austria, Netherlands, July and August 2011.

Tick-borne encephalitis (TBE) is not endemic in the Netherlands and diagnostics are seldom requested. Here, we report about the rare event of TBE in two Dutch travellers returning from Austria in July and August 2011. This report serves to create awareness among physicians to consider travel-related TBE in their differential diagnosis of patients with neurological disease returning from TBE virus endemic regions and to promote awareness among professionals advising travellers.

Changing risk profile of hepatitis A in The Netherlands: a comparison of seroprevalence in 1995-1996 and 2006-2007.

The prevalence of antibodies to hepatitis A virus (HAV) was assessed in a nationwide sample (n=6229) in The Netherlands in 2006-2007, and compared to the seroprevalence in a similar study in 1995-1996 (n=7376). The overall seroprevalence increased from 34% in 1995-1996 to 39% in 2006-2007, mainly due to vaccination of travellers and an increased immigrant population. Risk factors remain travelling to, and originating from, endemic regions, and vaccination is targeted currently at these risk groups. Our results show a trend of increasing age of the susceptible population. These people would also benefit from HAV vaccination because they are likely to develop clinically serious symptoms after infection, and are increasingly at risk of exposure through imported viruses through foods or travellers. The cost-effectiveness of adding elderly people born after the Second World War as a target group for prophylactic vaccination to reduce morbidity and mortality after HAV infection should be assessed.

Controlled hypotension in patients suspected of a ruptured abdominal aortic aneurysm: feasibility during transport by ambulance services and possible harm.

OBJECTIVE: To evaluate a controlled hypotension protocol for patients suspected of a ruptured aneurysm of the abdominal aorta (RAAA) and to identify possible harm to patients with a final diagnosis other than RAAA. DESIGN: Retrospective analysis of patients suspected of RAAA and transported by Amsterdam ambulance services between January 2006 and October 2007. PATIENTS AND METHODS: Protocol was assessed by reviewing systolic blood pressure (<80 mmHg, 80-100 mmHg or >100 mmHg), administered fluid volume and verbal responsiveness during transport. Patients who could possibly have been harmed by controlled hypotension were identified by final diagnoses. RESULTS: Fluid administration was according to protocol in 220 of 266 patients analysed for protocol adherence. The remaining patients received too much (21 patients) or too little fluid (25 patients). Data were missing in 29 patients. A RAAA was diagnosed in 81 (27%) of all 295 patients analysed for final diagnosis. Controlled hypotension was achieved in 10% of all patients and in 17% of patients with RAAA. Three patients (1%) with diagnosis other than RAAA were possibly at risk by implementing controlled hypotension. CONCLUSIONS: Protocol was followed in 83% and protocol violations occurred in 17% of patients. The risk of implementing controlled hypotension for all patients suspected of an RAAA by the ambulance staff was low.

The hidden passenger of lucky bamboo: do imported Aedes albopictus mosquitoes cause dengue virus transmission in the Netherlands?

Since 2005, Aedes albopictus mosquitoes have been detected in companies in the Netherlands that import ornamental plants from China. To assess the risks of dengue transmission, a study was carried out in 48 persons who are professionally exposed to these mosquitoes. No evidence for non-travel-related flavivirus infections was found.

Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants.

BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic symptoms (eczema, wheeze and atopic sensitization) in the first and second year(s) of life. METHODS: In the KOALA Birth Cohort Study, we assessed IgG seropositivity for rota- and norovirus (GGI.1 and GGII.4) at 1 year of age. This was related to allergic sensitization [specific immunoglobulin E (IgE)] at 1 and 2 years, and parent reported eczema and wheeze in the first 2 years, using logistic regression analysis adjusted for confounders. RESULTS: Rotavirus seropositivity (39%) was associated with an unexpected higher risk of recurrent wheeze in the first and second year of life [adjusted odds ratio (OR) 3.1 and 95% confidence intervals (CI) 1.1-9.1] and persistent and new recurrent wheeze (adjusted OR 2.7 and 95% CI 1.1-6.2). No further associations were found between intestinal viral seropositivity and atopic manifestations. CONCLUSION: Our data did not show a clear protection by enteric viral infections in young children on development of IgE response to allergens, but rotavirus infection in the first year was a risk factor for wheeze. However, this needs to be followed up to older ages in order to establish the true importance of intestinal viral infections and especially cumulative effects in AD aetiology. Exposure to rotavirus may offer a new and interesting focus on infant wheeze and later asthma development.

Antibody responses to antigenic sites 1 and 3 of serotype 3 poliovirus after vaccination with oral live attenuated or inactivated poliovirus vaccine and after natural exposure.

Three important antigenic sites involved in virus neutralization on polioviruses in mouse experiments have been identified. These sites are located at the surface of the virion and have been designated antigenic sites 1, 2, and 3. In mice, the antibody response to antigenic site 1 of serotype 3 poliovirus is considered to be immunodominant, but little is known about the immunogenicity of these sites in humans. In the present study, we developed inhibition enzyme-linked immunosorbent assays specific for antigenic sites 1 and 3 to measure antibody responses to these sites in fully vaccinated inactivated poliovirus vaccine (IPV) (n = 63) and oral live attenuated poliovirus vaccine (OPV) (n = 63) recipients and in naturally infected persons (n = 25). Similar levels of antibodies to site 1 in IPV and OPV vaccinees were detected. However, significantly more OPV recipients (88.7%) had detectable antibodies to antigenic site 3 (P < 0.01) than did IPV-vaccinated persons (63. 1%). After an IPV booster vaccination, both previously IPV- and OPV-vaccinated persons responded with a significant increase in antibodies to sites 1 and 3 (P < 0.01). We conclude that the immune response to serotype 3 poliovirus in humans consists of both site 1- and site 3-specific antibodies and that these responses can be induced by either OPV or recent IPV vaccination.