The tip of the iceberg: incompleteness of measles reporting during a large outbreak in The Netherlands in 2013-2014.

Measles is a notifiable disease, but not everyone infected seeks care, nor is every consultation reported. We estimated the completeness of reporting during a measles outbreak in The Netherlands in 2013-2014. Children below 15 years of age in a low vaccination coverage community (n = 3422) received a questionnaire to identify measles cases. Cases found in the survey were matched with the register of notifiable diseases to estimate the completeness of reporting. Second, completeness of reporting was assessed by comparing the number of susceptible individuals prior to the outbreak with the number of reported cases in the surveyed community and on a national level.We found 307 (15%) self-identified measles cases among 2077 returned questionnaires (61%), of which 27 could be matched to a case reported to the national register; completeness of reporting was 8.8%. Based on the number of susceptible individuals and number of reported cases in the surveyed community and on national level, the completeness of reporting was estimated to be 9.1% and 8.6%, respectively. Estimating the completeness of reporting gave almost identical estimates, which lends support to the credibility and validity of both approaches. The size of the 2013-2014 outbreak approximated 31 400 measles infections.

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.

Outbreak of Salmonella Thompson in the Netherlands since July 2012.

An ongoing outbreak of salmonellosis due to Salmonella Thompson is affecting the Netherlands. Between 2 August and 19 October 2012, 866 cases were confirmed. Their median age was 44 years (range: 0-95 years), 63% were female and 36% were hospitalised. A matched case-control study suggested smoked salmon as the vehicle. Salmonella Thompson was confirmed in four of nine batches of smoked salmon from one producer. A recall of all concerned smoked salmon products was executed starting end of September.

DNA methylation epi-signature is associated with two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

BACKGROUND: Phelan-McDermid syndrome is characterized by a range of neurodevelopmental phenotypes with incomplete penetrance and variable expressivity. It is caused by a variable size and breakpoint microdeletions in the distal long arm of chromosome 22, referred to as 22q13.3 deletion syndrome, including the SHANK3 gene. Genetic defects in a growing number of neurodevelopmental genes have been shown to cause genome-wide disruptions in epigenomic profiles referred to as epi-signatures in affected individuals. RESULTS: In this study we assessed genome-wide DNA methylation profiles in a cohort of 22 individuals with Phelan-McDermid syndrome, including 11 individuals with large (2 to 5.8 Mb) 22q13.3 deletions, 10 with small deletions (< 1 Mb) or intragenic variants in SHANK3 and one mosaic case. We describe a novel genome-wide DNA methylation epi-signature in a subset of individuals with Phelan-McDermid syndrome. CONCLUSION: We identified the critical region including the BRD1 gene as responsible for the Phelan-McDermid syndrome epi-signature. Metabolomic profiles of individuals with the DNA methylation epi-signature showed significantly different metabolomic profiles indicating evidence of two molecularly and phenotypically distinct clinical subtypes of Phelan-McDermid syndrome.

Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study.

BACKGROUND: A polymorphism (rs143383; T to C) near the GDF5 gene has been associated with height and osteoarthritis (OA), but debate exists about whether its primary biological action is directed to cartilage or bone. OBJECTIVE: To study the association between genetic variation in the GDF5 region and radiographic osteoarthritis (ROA) susceptibility, height, bone size parameters and fracture risk in a large population-based cohort of Caucasian elderly subjects. METHODS: 6365 men and women had genotype data available. ROA was defined as a Kellgren/Lawrence (K/L) score > or =2 for hand, knee and hip joints. CTX-II levels, height, bone mineral density (BMD), bone size and fracture risk were also assessed. RESULTS: rs143383 and three highly correlated single nucleotide polymorphisms (SNPs) in the GDF5 region were found to be independently associated with OA, height, bone size and fracture risk in women. Women with homozygotes for the rs143383 C allele had a 37% lower risk for hand OA (p = 8 x 10(-6)) and a 28% lower risk for knee OA (p = 0.003). In addition, they were 1.1 cm taller (p = 0.001), had a larger hip axis length (HAL) (p = 4 x 10(-4)) and had a 29% increased risk of incident non-vertebral fractures (p = 0.02). No associations with hip OA or BMD were detected. No associations were found in men. CONCLUSION: This population-based study shows that GDF5 gene variants are associated with hand OA, knee OA and fracture risk in elderly women. It also replicates previous association between GDF5 variation and height. Furthermore, our findings for HAL suggest that GDF5 action is primarily directed to the long bones, rather than the axial skeleton.

Norovirus outbreaks in nursing homes: the evaluation of infection control measures.

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.

Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts.

OBJECTIVE: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study. METHODS: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score > or = 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L > or = 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Taqman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3. RESULTS: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population. While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA separately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females. CONCLUSION: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis.

[Imported Zika virus infection in the Netherlands]. / Import van zikavirus-infectie in Nederland.

Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications.

The ISFET based heparin sensor with a monolayer of protamine as affinity ligand.

The ion-step measuring method was used to determine absolute heparin concentrations in PBS and blood plasma with a Ta2O5 ISFET on to which a monolayer of protamine had been immobilized. Heparin is a highly negatively charged polysaccharide, which is used clinically to delay the clotting of blood. Protamine acts as an affinity ligand for heparin. The response of the ISFET system on a step-wise increase in the electrolyte concentration (a so-called ion-step) is a transient change of the output voltage, which is related to the surface charge density of the ISFET gate oxide. After 2 mins of incubation in a plasma sample containing heparin, the amplitude of the transient ISFET response to an ion-step showed a linear relation to the heparin concentration. In blood plasma, heparin concentrations between 0.3 and 2.0 Units/ml could be determined with an accuracy of +/- 0.08 Units/ml. Heparin concentrations in different plasma samples of heparinized patients were determined and compared with the APTT. No direct relation was found between the APTT and the heparin concentration, but this result was not surprising.

Four cases of hemolytic uremic syndrome--source contaminated swimming water?

In June '93, 4 children, aged 1.5-3.5 years, all living in one town, were admitted to our hospital with the diagnosis hemolytic uremic syndrome (HUS) within one week. In cooperation with the local health authorities a common source was searched for. Questionnaires indicated that the single condition shared by all patients was swimming water. The patients were not acquainted, visited different daycares, and had no food resources in common. All 4 patients bathed in the same, shallow, recreational lake within a period of 5 days. During this time the air temperature was high according to Dutch standards (around 27 degrees C), and many people visited the lake, estimated several hundreds a day. The water level was lower than normal. Diarrhea followed 3-11 days after swimming and the first clinical symptoms of HUS developed 6-7 days after the onset of diarrhea. The lake was closed for swimming when the fourth HUS patient was diagnosed and the possibility of transmission by way of the lake was mentioned. E. coli O157: H7 was demonstrated in the fecal samples of 2 index patients. The samples were taken 9-20 days after the start of diarrhea. Antibodies to O157 and verotoxin 2 were strongly positive in all patients. A local outbreak of diarrheal illness was not registered. Of 16 family members who also swam in the same lake, 7 developed symptoms of enteritis, 3 had positive cultures of their fecal samples and 5 had positive serology. Pulsed-field gel electrophoresis of the E. coli isolates of the patients and family members showed an identical pattern. No O157: H7-DNA could be detected in filter concentrated lake water samples using polymerase chain reaction (PCR) enhancement. These samples were, however, taken 16 days after the latest possible date of contamination of our patients, 15 days after decrease of the air temperature to 15-17 degrees C, and 14 days after the inlet from water from the environment. It could thus very well be that the microorganism was no longer present. This third report of swimming water associated HUS should direct environmental surveys in similar cases of local HUS outbreaks.

Classification of attempted suicide: a review of empirical studies, 1963-1993.

A review was carried out on empirical studies on the classification of attempted suicide over the period 1963-1993. Our aim was to investigate whether there is research evidence for a valid classification of homogeneous subgroups of suicide attempters. After assessment of the research quality, 32 studies were selected for comparison. Although there is lack of consistency among the studies, indications were found for two clearly distinguished subgroups characterized by mild and severe suicide attempts, which constitute the opposite poles of a one-dimensional concept of severity.

A cross-cultural study of suicide intent in parasuicide patients.

As part of the WHO/EURO Multicentre Study on Parasuicide, the level of suicide intent among female and male parasuicide patients from various European regions was compared. From nine regions, a total of 1,212 parasuicide patients, 752 females and 460 males, were included in the study. Although some statistical significant differences in level of suicide intent between the regions and genders were found, the effect sizes of these relationships were so small that the differences have neither theoretical nor practical significance. As far as level of suicide intent is concerned, the WHO study has succeeded in recruiting a relatively homogeneous group of self-harming patients across borders of region, culture, and country.

Why people engage in parasuicide: a cross-cultural study of intentions.

Information obtained at interview from 1,646 parasuicide patients in 14 regions in 13 European countries participating in the WHO/EURO Multicentre Study on Suicidal Behaviour was used to study self-reported intentions involved in parasuicide. Comparisons were made across cultures, genders, and age groups. Although some statistically significant differences were found, the effect sizes were very small. The main finding from this study is thus that parasuicide patients in different countries tend to indicate that similar types of intentions are involved in their acts of parasuicide, and that the intentions do not vary greatly with gender or age. The hypothesis that rates of suicide and parasuicide vary between regions with the frequency with which suicidal intention is indicated by the patients was also tested, but was supported only for women and in relation to national suicide rates. The findings from this study are likely to be generalizable to other settings and have implications for clinical practice.

Response to a suspected case of diphtheria in Dordrecht, the Netherlands.

About 50 of the refugees in Dordrecht are from the Newly Independent States (NIS) of the former USSR, where diphtheria is rife. Cases have arisen in western Europe through contact with cases from the NIS. No NIS-related cases of diphtheria have been seen

[Measles epidemic in the Netherlands, 1999-2000]. / Mazelenepidemie in Nederland, 1999-2000.

OBJECTIVE: Description of measles epidemic in the Netherlands, 1999-2000. DESIGN: Observational descriptive study. METHODS: Intensified surveillance of measles cases by means of a case register established at the 'Landelijke Coördinatiestructuur Infectieziektebestrijding (LCI)' [National Co-ordination Centre for Communicable Disease Outbreak Management]. RESULTS: There were 3,292 reported measles patients, most of whom came from areas with low vaccine coverage. Of these patients, 94% had not been vaccinated; in 85% of cases this was for religious reasons. Of the 158 (5%) vaccinated patients, 157 had not (yet) received a second dose of vaccine. The incidence of measles increased with decreasing vaccine coverage in a municipality, both for unvaccinated and vaccinated persons. Three of the reported patients died. The percentage of patients with one or more complications was 22% in the group < 15 months of age, 19% in the group 15 months-4 years, 16% in the group 5-9 years, 11% in the group 10-19 years, and 15% in the group > 19 years of age. CONCLUSION: Considering the complications observed, the epidemic described involved a serious disease. Vaccination was accompanied by effective protection against measles infection and its complications. Herd immunity outside the unvaccinated groups was sufficient to prevent an epidemic there. However, incidental spread to vaccinated children did occur; the greatest risk factor for acquiring measles for vaccinated children is a stay in an area with low vaccine coverage.