Staat van infectieziekten in Nederland, 2013

In dit rapport wordt gelinked naar een bijlage: appendix150205001.De uitbraak van mazelen in 2013 was de meest in het oog springende infectieziekte van dat jaar. Dit blijkt uit de Staat van Infectieziekten in Nederland 2013, die inzicht geeft in ontwikkelingen van infectieziekten bij de Nederlandse bevolking. Daarnaast worden de ontwikkelingen in het buitenland beschreven die voor Nederland relevant zijn. Met deze jaarlijkse uitgave informeert het RIVM beleidsmakers van het ministerie van Volksgezondheid, Welzijn en Sport (VWS). Elk jaar komt in de Staat van Infectieziekten een thema aan bod; dit jaar is dat de hoeveelheid jaren in goede gezondheid die verloren gaan (ziektelast) door infectieziekten. Sommige infectieziekten, zoals maag-darminfecties, komen erg vaak voor maar veroorzaken over het algemeen geen ernstige klachten. Andere daarentegen, bijvoorbeeld tetanus, komen slechts zelden voor maar veroorzaken relatief veel sterfgevallen. Een gezondheidsmaat die deze aspecten van ziekten combineert is de Disability Adjusted Life Year (DALY). Voor 32 infectieziekten is de ziektelast in Nederland tussen 2007 en 2011 geschat. De gemiddelde jaarlijkse ziektelast voor de totale Nederlandse bevolking was het hoogst voor ernstige pneumokokkenziekte (9444 DALY's per jaar) en griep (8670 DALY's per jaar), die respectievelijk 16 en 15 procent van de totale ziektelast van alle 32 infectieziekten vertegenwoordigen. Na polio en difterie (0 gevallen in de onderzochte periode), werd de laagste ziektelast geschat voor rodehond op 0,14 DALY's per jaar. De ziektelast voor deze ziekten is zo laag dankzij het Rijksvaccinatieprogramma. De ziektelast per individu varieerde van 0,2 DALY's per honderd infecties voor giardiasis (diarree die wordt veroorzaakt door een parasiet), tot 5081 en 3581 DALY's per honderd infecties voor respectievelijk hondsdolheid en een variant van de ziekte van Creutzfeldt-Jakob. Voor alle ziektelaststudies geldt dat de resultaten afhankelijk zijn van de modelparameters en aannames, en van de beschikbaarheid van accurate gegevens over de mate waarin de ziekten voorkomen. Toch kunnen deze schattingen informatief zijn voor beleidsmakers binnen de gezondheidszorg om prioriteiten te kunnen aanbrengen in preventieve en andere maatregelen.The measles outbreak in 2013 was the most striking infectious disease of that year. This is demonstrated in the State of Infectious Diseases in the Netherlands 2013, which provides insight into infectious disease trends in the Dutch population. Developments in other countries that are relevant for the Netherlands are also described. This annual RIVM publication informs policy-makers from the Ministry of Health, Welfare and Sport (VWS). Every year the State of Infectious Diseases in the Netherlands publishes reports on a particular theme. This year's topic concerns the estimation of disease burden: how many years of health life are lost due to infectious diseases? Some infectious diseases, such as gastrointestinal infections, occur frequently in the population, but do not generally give rise to serious complaints. In contrast, other diseases, for example tetanus, occur rarely but may lead to a high risk of death. A summary measure of population health that combines the morbidity and premature mortality attributable to a disease in a single quantity is the Disability Adjusted Life Year (DALY). For 32 infectious diseases, we estimated the disease burden in the Netherlands between 2007 and2011. The highest average annual burden for the total Netherlands population was estimated for invasive pneumococcal disease (9444 DALYs per year) and influenza (8670 DALYs per year), which represent 16 and 15 percent, respectively, of the total burden of all 32 diseases considered. After poliomyelitis and diphtheria (no cases in the period investigated), the lowest burden was estimated for rubella, at 0.14 DALYs per year. The extremely low burden for these diseases is due to the National Immunization Programme. The disease burden per individual varied from 0.2 DALYs per 100 infections for giardiasis (diarrhea that is caused by a parasite), to 5081 and 3581 DALYs per 100 infections for rabies and variant Creutzfeldt-Jakob disease, respectively. As with all burden of disease studies, results depend on disease model parameters and assumptions and on the availability of accurate data on the incidence of infection. Nevertheless, estimates of disease burden can be informative for public health policy-makers regarding the prioritization of preventive and other measures.Ministerie van VW

Reemergence of pertussis in the highly vaccinated population of the Netherlands: observations on surveillance data.

We analyzed pertussis reporting, death, hospitalization, and serodiagnostic data from 1976 to 1998 to help explain the cause of the 1996 pertussis outbreak in the Netherlands. The unexpected outbreak was detected by an increase in pertussis reporting and by other surveillance methods. In 1996, according to reporting and serologic data, the increase in pertussis incidence among (mostly unvaccinated) children less than 1 year of age was similar to the increase in hospital admissions. Among older (mostly vaccinated) persons, the increase in hospital admissions was relatively small. The increase in pertussis incidence was higher among vaccinated than among unvaccinated persons of all ages. This resulted in lower estimates of vaccine effectiveness. The proportion of pertussis infections resulting in recognizable symptoms may have increased among vaccinated persons because of a mismatch of the vaccine strain and circulating Bordetella pertussis strains. The small immunogenicity profile of the Dutch vaccine may have resulted in greater vulnerability to antigenic changes in B. pertussis

Ongoing mumps outbreak in a student population with high vaccination coverage, Netherlands, 2010.

Since December 2009, mumps incidence has increased in the Netherlands. As of 20 April 2010, 172 cases have been notified on the basis of laboratory confirmation or linkage to a laboratory-confirmed case. Of these, 112 were students, the majority of whom had been vaccinated (81%). Although outbreaks in vaccinated populations have been described before, risk factors for exposure and susceptibility, and dose-dependent vaccine effectiveness in a student population of this nature are relatively unknown

Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a “one-size-fits-all” clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0–3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required

Estimating the Duration of Pertussis Immunity Using Epidemiological Signatures

Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable

Clinical presentation of pertussis in fully immunized children in Lithuania

BACKGROUND: In Lithuania, the vaccination coverage against pertussis is high. Nevertheless, there is a significant increase in pertussis cases in fully immunized children. The aim of our study was to determine the frequency of classical symptoms of laboratory confirmed pertussis and describe its epidemiology in children fully vaccinated against pertussis. METHODS: From May to December 2001, 70 children aged 1 month to 15 years, suffering from prolonged cough were investigated in the Centre of Paediatrics, Vilnius University Children's Hospital. The collected information included personal data, vaccination history, clinical symptoms of the current illness, and treatment before hospitalization. At the admission to the hospital blood samples were taken from all studied children for Bordetella pertussis IgM and IgA. RESULTS: A total of 53 (75.7%) of the 70 recruited patients with prolonged cough showed laboratory evidence of pertussis. 32 of them were fully vaccinated with whole cell pertussis vaccine (DTP). The age of fully vaccinated patients varied from 4 to 15 years (average 10.9 ± 3.1; median 11). The time period between the last vaccination dose (fourth) and the clinical manifestation of pertussis was 2.6–13 years (average 8.9 ± 3.0; median 9). More than half of the children before the beginning of pertussis were in contact with persons suffering from long lasting cough illness in the family, school or day-care center. The mean duration from onset of pertussis symptoms until hospitalization was 61.4 ± 68.3 days (range, 7 to 270 days; median 30). For 11 patients who had had two episodes (waves) of coughing, the median duration of cough was 90 days, and for 21 with one episode 30 days (p < 0.0002). Most of the children (84.4%) had paroxysmal cough, 31.3% had post-tussive vomiting, 28.1% typical whoop, and 3.1% apnea. Only 15.6% children had atypical symptoms of pertussis. CONCLUSION: Fully vaccinated children fell ill with pertussis at the median of 11 years old, 9 years following pertussis vaccination. More than half of the children could catch pertussis at home, at school or day-care center. Clinical picture of pertussis in previously immunized children is usually characterized by such classical symptoms as prolonged and paroxysmal cough, rarely by whopping and post-tussive vomiting, and very rarely by apnea

Increased Population Prevalence of Low Pertussis Toxin Antibody Levels in Young Children Preceding a Record Pertussis Epidemic in Australia

Background: Cross-sectional serosurveys using IgG antibody to pertussis toxin (IgG-PT) are increasingly being used to estimate trends in recent infection independent of reporting biases. Methods/Principal Findings: We compared the age-specific seroprevalence of various levels of IgG-PT in cross-sectional surveys using systematic collections of residual sera from Australian diagnostic laboratories in 1997/8, 2002 and 2007 with reference to both changes in the pertussis vaccine schedule and the epidemic cycle, as measured by disease notifications. A progressive decline in high-level ($62.5 EU/ml) IgG-PT prevalence from 19 % (95 % CI 16–22%) in 1997/98 to 12 % (95 % CI 11–14%) in 2002 and 5 % (95 % CI 4–6%) in 2007 was consistent with patterns of pertussis notifications in the year prior to each collection. Concomitantly, the overall prevalence of undetectable (,5 EU/ml) levels increased from 17 % (95 % CI 14– 20%) in 1997/98 to 38 % (95 % CI 36–40%) in 2007 but among children aged 1–4 years, from 25 % (95 % CI 17–34%) in 1997/98 to 62 % (95 % CI 56–68%) in 2007. This change followed withdrawal of the 18-month booster dose in 2003 and preceded record pertussis notifications from 2008 onwards. Conclusions/Significance: Population seroprevalence of high levels of IgG-PT is accepted as a reliable indicator of pertussis disease activity over time within and between countries with varying diagnostic practices, especially in unimmunised age groups. Our novel findings suggest that increased prevalence of undetectable IgG-PT is an indicator of waning immunit

Epidemic of mumps among vaccinated persons, the Netherlands, 2009-2012

To analyze the epidemiology of a nationwide mumps epidemic in the Netherlands, we reviewed 1,557 notified mumps cases in persons who had disease onset during September 1, 2009-August 31, 2012. Seasonality peaked in sprin

Nuclear expression of FLT1 and its ligand PGF in FUS-DDIT3 carrying myxoid liposarcomas suggests the existence of an intracrine signaling loop

<p>Abstract</p> <p>Background</p> <p>The FUS-DDIT3 fusion oncogene encodes an abnormal transcription factor that has a causative role in the development of myxoid/round-cell liposarcomas (MLS/RCLS). We have previously identified <it>FLT1 </it>(<it>VEGFR1</it>) as a candidate downstream target gene of FUS-DDIT3. The aim of this study was to investigate expression of FLT1 and its ligands in MLS cells.</p> <p>Methods</p> <p>HT1080 human fibrosarcoma cells were transiently transfected with <it>FUS-DDIT3</it>-GFP variant constructs and FLT1 expression was measured by quantitative real-time PCR. In addition, <it>FLT1</it>, <it>PGF, VEGFA and VEGFB </it>expression was measured in MLS/RCLS cell lines, MLS/RCLS tumors and in normal adiopocytes. We analyzed nine cases of MLS/RCLS and one cell line xenografted in mice for FLT1 protein expression using immunohistochemistry. MLS/RCLS cell lines were also analyzed for FLT1 by immunofluorescence and western blot. MLS/RCLS cell lines were additionally treated with FLT1 tyrosine kinase inhibitors and assayed for alterations in proliferation rate.</p> <p>Results</p> <p><it>FLT1 </it>expression was dramatically increased in transfected cells stably expressing FUS-DDIT3 and present at high levels in cell lines derived from MLS. The FLT1 protein showed a strong nuclear expression in cells of MLS tissue as well as in cultured MLS cells, which was confirmed by cellular fractionation. Tissue array analysis showed a nuclear expression of the FLT1 protein also in several other tumor and normal cell types including normal adipocytes. The FLT1 ligand coding gene <it>PGF </it>was highly expressed in cultured MLS cells compared to normal adipocytes while the other ligand genes <it>VEGFA </it>and <it>VEGFB </it>were expressed to lower levels. A more heterogeneous expression pattern of these genes were observed in tumor samples. No changes in proliferation rate of MLS cells were detected at concentrations for which the kinase inhibitors have shown specific inhibition of FLT1.</p> <p>Conclusions</p> <p>Our results imply that <it>FLT1 </it>is induced as an indirect downstream effect of FUS-DDIT3 expression in MLS. This could be a consequence of the ability of FUS-DDIT3 to hijack parts of normal adipose tissue development and reprogram primary cells to a liposarcoma-like phenotype. The findings of nuclear FLT1 protein and expression of corresponding ligands in MLS and normal tissues may have implications for tissue homeostasis and tumor development through auto- or intracrine signaling.</p