Recent Submissions

  • Using data on social contacts to estimate age-specific transmission parameters for respiratory-spread infectious agents.

    Wallinga, Jacco; Teunis, Peter F M; Kretzschmar, Mirjam (2006-11-15)
    The estimation of transmission parameters has been problematic for diseases that rely predominantly on transmission of pathogens from person to person through small infectious droplets. Age-specific transmission parameters determine how such respiratory agents will spread among different age groups in a human population. Estimating the values of these parameters is essential in planning an effective response to potentially devastating pandemics of smallpox or influenza and in designing control strategies for diseases such as measles or mumps. In this study, the authors estimated age-specific transmission parameters by augmenting infectious disease data with auxiliary data on self-reported numbers of conversational partners per person. They show that models that use transmission parameters based on these self-reported social contacts are better able to capture the observed patterns of infection of endemically circulating mumps, as well as observed patterns of spread of pandemic influenza. The estimated age-specific transmission parameters suggested that school-aged children and young adults will experience the highest incidence of infection and will contribute most to further spread of infections during the initial phase of an emerging respiratory-spread epidemic in a completely susceptible population. These findings have important implications for controlling future outbreaks of novel respiratory-spread infectious agents.
  • High and persistent excretion of hepatitis A virus in immunocompetent patients.

    Tjon, Grace M S; Coutinho, Roel A; Hoek, Anneke van den; Esman, Sylvia; Wijkmans, Clementine J; Hoebe, Christian J P A; Wolters, Bert; Swaan, Corien; Geskus, Ronald B; Dukers, Nicole H T M; Bruisten, Sylvia M (2006-11-01)
    The duration and level of virus excretion in blood and faeces of patients with hepatitis A virus (HAV) infection were studied in relation to levels of alanine aminotransferase (ALT), disease severity and HAV genotype. Clinical data, blood and faeces were collected from 27 patients with acute hepatitis A (median age: 33 years) for a maximum of 26 weeks. Single blood donations from 55 other patients with acute HAV (median age: 32 years) were also used. Virus loads were quantified by competitive nested RT-PCR. HAV was excreted in faeces for a median period of 81 days after disease onset, with 50% of patients still excreting high levels at Day 36 (2 x 10(6) - 2 x 10(8) copies/ml faeces suspension). Viraemia was detected, but not quantifiable, for a median period of 42 days. In the first 10 days of illness, higher ALT levels were correlated with higher viraemia levels. Comparison of patients infected with genotype 1a with those infected with type 1b did not differ significantly in terms of the duration of HAV excretion or jaundice. In conclusion, faecal excretion of HAV is at a high titre in the first month, perhaps making patients infectious for a longer period than assumed currently. Blood banks should be aware that viraemia may be present for more than 1 month, and genotype did not affect the duration of virus excretion or jaundice.
  • Diagnosis of Norovirus outbreaks by commercial ELISA or RT-PCR.

    Bruin, Erwin de; Duizer, Erwin; Vennema, Harry; Koopmans, Marion P G (2006-11-01)
    The IDEIA Norwalk-like virus (Dakocytomation Ltd., Ely, United Kingdom) and the Ridascreen Norwalk-like virus enzyme immunoassay (R-Biopharm AG, Darmstadt, Germany), were evaluated for the diagnosis of outbreaks of acute gastroenteritis. A panel of 158 fecal samples from 23 outbreaks, including confirmed rotavirus and astrovirus outbreaks, was used to determine the sensitivity and specificity of both ELISA kits relative to an RT-PCR protocol that was followed by Southern blot hybridization. Another panel consisted of 6 different genogroup I strains, 12 genogroup II strains and 1 genogroup IV strain and was used to determine the scope of the tests. Compared to the RT-PCR, sensitivities of 38% and 36% and specificities of 96% and 88% were found for the Dako kit and the Ridascreen kit, respectively. Two genogroup I strains, and one genogroup II strain were not detected by the Dako kit, while five genogroup I and five genogroup II strains were not detected by the Ridascreen kit. The sensitivity of both ELISA kits, and the scope of the Ridascreen are considered disappointing. However, the ELISA kits can be useful for a preliminary screening, provided that ELISA negative outbreaks will be re-tested by RT-PCR methods.
  • Spatial spreading of Echinococcus multilocularis in Red foxes (Vulpes vulpes) across nation borders in Western Europe.

    Vervaeke, Muriel; Giessen, Joke van der; Brochier, Bernard; Losson, Bernard; Jordaens, Kurt; Verhagen, Ron; Lezenne Coulander, Cor de; Teunis, Peter F M (2006-10-17)
    The occurrence of the fox tapeworm Echinococcus multilocularis in Red foxes was studied in Belgium and a neighbouring region in The Netherlands. A total number of 1202 foxes were analysed (1018 in Belgium and 184 in The Netherlands) of which 179 were infected with E. multilocularis (164 in Belgium and 15 in The Netherlands). Further, the spatial distribution of infection among sampled foxes was analysed with an ellipsoidal gradient, demonstrating a decreasing prevalence in northwestern direction. Using this gradient, we showed that the spatial patterns of infection in Belgium and the neighbouring region in The Netherlands correspond, indicating a continuous distribution of E. multilocularis across the nation borders. Part of the Belgian data allowed investigating temporal changes in the spatial distribution of E. multilocularis. This revealed a northwestern spread of E. multilocularis.
  • Methicillin-resistant Staphylococcus aureus in Dutch soccer team.

    Huijsdens, Xander W; Lier, Ans M C van; Kregten, Eric van; Verhoef, Liesbeth; Santen-Verheuvel, Marga G van; Spalburg, Emile; Wannet, Wim J B (2006-10-01)
    An outbreak of community-acquired methicillin-resistant Staphylococcus aureus occurred among members and close contacts of a soccer team. Typing of the isolates showed the outbreak was caused by the well-known European ST80-IV strain. To our knowledge, this is the first report of an outbreak of this strain among members of a sports team.
  • Serotypes, genotypes, and antibiotic susceptibility profiles of group B streptococci causing neonatal sepsis and meningitis before and after introduction of antibiotic prophylaxis.

    Trijbels-Smeulders, Monique A J M; Kimpen, Jan L L; Kollée, Louis A A; Bakkers, Judith; Melchers, Willem; Spanjaard, Lodewijk; Wannet, Wim J B; Hoogkamp-Korstanje, Mieke A A (2006-10-01)
    We studied the characteristics of strains isolated from neonates with group B streptococci sepsis and meningitis, before and after the introduction of antibiotic prophylaxis in The Netherlands. In 1999, 1 year after this introduction the serotype and genotype distribution and the susceptibility patterns of the GBS strains had not changed. Penicillins remain drugs of first choice to prevent and treat neonatal GBS disease.
  • Genes for the majority of group a streptococcal virulence factors and extracellular surface proteins do not confer an increased propensity to cause invasive disease.

    McMillan, David J; Beiko, R G; Geffers, R; Buer, Jan; Schouls, Leo M; Vlaminckx, B J M; Wannet, Wim J B; Sriprakash, K S; Chhatwal, G S (2006-10-01)
    BACKGROUND: The factors behind the reemergence of severe, invasive group A streptococcal (GAS) diseases are unclear, but it could be caused by altered genetic endowment in these organisms. However, data from previous studies assessing the association between single genetic factors and invasive disease are often conflicting, suggesting that other, as-yet unidentified factors are necessary for the development of this class of disease. METHODS: In this study, we used a targeted GAS virulence microarray containing 226 GAS genes to determine the virulence gene repertoires of 68 GAS isolates (42 associated with invasive disease and 28 associated with noninvasive disease) collected in a defined geographic location during a contiguous time period. We then employed 3 advanced machine learning methods (genetic algorithm neural network, support vector machines, and classification trees) to identify genes with an increased association with invasive disease. RESULTS: Virulence gene profiles of individual GAS isolates varied extensively among these geographically and temporally related strains. Using genetic algorithm neural network analysis, we identified 3 genes with a marginal overrepresentation in invasive disease isolates. Significantly, 2 of these genes, ssa and mf4, encoded superantigens but were only present in a restricted set of GAS M-types. The third gene, spa, was found in variable distributions in all M-types in the study. CONCLUSIONS: Our comprehensive analysis of GAS virulence profiles provides strong evidence for the incongruent relationships among any of the 226 genes represented on the array and the overall propensity of GAS to cause invasive disease, underscoring the pathogenic complexity of these diseases, as well as the importance of multiple bacteria and/or host factors.
  • The polio eradication effort has been a great success--let's finish it and replace it with something even better.

    Kimman, Tjeerd G; Boot, Hein J (2006-10-01)
    The polio eradication campaign has greatly reduced the effects of this disease, but many new challenges have emerged. These challenges include the occurrence of polio outbreaks caused by wild-type polioviruses or circulating vaccine-derived polioviruses (cVDPVs) in areas where vaccination coverage is low, the existence of people who excrete poliovirus persistently, and the inability to know definitely that poliovirus has gone. As a result, there is uncertainty about if, when, and how we can end polio immunisation. In this article, we discuss several scenarios for the future of polio control. Because the emergence of cVDPVs necessitates discontinuing the use of live oral polio vaccine, we propose to strive towards a global coverage of near 100% vaccination against all major childhood infections using combination vaccines that contain inactivated poliovirus vaccine. Such a policy will present multiple challenges.
  • Wiskundige modellering voor bestrijding van infectieziekten

    Kretzschmar, Mirjam; Wallinga, Jacco; Coutinho, Roel A (2006-09-09)
    When determining interventions against threatening infectious diseases such as HIV-infection, severe acute respiratory syndrome (SARS), smallpox and pandemic influenza, the use of mathematical models of the spread of infectious diseases is becoming increasingly popular. These models contribute to the structuring of the knowledge already available in various disciplines, to finding epidemiological connnections, to demonstrating lacunas within the pool of knowledge and to the comparison of the expected effects and costs of preventative and intervention measures. The use of models leads to a 'made-to-measure' analysis ofthe effects and costs of preventative and intervention measures which takes account of the specific characteristics of infectious diseases. The integration of knowledge from various disciplines can be supported by more research into the theoretical epidemiology of infectious disease and by better integration of mathematical models into policy development. The resulting and better foundations of this policy that are achieved by means of infectious disease modelling translate into more effective combating of infectious disease.
  • Antibiotic resistance, integrons and Salmonella genomic island 1 among non-typhoidal Salmonella serovars in The Netherlands.

    Vo, An T T; Duijkeren, Engeline van; Fluit, Ad C; Wannet, Wim J B; Verbruggen, Anjo J; Maas, Henny M E; Gaastra, Wim (2006-09-01)
    The objective of this study was to investigate the antimicrobial resistance patterns, integron characteristics and gene cassettes as well as the presence of Salmonella genomic island 1 (SGI1) in non-typhoidal Salmonella (NTS) isolates from human and animal origin. Epidemiologically unrelated Dutch NTS strains (n=237) originating from food-producing animals and human cases of salmonellosis were tested for their susceptibility to 15 antimicrobial agents. Resistance to 14 of these antimicrobials, including the third-generation cephalosporins, was detected. Resistance to sulphonamides, ampicillin, tetracycline, streptomycin, trimethoprim and nalidixic acid was common (>/=10% of the strains were resistant). Resistance against three or more antimicrobials was observed in 57 isolates. The same 237 strains were studied for the prevalence of class 1 integrons, their gene cassettes and the presence of SGI1. Thirty-six isolates (15.2%) carried class 1 integrons. These integrons had ten distinct profiles based on the size of the integron and restriction fragment length polymorphism analysis. Integrons were detected for the first time in serovars Indiana and Senftenberg. Multidrug resistance was strongly associated with the presence of class 1 integrons in which the aadA2, aadA1, bla(PSE-1), dfrA1, dfrA5, dfrA14 or sat genes were present, as determined by nucleotide sequence determination. The presence of gene cassettes or combinations of gene cassettes not previously found in integrons in Salmonella was observed. SGI1 or its variants (SGI-B, -C and -F) were present in 16 isolates belonging to either serovar Typhimurium, Derby or Albany. Regardless of whether the isolate was of human or animal origin, the same resistance phenotype, integron profile and SGI1 structure could be observed.
  • Rubella-epidemie 2004-2005: surveillance van congenitale gevolgen

    Veen, Y van der; Hahné, Susan J M; Ruijs, H; Timen, A; Binnendijk, R S van; Loon, T van; Melker, Hester E de (RIVM, 2006-09-01)
    In 2004-2005, the Netherlands experienced an outbreak of rubella. The Centre for Infectious Disease Control (CIb/RIVM) monitors characteristics and the extent of the outbreak and reports on the disease-burden of rubella, congenital rubella-virus infection (CRI) and congenital rubella syndrome (CRS). In this article, the used methods for surveillance and the results are presented and discussed. Data available so far, indicate that 32 pregnant women were infected during the outbreak, resulting in 15 cases of CRI. Nine of these infants showed symptoms associated with CRS. Surveillance of the congenital consequences of the rubella-epidemic is a difficult task, but important for effective treatment, increasing of the knowledgebase and immunization and antenatal screening policy
  • Geen paniek! : Zelfredzaamheid bij uitbraken van infectieziekten

    Helsloot, I (RIVM, 2006-09-01)
    The understanding of citizen response to disaster is crucial to outbreak management of infectious diseases. Large scale outbreaks cannot be mitigated without the active corporation of citizens. This article shows that citizens in general will not panic, are not helpless and will not start plundering. Inappropriate actions and communication of authorities may cause unwanted reactions of citizen which then are labelled by both authorities and media as panic or irrational behaviour.
  • Legionella-uitbraak in Amsterdam: koeltoren als bron

    Hoek, J A R van den; IJzerman, E P F; Coutinho, Roel A (2006-08-19)
    During the period 6-28 July 2006, 30 confirmed cases of Legionella infection were identified in Amsterdam, 2 of which were fatal. All had a positive urinary antigen test, by which Legionella pneumophila serogroup I could be demonstrated. Consultations between the parties involved in the control of infectious diseases started on July 7th, as soon as it became clear that there was an outbreak. On July 10th it was established that relatively many of these patients lived in the eastern part of the city centre. After a study of the prevailing winds during the past 3 weeks, the search for installations containing water was started. A cooling tower in the town centre was closed on July 11th by way of precaution. During the following week, this tower was proven to be the source of the outbreak.
  • Twee patienten met de bof

    Brummelen, S E van; Vries, E de; Schneeberger, P M; Binnendijk, R S van; Lestrade, P; Wever, P C (2006-08-05)
    Two patients, men aged 17 and 19 years respectively, were admitted with parotitis epidemica and orchitis caused by mumps. The second patient also had meningitis. PCR analysis revealed that, in both cases, the causative agentwas a mumps virus that was genetically related to a wild-type virus responsible for an outbreak in Singapore. This viral strain was also responsible for a mumps outbreak at Hotel School The Hague in September 2004. Both patients were not fully vaccinated. Both patients were from regions in which clustering of patients with clinical signs of mumps has been seen. Interestingly, a number of patients with confirmed mumps had been fully vaccinated. Possible explanations for the increase in mumps cases include low vaccination and immunity levels, primary and secondary vaccine failure and the emergence of genetically disparate mumps viruses.
  • Praktijkevaluatie van de regionale toepassing van artikel 7 van de Infectieziektenwet

    Petrignani, M W F; Yap, K B (RIVM, 2006-08-01)
    In 1999 a new Dutch law on notifiable diseases is implemented. It contains article 7, which states that institutions are obliged to report unusual numbers of inhabitants or staff with symptoms of infectious diseases to the local public health service. We think evaluation of the actions deriving from article 7 is in place. We analysed regional data from these reports in the years 2003, 2004 and 2005. Thereby categorizing medical and non-medical institutions. Most of the reports come from non-medical institutions and can be dealt with by giving information and advice. Skin infections and rashes were reported the most. Medical institutions often reported actual outbreaks. 41% Of all institutions in our region contacted us in the period that was analyzed. We conclude that our role is well known to the regional institutions and that we have a good idea of how they report. Because of the large diversity in registration of article 7 reports, national surveillance is not useful. Registration of certain reports might attribute to surveillance of specific syndromes. A more uniform registration can attribute to an improvement in the quality of local public health services.
  • Malariameldingen in 2005: Evaluatie van de richtlijnen van het Landelijk Coördinatiecentrum Reizigersadvisering (LCR) voor malariaprofylaxe

    Sondera, G J B; Plas, Simone M van der (RIVM, 2006-08-01)
    In The Netherlands, malaria is a notifiable disease in group C since 1999: the laboratory where the patient tested positive has to report the test results, together with a few demographic data, to the National Center for Disease Control (CIb). Since January 2005, the National Coordination Center for Travelers Health Advice (LCR) added some questions to the voluntary part of these reports in order to obtain more insight in the prevalence of malaria in people who used prophylaxis according to the LCR guidelines, and to evaluate these guidelines. The goal of the LCR guidelines is to prevent malaria caused by P. falciparum. All reported cases with a disease onset date in 2005 were evaluated. In 2005, 288 cases of malaria were reported. Seventy-five (26%) malaria patients used chemoprophylaxis. In total, 32 (11%) contracted malaria despite the use of chemoprophylaxis according to the LCR guidelines. Eight of these cases concerned malaria caused by P. falciparum. Four of these had used second choice chemoprophylaxis, to which parasitic resistance is common. In the blood sample of one patient no mefloquine was detected. Of the other three, the thick smear or EDTA blood was not available for resistance tests. Most likely, all other cases had a delayed onset malaria, which cannot be prevented by the currently available chemoprophylaxis. Based on these data, we conclude that the LCR guidelines are still valid. It is advised that in cases of breakthrough malaria caused by P. falciparum blood samples are taken to determine chloroquine or mefloquine levels where applicable, and to save EDTA blood for molecular confirmation of the species and determination of resistant parasites.
  • Molecular epidemiology of Neisseria gonorrhoeae in Amsterdam, The Netherlands, shows distinct heterosexual and homosexual networks.

    Kolader, Marion-Eliëtte; Dukers, Nicole H T M; Bij, Akke K van der; Dierdorp, Mirjam; Fennema, Johan S A; Coutinho, Roel A; Bruisten, Sylvia M (2006-08-01)
    Molecular typing, added to epidemiological data, can better identify transmission patterns of gonorrhea in Western countries, where the incidence has recently been rising. From September 2002 to September 2003, patients with a laboratory-confirmed diagnosis of gonorrhea at the Clinic for Sexually Transmitted Infections in Amsterdam, The Netherlands, were subjected to a questionnaire pertaining to sexual risk behavior and sexual partners in the 6 months prior to the diagnosis. The Neisseria gonorrhoeae isolates were all genotyped using PCR-restriction fragment length polymorphism of the porin and opacity genes. All patients with a completed questionnaire and genotyped isolates were included in the study. We obtained 885 N. gonorrhoeae isolates from 696 patients that revealed 88 clusters and 46 unique genotypes. Patients infected at multiple anatomical sites with one or more strains and patients infected several times during the study period were shown to pursue high-risk sexual behavior and were considered core groups. There were 11 clusters of > or =20 patients; in seven clusters, 81% to 100% of patients were men who have sex with men (MSM), three clusters contained 87 to 100% heterosexual men and women, and one cluster was formed by equal proportions of MSM and heterosexual male and female patients. However, the various clusters differed in characteristics such as types of coinfections, numbers of sexual partners, Internet use to seek sexual partners, and locations of sexual encounters. Molecular epidemiology of gonococcal isolates in Amsterdam revealed core groups and clusters of MSM and heterosexual patients that probably indicate distinct transmission networks.
  • Multiple cases of familial transmission of community-acquired methicillin-resistant Staphylococcus aureus.

    Huijsdens, Xander W; Santen-Verheuvel, Marga G van; Spalburg, Emile; Heck, Max E O C; Pluister, Gerlinde N; Eijkelkamp, B A; Neeling, Albert J de; Wannet, Wim J B (2006-08-01)
    The worldwide emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) can have severe public health implications. Familial transmissions of CA-MRSA in The Netherlands were investigated. Among the families studied, two clusters of CA-MRSA could be identified. This report demonstrates that family members can serve as reservoirs of CA-MRSA which may become a serious problem in containing the spread of MRSA.
  • The incidence of Bordetella pertussis infections estimated in the population from a combination of serological surveys.

    Melker, Hester E de; Versteegh, Florens G A; Schellekens, Joop F P; Teunis, Peter F M; Kretzschmar, Mirjam (2006-08-01)
    OBJECTIVES: Bordetella pertussis circulates even in highly vaccinated populations. There is a considerable amount of infection in adults. For designing more effective vaccination schedules it is important to quantify the age-dependent relation between the number of notified cases and the number of infections. METHODS: We used a statistical relationship between the time since infection and the IgG antibody titers against pertussis toxin, derived from a longitudinal data set, to estimate time since infection for all individuals in a cross-sectional population-based study (1995-1996) based on their titers. Age-specific incidence of infection with B. pertussis was calculated and compared with the age-distribution of notified cases of pertussis in 1994-1996. RESULTS: Estimated incidence of infection was 6.6% per year for 3-79-year olds, annual incidence of notified cases 0.01%. Estimated age-specific incidence of infection was lowest for 3-4-year olds (3.3%) and increased gradually up to the age of 20-24 years (10.8%). The number of notified cases was highest for 3-9-year olds. CONCLUSIONS: In the Dutch population B. pertussis infections occur more frequently and in elder age-categories then suggested by notifications. Mathematical modeling could explore what booster vaccination strategies are most effective in reducing severe disease among not (completely) vaccinated infants.
  • Intensieve surveillance van Shigatoxine-producerende Escherichia coli O157 in Nederland, 2005

    Friesema, I H M; Jager, C M de; Heuvelink, A E; Zwaluw, W K van der; Maas, Henny M E; Pelt, W van; Wannet, Wim J B; Duynhoven, Yvonne T H P van (RIVM, 2006-08-01)
    Since January 1999, an enhanced surveillance of Shiga toxin-producing Escherichia coli (STEC) O157 has been implemented in the Netherlands. In 2005, 53 symptomatic patients were diagnosed with STEC O157. This was relatively high compared with the number in previous years (annually 36 to 57), due to a national outbreak with 21 patients involved. Of the patients, 33% were hospitalised, 8% developed the haemolytic-uraemic syndrome (exclusion of outbreak-cases: 13%), including one one-year-old boy who died. Consumption of raw or undercooked beef and contact with farm animals and manure are still most frequently mentioned by the patients as possible cause. In 2005, cluster analyses of the fingerprints of bacterial DNA from the STEC O157 isolates (by pulsed-field gel electrophoresis) nine times suggested a relationship between several patients. For three clusters this was supported by additional epidemiological information. One cluster, consisting of two sub clusters, comprises the national outbreak caused by filet américain, except for two patients who fell ill two and one month before this outbreak. Furthermore, one household cluster was identified for which an indistinguishable PFGE pattern was found in a manure isolate taken from their cattle. In addition, an isolate from one individual case could be matched with an isolate taken from their neighbours cattle. As other serogroups than O157 can cause serious illness, a collaboration between RIVM and eight medical microbiological laboratories to assess the relative importance of non-O157 serogroups was started in the Netherlands in the autumn of 2005.

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