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  • The sample of choice for detecting Middle East respiratory syndrome coronavirus in asymptomatic dromedary camels using real-time reversetranscription polymerase chain reaction.

    Mohran, K A; Farag, E A B; Reusken, C B E; Raj, V S; Lamers, M M; Pas, S D; Voermans, J; Smits, S L; Alhajri, M M; Alhajri, F; Al-Romaihi, H E; Ghobashy, H; El-Maghraby, M M; Al Dhahiry, S H S; Al-Mawlawi, N; El-Sayed, A M; Al-Thani, M; Al-Marri, S A; Haagmans, B L; Koopmans, M P G (2016-12)
    The newly identified Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease, particularly in people with comorbidities, requires further investigation. Studies in Qatar and elsewhere have provided evidence that dromedary camels are a reservoir for the virus, but the exact modes of transmission of MERS-CoV to humans remain unclear. In February 2014, an assessment was made of the suitability and sensitivity of different types of sample for the detection of MERSCoV by real-time reverse-transcription polymerase chain reaction (RT-PCR) for three gene targets: UpE (upstream of the E gene), the N (nucleocapsid) gene and open reading frame (ORF) 1a. Fifty-three animals presented for slaughter were sampled. A high percentage of the sampled camels (79% [95% confidence interval 66.9-91.5%, standard error 0.0625]; 42 out of 53) were shown to be shedding MERS-CoV at the time of slaughter, yet all the animals were apparently healthy. Among the virus-positive animals, nasal swabs were most often positive (97.6%). Oral swabs were the second most frequently positive (35.7%), followed by rectal swabs (28.5%). In addition, the highest viral load, expressed as a cycle threshold (Ct) value of 11.27, was obtained from a nasal swab. These findings lead to the conclusion that nasal swabs are the candidate sample of choice for detecting MERS-CoV using RT-PCR technology in apparently healthy camels.
  • Environmental risk assessment for veterinary medicinal products . Part 1. Other than GMO-containing and immunological products

    Montforts MHMM; CSR (1997-10-31)
    The EC directives (1981, 1992) stipulate that in requesting registration of a veterinary medicinal product, information will have to be provided for carrying out an environmental risk assessment. The risk assessment methodology presented here is, on the whole, structured around the risk-quotient approach. Calculated environmental concentrations are compared with effect data established in toxicity studies. Directive 81/852/EEC describes the assessment process in two phases. Phase I is to assess if the product, the ingredients or the relevant metabolites will, in fact, result in environmental exposure. For this reason the first phase is limited to product identification and to exposure assessment. Several exemptions for further testing are given, e.g. the limit values for calculated environmental concentrations. If these exemptions do not apply , and limit values are exceeded, one enters Phase II. Once again, Phase II is split into Tiers A and B. Tier A begins with an elaborate evaluation of the possible fate and effects. If the applicant is unable to demonstrate that exposure is minimised to a level of no concern to the environment, the effects in the relevant compartments must be adequately investigated in Tier B. The non-uniform Tier B evaluation is dependent on expert judgement, therefore beyond the scope of this document.
  • Local tolerance and general toxicity of tetravalent pneumococcal conjugate vaccine

    Dortant PM; Loveren H van; Wester PW; LPI (1999-12-15)
    In order to evaluate the safety of a tetravalent pneumococcal conjugate vaccine, the final product was tested in 24 female rats, 6 weeks of age, by duplicate intramuscular injections. Parameters for general toxicity were body weight gain, food consumption, general clinical parameters and hematology. Local tolerance was evaluated by histopathology of injection sites and regional (iliac and popliteal) lymph nodes. The latter were also weighed. Results indicated no effect of the test vaccine on clinical parameters, body weight gain, food consumption and hematology. The weight of the regional lymph nodes was slightly increased (though without statistical significance), but not as dramatically as in the reference control vaccine (DPT-polio). Local reactions after adjuvant or complete vaccine were mild compared to the reference control vaccine (DPT-polio). Provided a protective immune response is conferred, the responses after pneumococcal conjugate vaccines in rats as observed in this study, are acceptable because: 1- The widely accepted local reaction after DPT-polio injection is more severe. 2- The administered doses in this local tolerance and general toxicity study are 1/4 of the DPT-polio human dose and 1/2 of the pneumococcal vaccine human dose, which are great overdoses on body weight basis for the animals used in this study.
  • 'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?

    Anthony, R M; den Hertog, A L; van Soolingen, D (2018-03-08)
    A low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.
  • De bereikbaarheid bestaat niet - Definiering en operationalisering van bereikbaarheid

    Hagoort MJ; LAE (1999-02-09)
    On the basis of this literature review on "accessibility", a proposal has been made for a new measure of accessibility, which can be used to estimate if jobs are accessible to the employment market. Generally speaking, accessibility relates to the amount of money, time and trouble required to travel from the place of origin to the desired destination (either for persons or goods). The literature review also showed the notion of "accessibility" to be multi-interpretable. "Accessibility" is only meaningful when it is clear, for instance, from what perspective and for what goal, activity, travel motivation and travel mode accessibility is applied. Even then, the usefulness of the different accessibility measures found in the literature strongly depends on the precise research issue.

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