Marco W G van de Bildt

Publications of Marco W G van de Bildt

• Influenza a and B virus attachment to respiratory tract in marine mammals.

  Authors: Antonio J Ramis, Debby van Riel, Marco W G van de Bildt, Albert Osterhaus, Thijs Kuiken

  Emerging infectious diseases. 05/2012; 18(5):817-20.

  Patterns of virus attachment to the respiratory tract of 4 marine mammal species were determined for avian and human influenza viruses. Attachment of avian influenza A viruses (H4N5) and (H7N7) andPatterns of virus attachment to the respiratory tract of 4 marine mammal species were determined for avian and human influenza viruses. Attachment of avian influenza A viruses (H4N5) and (H7N7) and human influenza B viruses to trachea and bronchi of harbor seals is consistent with reported influenza outbreaks in this species.

• Marked endotheliotropism of highly pathogenic avian influenza virus H5N1 following intestinal inoculation in cats.

  Authors: Leslie A Reperant, Marco W G van de Bildt, Geert van Amerongen, Lonneke M E Leijten, Simon Watson, Anne Palser, Paul Kellam, Anko C Eissens, Hendrik W Frijlink, Albert D M E Osterhaus, Thijs Kuiken

  Journal of virology. 11/2011; 86(2):1158-65.

  Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since influenza viruses typically infect mammals via the respiratory tract. TheHighly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since influenza viruses typically infect mammals via the respiratory tract. The dissemination of HPAIV H5N1 following intestinal entry and associated pathogenesis are largely unknown. To assess the route of spread of HPAIV H5N1 to other organs and to determine its associated pathogenesis, we inoculated infected chicken liver homogenate directly into the intestine of cats by use of enteric-coated capsules. Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease. The spread of HPAIV H5N1 from the lumen of the intestine to other organs took place via the blood and lymphatic vascular systems but not via neuronal transmission. Remarkably, the systemic spread of the virus via the vascular system was associated with massive infection of endothelial and lymphendothelial cells, resulting in widespread hemorrhages. This is unique for influenza in mammals and resembles the pathogenesis of HPAIV infection in terrestrial poultry. It contrasts with the pathogenesis of systemic disease from the same virus following entry via the respiratory tract, where lesions are characterized mainly by necrosis and inflammation and are associated with the presence of influenza virus antigen in parenchymal, not endothelial cells. The marked endotheliotropism of the virus following intestinal inoculation indicates that the pathogenesis of systemic influenza virus infection in mammals may differ according to the portal of entry.

• Replication of low pathogenic avian influenza virus in naturally infected Mallard ducks (Anas platyrhynchos) causes no morphologic lesions.

  Authors: Pierre-Yves Daoust, Frederick S B Kibenge, Ron A M Fouchier, Marco W G van de Bildt, Debby van Riel, Thijs Kuiken

  Journal of wildlife diseases. 04/2011; 47(2):401-9.

  Although the Mallard (Anas platyrhynchos) is considered an important maintenance host for low pathogenic avian influenza (LPAI) viruses, viral cell tropism and pathology in naturally infected birdsAlthough the Mallard (Anas platyrhynchos) is considered an important maintenance host for low pathogenic avian influenza (LPAI) viruses, viral cell tropism and pathology in naturally infected birds are largely unknown. In August 2006, we collected 19 free-living hatch-year Mallards that were positive for LPAI virus by real-time reverse-transcriptase polymerase chain reaction (RRT-PCR) in combined oropharyngeal and cloacal swabs. We investigated virus infection and associated lesions in the digestive and respiratory tracts by RRT-PCR, virus culture, immunohistochemistry (IHC), and histology. By RRT-PCR, 15 birds were positive in cloacal bursa, colon/cloaca, or both, and three were positive in lungs. Virus was isolated from eight birds and typed as H2N3 (three birds), H3N3 (two birds), H3N8 (one bird), H4N6 (one bird), and H?N3 (one bird). By IHC, birds were positive in the cloacal bursa (eight birds), colon (three), cecum (two), or ileum (one). Cell types infected were superficial epithelial cells of the bursa and epithelial cells of the intestinal villi and, less commonly, mucosal glands. By histology, there was no evidence of lesions associated with LPAI virus infection. These results show that epithelia of the cloacal bursa and of the lower intestine are important sites of natural LPAI virus infection in free-living hatch-year Mallards. The lack of lesions associated with this infection suggests that there is a strong selection by LPAI virus to cause minimal virulence in this maintenance host species.

• Highly pathogenic avian influenza virus H5N1 infection in a long-distance migrant shorebird under migratory and non-migratory states.

  Authors: Leslie A Reperant, Marco W G van de Bildt, Geert van Amerongen, Debbie M Buehler, Albert D M E Osterhaus, Susi Jenni-Eiermann, Theunis Piersma, Thijs Kuiken

  PloS one. 01/2011; 6(11):e27814.

  Corticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for theCorticosterone regulates physiological changes preparing wild birds for migration. It also modulates the immune system and may lead to increased susceptibility to infection, with implications for the spread of pathogens, including highly pathogenic avian influenza virus (HPAIV) H5N1. The red knot (Calidris canutus islandica) displays migratory changes in captivity and was used as a model to assess the effect of high plasma concentration of corticosterone on HPAIV H5N1 infection. We inoculated knots during pre-migration (N = 6), fueling (N = 5), migration (N = 9) and post-migration periods (N = 6). Knots from all groups shed similar viral titers for up to 5 days post-inoculation (dpi), peaking at 1 to 3 dpi. Lesions of acute encephalitis, associated with virus replication in neurons, were seen in 1 to 2 knots per group, leading to neurological disease and death at 5 to 11 dpi. Therefore, the risk of HPAIV H5N1 infection in wild birds and of potential transmission between wild birds and poultry may be similar at different times of the year, irrespective of wild birds' migratory status. However, in knots inoculated during the migration period, viral shedding levels positively correlated with pre-inoculation plasma concentration of corticosterone. Of these, knots that did not become productively infected had lower plasma concentration of corticosterone. Conversely, elevated plasma concentration of corticosterone did not result in an increased probability to develop clinical disease. These results suggest that birds with elevated plasma concentration of corticosterone at the time of migration (ready to migrate) may be more susceptible to acquisition of infection and shed higher viral titers--before the onset of clinical disease--than birds with low concentration of corticosterone (not ready for take-off). Yet, they may not be more prone to the development of clinical disease. Therefore, assuming no effect of sub-clinical infection on the likelihood of migratory take-off, this may favor the spread of HPAIV H5N1 by migratory birds over long distances.

• Experimental pandemic (H1N1) 2009 virus infection of cats.

  Authors: Judith M A van den Brand, Koert J Stittelaar, Geert van Amerongen, Marco W G van de Bildt, Lonneke M E Leijten, Thijs Kuiken, Albert D M E Osterhaus

  Emerging infectious diseases. 11/2010; 16(11):1745-7.

  To demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicatedTo demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicated cat-to-cat virus transmission. Unlike in cats infected with highly pathogenic avian influenza virus (H5N1), extrarespiratory lesions did not develop in cats infected with pandemic (H1N1) 2009 virus.

• Herpesvirus in bottlenose dolphins (Tursiops truncatus): cultivation, epidemiology, and associated pathology.

  Authors: Cornelis E van Elk, Marco W G van de Bildt, Antonius A W de Jong, Albert D M E Osterhaus, Thijs Kuiken

  Journal of wildlife diseases. 10/2009; 45(4):895-906.

  We studied the pathology, epidemiology, and clinical significance of genital herpesvirus infection in a zoo collection of bottlenose dolphins (Tursiops truncatus). Samples from the genital mucosa ofWe studied the pathology, epidemiology, and clinical significance of genital herpesvirus infection in a zoo collection of bottlenose dolphins (Tursiops truncatus). Samples from the genital mucosa of male (n=21) and female (n=15) dolphins were tested by nested polymerase chain reaction (PCR) targeting the DNA polymerase of herpesvirus. Herpesvirus infection was significantly associated with the occurrence of mucosal plaques on penis (n=3) or vulva (n=4). Biopsies from a penile plaque showed epithelial hyperplasia by histology, contained herpesvirus-like particles by electron microscopy, and tested positive for herpesvirus by PCR. Herpesvirus was successfully cultivated from penile plaque samples and identified as a member of the Gammaherpesvirinae by DNA sequencing and phylogenetic analysis. We used the newly cultivated bottlenose dolphin herpesvirus (TTHV) to develop a direct enzyme-linked immunosorbent assay for anti-TTHV antibodies in banked sera of these dolphins. The percentage of positive samples was higher in adults (20/21, 95%) than in juveniles (7/15, 47%). Seroconversion occurred around the age of onset of sexual behavior. Although herpesvirus infection has been associated with abortion, perinatal mortality, and urogenital neoplasia in other species, we found no evidence of herpesvirus infection by PCR in tissues from six cases of abortion and perinatal mortality, and no diagnoses of urogenital tumors in 24 bottlenose dolphins from this zoo collection that died since 1990. Together, we here report the first successful cultivation from bottlenose dolphins of a herpesvirus that probably causes benign genital plaques, is endemic in this group of dolphins, and is likely transmitted by sexual contact.

• Canine distemper virus-associated encephalitis in free-living lynx (lynx canadensis) and bobcats (lynx rufus) of eastern Canada.

  Authors: Pierre-Yves Daoust, Scott R McBurney, Dale L Godson, Marco W G van de Bildt, Albert D M E Osterhaus

  Journal of wildlife diseases. 08/2009; 45(3):611-24.

  Between 1993 and 1999, encephalitis caused by morbillivirus was diagnosed by immunohistochemistry and histology in six lynx (Lynx canadensis) and one bobcat (Lynx rufus) in the eastern CanadianBetween 1993 and 1999, encephalitis caused by morbillivirus was diagnosed by immunohistochemistry and histology in six lynx (Lynx canadensis) and one bobcat (Lynx rufus) in the eastern Canadian provinces of New Brunswick and Nova Scotia. Five of the six cases in lynx occurred within an 11-mo period in 1996-97. A second bobcat with encephalitis caused by unidentified protozoa and a nematode larva also had immunohistochemical evidence of neurologic infection by morbillivirus. The virus was identified as canine distemper virus (CDV) by reverse transcriptase polymerase chain reaction and nucleotide sequencing in four of five animals from which frozen tissue samples were available, and it was isolated in cell culture from one of them. To our knowledge, this is the first report of disease caused by CDV in free-living felids in North America.

• Highly Pathogenic Avian Influenza Virus (H5N1) Infection in Red Foxes Fed Infected Bird Carcasses.

  Authors: Leslie A Reperant, Geert van Amerongen, Marco W G van de Bildt, Guus F Rimmelzwaan, Andrew P Dobson, Albert D M E Osterhaus, Thijs Kuiken

  Emerging infectious diseases. 01/2009; 14(12):1835-41.

  Eating infected wild birds may put wild carnivores at high risk for infection with highly pathogenic avian influenza (HPAI) virus (H5N1). To determine whether red foxes (Vulpes vulpes) areEating infected wild birds may put wild carnivores at high risk for infection with highly pathogenic avian influenza (HPAI) virus (H5N1). To determine whether red foxes (Vulpes vulpes) are susceptible to infection with HPAI virus (H5N1), we infected 3 foxes intratracheally. They excreted virus pharyngeally for 3-7 days at peak titers of 103.5-105.2 median tissue culture infective dose (TCID50) per mL and had severe pneumonia, myocarditis, and encephalitis. To determine whether foxes can become infected by the presumed natural route, we fed infected bird carcasses to 3 other red foxes. These foxes excreted virus pharyngeally for 3-5 days at peak titers of 104.2-104.5 TCID50/mL, but only mild or no pneumonia developed. This study demonstrates that red foxes fed bird carcasses infected with HPAI virus (H5N1) can excrete virus while remaining free of severe disease, thereby potentially playing a role in virus dispersal.

• Phocine distemper outbreak, The Netherlands, 2002.

  Authors: Jolianne M Rijks, Marco W G van de Bildt, Trine Jensen, Joost D W Philippa, Albert D M E Osterhaus, Thijs Kuiken

  Emerging infectious diseases. 01/2006; 11(12):1945-8.

  During the 2002 phocine distemper epidemic, 2,284 seals, primarily harbor seals (Phoca vitulina), were found stranded along the Dutch coast. Stranding pattern varied with age, sex, state ofDuring the 2002 phocine distemper epidemic, 2,284 seals, primarily harbor seals (Phoca vitulina), were found stranded along the Dutch coast. Stranding pattern varied with age, sex, state of decomposition, wind, and location. Cumulative proportion of deaths (54%) was comparable to that in the first reported epidemic in 1988.

• Immunogenicity and efficacy of recombinant subunit vaccines against phocid herpesvirus type 1.

  Authors: Byron E E Martina, Marco W G van de Bildt, Thijs Kuiken, Geert van Amerongen, Albert D M E Osterhaus

  Vaccine. 06/2003; 21(19-20):2433-40.

  Phocid herpesvirus type 1 (PhHV-1) is an alpha-herpesvirus that causes significant morbidity and mortality among young and immunocompromised harbour seals (Phoca vitulina) and therefore represents aPhocid herpesvirus type 1 (PhHV-1) is an alpha-herpesvirus that causes significant morbidity and mortality among young and immunocompromised harbour seals (Phoca vitulina) and therefore represents a major problem for seal rehabilitation centres. Consequently, there is a need for a safe and effective PhHV-1 vaccine. We tested an ISCOM-based recombinant PhHV-1 gB vaccine alone (gB) or with the addition of recombinant PhHV-1 gD (gBD) for (i). immunogenicity and protective efficacy against feline herpesvirus (FHV) infection in cats and (ii). their immunogenicity in seals. The FHV-cat model was chosen based on the close antigenic relationship between PhHV-1 and FHV. Upon challenge, all vaccinated (gB and gBD) cats excreted significantly less FHV (P<0.01) and gBD vaccinated cats showed less weight loss (P=0.05) than the mock-vaccinated cats. However, adding gD to the gB vaccine did not result in significantly better protection. Based on these data, immunogenicity studies in seals under rehabilitation were performed with the gB vaccine only. To this end, gB vaccine was tested at two different doses (20 or 40 microg). PhHV-1 specific antibody titres and in vitro proliferative T cell responses were measured in all seals upon vaccination. No differences were observed in antibody titres between seals vaccinated with either 20 or 40 microgB, but the higher gB concentration did result in higher specific proliferative T cell responses (P<0.01). Based on the close antigenic relationship between PhHV-1 and FHV, the safety and efficacy data in the FHV-cat model, and the immunogenicity data in the vaccinated seals, the gB based vaccine is expected to be safe and effective in protecting against PhHV-1 related disease in harbour seals.

• Distemper outbreak and its effect on African wild dog conservation.

  Authors: Marco W G van de Bildt, Thijs Kuiken, Aart M Visee, Sangito Lema, Tony R Fitzjohn, Albert D M E Osterhaus

  Emerging infectious diseases. 03/2002; 8(2):211-3.

  In December 2000, an infectious disease spread through a captive breeding group of African wild dogs (Lycaon pictus) in Tanzania, killing 49 of 52 animals within 2 months. The causative agent wasIn December 2000, an infectious disease spread through a captive breeding group of African wild dogs (Lycaon pictus) in Tanzania, killing 49 of 52 animals within 2 months. The causative agent was identified as Canine distemper virus (CDV) by means of histologic examination, virus isolation, reverse transcriptase-polymerase chain reaction analysis, and nucleotide sequencing. This report emphasizes the importance of adequate protection against infectious diseases for the successful outcome of captive breeding programs of endangered species.