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1.  Neuralgic amyotrophy and hepatitis E virus infection 
Neurology  2014;82(6):498-503.
To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection.
HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011–2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004–2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR).
Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome.
Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms.
PMCID: PMC3937863  PMID: 24401685
2.  Small risk of developing symptomatic tick-borne diseases following a tick bite in the Netherlands 
Parasites & Vectors  2011;4:17.
In The Netherlands, the incidence of Lyme borreliosis is on the rise. Besides its causative agent, Borrelia burgdorferi s.l., other potential pathogens like Rickettsia, Babesia and Ehrlichia species are present in Ixodes ricinus ticks. The risk of disease associated with these microorganisms after tick-bites remains, however, largely unclear. A prospective study was performed to investigate how many persons with tick-bites develop localized or systemic symptoms and whether these are associated with tick-borne microorganisms.
In total, 297 Ixodes ricinus ticks were collected from 246 study participants who consulted a general practitioner on the island of Ameland for tick bites. Ticks were subjected to PCR to detect DNA of Borrelia burgdorferi s.l., Rickettsia spp., Babesia spp. or Ehrlichia/Anaplasma spp.. Sixteen percent of the collected ticks were positive for Borrelia burgdorferi s.l., 19% for Rickettsia spp., 12% for Ehrlichia/Anaplasma spp. and 10% for Babesia spp.. At least six months after the tick bite, study participants were interviewed on symptoms by means of a standard questionnaire. 14 out of 193 participants (8.3%) reported reddening at the bite site and 6 participants (4.1%) reported systemic symptoms. No association between symptoms and tick-borne microorganisms was found. Attachment duration ≥24 h was positively associated with reddening at the bite site and systemic symptoms. Using logistic regression techniques, reddening was positively correlated with presence of Borrelia afzelii, and having 'any symptoms' was positively associated with attachment duration.
The risk of contracting acute Lyme borreliosis, rickettsiosis, babesiosis or ehrlichiosis from a single tick bite was <1% in this study population.
PMCID: PMC3050846  PMID: 21310036
3.  Changes in Small Intestinal Homeostasis, Morphology, and Gene Expression during Rotavirus Infection of Infant Mice 
Journal of Virology  2003;77(24):13005-13016.
Rotavirus is the most important cause of infantile gastroenteritis. Since in vivo mucosal responses to a rotavirus infection thus far have not been extensively studied, we related viral replication in the murine small intestine to alterations in mucosal structure, epithelial cell homeostasis, cellular kinetics, and differentiation. Seven-day-old suckling BALB/c mice were inoculated with 2 × 104 focus-forming units of murine rotavirus and were compared to mock-infected controls. Diarrheal illness and viral shedding were recorded, and small intestinal tissue was evaluated for rotavirus (NSP4 and structural proteins)- and enterocyte-specific (lactase, SGLT1, and L-FABP) mRNA and protein expression. Morphology, apoptosis, proliferation, and migration were evaluated (immuno)histochemically. Diarrhea was observed from days 1 to 5 postinfection, and viral shedding was observed from days 1 to 10. Two peaks of rotavirus replication were observed at 1 and 4 days postinfection. Histological changes were characterized by the accumulation of vacuolated enterocytes. Strikingly, the number of vacuolated cells exceeded the number of cells in which viral replication was detectable. Apoptosis and proliferation were increased from days 1 to 7, resulting in villous atrophy. Epithelial cell turnover was significantly higher (<4 days) than that observed in controls (7 days). Since epithelial renewal occurred within 4 days, the second peak of viral replication was most likely caused by infection of newly synthesized cells. Expression of enterocyte-specific genes was downregulated in infected cells at mRNA and protein levels starting as early as 6 h after infection. In conclusion, we show for the first time that rotavirus infection induces apoptosis in vivo, an increase in epithelial cell turnover, and a shutoff of gene expression in enterocytes showing viral replication. The shutoff of enterocyte-specific gene expression, together with the loss of mature enterocytes through apoptosis and the replacement of these cells by less differentiated dividing cells, likely leads to a defective absorptive function of the intestinal epithelium, which contributes to rotavirus pathogenesis.
PMCID: PMC296055  PMID: 14645557
4.  Genetic Basis for Immunological Aberrations in Poliovirus Sabin Serotype 3 Strains Imported in The Netherlands 
Journal of Clinical Microbiology  1999;37(8):2393-2398.
During the characterization of poliovirus type 3 strains imported in The Netherlands, Sabin serotype 3 strains that reacted with both specific antisera against Sabin-like (vaccine) and non-Sabin-like (wild-type) strains by the intratypic strain differentiation assay have been found. The present study was done to determine the pathogenic potential of these virus strains for humans. Characterization of these so-called double-reactive strains with neutralizing monoclonal antibodies (MAbs) against the major antigenic sites of serotype 3 Sabin virus led to the identification of two groups with different antigenic properties. Six of the seven strains were resistant to neutralization with MAbs against sites 2B and 3B and one strain was neutralized by all the MAbs in a manner similar to that for the Sabin serotype 3 virus. Partial sequencing of the coding regions confirmed the antigenic changes for all six antigenically distinct strains. By inoculation of these viruses into transgenic mice which express the human poliovirus receptor, one strain was identified as highly neurovirulent, three were identified as intermediate, and three were identified as attenuated. Sera from vaccinated persons efficiently neutralized the mutants. Our data suggest that some double-reactive strains are a potential risk to the unvaccinated community but not to the vaccinated population.
PMCID: PMC85236  PMID: 10405373

Results 1-4 (4)