http://repub.eur.nl/res/aut/34192/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39195/ 2012-02-05T00:00:00Z Following an increase in detection of enterovirus 68 (EV68) in community surveillance of respiratory infections in The Netherlands in 2010, epidemiological and virological analyses were performed to investigate the possible public health impact of EV68 infections. We retrospectively tested specimens collected from acute respiratory infections surveillance and through three children cohort studies conducted in The Netherlands from 1994 through 2010. A total of 71 of 13,310 (0.5%) specimens were positive for EV68, of which 67 (94%) were from symptomatic persons. Twenty-four (34%) of the EV68 positive specimens were collected during 2010. EV68-positive patients with respiratory symptoms showed significantly more dyspnea, cough and bronchitis than EV68-negative patients with respiratory symptoms. Phylogenetic analysis showed an increased VP1 gene diversity in 2010, suggesting that the increased number of EV68 detections in 2010 reflects a real epidemic. Clinical laboratories should consider enterovirus diagnostics in the differential diagnosis of patients presenting with respiratory symptoms. http://repub.eur.nl/res/pub/30802/ 2012-01-06T00:00:00Z Viruses belonging to the family Picornaviridae are small, non-enveloped viruses with a single-stranded, positive-sense RNA genome. Up to present, thirteen genera within this large family have been designated by the International Committee on Taxonomy of Viruses: Aphtovirus, Erbovirus, Teschovirus, Sapelovirus, Senecavirus, Tremovirus, Avihepatovirus, Cardiovirus, Hepatovirus, Cosavirus, Parechovirus, Kobuvirus and Enterovirus (Fig. 1). Members within the latter six genera have been reported to cause human disease. Enteroviruses are, next to viruses of the Herpesviridae family, the major viral cause of neurologic disease with a known etiology in humans, including meningitis, encephalitis and acute flaccid paralysis (24, 38, 47). By that they form a serious threat for human health. A well known representative of these is poliovirus (species Human enterovirus C), which has inextricably been associated with large outbreaks of neurologic disease in children. This thesis will focus on prevalence and genetic diversity of human enteroviruses (belonging to species A to D) in the context of poliovirus eradication. http://repub.eur.nl/res/pub/34488/ 2011-07-01T00:00:00Z Evolutionary history of human enterovirus 71 (EV71) in the Netherlands shows displacement of virus subgenogroups, that only partly can be explained by antigenic changes. Additionally, occasional epidemics have occurred that remain to be explained. Previous studies have shown subgenogroup specific recombination events in the genome of Asian EV71 strains. To find clues on the role of genome recombination in evolution of the EV71 subgenogroups found in Europe and in the evolution of strains capable of causing outbreaks, we analyzed the genomes of 19 strains representing the genetic diversity of EV71 in the Netherlands between 1963 and 2010. We selected viruses from EV71 endemic and epidemic years (1986 and 2007). Subgenogroup specific genome recombination events were detected for subgenogroup B0, B1 and B2 viruses, in line with observed genome recombination events in Asian subgenogroup B3 and B4 viruses. Considering recombination events distinguishing strains from epidemic years from those of non-epidemic years, breakpoints for recombination were detected in the 5′UTR of B2 viruses from the outbreak in 1986, with highest similarity of the 5′UTR to B4 and B3 strains isolated during outbreaks in the Asian Pacific region. No indications for recombination were found in genogroup C isolates. Except for the '86 B2 isolates' Dutch isolates phylogenetically interspersed with international reference strains of the same subgenogroup, indicating a global dissemination of (recombinant) EV71 viruses. The difference observed in the 5′UTR of EV71 strains isolated in endemic versus epidemic years suggests that changes in the 5′UTR cause evolution of strains capable of causing outbreaks. http://repub.eur.nl/res/pub/27377/ 2010-08-01T00:00:00Z From 1963 to 1986, human enterovirus 71 (HEV71) infections in the Netherlands were successively caused by viruses of subgenogroups B0, B1 and B2. A genogroup shift occurred in 1987, after which viruses of subgenogroups C1 and C2 were detected exclusively. This is in line with HEV71 typing in Australia, Europe and the USA, but is distinct from that in the Asian Pacific region, where HEV71 subgenogroups B3-B5 and C4-C5 have caused large outbreaks since 1997. To understand these observations in HEV71 epidemiology, the VP1-encoding regions of 199 HEV71 strains isolated in the Netherlands between 1963 and 2008 were used to study the detailed evolutionary trajectory and population dynamics of HEV71. Genogroup B viruses showed an epochal evolution, whereas genogroup C viruses evolved independently, which is in line with the co-circulation of C1 and C2 viruses in the Netherlands since 1997. Considering that strains from the Netherlands are interspersed phylogenetically with GenBank reference strains, the evolution of B1-B2, C1-C2 viruses has a global nature. Phylodynamic analysis confirmed that increased reporting of HEV71 infections in 1986 and 2007 reflected true epidemics of B2 and C2 viruses, respectively. Sequence analysis of the complete capsid region of a subset of isolates revealed several (sub)genogroup-specific residues. Subgenogroup B2-specific rabbit antiserum showed cross-neutralization of B0, B1 and B2 viruses, but not of subgenogroup C1 or C2 viruses, probably explaining the global shift to genogroup C in 1987 following a B2 epidemic. Anti-C1 rabbit serum neutralized both genogroup B and C viruses. Global herd immunity against C1 and C2 viruses possibly explains why epidemics with subgenogroups B4 and C4 are restricted to the Asian Pacific region. http://repub.eur.nl/res/pub/25245/ 2009-09-22T00:00:00Z For the final stages in the eradication of poliovirus type 1 (P1), the World Health Organization advocates the selective use of monovalent type 1 oral poliovirus vaccine (mOPV1). To compare the immunogenicity of mOPV1 with that of trivalent OPV (tOPV) in infants, a study was performed in Egypt in 2005. Newborns were vaccinated with mOPV1 or tOPV immediately after birth and were challenged with mOPV1 after 1 month. Vaccination with mOPV1 at birth resulted in significantly higher seroconversion against P1 viruses and lower excretion of P1 viruses than vaccination with tOPV. Intratypic differentiation of the viruses shed by the newborns revealed the presence of remarkably high numbers of antigenically divergent (AD) P1 isolates, especially in the mOPV1 study group. The majority of these AD P1 isolates (71%) were mOPV1 challenge derived and were shed by newborns who did not seroconvert to P1 after the birth dose. Genetic characterization of the viruses revealed that amino acid 60 of the VP3 region was mutated in all AD P1 isolates. Isolates with substitution of residue 99 of the VP1 region had significantly higher numbers of nonsynonymous mutations in the VP1 region than isolates without this substitution and were preferentially shed in the mOPV1 study group. The widespread use of mOPV1 has proven to be a powerful tool for fighting poliovirus circulation in the remaining areas of endemicity. This study provides another justification for the need to achieve high vaccination coverage in order to prevent the circulation of AD strains. Copyright http://repub.eur.nl/res/pub/25237/ 2009-09-01T00:00:00Z The incidence of enterovirus 71 (EV71) infection has greatly increased in the Asian Pacific region since 1997. Several large outbreaks, caused by different subgenogroups of EV71, occurred with high rates of morbidity and a substantial number of deaths. In 2007, 58 cases of EV71 infection requiring hospitalization were reported in The Netherlands after a period of low endemicity of 21 years. These events triggered a study on the epidemiology of EV71 in The Netherlands. Genetic analysis of the VP1 capsid region of 199 EV71 isolates collected from 1963 to 2008 as part of enterovirus surveillance activities revealed a change in the prevailing subgenogroups over time. From 1963 to 1986 infections were caused by three different and successive lineages belonging to subgenogroup B (the novel lineage designated B0, as well as B1 and B2). In 1987, following a major epidemic the previous year, the B genogroup was replaced by genogroup C strains of lineages C1 and, later, C2. Analyses of the clinical data suggested that there were differences between infection with genogroup B and with genogroup C strains in terms of the age groups affected and the severity of illness. From comparative analysis with genomic data available in the public domain, we concluded that EV71 strain evolution shows a global pattern, which leads to the question of whether the recently emerged C4 lineage strains will also spread outside of Asia. Copyright http://repub.eur.nl/res/pub/29004/ 2008-09-01T00:00:00Z Infection with human parechovirus 3 (HPeV3) was described for the first time in Japan in 2004 and reportedly is more often associated with severe disease than infection with HPeV1 or HPeV2. In 2004, infections with HPeV3 were observed for the first time in The Netherlands. Genetic analysis showed several different lineages, suggesting endemic circulation. We analyzed 163 cell culture isolates from the same number of patients tested in routine virological laboratories as part of the national enterovirus surveillance program. Isolates were collected between 2000 and 2007 and could not be characterized by routine methods. In total, 155 isolates (95%) were found positive for HPeV by a reverse transcription-PCR assay targeting the 5′ untranslated region, explaining the majority of the diagnostic deficit in enterovirus surveillance for these years. Typing of the isolates by use of partial genome sequencing of the VP1/2A region revealed the presence of 55 HPeV1, 2 HPeV2, 89 HPeV3, 1 HPeV4, and 8 HPeV5 isolates. We compared isolation dates, age groups affected, and clinical pictures, which were reported as part of the routine surveillance. Clear differences in epidemiology were observed, with HPeV3 occurring at intervals of 2 years and in the spring-summer season, whereas HPeV1 was observed in small numbers throughout each year, with a low in the summer months. HPeV3 infection affected younger children than HPeV1 infection and was significantly more often associated with fever, meningitis, and viremia. Copyright