Gábor Reuter

Norovirus illness is a global problem: emergence and spread of norovirus GII.4 variants, 2001-2007.

BACKGROUND Noroviruses (NoVs) are the most common cause of viral gastroenteritis. Their high incidence and importance in health care facilities result in a great impact on public health. Studies from around the world describing increasing prevalence have been difficult to compare because of differing nomenclatures for variants of the dominant genotype, GII.4. We studied the global patterns of GII.4 epidemiology in relation to its genetic diversity. METHODS Data from NoV outbreaks with dates of onset from January 2001 through March 2007 were collected from 15 institutions on 5 continents. Partial genome sequences (n=775) were collected, allowing phylogenetic comparison of data from different countries. RESULTS The 15 institutions reported 3098 GII.4 outbreaks, 62% of all reported NoV outbreaks. Eight GII.4 variants were identified. Four had a global distribution--the 1996, 2002, 2004, and 2006b variants. The 2003Asia and 2006a variants caused epidemics, but they were geographically limited. Finally, the 2001 Japan and 2001 Henry variants were found across the world but at low frequencies. CONCLUSIONS NoV epidemics resulted from the global spread of GII.4 strains that evolved under the influence of population immunity. Lineages show notable (and currently unexplained) differences in geographic prevalence. Establishing a global NoV network by which data on strains with the potential to cause pandemics can be rapidly exchanged may lead to improved prevention and intervention strategies.

Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant

BACKGROUND Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. METHODS We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. FINDINGS Three regions (England and Wales, Germany, and the Netherlands) had sustained epidemiological and viral characterisation data from 1995 to 2002. In all three, we noted a striking increase in norovirus outbreaks in 2002 that coincided with the detection and emergence of a new predominant norovirus variant of genogroup II4, which had a consistent mutation in the polymerase gene. Eight of nine regions had an annual peak in 2002 and the new genogroup II4 variant was detected in nine countries. Also, the detection of the new variant preceded an atypical spring and summer peak of outbreaks in three countries. INTERPRETATION Our data from ten European countries show a striking increase and unusual seasonal pattern of norovirus gastroenteritis in 2002 that occurred concurrently with the emergence of a novel genetic variant. In addition to showing the added value of an international network for viral gastroenteritis outbreaks, these observations raise questions about the biological properties of the variant and the mechanisms for its rapid dissemination.

Analysis of Integrated Virological and Epidemiological Reports of Norovirus Outbreaks Collected within the Foodborne Viruses in Europe Network from 1 July 2001 to 30 June 2006

ABSTRACT The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

Emergence of a novel GII.17 norovirus – end of the GII.4 era?

In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.

Characterization and zoonotic potential of endemic hepatitis E virus (HEV) strains in humans and animals in Hungary.

BACKGROUND Hepatitis E virus (HEV) is a common cause of acute, fecally transmitted hepatitis in developing countries. Identification of HEV in indigenous human infection and in domestic pig raising the possibility that HEV infection is also a zoonosis. OBJECTIVES/STUDY DESIGN Molecular detection and epidemiology of HEV in humans (South-East Hungary) with acute hepatitis and in domestic (pig, cattle) and wild (boar and roe-deer) animals (countrywide) by ELISA and RT-PCR. RESULTS Between 2001 and 2006, a total of 116 (9.6%) of 1203 human sera were positive by HEV IgM ELISA and 13 (24.5%) of 53 samples were also confirmed by RT-PCR and sequencing. Forty-two (27.3%) of 154, 11 (34.4%) of 32 and 9 (12.2%) of 74 samples were RT-PCR-positive from swine (feces: 22.7%; liver: 30.8%), roe-deer (liver) and wild boar (liver), respectively. Except for an imported infection caused by genotype 1, 19 sequences (human: 12, swine: 4, roe-deer: 1, wild boar: 2) belong to genotype 3 HEV. Genetically identical strains were detected in human and roe-deer and in 2 other human clusters. CONCLUSIONS HEV is an endemic agent in Hungary. Consumption of raw or undercooked meat-products is one of the possible sources of the indigenous HEV infections. Cross-species infection with genotype 3 HEV potentially involves a food-borne transmission route in Hungary.

Kobuviruses - a comprehensive review.

Kobuviruses are members of the large and growing family Picornaviridae. Until now, two official, Aichi virus and Bovine kobuvirus, and one candidate kobuvirus species, ‘porcine kobuvirus’, have been identified in human, cattle and swine, respectively. In addition, kobu‐like viruses were detected very recently in the bat. Aichi virus could be one of the causative agents of gastroenteritis in humans, and kobuviruses probably also cause diarrhoea in cattle and swine. Although Aichi virus has been detected relatively infrequently (0–3%) in human diarrhoea, high seroprevalence, up to 80–95% at the age of 30–40, was found indicating the general nature of infection in different human populations. In the previous years, much new information has accumulated relating to kobuviruses and their host species. This review summarises the current knowledge on kobuviruses including taxonomy, biology and viral characteristics, and covers all aspects of infection including epidemiology, clinical picture, host species diversity, laboratory diagnosis and it gives a summary about possible future perspectives. Copyright

Emergence of new norovirus variants on spring cruise ships and prediction of winter epidemics.

In June 2006, reported outbreaks of norovirus on cruise ships suddenly increased; 43 outbreaks occurred on 13 vessels. All outbreaks investigated manifested person-to-person transmission. Detection of a point source was impossible because of limited investigation of initial outbreaks and data sharing. The most probable explanation for these outbreaks is increased norovirus activity in the community, which coincided with the emergence of 2 new GGII.4 variant strains in Europe and the Pacific. As in 2002, a new GGII.4 variant detected in the spring and summer corresponded with high norovirus activity in the subsequent winter. Because outbreaks on cruise ships are likely to occur when new variants circulate, an active reporting system could function as an early warning system. Internationally accepted guidelines are needed for reporting, investigating, and controlling norovirus illness on cruise ships in Europe.

Sequence heterogeneity among human picobirnaviruses detected in a gastroenteritis outbreak

Summary. Human picobirnaviruses characterised in this study were serendipitously detected in a non-bacterial gastroenteritis outbreak when specimens were examined for the presence of human rotaviruses using polyacrylamide gel electrophoresis. Of ten stool samples sent for virological examination, two, three, and one specimens were positive for human caliciviruses, picobirnaviruses, and both viruses, respectively. Partial sequences of the RNA-dependent RNA polymerase gene were determined for three picobirnavirus-positive samples. The sequence identity among these three strains was 60% to 65% for the nucleic acid and 64% to 70% for the deduced amino acid sequences. Phylogenetic analysis revealed that each of the three strains clustered with strains identified in geographically separate areas. In contrast, human calicivirus strains co-incidentally identified, showed complete nucleotide sequence identity. These findings demonstrate a lack of common exposure to or point of source for picobirnavirus infection, suggesting that the outbreak was caused by human caliciviruses. Further studies are needed to determine the etiologic role and to establish the taxonomic basis of picobirnaviruses.

The Viruses of Wild Pigeon Droppings

Birds are frequent sources of emerging human infectious diseases. Viral particles were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We identified sequences from known and novel species from the viral families Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae, and Caliciviridae (listed in decreasing number of reads), as well as plant and insect viruses likely originating from consumed food. The near full genome of a new species of a proposed parvovirus genus provisionally called Aviparvovirus contained an unusually long middle ORF showing weak similarity to an ORF of unknown function from a fowl adenovirus. Picornaviruses found in both Asia and Europe that are distantly related to the turkey megrivirus and contained a highly divergent 2A1 region were named mesiviruses. All eleven segments of a novel rotavirus subgroup related to a chicken rotavirus in group G were sequenced and phylogenetically analyzed. This study provides an initial assessment of the enteric virome in the droppings of pigeons, a feral urban species with frequent human contact.

Detection of hepatitis E virus in samples of animal origin collected in Hungary.

Hepatitis E virus (HEV) is an enterically transmitted human pathogen. HEV infections are mainly associated with acute, self-limited, icteric hepatitis with an average mortality rate of 1%. Animal reservoirs are considered to play an important role in the maintenance of the virus and in the spread of HEV to humans. HEV-induced seroconversion was described in several species, however clinical hepatitis in animals has not been observed to date. HEV strains from animals are genetically closely related to human HEV isolates, which supports the opinions on the zoonotic transmission of the virus. In this expansive study the occurrence of HEV was investigated in Hungarian wild and domesticated animal samples. HEV RNA was detected by reverse transcription-polymerase chain reaction in liver samples of wild boars, roe deer, and deer. The investigations of domestic swine samples detected HEV in 39% of the investigated Hungarian pig farms. Simultaneous investigation revealed no definite difference between liver and faeces samples of domestic pigs in the frequency of HEV positivity. The highest (36%) incidence of HEV infection was found among the 11-16-week-old pigs. Samples from domestic cattle and rodents collected in pig farms, forests and meadows were tested negative for HEV RNA. Phylogenetic analysis of partial sequences amplified within the ORF1 and ORF2 regions of selected strains revealed that the detected viruses belong to three subgroups of the third genogroup of HEV, and are closely related to human and swine HEV strains detected in different countries. The investigations revealed widespread distribution of HEV in Hungarian wild ungulate and domesticated swine populations, with considerable genetic diversity among the strains.