Epidemiology and public health significance of "Norovirus" in Switzerland

Epidemic and sporadic gastroenteritis is an important public health problem in both highincome
and low-income countries. In the last 30 years, several viruses have been identified as
etiological agents of gastroenteritis in humans. Outbreaks of gastroenteritis may be caused by
rotaviruses, astroviruses, adenoviruses and the human caliciviruses. The human caliciviruses
are assigned to two genera, the Norovirus (NV) and Sapovirus (SV). The NV cause illness in
people of all age groups, whereas the SV predominantly cause illness in children. Epidemic
viral gastroenteritis or “winter vomiting disease” was described as early as 1929 but it took
over 40 years to the discovery of the Norwalk virus using immune electron microscopy (IEM)
in faecal samples in 1972. These specimens were collected during an outbreak of acute
gastroenteritis which occurred in 1968 in an elementary school in Norwalk, Ohio, USA.
Following an incubation period of approximately 1-2 days, persons infected with NV develop
the main symptoms of projectile vomiting and diarrhoea, accompanied by rather unspecific
symptoms like abdominal cramps, muscle pain, headache and in some cases low-grade fever.
The illness generally is considered mild and self-limiting, with symptoms lasting in the mean
2-3 days. The potential of the NV to rise outbreaks with attack rates ranging between 30-90%
is massive. This can be explained mainly by the high infectivity and environmental stability
and by the facilitated spread of NV either by contaminated fomites (such as food and water)
and environment, or directly from person-to-person. The faecal-oral route is described to be
the most common route of transmission. Recent international studies have shown that NV
infections are the most frequent cause of gastroenteritis in the community regarding the
endemic and the epidemic situation. These viruses account for an estimated 6% and 11% of
all infectious intestinal diseases in England and The Netherlands, respectively, and for an
estimated 23 million cases in the United States each year. In the past ten years, NV-outbreaks
were increasingly recognised in Switzerland. However, reliable epidemiological data were
missing due to the fact that NV are not routinely searched for in diagnostic laboratories and
there is no obligation to report known cases.
For this reason, the Swiss Federal Office of Public Health (SFOPH) launched a series of
studies for a first epidemiological assessment of the situation of the NV in Switzerland.
Within this program, several studies (also within the frame of this thesis) were conducted.
Three main study designs were used during this thesis: firstly, a NV screening of
bacteriological-negative tested patient stool samples, secondly, a general practitioner (GP)
based case-control study on sporadic NV infections and thirdly, a systematic compilation of
epidemiological information on NV outbreaks from the whole country and the conducting of
separate outbreak investigations.
The screening for the presence of NV in previously analysed human stool samples at least
negative for Campylobacter spp., Shigella spp. and Salmonella spp. from July 2001 to July
2003 revealed that 17.9% (125) of totally 699 stool samples tested positive for NV by RTPCR.
Additionally, a winter seasonality could be observed within both years under study. The
highest rate of NV-positives (38.3%) was detected in the first quarter 2002. The time trend of
the positivity-rate has to be seen in the context of a newly emerged variant of NV thought to
possess certain characteristics like a higher virulence and/or a higher environmental stability
than the previous circulating NV. Parallel to the mentioned study, a second screening was
carried out to assess the importance of NV mix-infections. Only in one specimen of totally
132 bacteriologically-positive stool samples from gastroenteritis patients NV were detected.
The GP-based case-control study was performed between July 2001 and July 2003 in the
German speaking part of Switzerland in order to identify risk factors for sporadic NV
infections. Different transmission modes under study, e.g. the consumption of certain
foodstuff and mineral waters, displayed no measurable risk association. These findings are
consistent with person-to-person transmission as the most important route of transmission for
community-acquired, sporadic NV infection, in that 39% of all patients reported they had had
contact with ill persons before their illness. The fact that 33% reported contact with ill
persons, mainly within family groups, after their own illness suggested that a substantial
proportion of patients were part of family mini-outbreaks.
Between 2001 and 2003, a study was launched to compile actively and systematically NV
outbreak information, mostly from the German speaking part of the country. In total, 73 NVoutbreaks
were registered. Most affected were closed settings, like nursing homes (34% of all
outbreaks) and hospitals (25%). Transmission pathways were identified in 74% of the
outbreaks. In 81% of these cases person-to-person transmission was the primary route of
infection and on seven occasions (13%), a foodborne transmission was the possible cause.
Finally, a broad phylogenetic analysis of the human NV sequences solely and in comparison
with NV sequences obtained from a recent mineral water study and from an oyster screening
in Switzerland was conducted. 63 of the 74 (85%) human NV sequences belonged to NV
Genogroup II and a temporal clustering was observed within the NV sequences,
corresponding to the described emergence of a new NV Genogroup II variant. The
phylogenetic comparison revealed that the NV sequences derived from mineral waters were
highly related and clustered predominantly separate to the human NV sequences. However,
single human NV sequences were also found within the mineral water clusters. Additionally,
a temporal correlation between the dates of the stool specimen with the period of bottling of
the mineral waters was observed. The oyster sequences displayed a far greater variability and
no specific clustering with either mineral water or human NV sequences was found.
The results from the present studies – together with the findings from earlier Swiss studies in
the field of the NV – allowed for the first time the generation of an overview on the current
epidemiological situation of the NV in Switzerland.