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Introduction
Norwalk-like virus (NLV or Small Round Structured Virus, renamed Norovirus
in 2002 (1)) is increasingly recognised as a cause of sporadic and epidemic
viral gastroenteritis. The clinical syndrome caused by NLV was first
described in 1929 (2). The causative agent, a small RNA virus, classified
as a human enteric calicivirus, was identified by electron microscopy
in 1972, from clinical samples taken in 1968 during a school outbreak
of gastroenteric illness in Norwalk, Ohio, United-States of America
(3). The Norwalk-like virus is distributed widely in nature; its only
known reservoir is human (4). The virus causes a relatively typical
illness characterised by sudden-onset, forceful vomiting and nausea
with variable amounts of mild diarrhoea (5). These gastrointestinal
symptoms may be associated with fever, myalgia and headache. The incubation
period varies from 15 to 50 hours and the mean duration is between 12
and 60 hours. Transmission has been demonstrated through food (in particular
raw shellfish), through water, ice, by person-to-person transmission,
and through aerosolisation of viral particles (6,7).
Background
On the morning of Sunday 27 January 2002 (11.30 am), an airplane carrying
ill holidaymakers returning from Andorra landed in Dublin, Ireland.
Many of the passengers had gastrointestinal symptoms. Emergency services
were alerted, and were in place to meet the plane on arrival. The flight,
coming from Toulouse, France, carried holidaymakers who had spent the
week from 20 to 27 January on a skiing holiday in Andorra. A second
flight from Toulouse, also carrying holidaymakers returning from Andorra
with the same tour operator, landed in Belfast, Northern Ireland, two
hours after the Dublin flight. Many of the passengers on board of this
flight were also ill. The principal symptoms described were vomiting
and diarrhoea. Initial interviews suggested that the illness was sudden
in onset and short in duration. At that stage no information about cases
of illness in Andorra was available. The National Disease Surveillance
Centre (NDSC) in Ireland and the Communicable Disease Surveillance Centre-Northern
Ireland (CDSC - NI) initiated a joint investigation in order to identify
the possible source and the vehicle of the infection.
Materials and Methods
Case definition
A case was defined as a passenger travelling on one of the two flights
from Andorra, who holidayed in Andorra from 20 to 27 January 2002, and
developed nausea, vomiting or diarrhoea (at least three loose stools
per day for 24 hours) at least 48 hours after arrival in Andorra, or
within 48 hours of return.
Case finding methods
The lists of passengers travelling on the two flights were obtained
from the tour operator. A questionnaire was mailed to passengers four
days after their arrival home in Ireland, in order to collect information
on the following: demographic details, holiday accommodation details
in Andorra (town and type of accommodation), symptoms of gastrointestinal
illness while on holiday, time of onset and duration of symptoms, contact
with other ill persons during the three days prior to the onset of illness,
food items consumed during the last three days of holidays or during
the three days preceding the onset of illness and place of consumption,
consumption habits and use of water during the holiday, whether the
family doctor was contacted because of the illness, whether hospitalisation
was required and length of hospital stay if admitted, and laboratory
results if a sample was taken.
The Andorran health authorities were informed about the outbreak and
it was suggested an active case finding be carried out in Andorra.
Analytical study design
A retrospective cohort study among passengers of the two charter flights
was conducted in order to identify any potential vehicle and the mode
of transmission of the infection in this outbreak.
Definition of exposure
As the outbreak occurred among holidaymakers travelling to Andorra,
the exposure was investigated in terms of water use and water consumption.
Travellers were also asked about food items consumed within 72 hours
before becoming ill and about the place of food consumption. No detail
about the amount of water or food consumed was collected.
Secondary transmission
To investigate secondary transmission of the disease we focused on
cases which occurred before and after the landing both in Belfast and
in Dublin.
Laboratory investigation
Microbiological investigation was performed on two samples from Andorran
holidaymakers living in the Eastern Region of the Republic of Ireland.
Stool specimens were tested for NLV using two different reverse transcriptase
polymerase chain reaction (RT–PCR) methods (8,9).
Statistical analysis
Attack rates, relative risks (RR), and 95% confidence intervals (CI)
were computed using EpiInfo software (version 6.04d) (10). Confounding
factors were assessed through logistic regression using SPSS package
(version 10.1.0 for Windows) (11).
Results
Epidemiological data
Over a total of 350 questionnaires sent, 234 (67%) were returned (table
1). The respondents were mainly young males (61%) with a mean age of
30.5 years [range 1 to 72 years]. An illness was reported in the questionnaire
by 95 travellers (41%) among whom 71 (75%) met the case definition (overall
attack rate: 30% (71/234)).
Table 1. Outbreak of gastroenteritis among travellers to Andorra,
study characteristics. January-February 2002
| |
Nombre / Number
|
Pourcentage / Percent
|
|
Cohorte des voyageurs / Traveller’s cohort
|
350
|
100
|
|
Vol de Dublin / Dublin flight
|
173 / 350
|
49
|
|
Vol de Belfast / Belfast flight
|
177 / 350
|
51
|
|
Personnes interviewées (taux de réponse) / Interviewed
(response rate)
|
234 / 350
|
67
|
|
Personnes malades / Ill people
|
95 / 234
|
41
|
|
Définition de cas remplie (population de l’étude)
/ Met Case Definition (study population)
|
71 / 95
|
75
|
|
Taux d’attaque global / Overall attack rate
|
71 / 234
|
30
|
Date and time of onset of illness for the 71 cases were collected.
The results showed a small number of cases occurred during the first
five days of the stay in Andorra, but most of the cases (37/71) occurred
on 27 January (figure 1). The number of cases subsequently decreased
dramatically. A small cluster seemed to have occurred on 23 January.
Data on date and time of onset were stratified by town of accommodation.
Most of cases occurring on 27 January (32/37) developed the disease
in Soldeu (figures 2 to 5).
Two travellers developed symptoms on 21 January, two on 22 and thirteen
after the 29 January. These travellers were not included in the analysis
as they did not meet the case definition.
Women (n=92) were 1.8 times (95% CI [1.23–2.62]) more likely to be
a case than men. The attack rate was lower in the age group 0-19, and
similar among other age groups (table 2).
Table 2. Age and sex specific attack rates of gastroenteritis (n=
71) among travellers to Andorra. January – February 2002
| |
Répondants
Respondents
|
Cas / Cases
|
Taux d’attaque (%)
Attack Rate° (%)
|
RR (IC 95%)
RR (95% CI)
|
|
Tous les cas / All cases
|
234
|
71
|
30
|
|
|
Sexe / Sex
|
|
|
|
|
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Femmes / Female
|
92
|
39
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42
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1.8 (1.2 – 2.6)
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Hommes / Male
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142
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32
|
22
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reference
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|
Groupe d’âge (années) /
Age class (years)
|
|
|
|
|
|
0 – 19
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28
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6
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21
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reference
|
|
20 – 29
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84
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28
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33
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1.4 (0.7 – 3.1)
|
|
30 – 39
|
74
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26
|
35
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1.5 (0.7 – 3.3)
|
|
>= 40
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32
|
11
|
34
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1.5 (0.6 – 3.5)
|
The main symptoms of cases were nausea (85%), vomiting (78%), diarrhoea
(74%), and abdominal pain (52%). Other symptoms included shivering (47%),
pyrexia (44%), headache (31%) and bloody diarrhoea (4%).
The duration of illness ranged from 10 hours to 11 days with a median
of 48 hours.
Geographical results
Among the respondents who gave details on the type of accommodation
(221/234 = 94%), 157 (71%) had stayed in hotels on their holiday, and
64 (29%) had chosen self-catering apartments. Respondents who gave information
on the town of accommodation (n=227) had stayed mainly in four Andorran
towns: Arinsal (19%, 42/227), El Tartar (12%, 27/227), Pas de la Casa
(38%, 86/227), and Soldeu (31%, 70/227).
Travellers who chose to stay in self-catering apartments were 1.5 times
more likely to be cases than those who stayed in hotels (95% CI [1.04–2.22]).
Travellers who stayed in Soldeu were 6.5 times more likely to be cases
than travellers in other towns (95% CI [3.44 – 12.25]) (table 3).
Table 3. Attack rates of gastroenteritis among travellers to Andorra,
by type and town of accommodation (n=71). January – February 2002
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Type d’hébergement Type of accommodation*
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Répondants
Respondents
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Cas
Cases
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Taux d’attaque (%)
Attack Rate (%)
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RR (IC 95%)
RR (95% CI)
|
|
Hôtel / Hotel
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144
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42
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29
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reference
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Appartements en location
Self – catering apartments
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61
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27
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44
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1.5 (1 – 2.2)
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Ville d’hébergement / Town of accommodation
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|
|
|
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Arinsal
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37
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9
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24
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2.2 (1 – 5.1)
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El Tartar
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25
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6
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24
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2.2 (1 – 5.5)
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Pas de la Casa
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82
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9
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11
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reference
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Soldeu
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66
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47
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71
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6.5 (3.4 – 12.3)
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* Données disponibles pour 69/71 cas / Data available for 69/71
cases.
Potential vehicle of the outbreak
Trawling questionnaires on food specific exposures or other common
exposure did not reveal any information on common exposures. Ninety-seven
per cent of cases (n=69) drank bottled water, 21% (n=15) drank tap water,
13% (n=9) consumed water in jugs during their meals, and 76% of cases
(n=54) had ice in their drinks. The percentage of people who attended
a swimming pool was 26%. Ninety five percent of cases used tap water
for personal hygiene purposes (table 4).
Table 4.
Water use and water consumption specific attack rates of gastroenteritis
among travellers to Andorra. January – February 2002
| |
Consommé / Utilisé Consumed-Used
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Non consommé/Non utilisé
Not consumed/Not used
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RR (IC95%)
RR (95% CI)
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% cas exposés / % cases exposed
|
|
Consommation d’eau
Water consumption
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Cas
Cases
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Total
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TA (%)
AR(%)
|
Cas
Cases
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Total
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TA (%)
AR(%)
|
|
|
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Eau minérale Bottled water
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69
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203
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34
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2
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12
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16
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2 (0.6 – 7.3)
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97
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Eau du robinet
Tap water
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15
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60
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25
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56
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155
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36
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0.7 (0.4 – 1.1)
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21
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Glaçons dans les boissons
Ice cubes in drinks
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54
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136
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39
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17
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79
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21
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1.9 (1.2 – 3)
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76
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Eau en carafe sur les tables
Water in jugs on table
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9
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24
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37
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62
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191
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32
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1.2 (1 – 2)
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13
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Utilisation de l’eau / Water use
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Douche / Shower
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67
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202
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33
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4
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13
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31
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1.1 (0.5 – 2.5)
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94
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Dents / Teeth
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68
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202
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34
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3
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13
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23
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1.5 (0.5 – 4)
|
96
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Piscine /
Swimming pool
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19
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41
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46
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52
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174
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30
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1.5 (1 – 2.3)
|
26
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Travellers who had ice in their drinks were approximately 2 times more
likely to be a case than people who did not consume any ice (95% CI
[1.2–3]).
Travellers who used tap water for personal hygiene purposes (showering
and brushing teeth) were 1.1 times and 1.5 times respectively more likely
to become ill than those who did not (95% CI [0.5–2.5]; 95% CI [0.5–4]).
Travellers who consumed bottled water were 2 times more likely to be
cases (95% CI [0.6–7.3]). Travellers who used a swimming-pool were 1.5
times more likely to be cases than travellers who did not (95% [CI 1–2.3]).
Data were stratified by place of residence. Most cases (79%, 19/24)
occurring in other towns than Soldeu developed the disease after flights
arrived home in Ireland. Among residents in Soldeu, the attack rate
was higher among those who had ice in drinks than among those who did
not (RR = 2.3, 95% CI [1.3–4.2]). Travellers who consumed bottle water
were less likely to be a case than those who did not (RR = 0.7 [95%
CI 0.6–0.8]) (table 5).
Table 5. Risk factor specific attack rates for gastroenteritis
(n=47) among travellers staying in Soldeu. January – February 2002
| |
Consommé-Utilisé Consumed-Used
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Non consommé-Non utilisé
Not consumed-Not used
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RR (IC95%)
RR (95% CI)
|
% de cas exposés
% cases exposed
|
|
Consommation d’eau
Water consumption
|
Cas
Cases
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Total
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TA (%)
AR(%)
|
Cas Cases
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Total
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TA (%)
AR(%)
|
|
|
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Eau minéale / Bottled water
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46
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65
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71
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1
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1
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100
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0.7 (0.6-0.8)
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98
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Eau du robinet /
Tap water
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8
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10
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80
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39
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56
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69
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1.15 (0.8 – 1.6)
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17
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Glaçons dans les boissons /
Ice cubes in drinks
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40
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47
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85
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7
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19
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37
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2.3 (1.3 – 4.2)
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85
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Eau plate sur la table /
Water in jugs on table
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7
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9
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77
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40
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57
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70
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1.1 (0.7 - 1.6)
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15
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Utilisation de l’eau / Water use
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Douche / Shower
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46
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65
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71
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1
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1
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100
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0.7 (0.6 - 0.8)
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98
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Dents / Teeth
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46
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64
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72
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1
|
2
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50
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1.4 (0.4 – 5.8)
|
98
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Piscine /
Swimming pool
|
16
|
22
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73
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31
|
44
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70
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1.1 (0.7 – 1.4)
|
34
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Results from a logistic regression analysis showed that after adjusting
for sex, water consumption and use, ice consumption among those staying
in Soldeu was still strongly associated with the likelihood of being
ill (OR = 2.5, 95% CI [1.3–4.6)]) (table 6).
Table 6. Results from a logistic regression adjusting for sex, water
consumption and use among travellers staying in Soldeu, January-February
2002
| |
Odds ratio
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Intervalle de confiance à 95%
95% Confidence Interval
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Glaçons dans les boissons
Ice cubes in drinks
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2.5
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1.3 - 4.6
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Secondary transmission
To investigate secondary transmission of the disease we focused on
ice consumption among cases that occurred in Soldeu before and after
the landing, both in Belfast and in Dublin. Ice consumption during the
stay in Soldeu was significantly associated with the likelihood of falling
ill (RR = 2.5, 95% CI [1.3–5]) (table 7).
Table 7. Ice consumption relative risk of gastroenteritis among
travellers to Soldeu, by date of onset, January 2002
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Vol (27 janvier 2002)
Flight (January, 27th 2002)
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Nr de cas
No of cases
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RR
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IC 95%
95% CI
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Avant / Prior to
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48
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2.5
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1.3-5
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Après / After
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23
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0.9
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0.8-1.1
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Microbiological investigation
Norwalk-like virus (NLV) was identified in a clinical sample from one
holidaymaker. The other result was negative but the specimen was of
questionable quality.
Environmental investigation
The outcome of the environmental investigations, performed by the Andorran
authorities is not known at this stage.
Discussion
The primary objectives of our investigation were to identify the mode
of transmission, the vehicle of the outbreak and to provide appropriate
recommendations to prevent future similar outbreaks.
The epidemic curve suggests that, apart from a stable number of gastroenteritis
cases that occured during the holiday in Andorra, possibly due to the
change of diet, the possible common source of infection was on 25 January.
Unfortunately, no information was available about whether a particular
event was held on that day in Soldeu.
The small cluster that occurred on 23 January included five cases that
stayed in three different towns. However the investigation did not highlight
any link among them.
Cases whose date of onset was after 27 January (date of arrival of
the two flights) may have occurred due to person-to-person transmission
during the return flights both to Dublin and Belfast.
One difficulty encountered was the limited number of stool samples
taken which led to difficulties in the microbiological confirmation
of the cause of the outbreak. The environmental component of the investigation
was also difficult, because the environmental sampling was conducted
in another country with different protocols and procedures. The epidemiological
component however demonstrated a clear statistically significant relationship
between ice consumption and illness, particularly in Soldeu. This result
was consistently found using both stratified and logistic regression
analysis.
Ice being traditionally made with tap water, a similar association
between risk exposure and tap water was expected. However no significant
association related to the use of tap water was found. This was probably
because only a small percentage of cases consumed tap water (17%), making
the association not strong enough to reach statistical significance.
As we did not enquire about the amount of water consumed, we were unable
to calculate the dose response. It was felt that this information would
not have been available or reliable. Trawling questionnaires on food
specific exposure did not reveal any information on common exposures.
Two potential biases have to be considered in the study: selection
and information bias. They are related to the way information was collected.
Both may have led to an over-estimation of the risk associated with
ice consumption. However, according to the response rate obtained, the
accuracy of the results should have been guaranteed.
Our data suggest, according to the symptomatology, laboratory findings
and duration of the disease, that the possible vehicle of transmission
was ice consumed with drinks. This is particularly evident in Soldeu,
and the data also suggest that the Norwalk-like Virus (Small Round Structured
Virus – SRSV) may be the pathogen responsible for this outbreak.
Norwalk-like viruses (NLVs) are now established as the most important
causative agents of epidemic gastroenteritis. They cause outbreaks of
gastroenteritis worldwide and are spread frequently through contaminated
food or water (12–15). In the United States, NLV are estimated to be
responsible for 23 million cases of gastroenteritis, 50 000 hospitalisations,
and 300 deaths annually (16). In the United Kingdom, it is estimated
that the incidence of illness due to NLVs is as much as 1% of the population
per year (17).
Gastroenteritis due to NLVs tend to occur in outbreaks, although sporadic
cases may occur. These viruses are highly contagious and different modes
of transmission have been recognised, such as fecal-oral and airborne
transmission from fomites, which has been suggested to explain the rapid
spread in hospital settings (18).
Recommendations
This investigation highlights the importance of international collaboration
in outbreaks involving holiday destinations where people of many different
nationalities may be affected. Tourism is a primary industry in Andorra
and prompt action in response to gastroenteric outbreaks such as these
is required.
Every travel guide emphasises the importance of water use and water
consumption, but very often ice may be a vehicle of gastroenteric infections
(19). Where water might be contaminated, travellers should be specifically
advised that ice cubes should also be considered contaminated, and should
not be used in beverages. Ice cubes may be made from unsafe water and
therefore should be avoided. If ice has been in contact with containers
used for drinking water, travellers should be advised to thoroughly
clean the containers, preferably with soap and hot water, after the
ice has been discarded (20,21).
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