Observational Study of Travelers Diarrhea

Brigitte Meuris

Background: European air travelers returning from Algeria, Egypt, Mexico, Morocco, and Tunisia were interviewed about
their experience of travelers diseases upon arrival in Brussels. Diarrhea was mentioned by 37% of the adults and 27%
of the children. These subjects were questioned about the types of measures taken, type and duration of drug treatment
(if any), and about duration of diarrhea and side effects experienced.
Methods: Final analysis was performed based on 2160 interviews. The largest proportion of diarrhea was reported in the
age group 15-24 years (46%).
Results:The majority of the 2160 subjects had opted for drug treatment (81%):927 subjects for loperamide alone, 235 for
loperamide in combination with nifuroxazide, and 178 for nifuroxazide alone. Other drugs had been used less frequently.
The median time t o recovery was 2.4 days with loperamide compared to 3.2 days with nifuroxazide and t o 3.4 days for
the no-treatment group.
Conclusions: A stratification of the results by severity of the diarrhea suggests a rank of antidiarrheal potency as follows: loperamide > nifuroxazide > no-drug treatment. The side effect with the highest incidence was constipation (2.4%
with loperamide). ( J Travel M e d 2:ll-15, 1995)

from some complaint during their stay abroad. By far the

most prominent travel ailment was diarrhea: 2000 sufferers (37.2%) in the adult population and 225 (27.5%)
in children. Although there were approximately 35%
more diarrhea sufferers in the adults, there was n o statistically significant difference in diarrhea incidence
between adults and children.Those who reported diarrheal disease were subjected to an extensive questionnaire
that included particulars on duration of illness; type of
accommodation while abroad; duration of stay abroad;
type of measures taken; type, dose, and duration of drug
treatment (if any);initial severity and duration of the diarrhea (frequency and appearance of bowel movements and
accompanying symptoms); and side effects experienced
during the use of medication.
In this paper, the most frequently used antidiarrheal medications, namely loperamide hydrochloride
(Imodium),nifuroxazide (Ercefuryl),and loperamide in
combination with nifuroxazide are compared with no
medication in those travelers who suffered from travelers diarrhea.

Travelers diarrhea is usually defined as the passage

of at least three unformed stools per day or any number
of such stools when accompanied by fever, abdominal
cramping, or vomiting. The definition may be broadened
to include more trivial bowel disturbance. The duration of this self-limited disease generally is 3 to 5 days.
Medical intervention aims at shortening the duration of
disease, thus allowing the sufferer to resume his or her
usual activities at an early stage. A shortened period of
recovery to physical well-being has obvious favorable economic implications if the traveler is on business and may
help the maintenance of a desired level of quality of life
while a traveler is on holiday.
An observational study of various medical complaints made by European travelers about their stay in areas
outside Europe (Algeria, Egypt, Mexico, Morocco, and
Tunisia) was conducted. Air travelers returning from
these areas between July 15 and August 16, 1992, were
interviewed upon arrival at Brussels airport by means of
a standardized questionnaire written up in lay language.
As shown in Table 1, the total number of complaints in
the adult group (2 15 years of age, n = 5373) was 4919
and 446 in the pediatric group (n = 818).With fever as
an exception, there were fewer complaints in children.
Only approximately 50% of the travelers did not suffer

Subjects and Methods

All European air travelers participating in this epidemiologic study, who had suffered from diarrhea and
returned from Algeria, Egypt, Mexico, Morocco and
Tunisia, were considered for this analysis. Since the severity of the diarrheal illness varied within the screened population, the subjects were divided into four subgroups
(with a comparable size of approximately 40G500 individuals each) based upon the severity.The severity classification was based on three parameters: stool frequency,

Brigitte Meuris, MD: Medical Officer, Flying Staff, SABENA.

Paper presented at the Third Conference on International
Travel Medicine, Paris, France, 1993.
This study was financially supported by the Janssen
Research Foundation.
Reprint requests: Brigitte Meuris, MD, SABENA, National
Airport - 1/158, 1930 Zaventem, Belgium

11

J o u r n a l o f T r a v e l M e d i c i n e , V o l u m e 2, N u m b e r 1

12

Table 1 Occurrence of Complaints in Travelers According

to Age Group
Complaint

Adult
(n* = 5373) (
9
9
)

Child
(a = 818) (!A)

Table 2

Diarrhea Severity Classification

Severity Class

Stool
Appearance

Stool
Frequency

Associated
Symptoms
(score*)

~~

Fever
Vomiting
Abdominal cramps
Common cold
Sore throat
Sunburn
Constipation
Diarrhea
Jaundice
Physical injury
Other complaints
No complaints

183
257
916
269
287
614
180
2000
2
86
125
2475

(3.4)
(4.8)
(17.0)
(5.0)
(5.3)
(11.4)
(3.4)
(37.2)
(0.04)
(1.6)
(2.3)
(46.1)

42 (5.1)
29 (3.5)
45 (5.5)
21 (2.6)
20 (2.4)
31 (3.8)
4 (0.5)
225 (27.5)
11 (1.3)
18 (2.2)
476 (58.2)

Mild

Loose

Moderate

Loose

Marked

Watery
Loose

Watery
Mucoid
Loose

Severe

*Number of subjects with available data.

NB, some subjects reported more than one complaint.

appearance of bowel movements, and the presence of

accompanying symptoms (before treatment).
The first parameter, number of stools, (scored as less
than two stools; three to five stools; six to eight stools; or
more than eight stools) was combined with stool appearance (loose, watery, with mucus, or bloody) to form four
new severity groups.The latter groups were subsequently
combined with the presence of associated symptoms (no
associated symptoms; abdominal cramps or nausea only;
malaise only; or vomiting, anorexia, or fever only) leading to the formation of four severity groups that were
eventually used as a basis for the analysis in this studyThese
groups were labeled mild, moderate, marked, and severe,
and their definition is described in detail in Table 2.
Before embarking upon the
the
relevance of this severity classification was first tested in
nonmedicated diarrhea sufferers.The difference between
the four severity groups in this population was statistically significant (p < .05, one-tailed Wilcoxon test), thus
confirming that the severity classification was clinically
relevant. Mild diarrhea was found in 471 subjects, moderate diarrhea in 551, marked diarrhea in 397, and severe
diarrhea in 478 subjects.
To enable basing the analysis on sufficient numbers
of travelers, only four groups of medication users were considered, namely, loperamide users, nifuroxazide users,
users of both loperamide and nifuroxazide, and the nonmedicated group.The remaining subjects had used a variety of medxations, either taken alone or in combination,
but the numbers for each medication group were small.
Because at the time of the interview at the airport,
diarrhea was still present in a number of travelers, the duration of the diarrheal episode was not always known.
Therefore, statistical evaluation of the treatment effect was
done using the Kaplan-Meier life-table method (generalized Wilcoxon test).

Watery

Mucoid

Bloody

$2
52
3-5
$2
52
3-5
6-8
$2
3-5
52
3-5
6-8
>8
52
3-5
26
52
23
any frequency

$2
3
52
$2
4
3
52
3
$2
<2
4
23
$4
4
23
$4
23
$4
$4

*The present symptoms were ranked according to the frequency

and appearance of the stools In the various diarrhea groups. The
following ranking was obtained: (1) no assoclated symptoms;
(2) only abdominal cramps or nausea; (3) only malaise; and
(4) only vomiting or anorexia or fever.

To test whether the groups were balanced, the

Cochran-Mantel-Haenszel test was used. Overall significance was defined as p I .05, two tailed.

Results
The total population of diarrhea sufferers consisted
of2000 adults and 225 &dren,The
oftravelers were returning fromTunisia (57%).Mexico had the
fewest visitors within this population (2%), followed by
Algeria (5%), Egypt (8%),and Morocco (26%). In 2%,
the site of embarkation was not registered.
Table 3 shows the age distribution in the diarrhea
population relative to the population interviewed.The
Table 3 Age Distribution of Diarrhea Sufferers Relative to
Population Interviewed
Age
(Y)
2-4
5-9
10-14
15-24
25-34
35-44
45-54
t 55
N o t evaluable

Traveler in
Each Age Group
(No.)

Diarrhea
Sufferers
(No.)

140
292
286
1791
1562
992
66 1
367
100
6191

35
72
90
831
581
313
218
56
29
2225

25
24.6
31.5
46.4
37.2
31.6
33
15.2
35.9

Me u r is, T r a v e l e r s D i a r r h e a

13

largest number of travelers was in the age group 15-24

years. In this age group, the highest proportion of diarrhea cases was reported (46%). The very young, and
those over 55 years of age, had the lowest incidence.
For the young age group, this incidence of diarrhea
was relatively constant across the five countries. The
incidence of diarrhea in children varied between approximately 30% in Mexico,Tunisia, and Egypt and slightly
above 20% in Algeria and Morocco. For the adults, however, the likelihood of contracting diarrhea differed significantly from one country to the other.The highest incidence was observed in Egypt (59%). A high incidence
of diarrhea was also found in Mexico (45%), Tunisia
(40%),and Morocco (30%).The lowest incidence was seen
in Algeria (13%).
The majority of subjects with diarrhea (n = 1487;
69%) had remained in the host country for approximately
2 weeks.The accommodation chosen was hotel/holiday
club in 74% of all cases.With respect to other types of
accommodation, it is unsure from the available material
how many subjects had taken care of their own food
preparation but this was probably the case only in a
small minority.

Treatment
Because 65 of the interviews of the 2225 diarrhea
sufferers were incomplete or inconsistent, only 2160
case reports could be used for the final analysis. O f the
2160 subjects who contributed useful data, the majority had chosen drug therapy (81%).Table 4 lists all treatment measures taken by the diarrhea population. This
drug-treated population was analyzed in detail, and more
specifically, attention was given to the more frequently
reported drug regimens, as mentioned above under the
heading Subjects and Methods.
The major drug treatments were the following: 927
subjects had used loperamide monotherapy; 235 had
used loperamide in combination with nifuroxazide; 178

Table 4

Measures Taken by the Population with Diarrhea

~~

Measure
Change of diet
N o food intake
More liquid intake (e.g., rice water)
Stayed indoors
Drug treatment
Specialized care*
Other
No special measures
Number of subjects
Number of measurest
*Includes advice from general practitioners.
+Some subjects took more than one measure.

Number

204
57
103
28
1742
25
17
288
2160
2464

9.4
2.6
4.8
1.3
80.6
1.2
0.8
13.3

had used nifuroxazide alone; and 402 subjects had not

taken any drug treatment.
The median recovery time associated with loperamide was 2.4 days compared to 3.4 days in the notreatment group.The median recovery time with nifuroxazide, namely 3.2 days, was only slightly below that of
the no-treatment group. Subjects on a combined
loperamide-nifuroxazide therapy had a median recovery
time (2.5 days), which was similar to that with loperamide alone.
These differences in median recovery, however,
could be biased by differences in diarrhea severity
because the various treatment groups were not established by randomizationTo avoid this potential bias, the
results were stratified by severity group. Table 5 shows
the percentage of subjects in each severity class for each
treatment group.The moderate differences observed in
this table fail to reach statistical significance. It was,
nonetheless, decided to maintain the stratification for further analysis.
As shown in Figure 1, the median recovery time is
shorter in loperamide-treated patients than i n the
untreated controls in each of the severity classes. Interestingly, the median recovery time under loperamide is
very similar, namely around 2 days in mild, moderate,
and marked diarrhea.This time is about 1 day longer in
patients with severe diarrhea. This may indicate that it
is more difticult to achieve a good clinical result with
loperamide when the diarrhea is severe than when it is
mild, moderate, or marked. I t is of note in this context,
however, that a substantial number (n = 217) ofthe subjects with severe diarrhea may actually have had a contraindication for the use of loperamide as a monotherapy since several of them had fever and/or were passing bloody stools. Finally, it is of some importance to
point out that, in contrast to suggestions in the literat ~ r ethere
, ~ is no evidence in this material that loperamide
might actually prolong or exacerbate diarrhea; this is further exemplified by the fact that there was very little difference between the groups with respect to the percentages of subjects who suffered from diarrhea for
more than 3 days.
In the mild-to-moderate diarrhea classes,the median reduction in recovery time, compared to the noTable 5 Choice of Treatment by Severity of Diarrhea
Category (Expressed as a Percentage)
Treatment Group

Miid

Moderate

Marked

Severe

Loperamide
Nifuroxazide
Loperamide plus
nifuroxazide
None

26
27
24

32
25
23

20
22
24

22
26
29

30

33

17

20

Journal o f Travel Medicine, Volume 2, N u m b e r 1

14

MODERATE DIARRHEA

MILD DIARRHEA
1

0.Q

0.Q

0.0

0.8

0.7

0.7

0.6

0.0 -

0.5

0.5

0.4

0.4

0.3

0.3-

0.2

0.2

0.1

/
1

.6

1.6

1 ,

,
2.6

/
/

/ ,

/
/

3.6

/
!

4.5

0.1 -

0 1 ,

/ ,

/ ,

/ ,

/ ,

/ ,

NO. OF DAYS POST INITIAllON OF THERAPY

LIFETABLEANALYSIS

MARKED DIARRHEA

SEVERE DIARRHEA
1

0.9
0.0
0.7

0.0
0.5
0.4

0.4

0.3

,,I
V.0

0.2
0.1

0.1

0 1 ,
0

.6

1
1.6
2
2.5
3
3.6
4
NO. OF DAYS POST INITIATIONOF THERAPY

I
LOPERAMIDE

4.5

.6

LOPERAMIDE

NO MEDICATION

>

,!

1
1.6
2
2.5
3
3.6
4
NO. OF DAVS POST INITIATIONOF THERAPY

4.5

NO MEDICATION

LIFETABLEANALYSIS

LIFETABLEANALYSIS

Figure 1 Duration of diarrhea as related to severity: loperamide versus no medication.

treatment group, was 0.5 days with nifuroxazide, whereas

it was 1 to 1.5 days with loperamide. In subjects with
marked or severe diarrhea there was no discernable benefit from nifuroxazide.
T h e combined loperamide-nifuroxazide group
behaved in a similar manner to the loperamide (alone)
group, including the reduced benefit in case of severe
diarrhea.There were no significant differences in eficacy between travelers below 15 years of age and
those of 15 years and older (adults).The different age
categories were proportionally divided over the treatment groups.

Side Effects
T h e incidence of side effects was very low in this
drug-treated population.There were n o serious adverse
effects.The side effect with the highest incidence was
constipation, namely 2.6% and 1.7% with the loperamide monotherapy and with the combination of loperamide and nifuroxazide group respectively; this

amounts to an incidence of 2.4% in the two groups

combined. Dry mouth was reported in 0.8% of the loperamide and in 0.6% of the nifuroxazide treated subjects. All other side effects were reported with lower
incidence. Also, all reported adverse experiences were
similar to diarrhea-related complaints as is illustrated
by the two above mentioned symptoms. In the group
over 55 years of age, only four subjects felt that they
had suffered a side effect, namely abdominal cramps
(three subjects on combination medication) and fever
(one subject on loperamide).
T h e incidence of side effects in children was
minimal: only dizziness was reported, and only by one
child.

Discussion
The prevalence of 37% diarrheal disease in the
group of travelers interviewed corresponds well with
the incidences reported elsewhere, including travel to
other destinations., In the present study, more adults

Meu ris, T r a v e l e r s ' D i a r r h e a

were affected than were young children, although this

difference was not statistically significant.This is in contrast to other findings2 where those under the age of
6 were considered most at risk for diarrhea.The percentage of diarrhea sufferers who took loperamide in
this survey (43%) corresponded well with that mentioned in an earlier study.' Although loperamide is
not recommended as a monotherapy in case of dysentery and/or fever, the drug may be used if combined
with an antibiotic in such cases.2There is some constraint about administration of loperamide to infants
and young children,J~~
although it has been shown to
be sufficiently safe in this age group as well as in
adults.'The very low incidence of side effects has also
been observed by others and may actually be similar
to that observed in untreated subjects.'
The only relevant adverse event related to loperamide in this study was constipation.The incidence
of adverse events was not higher in children or travelers over 55 years; also, no serious events were reported
in these populations. Furthermore, there was no evidence, not even in travelers with severe diarrhea, that
drug treatment may actually worsen the outcome of
diarrhea. This confirms findings of other authors.'-"'
In loperamide and nifuroxazide prescribing information, the recommended duration of treatment is 2 and
3 days respectively. In view of the results of this study,
this recommended treatment duration seems rather
short, since only approximately 50% of travelers appear
to be cured after such a short treatment interval.
The present study suggests that loperamide may
be superior to other drugs in the treatment of travelers' diarrhea; loperamide may, therefore, be recom-

15

mended to Europeans who travel to tropical and subtropical destinations.

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