an infectious disease caused by a spirochete from the Leptospira species
after an incubation period of 10 days. It has not been mandatorily notifiable
since 1986 in France. The current surveillance system is based on data
from the National reference centre (Centre National de Référence,
CNR) for leptospires, which receives serological requests from hospital
laboratories or laboratories for biological and medical analyses located
throughout the whole territory. The yearly incidence estimated by this
system in metropolitan France is low and stable, with an average of
290 new cases per year between 1984 and 2000 (268 cases in 2000, incidence
of 0.44 cases per 100 000 inhabitants) (1).
A case-control survey
carried out in metropolitan France identified the main risk factors
in 1999-2000 as the following: presence of wounds, canoeing-kayaking,
contact with fresh water for professional reasons, and contact with
wild rodents (2). Recently, a working group gathered by the Institut
de Veille sanitaire (InVS, National public health institute) aiming
at defining priorities in the field of non foodborne zoonoses (2000-01),
identified leptospirosis as a priority disease. In this context, reinforced
collaboration with the CNR was recommended to undertake epidemilogical
surveillance, and to implement an alert system for the human population,
as well the publication of a guide book for the investigation of clustered
On 14 June 2001,
the local health authorities of Charente-Maritime (DDASS, Direction
départementale des affaires sanitaires et sociales, Departmental
directorate of social and health affairs) was informed by the Rochefort
sub-prefecture that five teenagers hospitalised in Rochefort presented
clinical signs compatible with leptosirosis. For three of them, the
search for leptospires by PCR at the Pasteur Cerba laboratory was positive.
The patients had swum with thirty other teenagers in the Genouillé
canal, in the locality "Les 3 bras" situated two kilometres
away from the Libération area, just outside Rochefort (figure
On 26 June, the
DDASS and the InVS, in collaboration with the local epidemiological
centre, (Cellule inter-régionale d’épidémiologie,
CIRE), decided to send a team on site to carry out an epidemiological
investigation with the following objectives:
• confirm the common
origin of clustered cases,
• search for the
• identify risk
• identify additional
potential control and prevention measures,
• strengthen collaboration
with the CNR in order to improve the alert,
• design an investigation
guide book for clustered cases of leptospirosis.
investigation (exploratory and case-control) was conducted by the Charente-Maritime
DDASS, the CIRE Centre-Ouest, and the InVS. The objectives of the exploratory
phase were to describe the cases, to confirm the epidemic nature of
the clustered cases, to record other potential cases, and to raise hypotheses
to be tested during the analytic phase.
During the first
phase, a case was defined as a person living in Rochefort or in the
neighbourhood with leptospirosis diagnosed from 25 May 2001.
• Possible case:
with a unique serodiagnosis by a micro-agglutination test (MAT) positive
with one titre ≥ 1:100 or ELISA ≥ 1:400
• Confirmed case:
with positive PCR or culture or positive serology by MAT with two samples
taken at a two-week interval with titres ≥ 1:100, and at least
a four-fold increase between the two samples.
Cases were investigated
from the Pasteur-Cerba laboratory, the CNR for leptospires, the four
medical and biological laboratories in Rochefort, the Rochefort Hospital,
and the general practitioners of the Libération area.
were part of a group of teenagers, the study population, having bathed
at least once between 18 May and 10 June in the Genouillé canal,
in the locality of "Les 3 bras" (Figure 1). For the case-control
study, among these teenagers, a case was defined as any person having
bathed at least once during this period in the Genouillé canal,
locality "Les 3 bras", presenting a positive biology and an
acute infectious syndrome (temperature above or equal to 38.5°C), during
the period from 25 May to 17 June 2001. A control was considered as
any person who did not present temperature above 38.5°C since 25 May.
Moreover, the control should have no history of leptospirosis or vaccination
against this disease.
Thanks to the cases’
indications, it was possible to identify and detect among the thirty
teenagers exposed, 10 non-sick teenagers recruited as controls. Cases
and controls were interviewed by phone, by the same person, and using
the same questionnaire. As two controls were absent, a family member
Data collected were
• Demographic data;
• Presence, type
of symptoms, and date of onset;
• Exposure during
the three weeks before onset of symptoms: location and frequency of
contacts with the canal water;
• Estimation of
the total duration of the contact with water, use of protection, presence
of wounds and their type during swimming, knowledge of vaccination against
leptospirosis, presence of any chronic disease and its potential treatment,
knowledge of an antimicrobial ongoing treatment, during or a month before
and hospital clinical data;
• Biological data
and leptospirosis diagnosis (PCR, serology).
study’s objectives were to analyse the potential risk factors, namely
the presence of wounds during swimming, the use of protection, the duration
of contacts with the canal water, the presence of chronic diseases,
of a chronic or antimicrobial treatment during the exposure period.
The data analysis was carried out using Epi Info, version 6.04.
analysis (search for E.coli and coliforms) was carried out on 15 June
on the canal waters by the Departmental direction of water and forests
(Direction Départementale des Eaux et Forêts, DDAF).
Between August and
September, the veterinary school in Nantes (ENV, Laboratoire B2ML) and
the National federation of departmental groups for the protection of
cultures (Fédération Nationale des Groupes Départementaux
de la Protection des Cultures, FNGDPC) placed traps near the locality
of "Les 3 bras" to estimate the presence of rodents potentially
excreting of leptospires. Three rodent species were trapped: coypus,
muskrats and field rats, and serologies were undertaken.
of the cases
In total, 5 cases
(3 confirmed and 2 possible) were identified by the Hospital Centre
of Rochefort. All cases occurred in a clustered way between 4 and 12
June (date of onset of symptoms). This suggests an exposure period limited
in time. Depending on the dates of occurrence of the cases, and incubation
periods (between 4 and 19 days), the exposure period was estimated to
be between 18 May and 10 June (figure 2).
Four out of five
cases were male (sex ratio M/F = 4). The cases were aged between 10
and 19 years (average 13.2 years, median 11 years). All lived in the
Libération area located in the north east suburb of Rochefort,
two kilometres away from the suspected exposure area.
cases presented fever with headaches, abdominal pain and vomiting, and
in four cases, chills and myalgia. Three cases presented conjunctivitis,
one meningeal symptoms, and one a pulmonary attack. No jaundice was
observed (table 1). Four cases were hospitalised in the Rochefort Hospital,
the fifth consulted in the same hospital. The duration of hospitalisation
varied from two to eight days (median 6 days).
Tableau 1 / Table 1.
Fréquence des signes cliniques (n=5), cas groupés de leptospirose, Charente
Maritime, juin 2001 / Frequency of clinical signs (n=5), clustered
cases of leptospirosis, Charente Maritime, June 2001
Signes / Signs
No. de cas / Nr cases
Fièvre / Fever (³
Céphalées / Headache
Vomissements / Vomiting
Frissons / Chills
Myalgies / Myalgia
Conjonctivite / Conjunctivitis
Eruption cutanée / Rash
Hémoptysie / Hemoptysis
Splénomégalie / hepatomegaly
Ictère / Icterus
For three cases,
positive PCR and seroconversion were observed. The DNA sequences were
similar to each other and to the sequence of a strain from icterohaemorrhagiae
serovar. For the other two, only an IgM initial titre of 1/400th was
shown by ELISA.
In the case-control
study, the cases included are the five confirmed and probable cases
identified during the exploratory survey. One case and three controls
suffered from a chronic disease (asthma for one case and two controls,
and "convulsions" for another control), and were taking a
long term treatment (p=0.6). No case or control used protections (goggles,
shoes, other) while swimming. Only one control had wounds at the time
of swimming (p=0.7).
The average cumulated
duration of swims was significantly higher for the cases (median 23.8
hours) than for controls (median 14.4 hours), p=0.035.
survey and hydrologic data
The analyses of
the canal water testified a moderate quality (E.coli between 100 and
2000/100 ml), according to swimming water criteria.
At the locality
"Les 3 bras", three canals join and pour their fresh waters
in the Charente. Two locks regulate the flow between the canals fresh
waters and brackish waters. Between 28 May and 11 June, the locks had
not been opened.
The rodent traps
made by the ENV and the FNGDPC has permitted the analysis of serological
status of 130 rodents. The prevalence of seropositive rodents, all antigenes
considered, was 30.8%, 23.1% for L. icterohaemorrhagiae,
4.6% for L. saxkoebing , 3.8% for L. australis. The proportion
of rodents with positive serology for serovar icterohaemorrhagiae was
higher in coypus (30%) than in muskrats (11%) (p=0.014).
phase showed that all the recorded cases had bathed in the Genouillé
canal, in the locality called "Les 3 bras". As it was not
possible to reconstitute the cohort of all teenagers who swam at this
site, we have not been able to estimate the attack rate. This led us
to conduct a case-control study for the analytic phase of the investigation.
Swimming in this
canal from 18 May to 10 June was probably the origin of all leptospirosis
cases. The total duration of swims in this canal was associated with
acquiring leptospirosis. However, an information bias is possible due
to the tendency for cases to increase the length of their exposure,
or inversely, for controls to decrease it.
No other risk factor
(pre-existing conditions, wounds, ongoing treatments) was found. However,
the strength of this study remained weak due to the small study population.
Moreover, in the absence of serology for controls, asymptomatic persons
may have been misclassified as controls.
The occurrence of
clustered cases suggests recent contamination of the waters in "
Les 3 bras " that can be explained by one or several of the following
• The presence of
rodents excreting of leptospires was reported by residents around the
swimming area. A study on coypus (July 2000–May 2001) trapped in marshes
or rivers has shown that in Charente-Maritime, 52% of animals (63/120)
were seropositive for MAT, the icterohaemorrhagiae (61/63) being the
predominant serogroup; (3)
• An increase or
a shift of rodents’ population excreting of leptospires towards the
swimming zone may have interfered recently (because of heavy rains in
other areas more visited by rodents);
• The trapping results
carried out in August showed a predominance of the icterohaemorrhagiae
serogroup, although not specifically in the swimming area of cases,
especially in coypus, suggesting the potential role of these rodents
in the occurrence of clustered cases in Rochefort ;
• Between 28 May
and 11 June, the lock was not opened, and that could have facilitated
the concentration of leptospires in the swimming area due to water stagnation.
The occurrence of
clustered cases of leptospirosis raises the question of using doxycycline
as a secondary preventive measure. The use of this antibiotic in endemic
areas has shown a protective effect on morbidity and mortality during
epidemics, without however reducing the leptospires infection. As soon
as the first leptospirosis cases are detected, a chemoprophylaxis with
200 mg of doxycycline per week for individuals exposed to leptospires
could prevent the occurrence of clinical signs.
carried out on site has not only allowed us to describe clustered cases,
but also to sensitise clinicians and private laboratories to the existence
of the disease, and the notification of suspected cases, and to relaunch
discussions on the CNR’s role, the alert mechanism, and the potential
use of antibioprophylaxis for the persons exposed. It has also supplied
indications for the writing of an investigation guide book.
Upon the diagnosis
confirmation, the Rochefort hospital issued information on the risk
linked to swimming for the relatives of the teenagers hospitalised.
Press releases about the disease, its symptoms and the swimming area
were published by the DDASS through the media.
however seemed to have a limited impact: during the investigation, most
teenagers interviewed and their families ignored the transmission routes
of the disease, although these were indicated in the press releases.
Road signs around
the locality of "Les 3 bras" reminding the ban on swimming
was reinforced by the town hall. Surveillance measures were set up in
the community laboratories and the Rochefort hospital (reporting to
the DDASS of any new leptospirosis case, dispatch of strains to the
CNR for confirmation).
The occurrence of
clustered cases and the environmental conditions of the suburban area
of Rochefort justify the reinforcement of surveillance of human cases
of leptospirosis, during risk periods (swimmimg months). It would be
useful that all information from general practitioners, laboratories
and hospitals, could result in immediate reporting of any suspected
case (without waiting for biological confirmation), even if notification
is not mandatory, to local health authorities (DDASS), together with
the dispatch of samples to the CNR. This procedure could be set up in
the city of Rochefort, and applied every year.
Information to the
public need to be maintained in parallel (information on the disease,
banned swimming areas). In the context of developing investigation guidelines
for clustered cases of leptospirosis, it will be useful to study the
procedures to carry out serology in controls, in order to reduce the
classification bias in analytical studies.