Travel-Acquired Leptospirosis Androula Pavli , MD, FRACGP * and Helena C. Maltezou , MD, PhD †
* Offi ce for Travel Medicine and † Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Prevention, Athens, Greece
International travel is rapidly growing worldwide. Microbiology
It has been estimated that international travels
Leptospires are highly motile spirochetes of the
will reach nearly 1 billion by 2010 and 1.6 billion by
family Leptospiraceae that are divided into numer-
2020, with the highest increase concerning tropical
ous serovars. Pathogenic leptospires comprise the
and subtropical areas. 1 Furthermore, a rapidly in-
Leptospira interrogans sensu lato complex (more than
creasing number of travelers are engaged in adven-
200 serovars), whereas saprophytic leptospires
ture travel. 2 Travelers participating in athletic and
comprise the Leptospira bifl exa sensu lato complex
adventure activities may be exposed to various in-
(more than 60 serovars). Among some of the common
fectious agents often unfamiliar to physicians in
pathogenic serovars for humans are Leptospira canicola ,
their homeland that may demand immediate atten-
Leptospira hardjo , Leptospira hebdomadis , Leptospira
tion due to the potential of causing severe morbid-
autumnalis , and Leptospira weil . Leptospires can sur-
vive freely for weeks or months in soil and water. 9,21
Leptospirosis is an emerging zoonosis of global
importance. 4 – 8 Although transmission may occur in rural and urban areas worldwide, incidence of in-
Epidemiology
fection is signifi cantly higher in tropical areas. 5,8 – 12 Leptospirosis has been traditionally considered an
A wide spectrum of animal species, primarily small
occupational hazard among professionals in contact
mammals, may serve as sources of human infection
with urine of infected animals. 9,13 However, nowa-
with leptospires. Rodents, mainly rats and mice, are
days, cases and outbreaks are increasingly reported
the most important and widely distributed sources of
among adventure travelers and athletes participat-
infection. Hedgehogs, dogs, and farm animals may
ing in freshwater sports. 10,11,14 – 20 Due to the fact that
also serve as reservoirs. 9,21,22 Animal carriers harbor lep-
leptospirosis is a potentially fatal disease, 7,9,21 infor-
tospires in their kidneys and shed them through urine
mation regarding prophylactic measures should be
for prolonged time periods or even for their life span.
targeted to this group of travelers and leptospirosis
Infected animals usually remain asymptomatic. 9,22
should be considered among febrile travelers re-
Leptospira infection is transmitted to humans
turning with a compatible epidemiological associa-
through direct or indirect contact of mucous mem-
tion. We review the current state of knowledge on
branes or skin abrasions with urine from infected
travel-acquired leptospirosis with emphasis on its
animals or contaminated freshwater surfaces, in-
cluding mud or water in lakes, rivers, and streams. Ingestion or inhalation of contaminated water or aerosols may also result in infection. 4,10 – 17,19,20,23 – 28 Infection has been occasionally reported following
Corresponding Author: Helena C. Maltezou, MD,
animal bite, laboratory accident, blood transfusion,
PhD, Department for Interventions in Health-Care Facilities, Hellenic Center for Disease Control and Pre-
organ transplantation, breast feeding, sexual inter-
vention, 42 3rd Septemvriou Street, Athens, Greece.
course, and through congenital transmission.
Transmission between humans is very rare. 21
2008 International Society of Travel Medicine, 1195-1982
Journal of Travel Medicine, Volume 15, Issue 6, 2008, 447–453
Leptospirosis is considered the most widespread
in several developed countries in association with a
zoonosis, occurring worldwide except in polar re-
shift of its epidemiological profi le. In particular, a
gions. The precise incidence of leptospirosis re-
gradually decreasing portion of cases is attributed
mains unknown due to the lack of awareness and
to occupational exposure and a concomitant in-
systemic investigation for this illness worldwide.
creasing portion of cases linked to recreational ac-
Estimated annual incidence rates range from 0.02
of 100,000 to 1 of 100,000 persons in temperate
frequently diagnosed with leptospirosis compared
areas and from 10 of 100,000 to 100 of 100,000
with women, 31,35,36 and this has been traditionally
persons in humid tropics. During outbreaks and in
attributed to the overrepresentation of men in
high-risk exposure groups, incidence may reach 100
high-risk occupations. However, a recent study
of 100,000 persons. 6,22,30,31 Regional climate and
from Germany found that male sex was signifi cantly
rainfall, burden of animal reservoirs, and human
associated with more severe illness and higher case
behavior infl uence incidence and seasonality of
fatality rates compared with female sex and that
leptospirosis. The higher incidence in the tropics is
these sex-related differences were not associated
mainly due to the longer survival of leptospires in
with exposure risk, infecting serovars, or health-
the warm and humid environment of these areas.
seeking behavior. 31 It is possible that leptospirosis is
High endemicity of leptospirosis in tropical areas is
milder and thus less recognized among females.
also sustained by the presence of stagnant waters and poor sanitary conditions. There is underreport-
Leptospirosis in Travelers
ing of leptospirosis in parts of the world where high endemicity also owes to poor public health infra-
Although an increasing number of imported lepto-
structure. 32,33 In temperate areas, infections peak
spirosis cases and outbreaks following international
during summer and early autumn, whereas in the
travel and adventure activities have been published
tropics, cases occur all year around with increased
incidence during rainfall months. 4,5,13,23,34 Cases may
probably, leptospiral infections in this group
occur sporadically or within the frame of outbreaks.
remain unrecognized. Reasons include the nonspe-
Large outbreaks have been recorded following
cifi c symptoms commonly encountered in leptospi-
heavy rainfall and fl oods, accounting for the name
rosis, the lack of awareness of this illness as a cause
“ fl ood disease ” for leptospirosis. 10,11,14,17,19,27,32,33,35,36
of fever among returned travelers, and the relative
Leptospirosis has been traditionally considered
unavailability of testing. However, given the
an occupational hazard among sewer workers,
increasing popularity of travels and ecotourism in
farmers, abattoir workers, fi sh farmers, veterinari-
tropical areas, it appears that the risk and thus the
ans, and hunters. 4,9,21,23,34 During the past two de-
incidence of leptospirosis among travelers will
cades, however, leptospirosis appears to reemerge
Table 1 Characteristics of published leptospirosis cases and outbreaks acquired during international travel
Southeast Asia (1987 – 1991) 25 Contact
China and Ivory Coast (1992 – 2002) 30 Water
Southeast Asia, India, Oceania, Africa, and Europe (1997 – 2003) 5 Malaysia (2000) 10
Dominican Republic (2000 – 2001) 37 Water
Guam Island, United States (2002) 26 Water
NR = not reported; NA = not applicable. * Only travel-acquired cases are presented in this table. † 80 of 189 interviewed athletes.
We found in the literature nine publications re-
Clinical Manifestations
porting a total of 283 leptospirosis cases acquired
The incubation period of leptospirosis ranges from
during international travel, mainly in Southeast
1 to 30 days (average 7 – 14 d). 10,11,28,34 Leptospirosis
Asia, the Caribbean Islands, and Central and South
manifests with a wide clinical spectrum from asymp-
America ( Table 1 ). This is in accordance with a re-
tomatic infection to the severe form of Weil
cent review of worldwide incidence trends of lepto-
disease. Most infections are asymptomatic or mildly
spirosis from 1996 onward, revealing that the above-mentioned areas are the most signifi cant
symptomatic and self-limited. 9,21,31,41
foci of leptospirosis worldwide, including popular
Clinical leptospirosis typically manifests with a
travel destinations. 32 However, among 248 lepto-
biphasic course, with an acute phase (anicteric
spirosis cases reported in Germany from 1997
form) lasting approximately 1 week followed by the
through 2003 for whom epidemiological data were
immune phase characterized by antibody produc-
available, international travel emerged as the single
tion and leptospiruria. Only a minority of patients
most important exposure risk, accounting for 16%
develop biphasic illness. Patients typically present
of all cases, of whom 33% had a travel history within
with fever of abrupt onset, headache, myalgias lo-
Europe. 5 Thus, it should be kept in mind that infec-
calized mainly in calves, conjunctival suffusion,
tion may be acquired during travel in developed or
temperate countries as well. Travel-acquired lep-
Conjunctival suffusion is characterized by redness
tospirosis has been associated with the following
and edema of conjunctivae, mainly on the palpe-
recreational activities: freshwater swimming, raft-
bral conjunctiva. Conjunctival suffusion should be
ing, kayaking, canoeing, fi shing, hunting, and trail
differentiated from conjunctival injection (non-
biking. 4,5,10,11,14,15,17 – 19,23 – 26,37 Pretravel risk assess-
uniform redness) or subconjunctival hemorrhages.
ment for leptospirosis should mainly rely on infor-
Conjunctival suffusion and myalgias are consid-
mation about high-risk activities for acquisition of
ered pathognomonic of leptospirosis. Rash occurs
infection and travel destination should also be
occasionally and lasts 1 to 2 days. During the
immune phase, fever may recur after 3 to 4 days of
During the past decade, large leptospirosis out-
defervescence, accompanied by headache and
breaks occurred during international freshwater
myalgia and occasionally by cerebrospinal fl uid
athletic events. During an outbreak that occurred
pleocytosis. Aseptic meningitis develops in up to
in Springfi eld, IL in 1998 during the course of an
25% of leptospirosis cases. 9,21,34 The immune phase
international triathlon athletic event, the attack
may last up to 30 days. Mortality of anicteric form
rate was 12% among 834 participants. 11 In a lepto-
spirosis outbreak that occurred among 304 ath-
Icteric leptospirosis (Weil ’ s disease) develops in
letes from 27 countries in the “ Eco-Challenge ”
5% to 10% of clinical leptospirosis cases. This mul-
multisport race in Malaysia in 2000, attack rate
tisystem illness has a rapidly progressive and often
reached 42% among 189 interviewed athletes
fulminant course characterized by jaundice, hem-
(62% of all athletes). 10 Both outbreaks were pre-
orrhage, and acute renal failure. 9,13,21,31,34 Thrombo-
ceded by heavy rainfalls. Public health authorities
cytopenia occurs in up to 50% of cases and is
should keep in mind the potential of leptospirosis
associated with poorer prognosis. Serum bilirubin
outbreaks in the course of freshwater athletic
levels are high, and hepatic transaminase and amy-
events especially following heavy rainfalls and
lase levels are moderately increased. Hepatic func-
fl oods, provide appropriate counseling, and im-
tion normalizes following recovery. Pulmonary
plement syndromic surveillance for their early de-
involvement ranges from 20% to 70% and may
tection and control. Collection of water and soil
manifest with cough, chest pain, dyspnea, hemop-
samples for testing for leptospires is not justifi ed
tysis, hemorrhage, and adult respiratory distress
because it is associated with a low sensitivity,
syndrome. Pulmonary hemorrhage is an ominous
mainly due to the fact that water and soil samples
fi nding. 7,9,21,42,43 Cardiac involvement is also com-
often are not representative of a large environ-
mon, with electrocardiogram abnormalities in up
ment. 22 Military personnel also constitute an oc-
to 50% of cases. Weil ’ s disease is associated with a
cupational risk group for leptospirosis when they
5% to 15% case fatality rate. 9,13,21,34 Males experi-
participate in high-risk activities for acquisition of
ence more severe illness and have higher fatality
infection in endemic areas. In this setting, out-
breaks among military recruits have occurred with
Differential diagnosis of leptospirosis depends
attack rates up to 46%. 23,28,32,38 – 41
on clinical syndrome and area of acquisition of
infection and may include infl uenza, malaria, den-
leptospirosis should be kept in a febrile patient with
gue fever, viral hemorrhagic fevers, Hantavirus in-
headache, myalgias, and/or conjunctival suffusion
fection, Legionnaires ’ disease, yellow fever, aseptic
in association with a history of contact with fresh-
meningitis, sepsis, meningococcal disease, brucel-
water, soil, or animals. Health-care providers
losis, typhoid fever, rickettsial diseases, relapsing
should consider leptospirosis in the returned febrile
traveler in a compatible epidemiological context taking into account its incubation period and promptly introduce treatment. 9,21,43 Currently, dox-
Diagnostic Tests
ycycline, ampicillin, amoxicillin, erythromycin, and
Serology testing is the most commonly used method
azithromycin are recommended for less severe
for diagnosing leptospirosis worldwide. The mi-
cases, whereas penicillin G, ampicillin, cefotaxime,
croscopic agglutination test (MAT) is the reference
and ceftriaxone are the drugs of choice for severe
method; however, it usually requires paired sera 1
disease. 9,22,52 Ceftriaxone and penicillin G appear to
to 2 weeks apart, and thus, diagnosis is usually made
be equally effective for the treatment of severe lep-
during convalescence. In this test, antigens repre-
tospirosis; however, the former offers the advantage
senting more than 20 serogroups undergo reaction
of once-daily administration compared with every
with patient serum to detect agglutination antibod-
6-hour administration. 53 Fluoroquinolones consti-
ies, whereas cross-reactions between serogroups
tute an alternative option; however, adequate hu-
are common and limit the value of MAT for detect-
man trials are lacking to fully support their use. 52
ing the causative serovar in an individual case. 44
Variability in susceptibility appears to exist among
Furthermore, MAT is time consuming, requires
strains from different geographic areas. 54 Provision
signifi cant expertise, and may be subjected to per-
of adequate supportive care is imperative. 21
formance variations among laboratories and per-sonnel. 9,44 – 46 Diagnostic cutoffs depend on local
Chemoprophylaxis
(Ig) M enzyme-linked immunosorbent assay offers
The effi cacy of doxycycline prophylaxis against lep-
the advantage of providing results rapidly; however,
tospirosis at the dose of 200 mg/wk was demon-
IgM antibodies are detected 5 to 7 days following
strated in a fi eld trial among 940 US soldiers during a
the onset of illness. 9,21,23,45 As a rule, both conventional
3-week jungle training in Panama in 1982, where at-
and rapid antibody detection tests are of limited
tack rates were 4.2% in the placebo group compared
value during the fi rst week of illness; however, they
with 0.2% in the prophylaxis group ( p < 0.001) for
diagnose leptospirosis afterward with a sensitivity
an overall prophylaxis effi cacy rate of 95%. 38 A ran-
of at least 85%. 9,21,45,47 Rapid dipstick tests offer the
domized trial conducted in an endemic area in India
advantage of easy and rapid screening of patients;
revealed that doxycycline prophylaxis did not prevent
however, they do not cover all strains. 48,49
asymptomatic Leptospira infection but was associated
Polymerase chain reaction (PCR) may acutely
with a statistically signifi cant reduction in clinical ill-
and rapidly diagnose leptospirosis using sera and
ness (3.11% in the prophylaxis group vs 6.82% in the
urine specimens from the fi rst week of illness, in-
cluding cases with antibiotic administration. 9,50 Re-
doxycycline at 200 mg/wk for 4 weeks has been used
cently, a real-time PCR assay was developed
successfully for the containment of an outbreak in
targeting the lipL32 gene conserved among patho-
India in 2001. 13 Prophylactic doxycycline was also
genic Leptospira serovars and was associated with
administered to a total of 120,000 persons following
high sensitivity and specifi city for detecting lepto-
the heavy fl oods in Guyana in early 2005 and the
spiral DNA in sera and urine. 51 Culture of lepto-
subsequent onset of a leptospirosis outbreak. 33
spires in clinical specimens takes several weeks and
Preexposure doxycycline chemoprophylaxis at
is of low sensitivity and thus of no value in the man-
200 mg/wk p.o. should be considered for adventure
travelers, athletes, and military recruits likely to be in-volved in high-risk activities for acquiring Leptospira infection in endemic areas. High-risk activities
Treatment
include freshwater swimming, rafting, kayaking,
Febrile patients who return from an endemic area
canoeing, fi shing, hunting, and trail biking. The
with a history of exposure to freshwater, soil, or
3% to 5% risk of development of photodermatitis
animals should be advised to seek medical attention
in doxycycline-treated persons should be taken un-
as soon as possible. A high index of suspicion for
der consideration. Depending on travel destination,
doxycycline may also provide protection against ma-
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Phase filters Object light field distribution function f ( x ) can be consider as f ( x ) g ( x ) e So far we have discussed filters that deal with amplitude only. Let us consider a “pure” phase object of so that I ( x ) f ( x ) one cannot “see” the phase variation( x ) across the field. Phase contrast viewing If the phase variations ( x ) are
The New WBF IMP to VP Scales Technical Report of WBF Scoring Panel Technical Panel : Max Bavin, Henry Bethe, Bart Bramley, Peter Introduction This documents presents the theory and algorithms for producing the newWBF conversion tables from:The continuous scale gives a unique Victory Point (VP) to two decimalplaces for each integer IMP margin. The discrete scale, similar to existingWBF s