Travel-acquired leptospirosis

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- References
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