This outbreak was the first recognized international leptospirosis outbreak associated with the increasingly popular activity of adventure travel. Data from this outbreak investigation suggest that doxycycline may be effective as prophylaxis for leptospirosis in persons with identifiable, short-term exposure to high-risk activities and environments. Preexposure chemoprophylaxis could be increasingly important as more people engage in adventure travel and eco-tourism. In addition, physicians treating returning travelers should consider diseases such as leptospirosis in patients with a history of water exposures. Newer, rapid diagnostic assays may assist physicians in earlier and more accurate diagnosis and, therefore, earlier treatment.

Leptospirosis is a zoonotic disease of worldwide distribution that causes an acute febrile illness; the incubation period is usually 5–14 days but ranges from 2 to 30 days (9). The disease is associated with exposure to water or soil that has been contaminated by a variety of wild and domestic animals, which serve as reservoirs for leptospires and transmit infection by shedding the organisms in their urine (1). The illness is protean. It may be characterized by abrupt onset of fever, chills, myalgias, and headache, and may also include conjunctival suffusion, abdominal pain, vomiting, diarrhea, and skin rashes. Severe leptospirosis may include aseptic meningitis, jaundice, renal failure and hemorrhage; the more severe syndrome characterized by fever, meningismus, and renal and hepatic failure is referred to as Weil’s disease. Mild infections can be treated with oral tetracyclines; more severe infections generally require intravenous penicillin (9).

Among the Eco-Challenge athletes, symptoms and exposure history suggested a diagnosis of leptospirosis; this diagnosis was supported early in the investigation by laboratory testing. Our investigation showed a high attack rate in this cohort of athletes (nearly 50% in surveyed athletes). Illness was also severe, with a hospitalization rate of 36% for young, otherwise exceptionally healthy endurance athletes. On September 15, 2000, on the basis of this high attack rate and high proportion of hospitalizations, CDC recommended that all ill athletes be treated with empiric doxycycline and that asymptomatic athletes discuss the possible merits of a single dose of doxycycline with their physicians (10). In addition, asymptomatic athletes were advised to seek medical attention if signs and symptoms consistent with leptospirosis developed.

Although infection or coinfection with other pathogens in ill athletes remains a possibility, testing for antibodies to alternative pathogens commonly causing febrile disease in the tropics was negative in the serum samples tested; most ill athletes were likely infected with leptospires. The known epidemiology of leptospirosis and the epidemiologic data gathered from this investigation suggested a point source for the outbreak associated with exposure to water from the Segama River. The attributable risk of swimming in the river was 36%; those athletes whose illness could not be accounted for by swimming in the river were likely exposed to contaminated water or soil during some other race activity, such as kayaking, trekking, or contact with mud along the river banks. While our study did not find a significant association between swallowing river water and infection, a gastrointestinal route of infection after swallowing contaminated water has also been suggested (11).

Although previously reported in Malaysian Borneo, leptospirosis was not recognized as a cause of a substantial level of illness in Borneo at the time of Eco-Challenge. The known epidemiology and pathophysiology of leptospires suggest that the high attack rate among the athletes was multifactorial. Contact with water from the Segama River was preceded by prolonged treks through jungle vegetation, and all surveyed athletes reported cuts and abrasions (data not shown) that may have predisposed them to a larger inoculum of organisms (12). Another possible factor in the high attack rate may have been rainfall before the race. During Eco-Challenge, rainfall throughout much of the race was heavy, and in the 3 months preceding the event, regional monthly rainfall totals were approximately 250 mm greater than the average for the previous 3 years (National Oceanic and Atmospheric Administration, pers. comm.). Flooding, which has been associated with previous leptospirosis outbreaks, elevates the water table, saturating the soil with leptospires, preventing evaporation of contaminated animal urine, and potentially promoting the survival of leptospires in surface waters (13–16).

Leptospirosis is a relatively common zoonotic disease in the tropics (9); however, it is frequently underdiagnosed because of the nonspecific symptoms associated with infection and the difficulty confirming a diagnosis. MAT is considered the standard diagnostic criterion, but it is technically difficult, not widely available, and involves the use of live leptospires, which presents a hazard to laboratory personnel. A simple, accurate, rapid, and widely available assay for detecting leptospires is needed. In this study, initial screening for leptospires was performed with the Dip-S-Ticks immunoassay, an enzyme-linked dot immunoassay for detecting IgM antibodies; recent evaluations indicate an overall case sensitivity of 98% and specificity of 91% (17,18). The assay has benefits over previous methods of Leptospira serodiagnosis because of its ease of use and accessibility, as well as the rapidity of diagnosis; the Dip-S-Ticks assay also has greater sensitivity early in infection than other assays. Three Eco-Challenge athletes tested positive by Dip-S-Ticks but negative by IgM ELISA (data not shown). Detection of an early nascent immune response remains difficult; this low early sensitivity may partially explain the 50% seronegativity rate in surveyed athletes, given the 10-day median duration between onset of fever and drawing of serum. The inability to obtain MAT confirmation in all specimens that tested positive by rapid assay may similarly be explained by the relatively short interval between onset of fever and the drawing of serum. While MAT reactivity can be seen several days after infection, peak titers are frequently obtained in 2 to 3 weeks; sometimes, however, antibodies do not appear until 3–4 weeks after infection (1). Alternatively, serovars responsible for infection may not have been included in the testing battery used for the serum. The athletes did engage in activities that may have led to multiple exposure risks, and infection with other organisms might have accounted for a proportion of those who tested seronegative for leptospires. We tested some samples for pathogens that also cause acute febrile illness in the tropics; none was detected. However, infection with other organisms remains a possibility.

Due in part to the antigenic heterogeneity among the many different serovars of leptospires, a universally effective leptospirosis vaccine for humans has not been developed; in addition, the duration of immunity with current serovar-specific leptospiral vaccines appears to be short-lived (19). Prevention strategies for leptospirosis have traditionally relied on protective barriers such as wearing rubber boots and gloves and avoiding high-risk areas. However, several studies of persons from areas endemic for leptospirosis and of military recruits with no known prior exposure to leptospires have shown that doxycycline given before or shortly after exposure can reduce illness and death caused by leptospirosis (2–4). In our study, athletes who took doxycycline for malaria prophylaxis were less likely to become ill; although this finding did not reach statistical significance, we may not have had sufficient data to detect significance. Persons who travel to areas where leptospirosis is endemic or epidemic and who participate in high-risk exposure activities involving prolonged water exposure may be at increased risk for leptospirosis (11,14,20,21) and may benefit from chemoprophylaxis. Until additional efficacy data are available, persons at high risk for leptospirosis should consider chemoprophylaxis with doxycycline, 200 mg by mouth, beginning 1–2 days before exposure and continuing for the duration of suspected exposure. The role of other antimicrobial agents is not clear. Further randomized, controlled studies assessing the utility and efficacy of doxycycline and other antimicrobial agents for the prophylaxis of leptospirosis are needed.

More people are participating in exotic travel, adventure sports, and eco-tourism, and as a result, the potential for contact with pathogens less common in the temperate, industrialized world, such as Leptospira, is likely to increase. Outbreaks of leptospirosis have previously been documented in athletes participating in such activities as kayaking (14), swimming (20), and triathlons (11). Recently, leptospirosis in endurance athletes has been the subject of several reports (22–24). In addition, previous outbreaks of infectious disease attributable to other unusual pathogens have been documented in adventure travelers (25,26). Since leptospires are a common cause of febrile illness in the tropics, physicians should evaluate travelers with febrile illness returning from these areas for this and other emerging infections.