Etiology

Leptospira are aerobic spiral bacteria with a terminal hook at 1 or both ends. Pathogenic leptospires belong to a single species, Leptospira interrogans, which includes >200 distinct serovars. A single serovar can produce a variety of distinct syndromes, and a single clinical manifestation may be caused by multiple serotypes. Nonpathogenic leptospires are classified as Leptospira biflexa, with >60 serovars.

Epidemiology

Most human cases of leptospirosis occur in tropical and subtropical countries, but the distribution is worldwide. The rat is the principal source of human infection, but leptospires infect many species of domestic and feral animals, including livestock, birds, fish, dogs, cats, and wild animals, including reptiles. Infected animals excrete spirochetes in their urine for prolonged periods. Most human cases result from occupational exposure to water or soil contaminated with rat urine. Groups with a high incidence of leptospirosis include persons exposed occupationally or recreationally to contaminated soil or water, agricultural workers, veterinarians, abattoir workers, meat inspectors, rodent control workers, laboratory workers, and workers in other occupations that require contact with animals. The major animal reservoir in the USA is the dog. Transmission via animal bites and directly from person to person has been rarely reported.

Pathology and Pathogenesis

Leptospires enter humans through abrasions and cuts in the skin or through mucous membranes. After penetration, they circulate in the bloodstream to all body organs, causing endothelial lining damage of small blood vessels with secondary ischemic damage to the end organs.

Clinical Manifestations

The spectrum of human leptospirosis ranges from asymptomatic infection (most cases) to severe disease with multiorgan dysfunction and death. The onset is usually abrupt, and the illness tends to follow a biphasic course (Fig. 212-1). After an incubation period of 7-12 days, there is an initial or septicemic phase lasting 2-7 days, during which leptospires can be isolated from the blood, cerebrospinal fluid (CSF), and other tissues. This phase may be followed by a brief period of well-being before onset of a second symptomatic immune or leptospiruric phase. This phase is associated with the appearance of circulating antibody, disappearance of organisms from the blood and CSF, and appearance of signs and symptoms associated with localization of leptospires in the tissues. Despite the presence of circulating antibody, leptospires can persist in the kidney, urine, and aqueous humor. The immune phase can last for several weeks. Symptomatic infection may be anicteric or icteric.

Figure 212-1 Stages of anicteric and icteric leptospirosis. Correlation between clinical findings and presence of leptospires in body fluids, CSF, cerebrospinal fluid.

(Reprinted with permission from Feigin RD, Anderson DC: Human leptospirosis, CRC Crit Rev Clin Lab Sci 5:413–467, 1975. Copyright CRC Press, Inc, Boca Raton, FL.)

Diagnosis

Leptospirosis should be considered in the differential diagnosis of acute flulike febrile illnesses with a history of direct contact with animals or with soil or water contaminated with animal urine. This disease may be difficult to distinguish clinically from dengue or malaria.

Use of Warthin-Starry silver staining, polymerase chain reaction, and immunofluorescent and immunohistochemical methods permits diagnosis of leptospirosis from infected tissue or body fluids. The diagnosis is most often made by serologic testing and less often by isolation of the infecting organism from clinical specimens. Serologic tests for Leptospira include genus-specific and serogroup-specific tests. The reference method is the microscopic agglutination test, a serogroup-specific assay using live antigen suspension of leptospiral serovars and dark-field microscopy for agglutination. A 4-fold or greater increase in titer in paired sera confirms the diagnosis. Agglutinins usually appear by the 12th day of illness and reach a maximum titer by the 3rd wk. Low titers can persist for years. Approximately 10% of infected persons do not have detectable agglutinins, presumably because available antisera do not identify all Leptospira serotypes. Enzyme-linked immunosorbent assay (ELISA) methods, including an immunoglobulin M-specific dot-ELISA test, are also available. Phase-contrast and dark-field microscopy are insensitive for spirochete detection.

Unlike other pathogenic spirochetes, leptospires can be recovered from the blood or CSF during the first 10 days of illness and from urine after the 2nd week by repeated culture of small inoculum (i.e., 1 drop of blood or CSF in 5 mL of medium) on commercially available media-containing rabbit serum or bovine serum albumin and long-chain fatty acids. However, the inoculum in clinical specimens is small, and growth can take up to 13 wk.

Treatment

Despite in vitro sensitivity of Leptospira to penicillin and tetracycline, the effectiveness of these antibiotics in treating human leptospirosis is unclear due to the naturally high spontaneous recovery rates. Some studies suggest that initiation of treatment before the 7th day shortens the clinical course and decreases the severity of the infection; thus treatment with penicillin or tetracycline (in children ≥9 yr of age) should be instituted early when the diagnosis is suspected. Parenteral penicillin G (6-8 million U/m²/day divided every 4 hr IV for 7 days) is recommended, with tetracycline (10-20 mg/kg/day divided every 6 hr PO or IV for 7 days) as an alternative for patients allergic to penicillin. Oral amoxicillin is an alternative therapy for children <9 yr of age.

Prevention

Prevention of human leptospirosis infection is facilitated by instituting rodent control measures and avoiding contaminated water and soil. Immunization of livestock and family pets is recommended as a means of eliminating animal reservoirs. Attempts at a human vaccine have been challenging. Protective clothing should be worn by persons at risk for occupational exposure. Leptospirosis has been prevented in American soldiers stationed in the tropics by administering doxycycline (200 mg PO once a week) as prophylaxis. This approach may be similarly effective for travelers to highly endemic areas for short periods.