Author(s): Ilana Schafer, Renee Galloway, Robyn Stoddard

Infectious Agent

Leptospira spp., the causative agent of leptospirosis, are obligate aerobic, gram-negative spirochete bacteria.

Transmission

Leptospira are transmitted through abrasions or cuts in the skin, or through the conjunctiva and mucous membranes. Macerated skin resulting from prolonged water exposure is another suspected route of infection. Humans can be infected by direct contact with urine or reproductive fluids from infected animals, through contact with urine-contaminated freshwater sources or wet soil, or by consuming contaminated food or water. Infection rarely occurs through animal bites or human-to-human contact. Rodents are an important reservoir for Leptospira, but most mammals, including dogs, horses, cattle, and swine, and many wildlife species, can be infected and shed the bacteria in their urine.

Epidemiology

Leptospirosis has a worldwide distribution; incidence is greater in tropical climates, however. Regions with the highest estimated morbidity and mortality include parts of sub-Saharan Africa, parts of Latin America, and in the Caribbean, South and Southeast Asia, and Oceania. Travelers to endemic areas are at increased risk when participating in recreational freshwater activities (e.g., boating, swimming), particularly after heavy rainfall or flooding. Prolonged exposure to contaminated water and activities that involve head immersion or swallowing water increase the risk for infection.

Participating in activities involving mud (e.g., adventure races) also increases a traveler’s risk for infection, as does working directly with animals in endemic areas, especially when exposed to their body fluids, and visiting or residing in areas with rodent infestation. Leptospirosis occurs most commonly in adult males. The estimated worldwide annual incidence is >1 million cases, including ≈59,000 deaths.

Outbreaks can occur after heavy rainfall or flooding in endemic areas, especially in urban areas of low- and middle-income countries, where housing conditions and sanitation are poor and rodent infestation is common. Outbreaks of leptospirosis have occurred after flooding in popular US travel destinations, including Florida, Hawaii, Puerto Rico, and the US Virgin Islands. Nearly half of the leptospirosis cases reported in the continental United States during 2014–2018 that had an identified geographic source of infection were associated with international travel. Most US cases are reported outside the continental United States in the domestic travel destinations of Hawaii and Puerto Rico.

Clinical Presentation

The incubation period for leptospirosis is 2–30 days, but illness usually occurs 5–14 days after exposure. Most infections are thought to be asymptomatic, but clinical illness can present as a self-limiting acute febrile illness, estimated to occur in ≈90% of clinical infections, or as a severe, potentially fatal illness with multiorgan dysfunction in 5%–10% of patients. In patients who progress to severe disease, the illness can be biphasic, with a temporary decrease in fever between phases.

The acute, septicemic phase lasts ≈7 days and presents as an acute febrile illness with symptoms including headache, which can be severe and include photophobia and retro-orbital pain; chills; myalgias, characteristically involving the calves and lower back; conjunctival suffusion, characteristic of leptospirosis but not occurring in all cases; nausea; vomiting; diarrhea; abdominal pain; cough; and rarely, a skin rash.

The second or immune phase is characterized by antibody production and the presence of leptospires in the urine. In patients who progress to severe disease, clinical findings can include cardiac arrhythmias, hemodynamic collapse, hemorrhage, jaundice, liver failure, aseptic meningitis, pulmonary insufficiency, and renal failure. The classically described syndrome, Weil’s disease, consists of renal and liver failure.

Among patients with severe disease, the case-fatality ratio is 5%–15%. Severe pulmonary hemorrhagic syndrome is a rare but severe form of leptospirosis that can have a case-fatality ratio >50%. Poor prognostic indicators include older age, development of altered mental status, respiratory insufficiency, or oliguria.

Diagnosis

Submit a combination of samples for leptospirosis testing, including serum samples; whenever possible, obtain acute and convalescent sample pairs. During early disease, PCR analysis of whole blood (collected in the first week of illness) and urine (collected after the first week of illness) can be helpful. PCR analysis of cerebrospinal fluid (CSF) also can be helpful in diagnosing patients with signs of meningitis.

Diagnosis of leptospirosis is often based on serology; microscopic agglutination test (MAT) is the reference standard and can only be performed at certain reference laboratories. Various serologic screening tests are available at commercial laboratories, including ELISA and ImmunoDOT/DotBlot rapid diagnostic tests. The use of IgM-specific serologic screening tests is recommended, and positive screening tests should be confirmed with MAT.

Detection of the organism in acute whole blood using real-time PCR can provide a more timely diagnosis during the early, septicemic phase, and PCR also can be performed on CSF or convalescent urine. A positive PCR result is confirmatory for infection. Culture is insensitive, slow, and requires special media; it is therefore not recommended as the sole diagnostic method.

The Zoonoses and Select Agent Laboratory at the Centers for Disease Control and Prevention (CDC) performs MAT and PCR for diagnosis of leptospirosis as well as culture identification and genotyping of isolates. See clinician information on diagnostic testing at CDC and sample submission instructions. Clinicians can consult on a suspected leptospirosis case by contacting CDC’s Bacterial Special Pathogens Branch, by calling the CDC Emergency Operations Center (770-488-7100). Leptospirosis is a nationally notifiable disease see the Council for State and Territorial Epidemiologists’ case definition.

Treatment

If leptospirosis is suspected, initiate antimicrobial therapy as soon as possible, without waiting for diagnostic test results. Early treatment can be effective in decreasing the severity and duration of infection. For patients with mild symptoms, doxycycline is a drug of choice, unless contraindicated; alternative options include ampicillin, amoxicillin, or azithromycin. Intravenous penicillin is the drug of choice for patients with severe leptospirosis; ceftriaxone and cefotaxime are alternative antimicrobial agents. As with other spirochetal diseases, antibiotic treatment of patients with leptospirosis might cause a Jarisch-Herxheimer reaction; the reaction is rarely fatal. Patients with severe leptospirosis might require hospitalization and supportive therapy, including intravenous hydration and electrolyte supplementation, dialysis in cases of oliguric renal failure, and mechanical ventilation in cases of respiratory failure.

Prevention

The best way to prevent infection is to avoid exposure. Advise travelers to avoid exposure to potentially contaminated bodies of freshwater, flood waters, potentially infected animals or their body fluids, and areas with rodent infestation. Educate travelers who might be at increased risk for infection to consider taking additional preventive measures (e.g., wearing protective clothing, especially footwear), instructing them to cover cuts and abrasions with occlusive dressings, counseling them on boiling or chemically treating potentially contaminated drinking water, and providing chemoprophylaxis. Limited studies have shown that chemoprophylaxis with doxycycline (200 mg orally, weekly) begun 1–2 days before and continuing through the period of exposure, might be effective in preventing clinical disease in adults and could be considered for people at high risk and with short-term exposures. No human vaccine is available in the United States.

CDC website: Leptospirosis