Neurologic Infections in Travelers

Malveeka Sharma, MD, MPH; Joseph R. Zunt, MD, MPH


Semin Neurol. 2019;39(3):399-414. 

In This Article



Leptospirosis is an under-recognized zoonotic disease caused by the bacterium Leptospira. Estimates of leptospirosis vary from 0.1 to 1 per 100,000 people in temperate climates to 10 per 100,000 in tropical climates; during epidemics, rates can exceed 100 per 100,000 people.[31] Humans are infected through contact with water contaminated by urine of infected animals. Epidemics have been associated with times of flooding. Some occupations are at higher risk of infection, including rice farmers, military personnel, and veterinarians.

Life Cycle, Ecology, and Species

Leptospira are tightly coiled spirochetes that are obligate aerobes. Most animals can become carriers of this infection, but the most commonly implicated carriers are rodents.[32]

Clinical Manifestations

Complications of leptospirosis include renal, hepatic, and neurological abnormalities. The rate of neurologic manifestations from leptospirosis is unknown, but has been reported to affect as many as 10 to 20% of infected patients.[33] The progression to neurological disease typically follows a first phase characterized by altered mentation and meningismus. The most common neurological manifestation is aseptic meningitis.[34] Other presentations include facial palsy, Guillain–Barre syndrome (GBS), myeloradiculopathy, myelopathy, encephalitis, meningoencephalitis, intracranial hemorrhage (commonly subarachnoid or extradural), movement disorders, ataxia, dysautonomia, mononeuritis, polyneuritis, and polymyositis.[35] The neurological presentation is believed to be related to the host immune response, rather than direct bacterial pathogenesis. Uveitis is also a common manifestation.[34,36]


Diagnosis of leptospirosis is difficult, as clinical symptoms vary greatly and can mimic many other infectious diseases. A survey of GeoSentinel sites revealed suboptimal use of diagnostic tests which has resulted in underestimation of leptospirosis.[37] Suspicion should be high in travelers who have been in endemic areas, people with high-risk occupations, and recent activities involving fresh-water exposure. The erythrocyte sedimentation rate is typically elevated, and thrombocytopenia and leukocytosis may be present. CSF typically reveals elevated intracranial pressure, lymphocytic pleocytosis, elevated protein, and normal glucose. ELISA for leptospira antibody has 100% specificity and 94% sensitivity. The microscopic agglutination test is considered the gold standard but is not widely available.[32,34,38] As the clinical presentation and history may not narrow the differential diagnosis, next-generation sequencing has demonstrated promise as a new tool for identifying this organism.[36]


Although there is no standardized treatment algorithm, penicillin, doxycycline, as well as third- and fourth-generation cephalosporins are effective. A Cochrane review revealed no impact of antibiotic therapy upon mortality, but it may shorten the duration of clinical illness in survivors.[39] Due to high antigenicity of the Leptospira bacterium, successful development of an effective vaccine has been elusive. In developed countries, most pigs, cattle, and canines are vaccinated, with most vaccines requiring boosters.[32] The most important control measure for preventing human leptospirosis is avoiding potential sources of infection such as stagnant water and animal farm water runoff, rodent control, and protection of food from animal contamination. The WHO started the Leptospirosis Burden Epidemiology Reference Group (LERG) to increase efforts at lowering the incidence of leptospirosis in developing countries.[31] Chemoprophylaxis, with weekly doxycycline, was studied in a group of 940 U.S. soldiers. Twenty cases of leptospirosis occurred in the placebo group (attack rate: 4.2%) and one case in the treatment arm (attack rate: 0.2%).[40] There are no strong recommendations for chemoprophylaxis, although it may be considered for people at high risk of exposure.