Neurologic Infections in Travelers

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

Disclosures

Semin Neurol. 2019;39(3):399-414. 

In This Article

Rabies

Epidemiology

Rabies is a neurotropic virus in the genus Lyssavirus. Transmission is typically through the bite of an infected animal, with dog bites accounting for 85 to 95% of cases in Asia and Africa. The most common reservoirs are carnivores, bats, and dogs. The virus is found worldwide. Rabies is responsible for more than 60,000 human deaths annually.[69] Over 95% of deaths occur in Asia and Africa. The rate of rabies exposure among travelers is estimated to be 16 to 20 per 100,000 travelers.[70] Some countries have become "rabies-free," but with travel and susceptibility of reintroduction from other countries this typically does not last.[69]

Life Cycle, Ecology, and Species

The rabies virus is a single-stranded RNA genome. The virion is not viable outside the host and can be inactivated by sunlight, heat, or desiccation. There have been seven genotypes identified, with most human infections occurring from genotype 1 (classical).[69]

Clinical Manifestations

The incubation period is typically 2 to 3 months but can range from 1 week to 1 year. The virus infects the peripheral nervous system, traveling retrograde via synapses in axonal vesicles. The virus generally preserves the neuronal network and is effective in evading an immune response. Initial symptoms are usually flu-like, followed by paresthesias radiating from the bite. Most commonly, patients will progress to the encephalitic form of rabies, characterized by fever, hydrophobia, and pharyngeal spasm with rapid progression to coma and death. A rarer clinical form is paralytic rabies, which can mimic GBS with ascending paralysis. Death typically occurs within 2 weeks of coma onset. Autonomic nervous system and cardiac involvement often occur with advanced stages of disease. Case-fatality rates are extremely high for patients who develop neurological disease, approaching 100%.[70]

Diagnosis

History and clinical presentation can be very helpful in making the diagnosis of rabies. History of a bite from a potentially infected animal is very important to obtain, as well as identifying infected animals, if possible, for observation, biopsy, or necropsy to determine if the animal was rabid. Definitive diagnosis in the infected human requires at least two positive tests: virus isolation or positive RT-PCR in saliva, detection of antibodies in serum or CSF, and detection of viral antigen via RT-PCR or immunofluorescence of skin biopsy from the nape of the neck. The combination of samples and testing increases sensitivity to 100% compared with stand-alone testing. Antibody testing is unreliable, as testing may not be positive until late in the course.[69,70]

Treatment

If concern for exposure is high, postexposure prophylaxis should be administered with a combination of vaccine and human rabies immune globulin within 0 to 3 days of exposure. Extensive wound washing should also be performed. Of note, the use of human rabies immune globulin has been limited due to inability to cross blood–brain barrier; however, new drug-delivery mechanisms are improving delivery. Antivirals that have been tested for rabies include ribavirin, amantadine, interferon-alfa, and favipiravir. On rare occasions people have survived a rabies infection. The Milwaukee protocol was a proposed treatment regimen that includes therapeutic coma, ketamine infusion, amantadine, and the screening/prophylaxis/management of cerebral vasospasm, although there is a significant lack of efficacy. The more aggressive approach includes a combination of inactivated vaccine, human rabies immune globulin, antiviral therapy, and aggressive critical care support.[69–71] Given the high mortality of rabies, a palliative approach to alleviate suffering should be available. Rabies is a vaccine-preventable disease. Vaccine administration has been targeted to preexposure for people in high-risk occupations, travelers to endemic regions, and dogs. The vaccine is highly effective. Otherwise, prevention has been targeted to education on avoiding bites from mammals and identifying abnormal behavior in animals with subsequent elimination.[69–71]

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