Neurologic Infections in Travelers

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


Semin Neurol. 2019;39(3):399-414. 

In This Article

Scrub Typhus


Scrub typhus, also known as bush typhus, is a rickettsial infection caused by Orientia tsutsugamushi, a gram-negative obligate intracellular bacillus. Up to one million people in the Asia-Pacific area contract the illness each year, and upwards of one billion people are at risk of infection.[25] The endemic region covers an area from Russia in the far north, to Pakistan in the west, Australia in the south, and Japan in the west. With globalization, infections have been reported in North and South America and Africa, associated with travel through endemic regions.[25] Case reports of local infection in the Middle East and Chile, outside the Asia-Pacific triangle, indicate a potential new global threat.[26]

Life Cycle, Ecology, and Species

Orientia tsutsugamushi is transmitted via the bite of the larval stage of the trombiculid mite (chigger) of the genus Leptotrombidium. Chiggers thrive in tropical climates, especially in areas of heavy scrub vegetation and during the rainy season.[27] Infection is spread via the bite of the chiggers, which leads to development of an eschar on the human host, containing a high bacterial load. The bacteria will then spread through blood and lymphatic fluid.[26]

Clinical Manifestations

After a bite, the incubation period ranges from 6 to 21 days, with headache and fever almost always present during the initial stages of infection.[27] Orientia tsutsugamushi invades peripheral endothelial cells and blood. Clinical manifestations include high fever, generalized headache, and myalgias. Systemic illness can lead to pulmonary and cardiac collapse.[25] Neurologic manifestations are highly variable, with reports of meningitis, encephalitis, cranial nerve palsies, cerebellitis, stroke due to vasculitis, central venous thrombosis, parkinsonism, transverse myelitis, acute inflammatory demyelinating polyradiculoneuropathy, peripheral neuropathy, and psychiatric manifestations with visual hallucinations.[28] The risk of developing neurologic manifestations is unknown. A small series of 25 infected patients without clinical CNS findings had CSF findings of mononuclear pleocytosis in 48% and PCR identification of the bacteria in 24% indicates that CNS invasion can occur without clinical manifestations.[29] Case fatality is up to 30% in untreated patients.[27]


The clinical presentation and history along with travel or residence in endemic areas help support the diagnosis of scrub typhus. Presence of an eschar can be helpful but is not always present. CSF analysis typically reveals a mononuclear pleocytosis with normal glucose levels.[27,28] The gold standard for diagnosis is indirect immunofluorescence assay; however, the test is expensive and requires extensive training to perform; in addition, false-negative results are common when the assay is performed early during the clinical course. Other serological tests include the immunoperoxidase assay, with approximately 80% sensitivity, the Weil–Felix test, ELISA, and immunochromatographic tests.[25] ELISA is sensitive and specific and can detect IgM antibodies early during the course of infection.[27] Molecular-based studies, such as PCR, can also be used on CSF.[25] No pathognomonic neuroimaging findings are associated with scrub typhus.


A recent Cochrane review of various antibiotic treatments showed few treatment failures with tetracycline, doxycycline, azithromycin, and rifampicin. The review included head-to-head trials of tetracycline to doxycycline, azithromycin to doxycycline, and doxycycline to rifampicin, which did not reveal any significant differences in treatment failure, or resolution of fever within 48 hours in any of the comparisons.[30] No vaccine is currently available for scrub typhus, and due to the antigenic heterogeneity, future development is unlikely. Prevention targets vector control, avoidance, and chemoprophylaxis. Protective measures include avoiding areas of outbreak, and limiting potential areas of exposure through appropriate clothing, insect repellent (i.e., DEET), and insecticide use. In a study of Taiwanese military personnel, chemoprophylaxis with a weekly dose of doxycycline reduced infection rates by 80%.[25,27]