Approach to the International Traveler With Neurological Symptoms

Kiran T Thakur; Joseph R Zunt


Future Neurology. 2015;10(2):101-113. 

In This Article

Headache With Meningismus

While there are many potential causes of headache with meningeal signs in the returning traveler, key historical features that allow the clinician to narrow the list of potential etiologies include the timing of symptom onset and travel location(s). In a traveler presenting with acute headache and signs of meningismus, acute bacterial meningitis must be considered and evaluated immediately, with presumptive treatment initiated when indicated. Of note, the clinical presentation may be subtle in at least 15% of patients, particularly young children, elderly patients and those who are immunocompromised – manifesting with lethargy and poor eating. Outbreaks of meningitis caused by group A strains of Neisseria meningitidis are common in the sub-Saharan Africa meningitis belt and a high suspicion for N. meningitis should be present in patients who traveled to this region during the dry season.[10] The prevalence of bacterial meningitis in all groups of returning travelers from the meningitis belt is unknown. In the past, travelers returning from Islam's Hajj pilgrimage were at increased risk for contracting meningitis or becoming carriers of N. meningitidis. In August 1987, an outbreak of group A meningococcal meningitis occurred during the annual pilgrimage to Mecca, Saudi Arabia, resulting in an attack rate among American pilgrims of 640 per 100,000.[11] Fortunately, there have been no Hajj-related outbreaks since the introduction in 2002 of the tetravalent meningococcus vaccine as a requirement for a Hajj visa. The vaccine does not cover all types of N. meningitidis and therefore should remain in the differential.[12] Although studies are few, the estimated incidence of bacterial meningitis in southeast Asia ranges from 18.3 to 24.6/100,000 people, with the highest incidence in Thailand, though the incidence in travelers is not known.[13]

Evaluation of the patient with subacute and chronic meningitis should assess not only the travel history, but also the host immune status and specific exposures (including bites, cave exploration, sick contacts). Japanese encephalitis (JE) should be strongly considered in patients who have traveled to continental south Asia and Indonesia. Following a 2-week incubation period, fever and meningismus develop, often associated with parkinsonian features, which can be an important diagnostic clue as the virus often targets the basal ganglia.[14–16] Diagnosis is frequently made clinically, but confirmatory tests are available, including the hemagglutination inhibition test, enzyme-linked immunosorbent assay and virus isolation from blood or CSF; unfortunately, all have a low sensitivity.[17] From 1973 through 2011, there were 58 published reports of travel-associated JE among travelers from nonendemic countries. From the time of licensure of a JE vaccine in the USA in 1992 through 2011, only seven JE cases among US travelers have been reported to the CDC. The overall incidence of JE among people from nonendemic countries traveling to Asia is estimated to be less than one case per 1,000,000 travelers. However, expatriates and travelers who stay for prolonged periods in rural areas with active JE virus transmission are likely at similar risk as the susceptible resident population (5–50 cases per 100,000 children per year).[18] In addition to Japanese encephalitis, nematodal infection (Angiostrongylus cantonensis, Gnathostoma spinigerum and Baylisascaris procyanis) should be considered in patients traveling through these regions.[19] A history of consuming raw fish or vegetables, in the setting of CSF eosinophilic pleocytosis, supports infection by any of these pathogens. Outbreaks have been described in travelers returning from the pacific islands in southeast Asia, the Caribbean and Cuba.[20–22] Analysis of the CSF in a returning traveler should include a differential including determination of CSF eosinophil count.

For travelers to Eastern Europe, especially those on wilderness trips, tick-borne encephalitides (TBE) should be included in the differential diagnosis. TBE is most often transmitted to humans through the bite of an infected Ixodes species tick, with most cases occurring between April and November, and peaks during early and late summer. Deciduous forests are the main endemic regions for infection. Infection can also be transmitted through consumption of unpasteurized dairy products from infected goats, sheep or cows. The risk of acquiring TBE for an unvaccinated visitor to a highly endemic area during the TBEV transmission season has been estimated at 1 case per 10,000 person-months of exposure. Most TBEV infections in travelers result from tick bites acquired in forested areas through activities such as camping; hiking; fishing; bicycling; collecting mushrooms, berries or flowers; and outdoor occupations such as forestry or military training.[23] The same ticks that transmit TBE can also transmit other pathogens, including Borrelia burgdorferi (Lyme disease), Anaplasma phagocytophilum (anaplasmosis) and Babesia spp. (babesiosis), which can also present with subacute headache and meningismus.[23]

When evaluating an immunocompromised patient with chronic meningismus or headaches, special consideration should be given to cryptococcal meningitis. Cryptococcal meningitis, most commonly caused by Cryptococcal neoformans, can present insidiously with fever, nausea, vomiting, headache, altered mental status and meningismus. Cryptococcal meningitis has a worldwide distribution, with high rates of infection in sub-Saharan Africa and North America, where the encapsulated yeast is found in contaminated soil, avian excrement and the rinds of citrus fruits.[24]C. gattii may cause chronic meningitis in immunocompetant hosts and is endemic to subtropical locations with outbreaks reported in the northwestern USA and British Columbia.[25] A case of infection has been described in a traveler to this region.[26] Diagnostic approach varies by region, with India ink staining of centrifuged CSF most often used in resource-constrained settings. A positive CSF fungal culture or detection of cryptococcal capsular polysaccharide antigen (CrAg) in CSF confirms the diagnosis. Coccidiomycosis (Coccidiomycosis immitus) is a fungus endemic to southwestern USA, northern Mexico and areas of South America, where it is found primarily in soil. Clusters of coccidioidomycosis cases among groups of travelers have been observed, including clusters in Pennsylvania[27] and Washington State[28] among church group members who had visited Mexico. Another cluster occurred in US Marine reserves from Tennessee who completed 3 weeks of training exercises in southern California.[29] CNS coccidiomycosis typically presents as a basilar meningitis and is often accompanied by a diffuse reticulonodular infiltrative pneumonia. As the organism is difficult to grow on CSF culture, presumptive diagnosis is often made through complement-fixation antibody assay, detection of C. immitus-specific antibodies or antigens or identification of C. immitus spherules in tissue, sputum, bronchoalveolar lavage (BAL) fluid or other body fluid.[30] Another cause of chronic meningitis is tuberculous meningitis (TBM), which is highly endemic in southeast Asia, India and South Africa. Immunosuppressed patients have a higher likelihood of developing disseminated tuberculosis, and suspicion for TBM should be high in travelers who are immunosuppressed and have been in close contact with persons with TB while in these regions. Travelers who anticipate possible prolonged exposure to TB including those who spend time in hospitals, prisons or homeless shelters, or those who stay for years in an endemic country should have a 2-step tuberculin skin test (TST) or a single IFN-γ release assay (IGRA), either the QuantiFERON TB test or T-SPOT TB test, before leaving the USA.[31] Importantly for travelers, the risk of TB transmission on an airplane does not appear to be higher than in any other enclosed space.[31] Marienau et al. presented aggregated data on 131 incidents evaluated by the Centers for Disease Prevention and Control (USA) where, among 758 successfully traced and tested contacts, one converter with no risk factor for prior TB infection was found.[32] Blastomycosis (Blastomyces dermatitides) is a thick-walled yeast that can cause subacute meningitis and is endemic to midwestern and southeastern USA, and the Canadian provinces bordering the Great Lake.[33] Sporadic cases have been described in continental Africa, the Arabian Peninsula and the Indian subcontinent. Diagnostic clues include pulmonary cavitary lesions and a pathognomonic fungating cutaneous skin lesion (Table 2). Diagnosis is made by CSF culture, though the organism typically takes several days to grow.[33]

In patients who have had unprotected intercourse while abroad, HIV seroconversion syndrome should be considered. Patients often present with fever, lymphadenopathy, myalgias and pharyngitis with associated meningeal signs that develop over a few weeks.[34] HIV testing should be performed on all patients who had unprotected intercourse while abroad. In patients with a history of painless genital ulceration (chancre), syphilitic meningitis should be considered (Table 2). Serologic testing and CSF VDRL should be performed, although a negative test result does not rule out the diagnosis.

Treatment algorithms for the diagnoses listed above are available in detail through a variety of resources including the Infectious Disease Society of America,[35] the CDC[36] and the WHO.[37]