Introduction

Increasing rates of travel are a major driver to the spread of infectious diseases internationally. Expanding globalization has led to the emergence of infectious diseases in travel medicine, including the recent global outbreak of Zika virus. International tourist arrivals rose to 1.2 billion in 2015, and annual rates are expected to increase by over 3% each year, reaching 1.8 billion by 2030, particularly in tropical regions [1]. Neuroinfectious diseases carry the most significant risk of morbidity and mortality among infections. In order to reduce the risk, accurately diagnose, and optimize treatment, it is imperative for healthcare providers to be well-versed in risk factors, clinical presentations, and management strategies of neuroinfectious diseases acquired internationally.

Table 1 Aspects of the pre-travel consultation for clinicians
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Pre-travel Assessment

Travelers should receive an individualized risk assessment that is followed by appropriate prevention strategies. Special conditions, including individuals that are pregnant, immunocompromised, or traveling with infants/children, require additional considerations that are highlighted in the following sections. Appropriate vaccination and prophylactic medications should be a primary consideration when assessing travel plans. According to the World Health Organization (WHO), vaccination prevents up to six million deaths annually [2]. Travelers should be up-to-date on their routine immunizations and receive any recommended vaccinations 4–6 weeks prior to travel. Table 2 outlines information on international travel vaccinations relevant to some neuroinfectious diseases. Travel-related risk factors (e.g., mosquito bites, poor hygiene, contaminated foods, animal contact), preventative education, emergency resources, self-treatment options, and other considerations should be discussed prior to travel (Table 1). For some diseases that require post-exposure prophylaxis, such as rabies, travelers should also prepare an emergency response plan [4].

Table 2 Vaccinations available for select neuroinfectious diseases
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Immunocompromised Travelers

Moderately and severely immunocompromised travelers carry a higher risk of serious infection during and after travel [5]. Careful considerations must be taken for immunocompromised travelers, including assessment of the level of immunosuppressed state, vaccination contraindications depending on disease or condition, vaccination interactions with current medications, and healthcare options while traveling in the event of emergency [6•]. In general, inactive vaccinations are considered safe, but may not elicit an adequate protective response. Follow-up serological testing is suggested to determine conferred immunity and whether boosters are necessary [7]. Live vaccination, such as the yellow fever vaccine, is contraindicated in severely immunocompromised individuals regardless of circumstance due to the risk of life-threatening adverse reactions [6•]. Mild to moderately immunocompromised individuals should only receive live vaccinations when unavoidable travel-related risks outweigh the vaccination risk [6•, 8].

Travelers with Human Immunodeficiency Virus

Asymptomatic HIV-infected adults with CD4 cell counts ≥ 500/mm3 can be vaccinated per standard recommendations [6•]. Asymptomatic HIV-infected adults with CD4 cell counts of 200–499/mm3 are considered to have limited immune suppression and should follow vaccination recommendations as outlined in Table 2. Symptomatic HIV-infected adults or those with CD4 cell counts of < 200/mm3, as well as patients with a history of AIDS-defining illness without immune reconstitution, are considered to be severely immunocompromised. These individuals should not receive live viral or bacterial vaccination due to risk of disseminated infection (Table 2). In addition, inactive vaccinations are considered inadequate in eliciting a protective response, and therefore, revaccination should be administered after immune reconstitution with antiretroviral therapy [6•]. For maximal vaccine response with minimal risk, it is advised to administer vaccinations at least 3 months after immune reconstitution [6•].

Specific Considerations in Patients with Neurological Conditions

Multiple Sclerosis

Though inactive vaccines including hepatitis B, influenza, pneumococcal disease, and tetanus vaccines are not associated with an increase in short-term risk of relapse, it is recommended that vaccination be delayed during multiple sclerosis (MS) relapses until the patient’s condition has stabilized or improved [6•, 32, 33]. In general, it is recommended that MS patients who are experiencing a serious relapse that affects their ability to carry out activities of daily living should defer vaccination until 4–6 weeks after the onset of the relapse [6•]. Inactivated vaccines are generally considered safe for people with MS, including those who are taking interferon medications, teriflunamide, glatiramir acetate, fingolamide, alemtuzamab, mitoxantrone, dimethyl fumarate, or natalizumab [33, 34]. Live, attenuated vaccines are generally not recommended for patients with MS. For patients who are prescribed ocrelizumab, all necessary vaccinations should be administered at least 6 weeks before a person starts treatment. [33, 35]. No live attenuated or live vaccines should be given during treatment or following treatment until B cells have returned to normal levels [33, 35]. For more detailed vaccine recommendations for MS patients, refer to Rutschmann, et al. [33] for the American Academy of Neurology guidelines and Mailand & Frederikson [34] for a systematic review.

Neuro-oncology Patients

Pre-travel assessment for cancer patients must take into consideration the severity of their illness, the individual’s physical capabilities, the mode of travel, and the travel destination. Travel may need to be delayed if a patient is undergoing chemotherapy, anticipating chemotherapy, or within 3 months of their last treatment [36]. If a patient is capable of travel, appropriate arrangements with healthcare providers abroad should be made prior to travel, including emergency care. Medication arrangements with special considerations of controlled drugs should also be made [36]. Patients with a history of cancer with malignancy in remission who completed their last chemotherapy treatment at least 3–6 months prior are able to be immunized similar to the general population [6•, 36].

Patients on Immunosuppressive Medications

Patients taking high-dose corticosteroids (receiving a dose of > 2 mg/kg body weight or ≥ 20 mg of prednisone or equivalent per day in patients weighing > 10 kg, who are receiving therapy ≥ 14 days), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents, tumor necrosis factor blockers, and other biologic agents are considered to be severely immunosuppressed [6•]. These patients should not receive live vaccinations due to the compromised host immunity, and inactive vaccinations may not elicit a protective response (Table 3). For patients receiving eculizumab, both MenACWY and MenB vaccines are recommended prior to treatment due to increased incidence of meningococcal infection [31]. Worryingly, recent studies suggest that eculizumab interference with antimeningococcal antibodies impedes conferred resistance from the vaccination [31]. Antimicrobial prophylaxis with penicillin is now recommended for long-term disease prevention [31].

Table 3 Immunosuppressive biologic agents that preclude the use of live vaccines [6•]
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Pregnant Travelers

Women that are pregnant should receive pre-travel consultation with an obstetrician to establish the gestational age of the pregnancy, evaluate potential high-risk conditions, and identify the mother’s blood type and Rh status [11]. An individualized assessment for pregnant travelers should consider the risk versus benefits for any vaccination, special contraindications (Table 2), and important considerations regarding the recent Zika virus outbreak. Zika virus has become one of the greatest infectious risks to pregnant travelers in recent years and is associated with congenital birth defects in infants of infected mothers [37]. Pregnant women should avoid travel to high-risk areas, with the most updated travel advice and developments from the CDC (https://www.cdc.gov/zika/) [38]. Currently, there is no vaccine or medication available to prevent or treat Zika [39]. If travel is unavoidable, pregnant travelers should otherwise strictly follow steps to prevent mosquito bites and prevent sexual transmission during and after the trip. If a woman is trying to become pregnant, she should wait at least 8 weeks from the last potential Zika exposure, and male partners should wait at least 6 months after the last possible exposure before trying to conceive [39]. The National Institute of Allergies and Infectious Diseases (NIAID) highlights some of the most prominent advances currently in Zika vaccination development, which is summarized in Table 4 [40].

Table 4 Current Zika vaccinations under development
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Traveling with Infants and Children

Studies have found that children are less likely to receive pre-travel advice prior to international travel but more likely to seek care after travel and require hospitalization [41]. The highest risk for infection is seen in very young travelers and those that visited sub-Saharan Africa, followed by South America and Southeast Asia [42]. Vaccinations should follow recommended age criteria based on potential adverse effects, efficacy data, safety data, and maternal antibodies [43]. Although neurological complications from infections are very unlikely in children, they may be more susceptible to post-vaccination side effects such as acute disseminated encephalomyelitis, an inflammatory demyelinating disease of the CNS [41, 44].

Malaria, rabies, and meningitis present some of the greatest risks in pediatric travelers, and exposure risk should be considered prior to travel. Malaria is among the most serious and life-threatening diseases that can be acquired by pediatric international travelers. Children can rapidly develop heavy parasitemia and severe malaria, with an increased risk of cerebral malaria which can cause seizures, coma, and death [45]. Initial diagnosis of malaria in children can often be delayed as symptoms mimic causes of common pediatric febrile illness [45]. Malaria chemoprophylaxis is strongly recommended for pediatric patients. Medications used for children are generally the same as adults, with two exceptions. Doxycycline should not be given to children < 8 years of age because of risk of teeth staining and atovaquone-proguanil should not be used for children < 11 lb due to lack of data on safety and efficacy [45].

Rabies exists in developing countries worldwide and is more common in children than adults due to increased contact with animals [46]. For young travelers to developing countries, it is recommended for children to receive a three-shot pre-exposure immunization to simplify post-exposure prophylaxis treatment. Recommendations for post-exposure prophylaxis can be found in Table 2. Numerous studies indicate that post-exposure prophylaxis with timely administration of vaccination and rabies Ig preceded by appropriate wound cleaning is uniformly effective in preventing rabies [47].

Bacterial meningitis, particularly meningococcal meningitis, can be found worldwide and is endemic in the meningitis belt of sub-Saharan Africa. Even when treated appropriately, pediatric patients that recover from bacterial meningitis often have long-term complications, including deafness, developmental delay, learning disabilities, spastic or paralyzed muscles, and seizures [48]. In a systematic literature review of pediatric bacterial meningitis cases, up to 49% of patients were reported to have one or more long-term sequelae [48]. Young travelers (> 2 months of age) who visit countries where meningococcal disease is endemic, including the meningitis belt of sub-Saharan Africa, should receive vaccination with a quadrivalent meningococcal vaccine (MenACWY). Infants and children immunized with Hib-MenCY-TT are not protected against serogroups A and W and thus should receive a quadrivalent vaccine before travel [48].

Specific Diseases by Region

South America, Central America, and Caribbean

Neurocysticercosis

Travel Risk

Neurocysticercosis (NCC) is a parasitic infection caused by the ingestion of eggs from the adult tapeworm Taenia solium. It is typically transmitted through fecal-oral contamination and is common in rural areas with poor sanitation where pigs have access to human feces. Endemic regions include Central and South America, sub-Saharan Africa, India, and East Asia [49, 50]. NCC is the most common parasitic infection of the brain and a leading cause of epilepsy in the world [51]. Recent systematic reviews found NCC to be present in 30–40% of patients with epilepsy in rural and endemic regions [52, 53]. NCC is rare among international travelers and is mainly seen in immigrants. The rate of clinical disease in travelers to endemic areas is estimated to be 1:250,000 per episode of travel [54]. Those at highest risk are long-term travelers, with an average length of 56.6 months of travel [49].

Clinical Presentation

When T. solium larvae migrate to the CNS, they can spread parenchymally or extraparenchymally. NCC has a median latent period between 2 and 5 years, and symptoms can vary depending on the number, location and stage of cysts, and the host immune response [49, 50, 54]. Cysts within the host tissue develop through several stages, from immature stages to larval cysts over several months. Clinical symptoms typically present once cysts begin to degenerate, and there is a significant host inflammatory response [55]. Parenchymal cysts occur in over 60% of patients with NCC. Clinical presentation is typically associated with seizures and headaches, although many lesions are found incidentally [56]. Epileptic seizures are the most common clinical manifestation of intraparenchymal cysts occurring in up to 70% of patients [49]. Cysts that are actively degenerating are the most epileptogenic and are typically associated with new-onset seizures [56]. These can present with edema and/or contrast enhancing lesions on imaging. Multiple active cysts with cerebral edema may clinically resemble encephalitis, which most commonly manifest in young women and children [56]. Calcified granulomas are usually associated with chronic epilepsy [57]. Extraparenchymal cysts (including subarachnoid, ventricular, and cisternal) can present with elevated intracranial pressure or hydrocephalus by blocking CSF flow through mass effect or inflammatory processes. Racemose NCC is a variant of extraparenchymal cysts, which manifest as multi-lobular basal subarachnoid cysts with significant morbidity and mortality [58].

Diagnosis

Any patient with new-onset epilepsy that has spent prolonged time in an endemic region should be evaluated for NCC. The revised diagnostic criteria have been simplified into three categories which take into consideration clinico-laboratory features, neuroimaging findings, and exposure history [59•]. Definitive diagnosis can be made with any of the following absolute criteria, including histopathological evidence of parasites, identification of a scolex within a cystic lesion radiographically, or evidence of subretinal cysts [59•]. One retrospective study found a 93.2% sensitivity and 81.4% specificity when using these diagnostic criteria to evaluate NCC [60].

Treatment

Prognosis depends on the number of cysts and degree of inflammation, with more favorable outcomes in those with a single enhancing lesion rather than multiple areas of involvement [61]. Brain magnetic resonance imaging (MRI) can provide information on the stage of the cyst which is important for treatment decisions. For treating active parenchymal NCC, recommendations include albendazole plus dexamethasone or prednisolone for adults and children to decrease the number of active lesions and reduce the frequency of long-term seizures [62]. Calcified cysts suggest a dead infection and thus do not require antiparasitic treatment. For chronic management of NCC with epilepsy, patients typically respond well to first-line epileptic drugs [62].

Since tuberculosis (TB) is endemic in many regions where NCC is, evaluation for latent TB should be performed in all patients with presumed NCC [63]. Strongyloides should also be tested for prior to corticosteroid therapy to avoid the risk of strongyloides dissemination [64]. Intraocular cysts must be ruled out by ophthalmic examination since antiparasitic therapy can lead to retinal detachment and blindness [65]. For patients with elevated intracranial pressure, antiparasitic therapy should not be used alone since cyst degeneration can worsen cerebral edema. In these cases, neurological management (e.g., steroids, mannitol) plus neurosurgical treatment should be used in conjunction with antihelminthic therapy [65, 66]. Surgical removal of cysts may be necessary for patients with spinal cord compression [65]. Patients with subarachnoid cysts, including racemose NCC, should receive antiparasitic treatment with immunosuppression until CSF and neuroimaging abnormalities have resolved [66].

Zika

Travel Risk

Zika is an arthropod-borne RNA flavivirus transmitted primarily by Aedes aegypti mosquitoes or through sexual transmission [37, 67]. Other modes of transmission include blood transfusion, organ transplantation, and laboratory exposure [68]. Between 2007 and 2016, transmission was reported in South America, Central America, the Caribbean, Africa, Southeast Asia, and the western Pacific [38, 69]. Pregnant women and women that are trying to become pregnant are high-risk travelers and are advised to avoid travel to endemic areas. More information can be found in the “Pregnant Travelers” section of this paper, and further information on Zika virus infection can be found in the chapter on “Neurologic Complications of Zika Virus” [70]

Africa

Tuberculosis

Travel Risk

TB is an infection caused by Mycobacterium tuberculosis, which can spread hematogenously from the lungs to the CNS to establish tuberculous foci in the brain, meninges, or adjacent bone [71]. TB meningitis (TBM) is the predominant form of CNS TB, resulting from abscesses in the meninges that can rupture and spread the infection throughout the subarachnoid space [28]. Other forms include intracranial tuberculoma and spinal tuberculous arachnoiditis [71]. TB predominates in developing countries, especially in sub-Saharan Africa and Southeast Asia [28]. Travelers with anticipated long-term exposure to TB, for example, in healthcare facilities, correctional facilities, or homeless shelters, or for those with extended travel duration in endemic regions are at higher risk for contracting the disease [28]. The most vulnerable populations are children and immunocompromised individuals [6•, 72].

Clinical Presentation

About one third of the world’s population has latent TB with a 10% lifetime risk of developing active infection [28, 73]. In about 1% of TB cases, CNS infection occurs [28]. TBM clinically progresses through three phases that are differentiated based upon mental status and focal neurologic signs. The prodromal phase lasts 2–3 weeks and presents with malaise, headache, mild fever, and personality changes but no focal neurologic signs. The following meningitic phase has more pronounced neurologic changes, including meningismus, vomiting, confusion, lethargy, protracted headache, and cranial nerve palsies or hemiparesis. The paralytic phase progresses rapidly into stupor, coma, and seizures. Vasculitis may develop leading to ischemic events, and blockage of CSF flow can lead to hydrocephalus [74]. If untreated, most patients die within 5–8 weeks from the onset of symptoms [28, 74, 75]. Intracranial tuberculomas may occur with or without TB meningitis and can be located in the cerebrum, cerebellum, or spinal cord or in the subarachnoid, subdural, or epidural space [74].

Diagnosis

CSF culture of M. tuberculosis is the gold standard for diagnosis though there are major delays due to the organism being slow-growing. The CSF of patients with TBM is characterized by a mononuclear pleocytosis with lymphocytic predominance, with elevated protein and lowered glucose [76]. Atypical CSF findings in co-infected HIV patients may include normal cell counts, polymorphonuclear cell predominance, and normal glucose levels [76]. Polymerase chain reaction (PCR) amplification of Mycobacterium DNA is a promising TB diagnostic with results available within 2 h and a 56% sensitivity and 99% specificity [28]. The WHO recommends using Xpert MTB/RIF assay on CSF as an initial test for TBM. In one systematic review, this method was found to have an 81% sensitivity and 98% specificity [77]. Neuroimaging can also be used to identify basal meningeal enhancement, hydrocephalus, and infarctions that are most commonly seen in the basal ganglia and midbrain [76]. Tuberculomas within brain parenchyma may also be observed histopathologically or on radiographic imaging. For patients co-infected with HIV, neuroimaging findings may be atypical. [74]

Treatment

Treatment should not be delayed for laboratory confirmation of TB, but should be started with any strong clinical suspicion of TB infection. The WHO recommends the same regimen for pulmonary and extrapulmonary TB, with an extension of treatment of 9–12 months for CNS TB [73]. Guidelines recommend a rifampicin, isoniazid, pyrazinamide, and ethambutol during the initial intensive phase, followed with rifampicin and isoniazid during the continuation phase of treatment [78]. Without appropriate treatment, 45% of HIV-negative people with CNS TB on average and nearly all HIV-positive people with CNS TB will die [73]. Some studies indicate that high-dose rifampicin and an oral fluoroquinolone early in the course of infection may decrease morbidity and mortality [78]. However, a randomized control trial (RCT) in Vietnam demonstrated no change in survival in TB meningitis patients with a higher dose rifampicin (15 mg/kg/day) and fluoroquinolone [79•]. Corticosteroids have been shown to reduce mortality in TBM in both adults and children and should be administered regardless of disease severity at presentation [80]. As part of the challenges to treatment, CNS penetration of first-line antituberculosis drugs can be variable, and few second-line drugs have adequate CNS penetration [81]. In addition, multi-drug resistant (MDR) TB is on the rise causing higher rates of mortality in disseminated patients [76, 78]. Further additional clinical trials are needed to define optimal treatment plans in these circumstances.

Asia

Rabies

Travel Risk

Rabies is a fatal and progressive encephalomyelitis caused by a member of the Lyssavirus genus and is almost exclusively transmitted through the bite of a rabid animal [22]. The majority of human deaths caused by canine-mediated rabies occur in regions of Asia, especially India, as well as in Africa, although rabies can be found almost anywhere in the world [21]. The estimated rate of rabies exposure in travelers ranges from 16 to 200 per 100,000 travelers, although true rates may vary significantly due to lack of sufficient data and reporting [22]. Pre-exposure vaccination is recommended for travelers who anticipate prolonged stays in rural areas with high levels of endemic rabies, including areas where canine rabies is poorly controlled, for those who plan to have high levels of animal contact and for those with exposure to caves (see “Traveling with Infants and Children” section) [20].

Clinical Presentation

Clinical presentation typically begins after an incubation period from 1 to 3 months, although this period can vary from days to years. Clinical symptoms rapidly progress from a prodromal phase to an acute neurological phase followed by coma and death, with rare exception [22, 82]. Rabies exposure in densely innervated areas, such as the head, neck, and face, can shorten the incubation period [46]. Most deaths occur within 2 weeks after the onset of clinical symptoms, most commonly as a result of secondary complications [82]. The acute neurological phase of classic rabies presents in two forms, either an encephalitic form (about two thirds of patients) or paralytic form, while non-classic rabies may present without any distinct neurological characteristics. Hydrophobia and aerophobia are both pathognomonic for encephalitic rabies, occurring in up to 50 and 9% of rabies patients, respectively [83, 84]. Encephalitic rabies can also present with fever, altered consciousness, autonomic instability, agitation, muscle spasticity, and increased muscular tone, which progresses to delirium, seizures, rapid coma, respiratory or vascular collapse, and death [20, 22, 82]. Paralytic rabies can present similarly to the Guillain-Barré syndrome and has a late onset of cerebral involvement. Acute paralysis starts at the site of infection with a loss of deep tendon reflexes, sensory changes, and occasional pain. Paralysis eventually spreads throughout the body, leading to dense paraplegia, respiratory collapse, and death [82].

Diagnosis

Rabies should be included in the differential diagnosis of undiagnosed encephalopathy in any patient returning from a country where rabies is endemic. Diagnosis can be straightforward in a patient with a compatible history and a classic clinical presentation; however, variations in clinical presentation or a lack of exposure history can complicate this [22]. The low sensitivity of certain individual tests can be improved to 100% by performing multiple diagnostic tests on various specimens (e.g., skin biopsies, serum, CSF, saliva, urine) [85]. In one prospective study, PCR of skin biopsies at the nape of the neck was found to have the highest sensitivity (98%) and specificity (98.3%) [85]. Skin biopsies may also be examined for antigen presence in the cutaneous nerves of hair follicles. Saliva samples can be tested by virus isolation or reverse transcription followed by PCR. Serological evidence of rabies virus in serum or CSF can confirm the disease in an unvaccinated patient [82]. However, antibodies in serum and CSF typically will not be detected until the disease is much later into progression. Prior to coma onset, neuroimaging using MRI can be used to identify T2 single intensity without contrast around areas of the brainstem, hypothalamus, and limbic structures [82].

Treatment

There is no evidence-based treatment for rabies, with patients managed with symptomatic and palliative care. There is an experimental approach known as the Milwaukee protocol, which involves inducing a coma and treating with antiviral drugs, though it carries a high risk for neurological sequelae [22]. Rabies is still considered 100% fatal once clinical symptoms have manifested [22, 47].

Eastern Europe

Tick-Borne Encephalitis

Travel Risk

Tick-borne encephalitis (TBE) is a central nervous system infection caused by a virus that belongs to the Flaviviridae family [15]. Transmission usually occurs through the bite of an infected tick of the Ixodes species, including Ixodes ricinus (European subtype) or Ixodes persulcatus (Siberian and Far Eastern subtypes). Although less common, TBE can also be acquired from ingesting unpasteurized dairy products from infected goats, sheep, or cows [15]. TBE is endemic in areas of eastern Europe and Asia, extending from eastern France to northern Japan and from northern Russia to Albania, with Russia having the largest number of reported cases. There are up to 13,000 TBE cases reported each year [15]. The overall risk of acquiring TBE for an unvaccinated traveler in an endemic area during the high season (April to November) is estimated at 1 case per 10,000 person-months of exposure, and the incidence and severity of TBE is highest in travelers over 50 years [15]. The majority of infectious tick bites are acquired in forested areas, often during outdoor activities such as camping, hiking, fishing, or military training, among others. There is minimal risk for travelers staying in an urban environment and for those that avoid unpasteurized dairy products [15].

Clinical Presentation

The median incubation period for TBE is 8 days (range 4–28 days) following a tick bite [86, 87]. TBE infection is typically recognized as an acute neuroinvasive disease, although the disease course can be milder or present in a biphasic course. The first phase typically lasts several days and includes a non-specific febrile illness with headache, myalgia, and fatigue. Up to two thirds of patients will recover following this first phase without any further complications [15]. The second phase presents as a CNS infection that includes aseptic meningitis, encephalitis, or myelitis [15]. The recovery period can be long, and many patients can incur permanent neurologic symptoms as well as neuropsychiatric sequelae. Death typically occurs 5–7 days after the presentation of neurological symptoms [16]. Disease severity increases with age and is least severe in children. In addition, the clinical course and long-term outcome vary by TBE virus subtype [11]. The European subtype is typically milder with less than a 2% mortality rate and 30% of patients having neurological sequelae. The far eastern subtype is associated with a more severe course, with up to a 40% mortality rate and a higher rate of neurological sequelae. The Siberian subtype typically presents with a chronic or progressive encephalitis, with only a 2–3% mortality rate [15].

Diagnosis

Serology tests are typically used for laboratory diagnosis. IgM-capture ELISA performed on serum or CSF is highly sensitive during the neuroinvasive phase of the illness, although cross reaction from other infections or vaccinations must be considered when interpreting results [15]. Prior to the neuroinvasive phase, TBE virus or viral RNA can sometimes be detected in serum by virus isolation or RT-PCR. However, once neurological symptoms present, virus or viral RNA is usually undetectable and thus should not be used to rule out the diagnosis [15]. Other common laboratory findings during the first phase include leukopenia and thrombocytopenia, with mild elevation of liver enzymes in the serum [16].

Treatment

There is no specific drug therapy for TBE [16]. A vaccine is available in some disease-endemic areas, although not currently in the USA and may present adverse vaccine reactions in children (see Table 2) [16].

Conclusion

Globalization and urbanization, coupled with environmental factors and microbial adaptation, are increasing the risk of emerging and reemerging infectious pathogens in global health. Additionally, antimicrobial resistance is occurring throughout the world, increasing the risk of disseminated disease and compromising our ability to treat infectious diseases. The primary role of healthcare personnel should be around preventative health care, including a comprehensive pre-travel risk assessment. Increased globalization requires clinician awareness to help mitigate the spread and impact of travel-related neuroinfectious diseases, recognizing clinical syndromes, and rapidly diagnosing and treating conditions.