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Objective. Review of neurocysticercosis in citizens from non-endemic countries who developed the disease after a travel to endemic regions, to estimate the magnitude of the disease and to determine the pattern of disease expression in travelers to disease-endemic areas.
Methods. MEDLINE and manual search of international travelers with neurocysticercosis diagnosed in countries where the disease is not endemic, from 1981 to October 2011. Abstracted data included: demographic profile of patients, clinical manifestations, form of neurocysticercosis, and therapy.
Results. A total of 35 articles reporting 52 patients were found. Most patients were originally from Western Europe, Australia, Israel, and Japan. Mean age was 36.5 ± 15.1 years, and 46% were women. Common places for travelling were the Indian Subcontinent, Latin America, and Southeast Asia. Mean time spent aboard was 56.6 ± 56.1 months. Most patients developed symptoms 2 years or more after returning home. Seizures were the most common clinical manifestation of the disease (73%), and all but six patients had parenchymal brain cysticercosis (a single cysticercus granuloma was the most common neuroimaging finding, in 21 patients). Twenty patients underwent surgical resection of the brain lesion for diagnostic purposes, and 22 received cysticidal drugs.
Conclusions. Neurocysticercosis is rare in international travelers to endemic countries, and most often occurs in long-term travelers. It is possible that most of these patients get infected by contact with a taenia carrier. The time elapsed between disease acquisition and symptoms occurrence suggests that, at least in some patients, clinical manifestations are related to reactivation of an infection that has previously been controlled by the host immune system.
Neurocysticercosis is the most common helminthic infection of the nervous system, and a major cause of acquired epilepsy worldwide.1 The disease occurs when humans become intermediate hosts of the tapeworm Taenia solium by ingesting its eggs from contaminated food or, most often, directly from a taenia carrier (fecal-oral route). Within the central nervous system, parasites may lodge in the brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing a myriad of pathological changes that are responsible for the clinical pleomorphism of neurocysticercosis.
Neurocysticercosis is endemic in most of the developing world. There, millions of people are infected by cysticerci, and many of them will eventually experience the clinical consequences of this infection.2 Neurocysticercosis was rare in developed countries up to the past few decades. Together with the growing number of immigrants from endemic areas, there has been an increase in the number of patients with cysticercosis in some of these countries.3,4 Also, increased tourism and international business affairs have rendered people from nonendemic areas more susceptible to acquire this parasitic disease. Neurocysticercosis in travelers has not been well characterized, and available information on these individuals is scarce and incomplete.5 The main purpose of this study is to present a review of the literature on neurocysticercosis in citizens from nonendemic countries who developed the disease after a travel to disease-endemic regions, to estimate the magnitude of the disease, and to describe the pattern of disease expression in this population.
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A literature search of neurocysticercosis occurring in citizens from nonendemic countries who had history of travel to disease-endemic countries over the past 30 years (1981–2011) was performed using the electronic database of MEDLINE (National Library of Medicine, Bethesda, MD, USA). Key words “cysticercosis” and “neurocysticercosis” were combined with “travel,”“traveler,” and with the name of each of the countries traditionally considered as nonendemic, including Western European countries, African and Middle-East countries of the Arab World, Israel, some American countries (Argentina, Belize, Canada, Surinam, United States, and Uruguay), Islands of the Caribbean Basin (except Haiti and Dominican Republic), and some countries of Asia and Oceania (Australia, Japan, Malaysia, and New Zealand). Limits were not applied to the search; instead, abstracts, clinical notes without an abstract, and letters to the editor were reviewed to identify potentially eligible articles. The only language limitations were Japanese and Hebrew. Thereafter, a manual search that included the author's files as well as the list of references of cysticercosis books, position papers, and selected articles was reviewed, and relevant information was requested to colleagues and cysticercosis experts.
Selected studies were those including original data on citizens from the above-mentioned nonendemic countries, who developed neurocysticercosis after returning to their country of origin from a sojourn in disease-endemic areas (Latin America, sub-Saharan Africa, the Indian Subcontinent, and Southeast Asia). Abstracted data of selected articles included (whenever possible): age and gender of reported patients, citizenship status, time spent abroad, places of living or traveling, time elapsed since their return home and the appearance of symptoms, specific form of neurocysticercosis (as shown on neuroimaging studies), clinical manifestations, and therapy.
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The search identified 35 papers that met inclusion criteria by describing clinical cases of citizens born in nonendemic countries who developed neurocysticercosis after returning from a trip to an endemic area.6–40 After reviewing data, a total of 52 patients were identified (Table 1). Of these, 28 (54%) were diagnosed from 2000 to 2011, 17 (33%) from 1990 to 1999, and the remaining 7 (13%) from 1981 to 1989. Most patients were originally from England, Australia, Israel, Japan, and France. Age (available in 51 patients) ranged from 4 to 70 years (mean, 36.5 ± 15.1 y), and 46% were women (gender available in all cases). Information on a single, specific country of travel was available in 24 patients, including: India in 9 patients, Thailand in 3, Bhutan in 2, and Bali, Bolivia, Indonesia, Madagascar, Mexico, Nepal, Peru, Taiwan, Tanzania, and Venezuela in 1 patient each. In the 28 remaining patients, information was less specific as they visited several countries of Asia (n = 16), Latin America (n = 7), Africa (n = 2), or even various continents (n = 3).
Table 1. Data of 52 citizens from nonendemic countries who developed neurocysticercosis after traveling to a disease-endemic area
|Author||Age/gender||Country of origin||Travel history||Duration of travel||Travel to symptoms||Clinical||Form of neurocysticercosis||EITB||Therapy||Prognosis|
|Aghakhani and colleagues6||—/ w||France||Latin America||—||—||Focal signs||Spinal||—||Surgery|| |
|Al-Khodari and colleagues7||52 / m||France||Bolivia||10 y||Recent||Asympt||Parenchymal active||Positive||Praziquantel|| |
|Ali-Khan and colleagues8||30 / w||Canada||India||13 mo||—||Seizures||Parenchymal active||—||Surgery|| |
|Bequet & Goasguen9||32 / w||France||Niger, Djibouti||3 y||1 wk||Seizures||Parenchymal active||—||Praziquantel|| |
|Brouwer and colleagues10||50 / w||Netherlands||Kenia, Thailand, Brazil||5 y||2 y||Focal signs||Parenchymal active||—||Praziquantel|| |
|Brouwer and colleagues10||40 / m||Netherlands||Mozambique, Tanzania||Frequent traveler||3 y||Seizures||Parenchymal active||—||Praziquantel|| |
|Castillo and colleagues11||58 / w||France||Madagascar||1 y||34 y||Int hypertension||Subarachnoid cyst||Positive||Albendazole|| |
|Chatel and colleagues12||43 / m||Italy||Latin America||1 mo||3 mo||Seizures||Parenchymal active||Positive||Albendazole|| |
|Débat-Zoguéreh and colleagues13||47 / w||France||Africa, Asia, SudAmer||Frequent traveler||4 y||Seizures||Parenchymal active||—||Surgery|| |
|Djientcheu and colleagues14||58 / m||Switzerland||Venezuela||8 y||14 y||Int hypertension||Hydrocephalus||Positive||Surgery|| |
|Egberts and colleagues15||26 / m||Germany||South America||—||20 y||Focal signs||Spinal||—||Surgery|| |
|Epelboin and colleagues16||23 / w||France||Thailand, Nepal||4 y||3 y||Seizures||Parenchymal active||Positive||Albendazole|| |
|Gubbay and colleagues17||30 / w||Australia||India||Several trips||—||Seizures||Single granuloma||—||Albendazole||Recover|
|Gubbay and colleagues17||43 / w||Australia||Indonesia||7 y||—||Seizures||Parenchymal active||—||Albendazole||Recover|
|Hansen and colleagues18||28 / w||Denmark||Thailand||4 mo||3 mo||Seizures||Parenchymal active||—||Praziquantel|| |
|Hitchcock19||4 / w||England||India||Lived for 1 y||2 y||Seizures||Single granuloma||—||Surgery|| |
|Hitchcock19||28 / w||England||Bhutan (Asia)||9 mo||3 mo||Seizures||Parenchymal active||—||Surgery|| |
|Hoare and colleagues20||38 / m||England||Southeast Asia||Several years||—||Seizures||Parenchymal active||—||Albendazole|| |
|Hellard and colleagues21||50 / m||Australia||Tanzania||5 y||1 wk||Focal signs||Parenchymal active||Positive||Surgery||Recover|
|Ito and colleagues22||46 / m||Japan||Several countries||12 y||—||Seizures||Single granuloma||—||Surgery|| |
|Ishikawa and colleagues23||38 / w||Japan||Nepal||—||5 y||Focal signs||Single granuloma||—||Surgery|| |
|Kamii and colleagues24||51 / m||Japan||Taiwan||—||4 y||Seizures||Parenchymal active||—||Surgery|| |
|Kennedy & Schon25||16 / m||England||India||3 mo||1 y||Seizures||Single granuloma||—||Spont resol|| |
|Khan and colleagues26||19 / m||Qatar||Thailand||Short trip||3 y||Seizures||Single granuloma||—||Albendazole|| |
|Klotz and colleagues27||13 / w||Germany||Thailand||2 y||—||Seizures||Calcified||Negative||Surgery|| |
|Lerch and colleagues28||56 / w||Switzerland||Peru||15 y||—||Seizures||Parenchymal active||Positive||Albendazole|| |
|Leshem and colleagues29||30 / m||Israel||Southeast Asia||—||2 y||Seizures||Single granuloma||—||—||Recover|
|Leshem and colleagues29||26 / m||Israel||South America||11 mo||5 y||Seizures||Single granuloma||—||Surgery||Recover|
|Leshem and colleagues29||28 / m||Israel||Various countries of Asia||9 mo||1 y||Seizures||Single granuloma||Positive||Albendazole||Recover|
|Leshem and colleagues29||27 / m||Israel||India, Nepal||4 mo||5 y||Seizures||Single granuloma||—||Albendazole||Recover|
|Leshem and colleagues29||26 / w||Israel||Southeast Asia||14 mo||3 y||Seizures||Single granuloma||Positive||—||Recover|
|Leshem and colleagues29||45 / m||Israel||India, Nepal||—||—||Seizures||Parenchymal active||Positive||Albendazole||Recover|
|Leshem and colleagues29||25 / m||Israel||Southeast Asia||—||—||Seizures||Parenchymal active||Positive||Albendazole||Recover|
|Leshem and colleagues29||24 / m||Israel||Southeast Asia||—||—||Seizures||Single granuloma||—||—||—|
|Leshem and colleagues29||25 / m||Israel||Southeast Asia||—||—||Seizures||Parenchymal active||—||—||Recover|
|Markwalder and colleagues30||49 / w||Switzerland||India||11 y||Few months||Seizures||Parenchymal active||—||Praziquantel|| |
|Markwalder and colleagues30||33 / m||Switzerland||Bhutan (Asia)||2 y||1 wk||Seizures||Parenchymal active||—||Praziquantel|| |
|Nakajima and colleagues31||70 / m||Japan||Southeast Asia||—||—||Seizures||Parenchymal active||—||Surgery|| |
|Oman and colleagues32||28 / m||Australia||Bali||Short trip||2 y||Seizures||Single granuloma||—||—||—|
|Praceres da Costa and colleagues33||60 / w||Germany||Mexico, Brazil||15 y||12 y||Int hypertension||Ventricular||Positive||Albendazole|| |
|Sheehan and colleagues34||16 / w||USA||Mexico||Short trip||10 y||Focal signs||Spinal||—||Surgery||Recover|
|Shimizu and colleagues35||49 / m||Japan||Central America||—||—||Seizures||Single granuloma||—||Surgery|| |
|Wadley and colleagues36||69 / m||England||India||—||—||Int hypertension||Single granuloma||Negative||No therapy|| |
|Wadley and colleagues36||19 / w||England||India||—||—||Seizures||Single granuloma||Negative||Surgery|| |
|Wadley and colleagues36||21 / w||England||India||—||—||Seizures||Single granuloma||Negative||No therapy|| |
|Wadley and colleagues36||31 / w||England||South America||—||—||Seizures||Parenchymal active||Positive||No therapy|| |
|Wadley and colleagues36||23 / m||England||India||—||—||Seizures||Single granuloma||Negative||No therapy|| |
|Walker and colleagues37||27 / m||Australia||Various countries of Asia||—||10 y||Seizures||Parenchymal active||Positive||Praziquantel||Recover|
|Walker and colleagues37||57 / m||Australia||Various countries of Asia||Frequent traveler||Several years||Headache||Parenchymal active||Positive||Praziquantel||Recover|
|Yamasaki and colleagues38||53 / w||Japan||India, Southeast Asia||9 y||1 y||Focal signs||Single granuloma||—||Surgery|| |
|Yanagida and colleagues39||46 / m||Japan||Nepal, Indonesia||12 y||10 y||Headache||Single granuloma||—||Surgery|| |
|Zimmermann & Jeffries40||37 / w||Australia||Southeast Asia||Frequent traveler||—||Seizures||Single granuloma||—||Surgery||Recover|
Information on the time spent aboard was available in only 26 patients, and varied widely from 1 month to 15 years (mean, 56.6 ± 56.1 months). Only two of these patients had history of short-term travel (up to 3 months), and seven additional patients spent up to 1 year aboard. So, long-term sojourns of several years duration were recorded in 17 patients. Information on the time elapsed between return of the traveler to the appearance of symptoms was mentioned in 32 patients. While this was imprecisely defined in most cases, it could be inferred that 21 of these patients became symptomatic at least 2 years after returning home (in seven of these patients, the asymptomatic period was of 10 years or more).
Seizures were the primary or sole manifestation of the disease in 38 patients (73%). Seven patients had focal neurologic signs, four had intracranial hypertension, two had headache, and in one patient the disease was incidentally discovered (asymptomatic). Regarding the specific form of neurocysticercosis (as documented by neuroimaging studies), 21 patients (40%) had a single cysticercus granuloma. Of the remaining patients, 25 had other forms of parenchymal brain cysticercosis and six had extraparenchymal neurocysticercosis (including three patients with spinal cysts). Twenty patients had an electroimmunotransfer blot (EITB) test for the detection of anticysticercal antibodies in serum, which was positive in 15 cases. Resection of the cerebral lesion for diagnostic purposes was performed in 20 patients, and 22 patients received specific therapy with cysticidal drugs (albendazole or praziquantel). All but three of the 52 patients had a definitive diagnosis of neurocysticercosis according to currently accepted diagnostic criteria.41 Evolution was available only in 15 cases (all recovered).
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Considering the millions of people who have traveled from nonendemic to cysticercosis-endemic countries during the past 30 years, and then the number of reported cases, the risk of neurocysticercosis acquisition by international travelers is very low, and it seems to be even lower for short-term travelers. As noted, the aim of this study is to provide objective evidence on the pattern of disease expression of neurocysticercosis in citizens from nonendemic countries who acquired neurocysticercosis after a travel to a disease-endemic region. There are some papers (mainly from the United States and Spain) which mention the occurrence of this parasitic disease in international travelers, but the information they provides is vague and data cannot be abstracted; that is why those publications were not considered in this review.42–44
To acquire the disease, travelers must be in contact with a taenia carrier, who will infect them by the fecal-oral route (most often through unhygienic handling of food). While possible, it is unlikely that a given person gets infected after sporadic contact. Another possibility is that travelers get in direct contact with human feces by visiting places where open-air defecation is a common practice, as occurs in rural villages of developing countries.45 Finally, it is also possible that travelers first become taenia carriers (by ingesting undercooked pork meat infected by cysticerci) and then infected themselves by the fecal-oral route.
The most common pattern of neurocysticercosis expression in travelers, ie, a single cysticercus granuloma, suggests that the usual form of disease acquisition is through sporadic contact with taenia carriers food-handlers. Otherwise, travelers would more often presented with heavier infections, which are typically observed in taenia carriers who infected themselves or in those who ingest a heavy load of T solium eggs directly from nature.46,47
A main unsolved issue is why most travelers developed symptoms several years after returning home. While it is true that cysticerci may live for years—even decades—within the nervous system, there are some forms of neurocysticercosis that most often represent “recent” infections producing symptoms in the very few months after disease acquisition. This is the case of the single cysticerci granuloma, a particular form of neurocysticercosis in which the host immune system actively reacts to the implantation of the metacestode of T solium in the brain parenchyma.48 As most travelers had this form of the disease, one would expect symptoms to occur while abroad or soon after returning home. So, it is possible that what we saw on neuroimaging studies performed at the time of symptoms (seizures) in these patients, were not active cysticerci granulomas, but the late sequelae of an infection that was previously handled by the host immune system without producing symptoms. Indeed, recent evidence has changed previous concepts regarding calcified parenchymal brain cysticerci as totally inert lesions. Calcifications may experience periodic morphological changes related to a mechanism of remodeling. This may expose parasitic antigenic material to the host, causing transient inflammatory changes in the brain parenchyma that may be the cause of seizures and changes on neuroimaging studies—brain swelling, ring-enhancing appearance of the lesion—resembling very much those seen in patients with acute cysticercal granulomas.49,50 This provides a rationale for the occurrence of late symptoms in travelers infected aboard.
While findings of this review suggest that the prevalence of neurocysticercosis among international travelers to endemic countries is low, it is probably that we are just seeing the tip of the iceberg, as many undiagnosed and unreported cases were not captured in this review. Improved physician's awareness of the possibility of neurocysticercosis among persons with seizures from nonendemic areas with history of traveling to disease-endemic areas, as well as the compulsory report of cases, will allow us to know the actual prevalence of this condition, and to better understand the mechanisms of disease acquisition in these patients. Also, improved knowledge on the natural history and current therapeutic guidelines for patients with neurocysticercosis by doctors living in developed countries will reduce the risk of unnecessary surgical procedures in most of these patients.51