Surveillance report of Zika virus among Canadian travellers returning from the Americas.

BACKGROUND: Widespread transmission of Zika virus in the Americas has occurred since late 2015. We examined demographic and travel-related characteristics of returned Canadian travellers with Zika infection acquired in the Americas to illuminate risk factors for acquisition and the clinical spectrum. METHODS: We analyzed demographic and travel-related data for returned Canadian travellers who presented to a CanTravNet site between October 2015 and September 2016 for care of Zika virus acquired in the Americas. Data were collected with use of the GeoSentinel Surveillance Network data platform. RESULTS: During the study period, 1118 travellers presented to a CanTravNet site after returning from the Americas, 41 (3.7%) of whom had Zika infection. Zika infection from the Americas was diagnosed at CanTravNet sites as often as dengue (n = 41) over the study period. In the first half of the study period, Zika virus burden was borne by people visiting friends and relatives in South America. In the latter half, coincident with the increased spread of Zika throughout the Caribbean and Central America, Zika virus occurred more often in tourists in the Caribbean. Forty (98%) of the travellers with Zika infection acquired it through probable mosquito exposure, and 1 had confirmed sexual acquisition. Congenital transmission occurred in 2 of 3 pregnancies. Two (5%) of those with Zika had symptoms resembling those of Guillain-Barré syndrome, 1 of whom also had Zika viral meningitis. INTERPRETATION: Even in this small cohort, we observed the full clinical spectrum of acute Zika virus, including adverse fetal and neurologic outcomes. Our observations suggest that complications from Zika infection are underestimated by data arising exclusively from populations where Zika is endemic. Travellers should adhere to mosquito-avoidance measures and barrier protection during sexual activity.

GeoSentinel surveillance of illness in returned travelers, 2007-2011.

BACKGROUND: International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. OBJECTIVE: To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. DESIGN: Descriptive, using GeoSentinel records. SETTING: 53 tropical or travel disease units in 24 countries. PATIENTS: 42 173 ill returned travelers seen between 2007 and 2011. MEASUREMENTS: Frequencies of demographic characteristics, regions visited, and illnesses reported. RESULTS: Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. LIMITATIONS: Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. CONCLUSION: Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Travel-associated illness trends and clusters, 2000-2010.

Longitudinal data examining travel-associated illness patterns are lacking. To address this need and determine trends and clusters in travel-related illness, we examined data for 2000-2010, prospectively collected for 42,223 ill travelers by 18 GeoSentinel sites. The most common destinations from which ill travelers returned were sub-Saharan Africa (26%), Southeast Asia (17%), south-central Asia (15%), and South America (10%). The proportion who traveled for tourism decreased significantly, and the proportion who traveled to visit friends and relatives increased. Among travelers returning from malaria-endemic regions, the proportionate morbidity (PM) for malaria decreased; in contrast, the PM trends for enteric fever and dengue (excluding a 2002 peak) increased. Case clustering was detected for malaria (Africa 2000, 2007), dengue (Thailand 2002, India 2003), and enteric fever (Nepal 2009). This multisite longitudinal analysis highlights the utility of sentinel surveillance of travelers for contributing information on disease activity trends and an evidence base for travel medicine recommendations.

Expatriates ill after travel: results from the Geosentinel Surveillance Network.

BACKGROUND: Expatriates are a distinct population at unique risk for health problems related to their travel exposure. METHODS: We analyzed GeoSentinel data comparing ill returned expatriates with other travelers for demographics, travel characteristics, and proportionate morbidity (PM) for travel-related illness. RESULTS: Our study included 2,883 expatriates and 11,910 non-expatriates who visited GeoSentinel clinics ill after travel. Expatriates were more likely to be male, do volunteer work, be long-stay travelers (>6 months), and have sought pre-travel advice. Compared to non-expatriates, expatriates returning from Africa had higher proportionate morbidity (PM) for malaria, filariasis, schistosomiasis, and hepatitis E; expatriates from the Asia-Pacific region had higher PM for strongyloidiasis, depression, and anxiety; expatriates returning from Latin America had higher PM for mononucleosis and ingestion-related infections (giardiasis, brucellosis). Expatriates returning from all three regions had higher PM for latent TB, amebiasis, and gastrointestinal infections (other than acute diarrhea) compared to non-expatriates. When the data were stratified by travel reason, business expatriates had higher PM for febrile systemic illness (malaria and dengue) and vaccine-preventable infections (hepatitis A), and volunteer expatriates had higher PM for parasitic infections. Expatriates overall had higher adjusted odds ratios for latent TB and lower odds ratios for acute diarrhea and dermatologic illness. CONCLUSIONS: Ill returned expatriates differ from other travelers in travel characteristics and proportionate morbidity for specific diseases, based on the region of exposure and travel reason. They are more likely to present with more serious illness.

Patterns of illness in travelers visiting Mexico and Central America: the GeoSentinel experience.

BACKGROUND: Mexico and Central America are important travel destinations for North American and European travelers. There is limited information on regional differences in travel related morbidity. METHODS: We describe the morbidity among 4779 ill travelers returned from Mexico and Central America who were evaluated at GeoSentinel network clinics during December 1996 to February 2010. RESULTS: The most frequent presenting syndromes included acute and chronic diarrhea, dermatologic diseases, febrile systemic illness, and respiratory disease. A higher proportion of ill travelers from the United States had acute diarrhea, compared with their Canadian and European counterparts (odds ratio, 1.9; P < .0001). During the 2009 H1N1 influenza outbreak from March 2009 through February 2010, the proportionate morbidity (PM) associated with respiratory illnesses in ill travelers increased among those returned from Mexico, compared with prior years (196.0 cases per 1000 ill returned travelers vs 53.7 cases per 1000 ill returned travelers; P < .0001); the PM remained constant in the rest of Central America (57.3 cases per 1000 ill returned travelers). We identified 50 travelers returned from Mexico and Central America who developed influenza, including infection due to 2009 H1N1 strains and influenza-like illness. The overall risk of malaria was low; only 4 cases of malaria were acquired in Mexico (PM, 2.2 cases per 1000 ill returned travelers) in 13 years, compared with 18 from Honduras (PM, 79.6 cases per 1000 ill returned travelers) and 14 from Guatemala (PM, 34.4 cases per 1000 ill returned travelers) during the same period. Plasmodium vivax malaria was the most frequent malaria diagnosis. CONCLUSIONS: Travel medicine practitioners advising and treating travelers visiting these regions should dedicate special attention to vaccine-preventable illnesses and should consider the uncommon occurrence of acute hepatitis A, leptospirosis, neurocysticercosis, acute Chagas disease, onchocerciasis, mucocutaneous leishmaniasis, neurocysticercosis, HIV, malaria, and brucellosis.

Sex and gender differences in travel-associated disease.

BACKGROUND: No systematic studies exist on sex and gender differences across a broad range of travel-associated diseases. METHODS: Travel and tropical medicine GeoSentinel clinics worldwide contributed prospective, standardized data on 58,908 patients with travel-associated illness to a central database from 1 March 1997 through 31 October 2007. We evaluated sex and gender differences in health outcomes and in demographic characteristics. Statistical significance for crude analysis of dichotomous variables was determined using chi2 tests with calculation of odds ratios (ORs) and 95% confidence intervals (CIs). The main outcome measure was proportionate morbidity of specific diagnoses in men and women. The analyses were adjusted for age, travel duration, pretravel encounter, reason for travel, and geographical region visited. RESULTS: We found statistically significant (P < .001) differences in morbidity by sex. Women are proportionately more likely than men to present with acute diarrhea (OR, 1.13; 95% CI, 1.09-1.38), chronic diarrhea (OR, 1.28; 95% CI, 1.19-1.37), irritable bowel syndrome (OR, 1.39; 95% CI, 1.24-1.57), upper respiratory tract infection (OR, 1.23; 95% CI, 1.14-1.33); urinary tract infection (OR, 4.01; 95% CI, 3.34-4.71), psychological stressors (OR, 1.3; 95% CI, 1.14-1.48), oral and dental conditions, or adverse reactions to medication. Women are proportionately less likely to have febrile illnesses (OR, 0.15; 95% CI, 0.10-0.21); vector-borne diseases, such as malaria (OR, 0.46; 95% CI, 0.41-0.51), leishmaniasis, or rickettsioses (OR, 0.57; 95% CI, 0.43-0.74); sexually transmitted infections (OR, 0.68; 95% CI 0.58-0.81); viral hepatitis (OR, 0.34; 95% CI, 0.21-0.54); or noninfectious problems, including cardiovascular disease, acute mountain sickness, and frostbite. Women are statistically significantly more likely to obtain pretravel advice (OR, 1.28; 95% CI, 1.23-1.32), and ill female travelers are less likely than ill male travelers to be hospitalized (OR, 0.45; 95% CI, 0.42-0.49). CONCLUSIONS: Men and women present with different profiles of travel-related morbidity. Preventive travel medicine and future travel medicine research need to address gender-specific intervention strategies and differential susceptibility to disease.

GeoSentinel: past, present and future†.

RATIONALE FOR REVIEW: In response to increased concerns about emerging infectious diseases, GeoSentinel, the Global Surveillance Network of the International Society of Travel Medicine in partnership with the US Centers for Disease Control and Prevention (CDC), was established in 1995 in order to serve as a global provider-based emerging infections sentinel network, conduct surveillance for travel-related infections and communicate and assist global public health responses. This review summarizes the history, past achievements and future directions of the GeoSentinel Network. KEY FINDINGS: Funded by the US CDC in 1996, GeoSentinel has grown from a group of eight US-based travel and tropical medicine centers to a global network, which currently consists of 68 sites in 28 countries. GeoSentinel has provided important contributions that have enhanced the ability to use destination-specific differences to guide diagnosis and treatment of returning travelers, migrants and refugees. During the last two decades, GeoSentinel has identified a number of sentinel infectious disease events including previously unrecognized outbreaks and occurrence of diseases in locations thought not to harbor certain infectious agents. GeoSentinel has also provided useful insight into illnesses affecting different traveling populations such as migrants, business travelers and students, while characterizing in greater detail the epidemiology of infectious diseases such as typhoid fever, leishmaniasis and Zika virus disease. CONCLUSIONS: Surveillance of travel- and migration-related infectious diseases has been the main focus of GeoSentinel for the last 25 years. However, GeoSentinel is now evolving into a network that will conduct both research and surveillance. The large number of participating sites and excellent geographic coverage for identification of both common and illnesses in individuals who have traversed international borders uniquely position GeoSentinel to make important contributions of travel-related infectious diseases in the years to come.

Globally mobile populations and the spread of emerging pathogens.

During the past decade, the global public health community has been challenged by the emergence and rapid worldwide spread of novel influenza strains, severe acute respiratory syndrome, chikungunya virus, drug-resistant tuberculosis, and other conditions and pathogens. Modern transportation and increased tourism, business travel, and immigration contributed to dissemination of these high-impact pathogens. The effectiveness of interventions such as airport screening, travel restrictions, and other community mitigation measures remains uncertain. However, human migration has occurred for centuries and will continue, despite the threats posed by microbes.

Spectrum of disease and relation to place of exposure among ill returned travelers.

BACKGROUND: Approximately 8 percent of travelers to the developing world require medical care during or after travel. Current understanding of morbidity profiles among ill returned travelers is based on limited data from the 1980s. METHODS: Thirty GeoSentinel sites, which are specialized travel or tropical-medicine clinics on six continents, contributed clinician-based sentinel surveillance data for 17,353 ill returned travelers. We compared the frequency of occurrence of each diagnosis among travelers returning from six developing regions of the world. RESULTS: Significant regional differences in proportionate morbidity were detected in 16 of 21 broad syndromic categories. Among travelers presenting to GeoSentinel sites, systemic febrile illness without localizing findings occurred disproportionately among those returning from sub-Saharan Africa or Southeast Asia, acute diarrhea among those returning from south central Asia, and dermatologic problems among those returning from the Caribbean or Central or South America. With respect to specific diagnoses, malaria was one of the three most frequent causes of systemic febrile illness among travelers from every region, although travelers from every region except sub-Saharan Africa and Central America had confirmed or probable dengue more frequently than malaria. Among travelers returning from sub-Saharan Africa, rickettsial infection, primarily tick-borne spotted fever, occurred more frequently than typhoid or dengue. Travelers from all regions except Southeast Asia presented with parasite-induced diarrhea more often than with bacterial diarrhea. CONCLUSIONS: When patients present to specialized clinics after travel to the developing world, travel destinations are associated with the probability of the diagnosis of certain diseases. Diagnostic approaches and empiric therapies can be guided by these destination-specific differences.

Global health surveillance and travelers' health.

PURPOSE OF REVIEW: Monitoring disease trends among travelers can inform both pretravel advice and posttravel management. Data from sentinel travelers upon their return to medically sophisticated environments can also benefit local populations in resource-limited countries. RECENT FINDINGS: Provider-based surveillance of travelers is increasingly sophisticated. Recently, networks such as GeoSentinel have provided cumulative trends in travel-related illness to assess pretravel risk for a mass gathering event--the Beijing Olympic Games. Data provided by the GeoSentinel also helped in determining the seasonality of dengue by region of travel and risk of acquiring schistosomiasis after a single short exposure. For chikungunya fever, detailed study of returned travelers exposed new clinical aspects of a disease previously studied in the tropics only. Clusters of hepatitis A, a vaccine-preventable disease, among European travelers, illustrated continued gaps in the preparation of the traveling public. Plasmodium knowlesi has emerged as the fifth human malaria parasite and is now a consideration in the diagnosis of febrile travelers from Asia. Automated global news scanning software is increasingly being able to detect and prioritize disease events. SUMMARY: Every year millions of travelers visit countries where they are exposed to pathogens that are usually rare in their home countries. Global surveillance of travel-related disease represents a powerful tool for the detection of infectious diseases. These data should encourage clinicians to take a detailed travel history during every patient encounter.

Vaccines for International Travel.

The pretravel management of the international traveler should be based on risk management principles. Prevention strategies and medical interventions should be based on the itinerary, preexisting health factors, and behaviors that are unique to the traveler. A structured approach to the patient interaction provides a general framework for an efficient consultation. Vaccine-preventable diseases play an important role in travel-related illnesses, and their impact is not restricted to exotic diseases in developing countries. Therefore, an immunization encounter before travel is an ideal time to update all age-appropriate immunizations as well as providing protection against diseases that pose additional risk to travelers that may be delineated by their destinations or activities. This review focuses on indications for each travel-related vaccine together with a structured synthesis and graphics that show the geographic distribution of major travel-related diseases and highlight particularly high-risk destinations and behaviors. Dosing, route of administration, need for boosters, and possible accelerated regimens for vaccines administered prior to travel are presented. Different underlying illnesses and medications produce different levels of immunocompromise, and there is much unknown in this discipline. Recommendations regarding vaccination of immunocompromised travelers have less of an evidence base than for other categories of travelers. The review presents a structured synthesis of issues pertinent to considerations for 5 special populations of traveler: child traveler, pregnant traveler, severely immunocompromised traveler, HIV-infected traveler, and traveler with other chronic underlying disease including asplenia, diabetes, and chronic liver disease.

Tafenoquine and G6PD: a primer for clinicians.

BACKGROUND: Tafenoquine, an 8-aminoquinoline, is now indicated for causal prophylaxis against all human malarias and as radical curative (anti-relapse) treatment against Plasmodium vivax and Plasmodium ovale. As with other 8-aminoquinolines, tafenoquine causes hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (hemizygous males and homozygous females) and is contraindicated in this population. Those with intermediate G6PD activity (heterozygous females) are also at risk for hemolysis. Awareness of how to prescribe tafenoquine in relation to G6PD status is needed so it can be used safely. METHODS: A standard literature search was performed on varying combinations of the terms tafenoquine, Arakoda, Kodatef, Krintafel, Kozenis, primaquine, G6PD deficiency, malaria prophylaxis and radical cure. The data were gathered and interpreted to review how tafenoquine should be prescribed in consideration of the G6PD status of an individual and traveller. RESULTS: Tafenoquine should only be given to those with G6PD activity >70% of the local population median. Qualitative G6PD tests are sufficient for diagnosing G6PD deficiency in males. However, in females quantitative G6PD testing is necessary to differentiate deficient, intermediate and normal G6PD statuses. Testing for G6PD deficiency is mandatory before tafenoquine prescription. Measures can be taken to avoid tafenoquine administration to ineligible individuals (i.e. due to G6PD status, age, pregnancy and lactation). Primaquine is still necessary for some of these cases. This review provides actions that can be taken to diagnose and manage hemolysis when tafenoquine is given inadvertently to ineligible individuals. CONCLUSION: Attention to G6PD status is required for safe prescription of tafenoquine. A high index of suspicion is needed if hemolysis occurs. Clinicians should seek evidence-based information for the management and treatment of iatrogenicy hemolysis caused by 8-aminoquinolines.

Seasonality, annual trends, and characteristics of dengue among ill returned travelers, 1997-2006.

We examined seasonality and annual trends for dengue cases among 522 returned travelers reported to the international GeoSentinel Surveillance Network. Dengue cases showed region-specific peaks for Southeast Asia (June, September), South Central Asia (October), South America (March), and the Caribbean (August, October). Travel-related dengue exhibited annual oscillations with several epidemics occurring during the study period. In Southeast Asia, annual proportionate morbidity increased from 50 dengue cases per 1,000 ill returned travelers in nonepidemic years to an average of 159 cases per 1,000 travelers during epidemic years. Dengue can thus be added to the list of diseases for which pretravel advice should include information on relative risk according to season. Also, dengue cases detected at atypical times in sentinel travelers may inform the international community of the onset of epidemic activity in specific areas.

Natural history, clinicoradiologic correlates, and response to triclabendazole in acute massive fascioliasis.

Fascioliasis is highly endemic in the Andean region of South America. Newer serological assays have improved our ability to diagnose acute fascioliasis. The diagnosis was established by Fasciola hepatica serology (Fas2-ELISA or Western blot) in 10 patients. Identifiable exposure included ingestion of watercress (N = 8), alfalfa juice (N = 5), and lettuce (N = 1). Computed tomography of the abdomen showed hepatomegaly (N = 9), track-like hypodense lesions with subcapsular location (N = 8), and subcapsular hematoma (N = 2). Radiologic sequelae included cyst calcifications detectable at least 3 years after treatment. Stool examinations were negative for F. hepatica eggs; serology was positive (Arc II [N = 2], Fas2-ELISA [N = 6], Western blot [N = 2]). The syndrome of eosinophilia, fever, and right upper quadrant pain, elevated transaminases without jaundice, hypodense liver lesions on CT, and an appropriate exposure history suggests acute fascioliasis. Fascioliasis is specifically treatable with a single dose of triclabendazole.