What's Old Is New Again: The Re-emergence of Yellow Fever in Brazil and Vaccine Shortages.

Yellow fever outbreaks have continued to occur and caused infection and deaths in travelers from non-endemic regions. Yellow fever vaccine has proven effective, but vaccination decisions require balancing benefits with risks. Of concern is the continued vaccine shortage worldwide, including of the YF-VAX® stockout in North America, which has presented many challenges.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Measles in the 21st Century, a Continuing Preventable Risk to Travelers: Data From the GeoSentinel Global Network.

Measles remains a risk for travelers, with 94 measles diagnoses reported to the GeoSentinel network from 2000 to 2014, two-thirds since 2010. Asia was the most common exposure region, then Africa and Europe. Efforts to reduce travel-associated measles should target all vaccine-eligible travelers, including catch-up vaccination of susceptible adults.

Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network.

BACKGROUND: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. OBJECTIVE: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. DESIGN: Descriptive, using GeoSentinel records. SETTING: 57 travel or tropical medicine clinics in 25 countries. PATIENTS: 805 ill returned travelers and new immigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. MEASUREMENTS: Frequencies of demographic and travel-related characteristics and illnesses reported. RESULTS: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non-P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n = 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. LIMITATION: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. CONCLUSION: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012.

BACKGROUND: Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011-2012. METHODS: Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology. Case confirmation required histologic observation of sarcocysts or isolation of Sarcocystis species DNA from muscle biopsy. RESULTS: Sixty-eight patients met the case definition (62 probable and 6 confirmed). All but 2 resided in Europe; all were tourists and traveled mostly during the summer months. The most frequent symptoms reported were myalgia (100%), fatigue (91%), fever (82%), headache (59%), and arthralgia (29%); onset clustered during 2 distinct periods: "early" during the second and "late" during the sixth week after departure from the island. Blood eosinophilia and elevated serum creatinine phosphokinase (CPK) levels were observed beginning during the fifth week after departure. Sarcocystis nesbitti DNA was recovered from 1 muscle biopsy. CONCLUSIONS: Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS, noting the apparent biphasic aspect of the disease, the later onset of elevated CPK and eosinophilia, and the possibility for relapses. The exact source of infection among travelers to Tioman Island remains unclear but needs to be determined to prevent future illnesses.

Travel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel.

BACKGROUND: US residents make 60 million international trips annually. Family practice providers need to be aware of travel-associated diseases affecting this growing mobile population. OBJECTIVE: To describe demographics, travel characteristics and clinical diagnoses of US residents who present ill after international travel. METHODS: Descriptive analysis of travel-associated morbidity and mortality among US travellers seeking care at 1 of the 22 US practices and clinics participating in the GeoSentinel Global Surveillance Network from January 2000 to December 2012. RESULTS: Of the 9624 ill US travellers included in the analysis, 3656 (38%) were tourist travellers, 2379 (25%) missionary/volunteer/research/aid workers (MVRA), 1580 (16%) travellers visiting friends and relatives (VFRs), 1394 (15%) business travellers and 593 (6%) student travellers. Median (interquartile range) travel duration was 20 days (10-60 days). Pre-travel advice was sought by 45%. Hospitalization was required by 7%. Compared with other groups of travellers, ill MVRA travellers returned from longer trips (median duration 61 days), while VFR travellers disproportionately required higher rates of inpatient care (24%) and less frequently had received pre-travel medical advice (20%). Illnesses of the gastrointestinal tract were the most common (58%), followed by systemic febrile illnesses (18%) and dermatologic disorders (17%). Three deaths were reported. Diagnoses varied according to the purpose of travel and region of exposure. CONCLUSIONS: Returning ill US international travellers present with a broad spectrum of travel-associated diseases. Destination and reason for travel may help primary health care providers to generate an accurate differential diagnosis for the most common disorders and for those that may be life-threatening.

Population-based surveillance of medical tourism among US residents from 11 states and territories: Findings from the Behavioral Risk Factor Surveillance System.

OBJECTIVE: To describe medical tourism among a subset of US residents; identify possible indicators for medical tourism. METHODS: The US Centers for Disease Control and Prevention collaborated with 11 states and territories to ask 6 questions about medical tourism, using the Behavioral Risk Factor Surveillance System. Data collected from January 1, 2016, through December 31, 2016, included whether respondents traveled internationally for preplanned care, travel reasons and destinations, procedures received, and occurrence and treatment of complications. A descriptive analysis of demographics, socioeconomic status and health access variables was performed, and a regression model with a log-link function and Poisson distribution was used to estimate prevalence ratios (PR) for medical tourism. RESULTS: Of 93,492 respondents, 517 (0.55%) traveled internationally during the previous year for care. Mexico was the most common destination (41% of trips). Dentistry accounted for 55% of treatments. Complications from care received abroad were reported by 5% of medical tourists; 67% sought care upon returning to the United States. The prevalence of medical tourism was 1.32% (95% CI, 1.00-1.64). The prevalence of medical tourism was higher in Hispanics and non-whites (PR, 3.97; 95% CI, 2.48-6.32) and higher among those without current health insurance (PR, 2.70; 95% CI, 1.69-4.34). CONCLUSIONS: This is the largest collection of population-based surveillance data describing medical tourism among US residents from multiple states and territories. Understanding the demographic and socioeconomic factors associated with medical tourism can inform evidence-based recommendations for travelers and clinicians who may advise or care for these individuals before, during, or after travel.

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.

What proportion of international travellers acquire a travel-related illness? A review of the literature.

INTRODUCTION: As international travel increases, travellers may be at increased risk of acquiring infectious diseases not endemic in their home countries. Many journal articles and reference books related to travel medicine cite that between 22-64% of international travellers become ill during or after travel; however, this information is minimal, outdated and limited by poor generalizability. We aim to provide a current and more accurate estimate of the proportion of international travellers who acquire a travel-related illness. METHODS: We identified studies via PubMed or travel medicine experts, published between January 1, 1976-December 31, 2016 that included the number of international travellers acquiring a travel-related illness. We excluded studies that focused on a single disease or did not determine a rate based on the total number of travellers. We abstracted information on traveller demographics, trip specifics, study enrollment and follow-up and number of ill travellers and their illnesses. RESULTS: Of 743 studies, nine met the inclusion criteria. The data sources were from North America (four studies) and Europe (five studies). Most travellers were tourists, the most frequent destination regions were Asia and Africa, and the median trip duration ranged from 8-21 days. Six studies enrolled participants at the travellers' pre-travel consultation. All studies collected data through either extraction from the medical record, weekly diaries, or pre- and post-travel questionnaires. Data collection timeframes varied by study. Between 6-87% of travellers became ill across all studies. Four studies provided the best estimate: between 43-79% of travellers who frequently visited developing nations (e.g. India, Tanzania, and Kenya) became ill; travellers most frequently reported diarrhoea. CONCLUSION: This is the most comprehensive assessment available on the proportion of international travellers that develop a travel-related illness. Additional cohort studies would provide needed data to more precisely determine the rates of illness in international travellers. KEYWORDS: International travel, travel, illness.

International travelers with infectious diseases determined by pathology results, Centers for Disease Control and Prevention - United States, 1995-2015.

BACKGROUND: The failure to consider travel-related diagnoses, the lack of diagnostic capacity for specialized laboratory testing, and the declining number of autopsies may affect the diagnosis and management of travel-related infections. Pre- and post-mortem pathology can help determine causes of illness and death in international travelers. METHODS: We conducted a retrospective review of biopsy and autopsy specimens sent to the Infectious Diseases Pathology Branch laboratory (IDPBL) at the Centers for Disease Control and Prevention (CDC) for diagnostic testing from 1995 through 2015. Cases were included if the specimen submitted for diagnosis was from a traveler with prior international travel during the disease incubation period and the cause of illness or death was unknown at the time of specimen submission. RESULTS: Twenty-one travelers, six (29%) with biopsy specimens and 15 (71%) with autopsy specimens, met the inclusion criteria. Among the 15 travelers who underwent autopsies, the most common diagnoses were protozoal infections (7 travelers; 47%), including five malaria cases, followed by viral infections (6 travelers; 40%). CONCLUSIONS: Biopsy or autopsy specimens can assist in diagnosing infectious diseases in travelers, especially from pathogens not endemic in the U.S. CDC's IDPBL provides a useful resource for clinicians considering infectious diseases in returned travelers.

Delayed Diagnosis, Leprosy Reactions, and Nerve Injury Among Individuals With Hansen's Disease Seen at a United States Clinic.

Background. Hansen's disease (HD), or leprosy, is uncommon in the United States. We sought to describe the characteristics of patients with HD in a US clinic, including an assessment of delays in diagnosis and HD reactions, which have both been associated with nerve damage. Methods. A retrospective chart review was conducted on patients seen at an HD clinic in the southern United States between January 1, 2002 and January 31, 2014. Demographic and clinical characteristics were summarized, including delays in diagnosis, frequency of reactions, and other complications including peripheral neuropathy. Results. Thirty patients were seen during the study time period. The majority of patients were male (73%) and had multibacillary disease (70%). Brazil, Mexico, and the United States were the most frequent of the 14 countries of origin. Hansen's disease "reactions", severe inflammatory complications, were identified among 75% of patients, and nerve damage was present at diagnosis in 36% of patients. The median length of time between symptom onset and diagnosis was long at 12 months (range, 1-96), but no single factor was associated with a delay in diagnosis. Conclusions. The diagnosis of HD was frequently delayed among patients referred to our US clinic. The high frequency of reactions and neuropathy at diagnosis suggests that further efforts at timely diagnosis and management of this often unrecognized disease is needed to prevent the long-term sequelae associated with irreversible nerve damage.

Ebola or Not? Evaluating the Ill Traveler From Ebola-Affected Countries in West Africa.

Background. The 2014-2015 Ebola epidemic in West Africa had global impact beyond the primarily affected countries of Guinea, Liberia, and Sierra Leone. Other countries, including the United States, encountered numerous patients who arrived from highly affected countries with fever or other signs or symptoms consistent with Ebola virus disease (EVD). Methods. We describe our experience evaluating 25 travelers who met the US Centers for Disease Control and Prevention case definition for a person under investigation (PUI) for EVD from July 20, 2014 to January 28, 2015. All patients were triaged and evaluated under the guidance of institutional protocols to the emergency department, outpatient tropical medicine clinic, or Emory's Ebola treatment unit. Strict attention to infection control and early involvement of public health authorities guided the safe evaluation of these patients. Results. None were diagnosed with EVD. Respiratory illnesses were common, and 8 (32%) PUI were confirmed to have influenza. Four patients (16%) were diagnosed with potentially life-threatening infections or conditions, including 3 with Plasmodium falciparum malaria and 1 with diabetic ketoacidosis. Conclusions. In addition to preparing for potential patients with EVD, Ebola assessment centers should consider other life-threatening conditions requiring urgent treatment, and travelers to affected countries should be strongly advised to seek pretravel counseling. Furthermore, attention to infection control in all aspects of PUI evaluation is paramount and has presented unique challenges. Lessons learned from our evaluation of potential patients with EVD can help inform preparations for future outbreaks of highly pathogenic communicable diseases.

Yellow fever and Japanese encephalitis vaccines: indications and complications.

Appropriate administration of yellow fever or Japanese encephalitis vaccines to travelers requires an assessment of the traveler's risk for infection with these vector-borne flaviviruses during their travels and the presence of risk factors for adverse events following immunization. Japanese encephalitis and yellow fever vaccines have been more frequently associated with serious adverse events following immunization since the early 1980s and the late 1990s, respectively. This article describes the adverse events, the magnitude of their risk, and associated risk factors.

A Bystander Effect of Lung Cancer Chemotherapy on Chronic Echinococcal Disease.

Hydatid cystic disease is a parasitic infestation caused by Echinococcus granulosus and commonly manifests as hepatic and pulmonary cysts. When feasible, based on cyst size and location, surgical resection is potentially curative. Post-surgical recurrence of disease is encountered in up to 25% of patients. Secondary peritoneal contamination is a recognized complication in 5-10% of cases. Disseminated disease is usually palliated using systemic anti-parasitic agents such as benzimidazoles, albendazole and mebendazole but worsening of disease post-systemic treatment is frequent in 14-25% of patients. In this report, we share our experience of a patient with long-standing, chronic disseminated hydatidosis and subsequent diagnosis of non-small cell lung cancer who manifested evidence of reduced activity of the echinococcal disease following institution of chemotherapy for his new diagnosis of lung cancer. There was significant reduction in the serum level of anti-echinococcal antibody titers in tandem with chemotherapy administration. There was also minimal but notable decrease in the size of the cysts on serial cross-sectional imaging obtained for monitoring cancer response to chemotherapy. This intriguing observation of a possible benefit of anticancer chemotherapy against echinococcal disease in this index case may provide new insights for therapeutic exploration in disseminated echinococcal disease.

Evaluation of the Coca-Cola company travel health kit.

BACKGROUND: The Coca-Cola travel health kit has been used for about one decade for international travelers and required evaluation to see if the items contained were appropriate for the employees. METHODS: Two hundred thirty-four travelers were sampled and filled out a voluntary survey including questions about demographic information, travel history, and usage and value of the contents of the travel health kit. RESULTS: One hundred eighty-one surveys were returned; 65% of the respondents were male, and the majority of travelers were between the ages of 36 and 45 years. The most useful items were analgesics and medications used for gastrointestinal problems. In general, the items identified as being the least useful were those requiring specialized use by a medical practitioner, such as needles and syringes. Suggestions of items to be added to the kit included vitamins, cough drops, sleep aids, and eye drops. A surprising result that Coca-Cola employees expressed the desire for brand name rather than generic items. CONCLUSIONS: Evaluation of the Coca-Cola Company travel health kit revealed it to be very useful to most corporate travelers. Suggestions that were made will be taken into consideration in designing a new kit, and consideration is being given to whether a basic travel health kit should be provided to which travelers can add other items depending on their personal needs.

Health and safety issues for travelers attending the World Cup and Summer Olympic and Paralympic Games in Brazil, 2014 to 2016.

IMPORTANCE: Travelers from around the globe will attend the 2014 Fédération Internationale de Football Association (FIFA) World Cup and the 2016 Olympic and Paralympic Games in Brazil. Travelers to these mass gathering events may be exposed to a range of health risks, including a variety of infectious diseases. Most travelers who become ill will present to their primary care physicians, and thus it is important that clinicians are aware of the risks their patients encountered. OBJECTIVE: To highlight health and safety concerns for people traveling to these events in Brazil so that health care practitioners can better prepare travelers before they travel and more effectively diagnose and treat travelers after they return. EVIDENCE REVIEW: We reviewed both peer-reviewed and gray literature to identify health outcomes associated with travel to Brazil and mass gatherings. Thirteen specific infectious diseases are described in terms of signs, symptoms, and treatment. Relevant safety and security concerns are also discussed. FINDINGS: Travelers to Brazil for mass gathering events face unique health risks associated with their travel. CONCLUSIONS AND RELEVANCE: Travelers should consult a health care practitioner 4 to 6 weeks before travel to Brazil and seek up-to-date information regarding their specific itineraries. For the most up-to-date information, health care practitioners can visit the Centers for Disease Control and Prevention (CDC) Travelers' Health website (http://wwwnc.cdc.gov/travel) or review CDC's Yellow Book online (http://wwwnc.cdc.gov/travel/page/yellowbook-home-2014).

International travelers as sentinels for sustained influenza transmission during the 2009 influenza A(H1N1)pdm09 pandemic.

BACKGROUND: International travelers were at risk of acquiring influenza A(H1N1)pdm09 (H1N1pdm09) virus infection during travel and importing the virus to their home or other countries. METHODS: Characteristics of travelers reported to the GeoSentinel Surveillance Network who carried H1N1pdm09 influenza virus across international borders into a receiving country from April 1, 2009, through October 24, 2009, are described. The relationship between the detection of H1N1pdm09 in travelers and the level of H1N1pdm09 transmission in the exposure country as defined by pandemic intervals was examined using analysis of variance (anova). RESULTS: Among the 203 (189 confirmed; 14 probable) H1N1pdm09 case-travelers identified, 56% were male; a majority, 60%, traveled for tourism; and 20% traveled for business. Paralleling age profiles in population-based studies only 13% of H1N1pdm09 case-travelers were older than 45 years. H1N1pdm09 case-travelers sought pre-travel medical advice less often (8%) than travelers with non-H1N1pdm09 unspecified respiratory illnesses (24%), and less often than travelers with nonrespiratory illnesses (43%; p < 0.0001). The number of days from first official H1N1pdm09 case reported by a country to WHO and the first GeoSentinel site report of a H1N1pdm09-exported case in a traveler originated from that country was inversely associated with each country's assigned pandemic interval, or local level of transmission intensity. CONCLUSION: Detection of travel-related cases appeared to be a reliable indicator of sustained influenza transmission within the exposure country and may aid planning for targeted surveillance, interventions, and quarantine protocols.