Margot Mutsch

Influenza Virus Infection in Travelers to Tropical and Subtropical Countries

BACKGROUND Influenza outbreaks have been reported among travelers, but attack rates and incidence are unknown. METHODS A cohort study was conducted. Travelers to subtropical and tropical countries recruited at the University of Zurich Travel Clinic (Switzerland), January 1998 to March 2000, were investigated with pre- and posttravel assessment of hemagglutination inhibition and by questionnaire. RESULTS Among 1450 travelers recruited who completed questionnaires and provided serum samples before departure, 289 (19.9%) reported febrile illness during or after traveling abroad; of these, 211 (73.0%) provided paired serum samples. Additionally, paired serum samples were collected from 321 frequency-matched afebrile control subjects among the remaining 1161 subjects of the study population. Seroconversion for influenza virus infection was demonstrated in 40 (2.8%) of all travelers; 18 participants (1.2%) had a > or = 4-fold increase in antibody titers. This corresponds to an incidence of 1.0 influenza-associated events per 100 person-months abroad. Among the 211 febrile participants, 27 (12.8%) had seroconversion, 13 (6.2%) with a > or = 4-fold increase; among the 321 afebrile control subjects, 13 (4.0%) had seroconversion, 5 (1.6%) with a > or = 4-fold increase. Twenty-five seroconverters (62.5%; P = .747) acquired influenza outside of the European epidemic season. Sixteen patients (40.0%) sought medical attention either abroad or at home, and 32 (80.0%) were asymptomatic at the time of completion of the survey. CONCLUSIONS This survey indicates that influenza is the most frequent vaccine-preventable infection among travelers to subtropical and tropical countries. Infections occur mainly outside the domestic epidemic season, and they have a considerable impact. Pretravel vaccination should be considered for travelers to subtropical and tropical countries.

Hepatitis A Virus Infections in Travelers, 1988–2004

BACKGROUND Uncertainty exists about the current risk of hepatitis A virus infection in nonimmune travelers to destinations with high or intermediate risk of transmission. We analyzed recent epidemiological data on imported hepatitis A to determine region-specific attack rates and incidences. METHODS Surveillance data on hepatitis A virus infections diagnosed during 1988-2004 were evaluated on the basis of notification by laboratories, additional reports of physicians, and travelers statistics. This study focuses on international travelers with hepatitis A virus infection detected after their return to Switzerland. RESULTS The rate of imported hepatitis A virus infections decreased 75% from 1988 to 2004 and accounted overall for 42% of all hepatitis A cases reported in Switzerland. The actual incidence of hepatitis A in travelers to countries of high or intermediate risk of transmission was 3.0-11.0 per 100,000 person-months abroad for all travelers and 6.0-28.0 per 100,000 for those presumed to be nonimmune. The actual proportion of those visiting friends and relatives among patients with hepatitis A has increased to 28.2%, with children aged 0-14 years predominating. Reductions in the incidence by hepatitis A vaccination were estimated to vary between 35.0% and 61.8% for different destinations. CONCLUSIONS The risk of hepatitis A virus infections has decreased by a factor of 10-50-fold over time, compared with findings from older studies. The risk, however, remains very considerable at many destinations, including frequently visited places, such as Mexico. Children of immigrants are a high-risk population. Strategies are needed to reach those at highest risk.

Health Risks Among Travelers—Need for Regular Updates

To be able to advise future travelers about preventive measures, travel health professionals must be aware about the various travel‐related health risks. Usually there may be no real‐time data; it remains the responsibility for anyone in the field to use the most recent evidence available. Far too often, one observes, eg, in scientific presentations, that old data are used as a reference. Since 1984, we have repeatedly published a logarithmic scale of such risks 1 but for 20 years have not detailed the sources used for this figure. In the initial versions, many results originated from a single prospective, meanwhile obsolete, study,2 but already then, data from previous retrospective surveys on cholera … Corresponding Author: Robert Steffen, MD, Centre for Travel Health, Institute of Social and Preventive Medicine, University of Zurich, Hirschengraben 84, CH‐8001 Zurich, Switzerland. E‐mail: travclin{at}ifspm.uzh.ch

Japanese Encephalitis: Defining Risk Incidence for Travelers to Endemic Countries and Vaccine Prescribing From the UK and Switzerland

BACKGROUND Large numbers of Western travelers visit countries endemic for Japanese encephalitis (JE). The risk of infection is unknown. This study attempts at estimating a risk incidence for visitors from two European countries with the available data. METHODS Using the total number of case reports between 1978 and 2008, the number of visits made by European tourists to endemic regions, and total doses of vaccines sold in the two study countries, the risk incidence of JE in travelers was estimated. The proportion of vaccinated visitors to endemic regions was retrieved from the data of two travel clinics (in London and Basel) and related to vaccine prescribing in UK and Swiss travelers. RESULTS In 2004, an estimated 0.16% to 0.3% of UK and Swiss travelers were vaccinated against JE, with no surveillance reports of JE cases. Between 116,000 and 152,000 European travelers would receive vaccination. More than 99% travel to endemic countries without vaccination. Only 40 cases of JE infection have been reported in travelers for the past 30 years. The risk incidence is thus 1.3 per year in 7.1 million visits of the 17 million European travelers who are at a potential risk of JE infection. CONCLUSIONS This study and the analysis of the existing literature support the recommendation that all travelers should be informed about the risk of JE infection but also suggest that there is no evidence for justifying a general recommendation for JE vaccination in travelers to endemic areas.

Measles associated with international travel in the region of the Americas, Australia and Europe, 2001-2013: a systematic review.

BACKGROUND Travel volumes are still increasing resulting in a more interconnected world and fostering the spread of infectious diseases. We aimed to evaluate the relevance of travel-related measles, a highly transmissible and vaccine-preventable disease. METHOD Between 2001 and 2013, surveillance and travel-related measles data were systematically reviewed according to the PRISMA guidelines with extraction of relevant articles from Medline, Embase, GoogleScholar and from public health authorities in the Region of the Americas, Europe and Australia. RESULTS From a total of 960 records 44 articles were included and they comprised 2128 imported measles cases between 2001 and 2011. The proportion of imported cases in Europe was low at 1-2%, which reflects the situation in a measles-endemic region. In contrast, imported and import-related measles accounted for up to 100% of all cases in regions with interrupted endemic measles transmission. Eleven air-travel related reports described 132 measles index cases leading to 47 secondary cases. Secondary transmission was significantly more likely to occur if the index case was younger or when there were multiple infectious cases on board. Further spread to health care settings was found. Measles cases associated with cruise ship travel or mass gatherings were sporadically observed. CONCLUSIONS Within both, endemic and non-endemic home countries, pretravel health advice should assess MMR immunity routinely to avoid measles spread by nonimmune travelers. To identify measles spread as well as to increase and sustain high vaccination coverages joint efforts of public health specialists, health care practitioners and travel medicine providers are needed.

Influenza vaccine: a travelers’ vaccine?

Seasonal influenza affects 5–15% of the world’s population annually and is considered to be the second most frequent vaccine-preventable infection in travelers. Despite increasing travel volume worldwide, guidelines on influenza vaccination for international travel are scarce. On the basis of some national recommendations, influenza vaccine should be used based on host criteria to usual risk groups, such as old (>50–65 years) or young (6–23 months) age and those with comorbidities. Additionally, environmental and behavioral factors must be considered. Close contact with high transmission has been documented in cruise ships and during mass gatherings. Travelers crossing to the opposite hemisphere in influenza-peak season may need protection. Those visiting the tropics are at moderate risk of infection and illness during the entire year. A summary on existing traveler recommendations relating to avian influenza is included.

Seroepidemiology of dengue in travellers: A paired sera analysis

BACKGROUND Dengue is a frequent cause of fever in travellers. The true extent is unknown as many infections are asymptomatic or undiagnosed. METHODS We used paired sera, with pre- and post-travel specimens from Swiss travellers to tropical destinations, to evaluate the seroepidemiology of travel-related dengue. Post-travel specimens were tested for the presence of IgG and IgM antibodies to dengue antigen serotypes (1, 2, 3 and 4) using an indirect enzyme-linked immunosorbent assay (ELISA). All post-travel sera that screened as positive for dengue IgG or IgM antibodies were re-tested with the corresponding pre-travel sera as paired assays in order to detect seroconversion. RESULTS There were 285 travellers with specimens available for analysis. Two hundred and fifty seven of the 285 individuals (90.2%) had negative dengue serology post-travel. Of the remaining 28 cases, 25 were dengue IgG positive and 3 had equivocal results. This corresponds to IgG seropositivity in 8.9%. Eighteen of these 25 individuals had a pre-travel specimen available for testing, of which 15 were positive for IgG consistent with possible past exposure. Three of the 18 had negative serology pre-travel, indicating possible recent infection. This corresponds to an attack rate of possible dengue of 1.1% and an incidence rate of 6.7 per 1000 person-months (95% CI 0-60.0). Two of these three individuals had received yellow fever vaccine for their trip, raising the potential of cross-reactivity. The confirmed dengue attack rate therefore was 0.23% with a corresponding incidence rate of 2.2 per 1000 person-months (95% CI-0-33.1). CONCLUSIONS Seroepidemiology provides additional evidence of an appreciable risk of acute dengue infection among travellers to tropical destinations.

Breastfeeding Travelers: Precautions and Recommendations

With increased travel globally, more women travel while breastfeeding their infants as well as during pregnancy. The transfer of drugs and chemicals into human milk differs from transfer via umbilical cord during pregnancy. Because there is little evidence‐based literature on recommendations for breastfeeding travelers, we review factors that influence drug passage into breast milk and available safety data on common medications that may be encountered by breastfeeding travelers. Biologic and immunologic events in the mother may affect the breastfeeding infant. We review those that are relevant to the breastfeeding woman who is preparing to travel. We also review the use of vaccines in breastfeeding women and the mechanisms by which they could affect the infant. Physiologic changes that occur with breastfeeding involve the hormones oxytocin and prolactin. The hyperplasia of milk ducts and production of immunologically rich human milk occur through the feedback mechanism of suckling. Changes to the mothers immune system following vaccine administration should not differ from the non‐breastfeeding state, though little research has been directed to this question. Breast milk does not adversely impact the response to vaccines administered directly to the infant. 1,2 Specific antibody responses to travel‐related vaccines have not been studied in nursing mothers. Maternal plasma volume expands by 50% through pregnancy and returns to normal level in most women by 8 weeks postpartum. 3 This increases the volume of distribution of drugs administered, related to the amount of protein binding of the given compound. Although most medications transfer into human milk, many are found at low concentrations in breast milk and are relatively safe for the infant. The clinician should consider the risk of the drug versus the benefit of breastfeeding for the infant. Maternal, drug, and infant factors influence the amount of drug available to the nursing infant. The factors influencing drug … Corresponding Author: Lin H. Chen, MD, Travel Medicine Center, Mount Auburn Hospital, 330 Mount Auburn Street, Cambridge, MA 02138, USA. E‐mail: lchen{at}hms.harvard.edu

Relationship of Serum Vitamin D Concentrations and Allostatic Load as a Measure of Cumulative Biological Risk among the US Population: A Cross-Sectional Study

Introduction The allostatic load (AL) index is a multi-systemic measure of physiologic dysregulation known to be associated with chronic exposure to stress and adverse health outcomes. We examined the relationship between AL and serum 25-hydroxyvitamin D (25(OH)D) concentration in non-institutionalized US adults. Methods Data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94) were used to calculate two versions of AL including 9 biomarkers and another two with 14 biomarkers (systolic and diastolic blood pressure, pulse rate, serum cholesterol, serum HDL-cholesterol, glycated hemoglobin, sex-specific waist-to-hip ratio, serum albumin, and serum C-reactive protein for AL1, and, additionally body mass index, serum triglyceride, serum creatinine, and serum herpes I & II antibodies for AL2), each set defined by predefined cut-offs or by quartiles. Serum vitamin D concentration was ranked into quartiles. Logistic regression, Poisson regression and linear regression were used to examine the association of serum 25(OH)D concentrations on AL, after adjusting for biological, physiological, socioeconomic, lifestyle, and health variables. Results Odds Ratios (OR) for high AL of the lowest 25(OH)D serum quartile were between 1.45 (95% CI: 1.28, 1.67) and 1.79 (95% CI: 1.39, 2.32) for the fully adjusted model, depending on AL version. Inverse relationships between vitamin D serum concentrations were observed for all AL versions and every adjustment. This relationship was consistent after stratification by sex, age or ethnic background. Sensitivity to low 25(OH)D concentrations was highest among the youngest group (20–39 years) with an OR of 2.11 (95% CI: 1.63, 2.73) for the lowest vitamin D quartile Q1. Conclusions Vitamin D had a consistent and statistically significant inverse association with all tested models of high AL, which remained consistent after adjusting for biological, socioeconomic, lifestyle and health variables. Our study adds evidence linking low 25(OH)D concentrations with poorer health, further-reaching than bone health.

The change in the sex ratio in multiple sclerosis is driven by birth cohort effects.

Birth cohort effects have greatly shaped long‐term trends in multiple sclerosis (MS). This study examined whether birth cohort effects have also determined trends in the sex ratio.