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Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References

Background. Travel medicine is the medical subspecialty which promotes healthy and safe travel. Numerous studies have been published that provide evidence for the practice of travel medicine, but gaps exist.

Methods. The Research Committee of the International Society of Travel Medicine (ISTM) established a Writing Group which reviewed the existing evidence base and identified an initial list of research priorities through an interactive process that included e-mails, phone calls, and smaller meetings. The list was presented to a broader group of travel medicine experts, then was presented and discussed at the Annual ISTM Meeting, and further revised by the Writing Group. Each research question was then subject to literature search to ensure that adequate research had not already been conducted.

Results. Twenty-five research priorities were identified and categorized as intended to inform pre-travel encounters, safety during travel, and post-travel management.

Conclusion. We have described the research priorities that will help to expand the evidence base in travel medicine. This discussion of research priorities serves to highlight the commitment that the ISTM has in promoting quality travel-related research.

In 2008, an estimated 924 million persons crossed international borders.1 An estimated 8% of travelers to the developing world seek medical care during or after travel.2,3 Travel medicine is the medical subspecialty which promotes healthy and safe travel. Travel medicine includes preventive and curative medicine within many specialties such as infectious disease, preventive medicine, emergency medicine, wilderness medicine, psychiatry, occupational health, military and migration medicine, and environmental health.

Numerous studies have been published that provide evidence for the practice of travel medicine, including investigations specifically in travelers and investigations in other populations that can be applied to travelers (eg, vaccine trials). Table 1 shows examples of recent studies on various travel medicine topics. These studies also demonstrate that a range of study designs can be utilized within travel medicine research. However, gaps exist in scientific evidence, due to the recent establishment of the specialty, the lack of a clear funding body for travel medicine research, and the diverse topics that need to be addressed.

Table 1.  Examples of studies contributing to the existing evidence base in travel medicine, organized by study design
Study designStudy title
  1. These studies were selected by the authors to present examples of recent high-quality research studies which utilized different study designs to investigate several of the many questions within travel medicine.

Cohort surveyHealth problems after travel to developing countries3
 Health problems in a large cohort of Americans traveling to developing countries2
Surveillance databaseGeoSentinel Surveillance Network. Illness in long-term travelers visiting GeoSentinel clinics4
 GeoSentinel Surveillance Network. Spectrum of disease and relation to place of exposure among ill returned travelers5
Systematic reviewInsecticide-treated bed nets and curtains for preventing malaria6
 Global etiology of travelers' diarrhea: systematic review from 1973 to the present7
Meta-analysisTyphoid fever vaccines: a meta-analysis of studies on efficacy and toxicity8
Multicenter prospective cohortRisk of infection with Mycobacterium tuberculosis in travelers to areas of high tuberculosis endemnicity9
Randomized controlled trialTolerability of malaria chemoprophylaxis in non-immune travelers to sub-Saharan Africa: multicenter, randomized, double blind, four arm study10
 Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomized controlled trial11
 Loperamide plus azithromycin more effectively treats travelers' diarrhea in Mexico than azithromycin alone12
SerosurveyInfluenza virus infection in travelers to tropical and subtropical countries13
Notifiable disease and national travel databasesRisk of travel-associated typhoid and paratyphoid fevers in various regions14 Hepatitis A virus infections in travelers, 1988–200415
Cross-sectional designTravelers' knowledge, attitudes and practices on the prevention of infectious diseases: results from a study at Johannesburg International Airport16
 Knowledge, attitudes and practices in travel-related infectious diseases: the European airport survey17
Adverse event reporting systemAdverse event reports following yellow fever vaccination18

Studying travelers offers unique challenges.19 Travelers generally have a defined and identifiable period of risk (eg, their trip) which makes some research questions easier to address and others more difficult. In general, randomized controlled trials are the gold standard in research, but in relation to travelers, the main type of question that can be answered with this approach is vaccine/chemoprophylaxis efficacy. Cohort studies are a good study design to answer questions about risks, but will generally only recruit from those who present for pre-travel advice which creates selection/recruitment bias. To understand more about illnesses that occur during travel, cross-sectional studies can be done, such as airport surveys, but these are usually questionnaire-based and can be subject to both selection and reporting biases. Also, it is often difficult for researchers situated in the patients' home country to make accurate diagnoses when symptoms occur during travel. The timing of follow-up for research into post-travel issues can be problematic—if done too early, infections with long incubation periods are missed, and if done too late, there is increased risk of loss to follow-up and also more problems with recall.

In cooperation with national and international health-care providers, academic centers, the travel industry and the media, the International Society of Travel Medicine (ISTM) advocates and facilitates education, service, and research activities in the field of travel medicine. As part of its commitment to research activities, ISTM advocates creation and distribution of this statement of research priorities.

This article is intended for an audience of researchers and research funding agencies.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References

Preliminary discussions of the need for research priorities occurred in May 2005 during the ISTM Research Committee's meeting at the ISTM Annual Meeting (Lisbon, Portugal). A Writing Group was established, and elected the following:

  • The intended outcome is a collection of research questions presented in priority listing within several categories (eg, pre- and post-travel).
  • Priority research questions are intended primarily to safeguard the traveler's health, not the population at destination countries.
  • Research questions with application to the largest population of travelers are favored.

The Writing Group then developed research priorities through an interactive process that included e-mails, phone calls, and smaller meetings. The initial list of questions was intentionally over-inclusive to allow for expert opinion to evaluate a wide range of potential research topics. At the June 2006 Northern European Conference on Travel Medicine (Edinburgh, Scotland), the research questions were presented, discussed, and revised by the attending members of the Research Committee. The questions were then offered for comment to the other committees of the ISTM. The research priorities were compared for consistency to the Travel Medicine Practice Guidelines20 and then transformed into a priority list which was presented at a poster session at the 10th Conference of the ISTM.21 A survey for modifications was administered to the convenience sample of those attending the poster session. The Writing Group made modifications then further reviewed to choose areas with: (1) the most commonly arising questions; (2) the highest impact on health (severe disease with lack of therapy); and (3) the most likely to effect on cost savings. A literature search was then done to ensure that adequate data answering these questions did not already exist.

The research questions listed below (and in Table 2) are not an exhaustive list of all possible study areas, particularly because new issues are continuously emerging, and research priorities inevitably change over time. Nevertheless, this provides a starting point by listing some of the data gaps that have been identified as priority areas and which could feasibly be addressed with further research. Some research questions that were raised early in the course of this initiative have been adequately answered by recent studies and have been removed from the current list.

Table 2.  Priority research questions in travel medicine
Research questions
  1. TNF = tumor necrosis factor.

Pre-travel interventions
What is the minimum training that pre-travel practitioners should have in order to practice competently as specialists?
What are the effective ways to access travelers who do not currently seek pre-travel consultations?
What are the ways to increase referrals from non-travel clinicians who see patients who would benefit from travel medicine? For example, what is the role of publicity in the medical community regarding the existence and availability of travel medicine (eg, at primary care conferences, advertisements in journals, or mailings)?
What is the benefit of pre-travel counseling (eg, what counseling leads to safer sexual behaviors, and fewer road traffic accidents, animal bites, drownings, and other noninfectious threats to health)?
What are the most effective methods for pre-travel counseling (videos, group, one-on-one, etc.)?
How effective is the pre-travel encounter for ensuring that the traveler is up to date with locally relevant immunizations (which may or may not be considered as travel immunizations)?
For which travelers should gastrointestinal protozoal (eg, giardia) self-treatment medications be prescribed?
What guidance best prepares travelers for correct use of malaria standby emergency treatment?
What is the frequency of medical tourism, who are the most likely medical tourists on what itineraries, and what is the best approach to prepare them?
What are the risks during medical tourism (eg, blood-borne pathogens, nosocomial infections, and procedure complications)?
Safety during travel
Compared with nontravelers, what is the magnitude of the incremental risk of travel for death and disability from trauma and how is it best mitigated?
What are the real and perceived obstacles to implementing best-practice preventive measures among health-care workers in developing country settings?
How should new antithrombotic agents be incorporated into guidelines for travelers?
Do long-term travelers behave differently from short-term travelers?
Which repellants are more likely to be used appropriately by travelers and under which circumstances?
Is the repeated or long-term use of permethrin and other insecticides safe in the ways that travelers use them (eg, on clothing)?
Do travelers who develop traveler's diarrhea take their standby antibiotics appropriately?
Are non-live vaccines effective in those receiving TNF-alpha inhibitors and other immunosuppressants?
What is the best method to improve sexually transmitted infections prevention in travelers?
Post-travel
What is the utility of common algorithms for the management of post-travel syndromes such as acute and chronic diarrhea fever?
What is the best management of post-infectious irritable bowel syndrome?
When should clinicians prescribe presumptive anti-relapse therapy (PART)?
Is routine screening for latent tuberculosis infection using the tuberculin skin test or the interferon gamma release assays more cost effective for travelers?
Under what circumstances is screening for schistosomiasis, strongyloidiasis, intestinal parasites, filariasis (and other infectious diseases) in asymptomatic returned travelers cost effective?
What is the role of travelers in spread of emerging infections such as Chikungunya fever?

An Evidence Base for Pre-Travel Interventions

Table 2 shows research questions for which data are currently lacking and for which an improved evidence base for pre-travel interventions is required. Of particular concern is that 60% to 80% of travelers from North America,22,23 68% from Australasia,24 and 48% from Europe17 do not access pre-travel services. There are guidelines based largely on expert opinion providing travel medicine recommendations for different types of travelers on different itineraries (Infectious Disease Society of America Guidelines20), but strategies to access these patients are lacking.

The lack of pre-travel preparation has been shown to result in a low overall level of knowledge of risk and preventive practices. There is an association between failing to seek travel medicine services and acquisition of malaria.25 Although difficult to prove and fraught with potential biases, this association may hold for other adverse health impacts associated with travel. Recent data have informed strategies to protect health of certain populations of travelers who might not otherwise seek travel clinic services, such as travelers who are visiting friends and relatives (VFRs) or undertaking international adoption.26,27

During a pre-travel encounter, the travel practitioner provides the traveler with information about risks and best practices to mitigate risks. Most pre-travel encounters advise regarding local conditions (potential for crime, trauma), safe food and water practices, avoiding endemic communicable diseases (vector avoidance and malaria prevention, safe sexual practices, rabies, tuberculosis), and routine, recommended, and required vaccines. Discussion of these topics can consume and exceed typically allotted time for the pre-travel encounter; yet, there are little data to ensure understanding and adherence. Priorities for research to facilitate better understanding of what constitutes effective counseling and how to maximize adherence are also shown in Table 2.

Research questions to fill knowledge gaps in immunization practice are also imperative. Obtaining accurate immunization history, providing advice regarding immunizations, and administering immunizations for vaccine-preventable travel-related infectious diseases are fundamental to a successful pre-travel encounter. Besides traditionally targeted diseases such as hepatitis A, yellow fever, and typhoid, intriguing data are emerging that demonstrate that respiratory tract infections are extremely common among even short-term travelers,28 and are a common cause for seeking medical attention following travel.29 Mutsch et al. reported that influenza may be the most common vaccine-preventable travel infection for travelers visiting tropical and subtropical regions, with an estimated incidence of 1.0 influenza-associated events per 100 person-months abroad.13 The recent global emergence of novel influenza A H1N1 illustrates the rapidity with which influenza viruses spread, and serves as a reminder of the imperative to protect travelers and also their home communities from imported respiratory viruses such as influenza.

Nearly 50% of travelers encounter diarrhea during travel.2,3 Research priorities around the common problem of travelers' diarrhea (TD) are included in Table 2.

Advising and equipping the traveler to avoid malaria is another paramount role for the pre-travel encounter. Malaria was one of the three most frequent causes of systemic febrile illness among travelers from every GeoSentinel region.29 Centers for Disease and Prevention surveillance shows that about 800 cases of malaria are reported in US civilians each year13 and 453 cases of Plasmodium falciparum were reported by TropNet Europe in 2007.31 Topics that are prioritized for research toward improved malaria chemoprophylaxis and treatment are shown.

Research questions concerning special populations and types of travel are included within Table 2. The former includes children, pregnant and/or nursing women, immunocompromised, elderly, and the latter including travelers VFRs, on religious pilgrimages such as the Hajj, and participating in medical tourism. Medical tourism, also called medical travel or health tourism, describes those who travel across international borders to obtain healthcare, usually because of anticipated cost savings, availability of procedures not available (and sometimes unproven) or not immediately available at home or to combine healthcare with exotic vacations. Medical tourism continues to grow, and the role of the travel medicine practitioner in preparing such patients has not been established.32

An Evidence Base for Safety During Travel

The most common health problems during travel include TD, skin problems, and respiratory symptoms.2,3,29 Many illnesses experienced are mild and resolve spontaneously, which complicates accurate etiological diagnoses, and reduces the feasibility and utility of further research aimed in this area. Nevertheless, there are some practical questions that have been suggested as foci of possible future research. These involve noninfectious and infectious health problems that arise during travel, for which an improved evidence base regarding incidence and/or management would be welcome (Table 2).

Noninfectious Dangers of Travel

Travelers and travel medicine practitioners usually emphasize prevention of infectious diseases as the priority during the pre-travel encounter. However, the highest risks of death and disability for travelers arise from trauma. Typically, for selected travelers, brief reference to security issues is made (eg, terrorism and crime risk, children's car seat use, the use of helmets when cycling during travel, and the use of life vests during water sports); however, novel approaches to improve security in travel should be explored.33

Data also suggest that travelers are at risk for thromboembolism during long flights; however, questions remain about appropriate targets for prophylaxis and optimal therapeutic approaches to thromboembolic prevention.

Sexually Transmitted Infections and Blood-borne Pathogen Transmission Risk

The risks of sexually transmitted infections are often not sufficiently emphasized during pre-travel encounters, particularly given the high incidence of casual sex during travel.34,35 Effective strategies to advise and promote adherence regarding safe sex practices are needed. In addition, medical volunteering is a common cause for travel that poses increased risk of transmission of blood-borne pathogens, such as HIV and hepatitis B and C.

Vector Avoidance

While vector avoidance is well recognized as an optimal approach to reduce the risks of many infectious diseases (including malaria), novel strategies to improve compliance with use of preventive measures such DEET (N,N-diethyl-m-toluamide) and permethrin should be explored.

An Evidence Base for Post-travel Medicine

Management of Ill-Returned Travelers

The GeoSentinel report has informed an evidence-based approach to the differential diagnosis of ill-returned travelers.29 The report showed significant regional differences in proportionate morbidity in most of the broad syndromic illness categories among travelers presenting to GeoSentinel sites. However, many questions remain about diagnostic and management approaches, particularly for diseases that have a diagnosis of exclusion such as post-infectious irritable bowel syndrome.36

Asymptomatic Screening

There are circumstances where travel practitioners are requested or tempted to conduct screening of asymptomatic returned travelers. Better evidence to support when such screening is appropriate and worthwhile would be valuable.

Conclusions

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References

We have described priority research questions for which answers will help to expand the evidence base in travel medicine. Proposing these potential topics for future research has been difficult in itself, but conducting high-quality research with findings that can be translated into improved travel medicine services will be even more challenging. This discussion of research priorities serves to highlight the commitment that ISTM has in promoting quality travel-related research.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References

L. H. C. has received CDC funding for research through the Boston Area Travel Medicine Network (BATMN), honoraria for serving on the editorial board of Travel Medicine Advisor, and honoraria for chairing ISTM courses on travel medicine.

C. S. has received royalties from Elsevier, University of Washington Press, and Merck, speaking fees for The Everett Clinic, Everett, WA, USA, and National Wilderness Medicine Conferences as well as consultant fee from the Boeing Company.

The other authors state that they have no conflicts of interest to declare.

Appendix

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References

Members of the Research Committee of the International Society of Travel Medicine include: Anne McCarthy, MD, Chair (University of Ottawa, Ottawa, ON, Canada), Irmgard Bauer, PhD, Co-chair (James Cook University, Townsville Queensland), Elizabeth A. Talbot, MD (Dartmouth Medical School, Lebanon, NH), Lin H. Chen, MD (Mount Auburn Hospital, Cambridge, MA, and Harvard Medical School, Boston, MA), Christopher Sanford, MD, MPH, DTM&H (University of Washington, Seattle, WA), Patricia Schlagenhauf, PhD (University of Zurich, Zurich, Switzerland), and Annelies Wilder-Smith, MD, PhD, MIH, DTM&H (National University Hospital Singapore).

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Conclusions
  5. Declaration of Interests
  6. Appendix
  7. References