Travel vaccines: current practice and future aspects

Nearly 1 billion people now cross international borders each year. In 2007, international arrivals reached an all-time high of more than 850 million [101]. These many millions of arrivals are made up of those who travel for holidays, recreation, business, visiting friends and relatives, health treatments, service projects, teaching, religious pilgrimages and unspecified purposes. Given the growth of international travel, the field of travel medicine has expanded accordingly. Travel medicine is devoted to maintaining the health of international travelers through health promotion and disease prevention. Vaccination for travel is, therefore, an integral part of the provision of pretravel medical care.

Seeking vaccination, particularly for yellow fever, is often the reason that a traveler comes for a pretravel visit. Although the risk of vaccine-preventable illness for an individual traveler is very low (usually less than one case per 1000 visits), vaccine use for the control of disease in populations has seen critical successes. The near complete control of invasive Haemophilus influenzae type b in children in the USA [1] and the recent decline by over 90% of measles deaths in Africa are both examples of the power of effectively applied vaccine programs [2]. However, depending upon the disease, initial success does not always translate into long-term control. There are complex issues of waning immunity, as has occurred with pertussis, requiring the introduction of new pertussis-containing vaccines for adolescents and adults [3] or the challenge of controlling poliomyelitis in India in a population where chronic diarrhea and gut infections interfere with the immunogenicity of oral polio vaccines [4].

The appropriate use of vaccination in travel medicine requires that the key principles of risk assessment and risk management be applied in every case when a vaccine is being considered. The blanket use of vaccines without a risk assessment is not appropriate and may expose the traveler to unnecessary adverse events. In order to aid risk assessment, the destination, season and duration of travel, as well as the planned activities, underlying health and immunization status of the traveler need to be recorded and considered. These factors are then matched against the destination-specific epidemiology of the vaccine-preventable disease and, if available, the pattern of imported disease. As an example, the risk of typhoid fever is highest for travel to the Indian subcontinent [5]; more than 90% of UK imported cases of typhoid originate from India, Pakistan and Bangladesh, with the highest risk from Bangladesh (21 cases per 100,000 visits) [102]. Cases predominantly occur in those who are returning to these countries for the purpose of visiting their friends and relatives [5,6,102]. Thus, the use of typhoid vaccine should, in most circumstances, be targeted to those traveling for the purpose of visiting friends and relatives in the Indian subcontinent. Risk management, however, will also need to include food and water hygiene since the available typhoid vaccines are only 50–70% protective against Salmonella enterica serovar Typhi [7] and do not provide reliable protection against S. enterica serovar Paratyphi [8], an increasingly common cause of imported enteric fever [102].

Vaccines used prior to international travel can be divided into three areas: those that are recommended according to the routine schedule of immunization in the traveler’s home country, those that may be required, either under International Health Regulations (2005) [103] or by an individual country, and those that are recommended because of risk. Travel medicine is preventive medicine and the pretravel visit becomes an ideal time to update routinely recommended immunizations. Ongoing outbreaks of measles in many high-income countries emphasize this point [104]. What is routine in one country, however, may not be considered routine in another. For example, in the USA, hepatitis A and B, rotavirus, influenza and varicella vaccines are administered routinely to infants, in addition to the more standard diphtheria, tetanus, acellular pertussis, H. influenzae type b, pneumococcal conjugate, poliomyelitis and measles–mumps–rubella vaccines [9]. By contrast, in the UK, meningococcal type C conjugate and bacille Calmette–Guérin (BCG) (for high-risk infants) are administered in addition to the standard vaccines [105]. For American travelers, there is also overlap with what is now routine and what might be recommended for travel based on risk: hepatitis A and B, influenza and rotavirus. As new vaccines are developed and become incorporated into routine schedules, this overlap is likely to increase.

Under International Health Regulations [103], there is only one vaccine that is currently required by some countries prior to entry: yellow fever vaccine [10]. This vaccine has been in use for more than 50 years with millions of doses administered. Over this period, it has had a good record of safety, efficacy and success in controlling yellow fever in many areas of the world where there is a risk of yellow fever transmission. However, recently recognized severe viscerotropic and neurologic adverse events [11,12] have challenged the travel-medicine community to carefully assess the risk of acquiring yellow fever and basic biologists to better understand the mechanisms and risk factors for these events [13]. At present, two risk factors have been determined: older age, specifically an age of 60 years and older [14], and thymectomy [15], where the latter is a contraindication to vaccination. Several countries have taken the step of tying the regulation of centers administering yellow fever vaccine to improving standards in travel medicine [16].

Countries may occasionally impose their own requirements for vaccination outside of International Health Regulations. This has been the case in Saudi Arabia, a country which has required evidence of Neisseria meningitidis A, C, Y, W-135 vaccination from pilgrims arriving for Hajj or Umrah, following the global spread of meningococcal W-135 disease that was traced to Hajj pilgrims in 2000 [17]. Recently, they have also added a requirement for polio vaccination in those arriving from countries with ongoing transmission of wild polio virus, to prevent pilgrims being a source of the international spread of polio [18].

Vaccination based on risk includes prevention against cholera, hepatitis A and B, Japanese encephalitis (JE), meningococcal meningitis, poliomyelitis, rabies, tick-borne encephalitis, typhoid and TB. While the killed whole-cell, B-subunit oral cholera vaccine provides acceptable protection against Vibrio cholerae, the risk for most travelers is extremely low, and the vaccine should be reserved for those who will work in refugee settings or who will travel in cholera endemic areas and will be remote from medical care [19]. The risk of hepatitis A during travel is declining [20]; however, the vaccine confers long-term protection, is well tolerated and has been included in routine immunization schedules for some countries. It should be considered for most travelers. For travelers who have not received hepatitis B vaccine as part of their routine immunization schedule, it should be administered to those with potential exposure to blood and body fluids and can be considered for all travelers. The risk of contracting JE is low for most travelers to Asia; care should be taken to look for delayed systemic allergic reactions with the mouse brain-derived vaccine product (JE-VAX^®, Biken) [21]. New tissue culture and live-attenuated chimeric vaccines [22,23] promise improved choices for vaccination against JE since the production of JE-VAX has been discontinued.

The highest risk for meningococcal disease is during travel to countries in the meningitis belt of Africa (generally extending from Senegal to Ethiopia) during December through to June. The quadrivalent polysaccharide or conjugated A, C, Y, W-135 vaccine should be used. Dog bites are the primary mode of rabies transmission in low-income countries. Travelers should be advised to thoroughly wash a bite wound with soap and water and promptly seek postexposure evaluation and treatment. Rabies vaccine before travel eliminates the need for rabies immunoglobulin (a difficult to obtain biologic) in the event of a bite [24]. The risk of contracting tick-borne encephalitis is low for travel primarily to rural, forested areas of central Europe. Finally, BCG vaccine can be considered for previously unimmunized children (aged under 16 years) who will be traveling for 3 months or more to regions with high incidence rates of TB (≥40 cases/100,000 population) or for healthcare workers traveling to at-risk countries [25].

The future

Vaccine use in travelers has progressed in important ways. There is now an improved evidence base for determining risk and it is critical that travel-medicine practitioners apply this evidence before administering a vaccine. Furthermore, rapid advances in biotechnology promise a revolution in the development of new vaccines using diverse approaches ranging from chimeric (such as JE), conjugate (such as typhoid and meningococcal) or DNA vaccines to transgenic plant vaccines. New vaccine candidates should have improved safety and efficacy compared with currently used vaccines.

It can also be expected that there will be development of vaccines against diseases for which there are currently no vaccines, such as dengue, malaria, enterotoxigenic Escherichia coli, leishmaniasis and hookworm. In addition to the scientific hurdles, however, there are equally formidable economic hurdles of adequate vaccine research funding. It is important that efforts to develop vaccines specifically for travelers contribute to the introduction and use of vaccines for the benefit of the world’s most vulnerable people. The development of rotavirus vaccine is a case in point [26]. Hepatitis A vaccine – traditionally a ‘travel vaccine’ – is also being used increasingly for universal vaccination of whole populations in certain countries [27].

This issue of Expert Review of Vaccines documents the promising future for several vaccines that will be used in travel medicine but, more importantly, vaccines that can be used to control disease in endemic populations. We look forward to seeing the developments in this field.

Financial & competing interests disclosure

Wilder-Smith has received honoraria and has been sponsored to attend conferences by Sanofi Pasteur, GlaxoSmithKline and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.