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Travel Vaccines and Elderly Persons: Review of Vaccines Available in the United States

  1. Charles D. Ericsson, Section Editor and
  2. Robert Steffen, Section Editor
  1. Karin Leder1,3,
  2. Peter F. Weller1,2,3, and
  3. Mary E. Wilson3,4,5
  1. 1Divisions of Infectious Diseases Beth Israel Deaconess Medical Center, Boston
  2. 2Divisions of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston
  3. 3Department of Medicine, Harvard Medical School, Boston
  4. 4Division of Population and International Health, Harvard School of Public Health, Boston
  5. 5Travel Resource Center, Mount Auburn Hospital, Cambridge, Massachusetts
  1. Reprints or correspondence: Dr. Karin Leder, Infectious Disease Division, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Dana-617, Boston, MA 02215 (kleder{at}hotmail.com).
 
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Abstract

Aging is associated with alterations in immune responses and may lead to clinically significant changes in the safety, immunogenicity, and protective efficacy of certain vaccines. This review summarizes published data regarding the effects of age on responses after immunization with vaccines generally administered before travel. The specific vaccines discussed in detail include hepatitis A, typhoid, yellow fever, Japanese encephalitis, and rabies vaccines. There is some evidence of diminished serological responses to hepatitis A and rabies vaccines in older individuals. In addition, increased toxic effects following yellow fever vaccination in elderly recipients have recently been reported. However, many travel-related vaccines have never been studied specifically in elderly populations. Consideration of potential age-related differences in responses to travel vaccines is becoming increasingly important as elderly persons more frequently venture to exotic destinations.

As the number of elderly persons worldwide increases, it becomes increasingly important to understand the health implications of aging. Elderly persons have an increased susceptibility to cancer, autoimmune diseases, and infectious diseases, but the relative importance of increased age in isolation from the effects of other comorbidities remains debated. There is now evidence of a remodeling of the immune system, even in healthy elderly individuals [1], resulting in changes involving humoral, cellular, and innate immunity. Frequently, the net effect observed is a decrease in the quantity and quality of immune responses in older individuals [2, 3].

This review summarizes what is known about responses that follow immunization of elderly individuals with vaccines currently available in the United States, a topic that is becoming increasingly relevant as the number of aged people traveling to exotic destinations increases. It has been estimated that 13%–15% of travelers are >65 years of age [4–6]. In one study of 1416 travelers who attended a pretravel clinic in the United States, 48% were ⩾50 years of age, one-third were >60 years of age, and almost 1.5% were >80 years of age [7]. Elderly persons are more vulnerable to acquisition of certain infections as well as to severe outcomes. In addition, they may not develop the same degree of immunoprotection as that which occurs in younger individuals after vaccination. General immunization guidelines for travel vaccines have been developed primarily from studying responses in young volunteers.

We review published information regarding the use of pretravel vaccines in older individuals, concentrating on data for individuals >60 years old but also reviewing results for those 40–60 years of age, and we highlight areas that have not yet been studied. It is possible that many aspects of immune response are affected by age, including the quality and magnitude of antibody and cellular responses, the duration of protection, the timing of seroresponses, and the adverse events that occur after vaccination (tables 1–6).

Table 1
Table 1

Data concerning age-related effects on immune response to hepatitis A vaccine.

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Hepatitis A Vaccine

Travelers to developing countries have a risk of hepatitis A infection estimated to be 3–20 cases per 1000 persons per month of stay, varying with destination and with living conditions while abroad [8, 9]. Although clinical illness is usually mild in the young, the risk of severe infection increases with increasing age, and mortality rates are ∼2% for patients >40 years of age [8]. Consequently, hepatitis A vaccine is recommended for nonimmune elderly travelers, despite a paucity of data regarding protective efficacy of the vaccine in this population.

The currently licensed hepatitis A vaccines in the United States are Havrix (GlaxoSmithKline) and Vaqta (Merck & Co.). Both have equivalent high immunogenicity and excellent safety profiles [10]. Cell-mediated reactions may play a minor role in the immune response to hepatitis A infection, but antibody alone is sufficient to protect against clinical disease, as has been clearly demonstrated by the excellent protection provided by passive immunization with Ig [11, 12]. Thus, measurement of serum antibody levels is useful for monitoring vaccination response, and a minimum level of 10 mIU/mL or 20 mIU/mL is generally considered necessary for protection [13].

Among young persons, seroconversion is seen in 80%–90% within 2 weeks of the first dose, and 95%–100% of vaccinees have had seroconversion by 4 weeks [13]. In large efficacy studies that involved children (1 study in Thailand and 1 study in the United States), protective efficacy against clinical disease was 95% and 100%, respectively [14, 15]. It has been projected that protective antibody levels will persist for >25 years after vaccination [16, 17].

Vaccination of elderly persons. A number of studies have looked at age-related effects on the immune response to hepatitis A vaccine (table 1). Some studies used the 2-dose vaccine regimen currently recommended for adults in the United States (Havrix [1440 enzyme units (EU)], or Vaqta [50 units/mL], at 0 and 6–12 months), but earlier studies used a half-dose, 3-inoculation schedule that was recommended previously. In one study, Havrix (1440 EU) administered at 0 and 6 months to seronegative people aged 20–39 years or 40–62 years led to lower seropositivity rates at day 15 in the older group (90% vs. 77%; P < .05) [18]. At 1 month after both the initial vaccination and after the booster, 97% and 100%, respectively, of the groups were seropositive. Similar results have been found in other studies: one showed that 94% of adults <40 years old had seroconversion 1 month after a single dose of Havrix (720 EU), compared with 84% of adults >40 years old (P =.08) [19], and a second study showed that 8 months after 2 doses of Havrix (720 EU), seroconversion rates were 85% and 60% for adults ⩽35 years and >35 years, respectively (P < .05) [20].

The same trend has also been seen after immunization with Vaqta (25 U): one study showed healthy adults aged 18–39 and 40–65 years had seroconversion at 2 weeks at rates of 60% and 23% (P < .017), respectively, and at 4 weeks at rates of 91% and 70% (P = .044) [21]. Another study that used varying Vaqta doses also showed that the 4-week seroconversion rate after immunization decreased progressively by age for each decade, with 99% seroconversion among 2–9-year-olds and 75% among 50–79-year-olds [22].

In addition to lower seroconversion rates, many studies have shown that titers of antibody to hepatitis A virus achieved after vaccination are inversely proportional to age, as shown in table 1 [18–21, 23–29]. None of these studies noted more severe adverse reactions to vaccination in the older groups.

Overall, 2 conclusions can be drawn. First, the antibody response tends to be slower in older people, and this may have implications on the timing of pretravel vaccination. The Centers for Disease Control and Prevention (CDC) currently recommends that the vaccine be given 4 weeks before travel; however, in clinical practice it is often administered ⩽2 weeks prior to departure. Second, significantly lower peak titers are reached after vaccination in elderly recipients. The distribution of responses appears to be unimodal, because most older individuals have a relatively low response when compared with younger populations, but there is no evidence of completely unresponsive subpopulations (table 1) [16, 30]. The clinical significance of this is unclear, because titers still exceed those required for seroprotection. Whether it translates into a shorter duration of immunoprotection is unknown. In addition, no study has examined hepatitis A vaccine responses in those patients aged >65 years; thus, it is not known whether the trend of poorer immune responses would become clinically significant in older patients. Finally, large clinical efficacy studies to date have involved only children.

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Typhoid Fever Vaccine

Typhoid fever remains a significant public health problem in many developing countries. The risk of infection varies according to the country visited and length of stay, but estimates range from 1.3 to 812 cases per million persons who travel from the United States to low-income countries [31]. Approximately 75% of cases of typhoid fever in the United States are acquired during a trip abroad [31, 32]. The mortality rate is significantly higher among individuals ⩾50 years old than among those <50 years old (3.3% vs. 0.4%; P = .009) [33]. Particularly with the additional risk conferred by the rising prevalence of multidrug-resistant organisms, typhoid vaccination should be considered for elderly travelers, especially those staying >2–3 weeks in countries with endemic or epidemic disease.

Killed whole-cell parenteral typhoid vaccines were used in the past, but because of significant side effects, they are no longer commercially available. A purified Vi polysaccharide parenteral vaccine (Aventis Pasteur) and a live-attenuated oral vaccine (Swiss Serum and Vaccine Institute) are currently licensed in North America. In addition, Vi conjugate vaccines have recently been developed, but they are still undergoing clinical trials and thus are not yet approved.

There is no measurable immunologic response that clearly correlates with protective efficacy after vaccination. Following typhoid Vi polysaccharide vaccination, Vi antibody levels can be measured, but the minimum titer required for protection from infection has not been defined (1.0–1.5 μg/mL is considered a conservative estimate) [34, 35]. Instead, seroconversion is generally defined by a 4-fold increase in serum Vi antibody titer. For the live-attenuated oral vaccine, mucosal IgA and cell-mediated responses are likely to be responsible for most of the protection conferred, but methods used to measure these are not widely available. Instead, the serum O antibody level is often used as a surrogate marker and has been shown to have some correlation with protection [36, 37]. Neither prior Salmonella typhi infection nor vaccination confers complete protection from (re)infection or clinical disease.

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Purified Vi Polysaccharide Parenteral Vaccine

The purified polysaccharide typhoid Vi vaccine is well tolerated, inducing only minor reactions in <10% of vaccinees [38]. Administration of booster doses after 2 years is recommended by the manufacturer. The vaccine elicits serum IgG Vi antibody responses in 85%–95% of children and young adults [38, 39]. Two large randomized, controlled field trials assessing vaccine efficacy have been performed: one involved South African schoolchildren and the other involved Nepalese individuals aged 5–55 years. The rate of protective efficacy against clinical infection was 64% at 21 months and 75% at 17 months after vaccination, respectively (table 2) [40, 41].

Table 2
Table 2

Data concerning age-related effects on immune response to typhoid Vi polysaccharide vaccine.

Vaccination of elderly persons. Most studies of immune response and vaccine efficacy have involved children in countries where typhoid is endemic. However, there is evidence of different antibody responses after vaccination, depending on past exposure to S. typhi, and immune responses in persons living in areas of endemicity are boosted by intervening infections [40, 41]. In addition, no studies have specifically addressed seroresponses in older adults. Close examination of the data from the Nepalese efficacy study shows that, at 1 month, children aged 5–14 years had a 77% seroconversion rate, adults aged 15–44 years had a 79% seroconversion rate, and adults 45–55 years had a 62.5% seroconversion rate, but this data cannot be extrapolated to nonimmune individuals (table 2) [41]. Because efficacy studies have also involved only young individuals in countries where typhoid is endemic, the relevance of this data to older travelers from countries of nonendemicity is unknown [42].

Ty21a Live-Attenuated Oral Vaccine

The live-attenuated oral vaccine comes in 2 formulations: an enteric-coated capsule (which is licensed but currently unavailable) and a liquid suspension (not licensed in the United States). The recommended schedule is administration of 4 doses on alternate days, with reimmunization after 5 years.

All major immunogenicity and efficacy studies of the Ty21a vaccine have been performed in countries where typhoid is endemic (table 3). A meta-analysis of published studies concluded that the overall rate of efficacy of vaccination for protection against illness was 71% for people aged 5–9 years and 63% for individuals aged 10–14 years [43]. The efficacy data for travelers is sparse, but one case-control study of travelers to India showed the protective efficacy of the oral vaccine to be only ∼23% [44]. Another study showed that ∼10% of travelers to Indonesia who developed typhoid had received prior Ty21a vaccination [45].

Table 3
Table 3

Data concerning age-related effects on immune response to oral typhoid vaccine.

Vaccination of elderly persons. There is no information on age-related effects on the safety, immunogenicity, or efficacy of the oral typhoid vaccine in elderly persons.

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Yellow Fever Vaccine

Most yellow fever vaccine is administered to young children living in areas where the disease is endemic. Yellow fever is rare in travelers, although there have been 4 recent deaths caused by yellow fever in unvaccinated travelers from the United States and Europe, and the incidence of infection with yellow fever is increasing in many regions [46–50]. Neonates and adults >50 years of age are both at increased risk of severe disease, and mortality rates after infection are highest in these age groups.

All yellow fever vaccines are live-attenuated vaccines derived from the 17D strain of the virus, and all are produced in embryonated eggs. There are currently multiple active manufacturers worldwide, but the only vaccine distributed in the United States is produced by Aventis Pasteur. The seroconversion rates, efficacy, duration of immune response, safety, and tolerability appear to be similar for each preparation, although comparative efficacy studies have not been performed [51, 52].

Mild local or systemic reactions are reported to occur in 5%–40% of vaccinees. Anaphylaxis after vaccination is estimated to occur in ∼1 of 131,000 recipients [53]. Encephalitis has been documented in 22 cases, from among >300 million doses of vaccine administered [54]. Three-quarters of these cases occurred in children aged <9 months, but at least 3 cases of encephalitis have been reported in adults [52, 55]. Although protective levels of antibody may persist for decades [56], revaccination is needed every 10 years to satisfy official entry requirements.

The exact mechanism of protective immunity is poorly understood, and documentation of antibodies may not equate perfectly with protection from clinical infection [52]. Antibody responses following vaccination have been measured by use of many different assays, but estimated seroconversion rates are similar in most studies, irrespective of the method used for detection [52]. On the basis of animal studies that have involved challenge with virulent yellow fever virus, it is presumed that a neutralizing antibody titer of ⩾1 : 10 or a log10 neutralization index of ⩾0.7 equates with protection from infection [52]. However, no cutoff correlating with protective antibodies, as measured by the plaque reduction neutralization test (the method used for antibody detection in most studies), has been established.

After vaccination, neutralizing antibodies appear within 7–10 days in >90% of young adult recipients. Peak titers are found at 3–4 weeks, and seroconversion occurs by day 28 in 96%–100% of vaccinees (table 4) [51, 57]. Immune responses to vaccination are qualitatively different in people with prior flavivirus immunity, in comparison with responses in flavivirus-naïve individuals [58–60]. As a result, the findings of studies in countries where flaviviruses are endemic can be difficult to interpret and thus cannot be extended to populations in which flaviviruses are not endemic. For ethical reasons, protective efficacy against infection has never been tested in a controlled trial; however, only rare cases of primary vaccine failure have been reported [52].

Table 4
Table 4

Data concerning age-related effects on immune response to yellow fever vaccine.

Vaccination of elderly persons. No studies of seroconversion rates, timing of seroresponse, antibody titers, or protective efficacy of the vaccine have involved elderly subjects. However, preliminary data suggest that serious adverse reactions after vaccination may be more common in older individuals than they are in younger individuals [61, 62]. An analysis of data from the Vaccine Adverse Events Reporting System showed that persons aged 65–74 years were 5.8 times more likely to experience serious adverse events after vaccination than were persons aged 25–44 years, and patients aged ⩾75 years had an 18-fold greater risk. Death or hospitalization was 3.5 times more common among those aged 65–74 years and 9 times more likely among those aged ⩾75 years. Confusion, renal failure, and thrombocytopenia were also more likely after vaccination of elderly individuals. This has not been confirmed by a prospective trial.

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Japanese Encephalitis Vaccine

The risk of developing Japanese encephalitis (JE) is very low for travelers; only 25 cases have been reported from among several million persons from the United States and Europe who have traveled to Asia during the past 20 years [63, 64]. Advanced age has been shown to increase the incidence, morbidity, and mortality of infection with JE virus [65]. Three JE vaccines are in widespread use worldwide, including a live-attenuated vaccine, and newer preparations are being developed. Currently only an inactivated Biken vaccine (distributed by Aventis Pasteur), produced in mouse brain, is available in the United States. Local side effects are seen in up to 20% of vaccine recipients, and mild systemic side effects are seen in up to 10% [66–68]. Severe reactions, including temporally related acute demyelinating encephalitis, have been reported to occur in 1 person per 50,000–75,000 vaccinees in some series [69–72]. In addition, allergic reactions, such as urticaria and angioedema, have been estimated to occur in 2.5–104 persons per 10,000 recipients of the Biken vaccine [64, 68, 72, 73].

Antibodies to JE virus are most commonly measured with a plaque reduction neutralization test, but other techniques are also available, and there is good overall correlation between the different methods [74]. No international standard for protective antibody units has been established; however, a neutralizing antibody titer of >1 : 10 is generally considered to indicate seroconversion [75]. It is unclear exactly how antibody levels correlate with immunity from infection, and failure to produce detectable neutralizing antibody titer may not correlate with lack of protection [76]. It is likely that T cell memory also contributes to protection after exposure.

Most serological studies following immunization have involved children aged <15 years in areas where JE is endemic and vaccination is routine. Serological responses differ between populations in areas where JE is endemic versus areas where it is not endemic, because previous exposure to JE or other flaviviruses results in augmentation of antibody titers. In children in countries where JE is endemic, subcutaneous administration of 2 doses of JE vaccine 1–4 weeks apart leads to development of neutralizing antibodies in 94%–100% [75, 77, 78]. This contrasts with the <85% seroconversion among young people after administration of 2 doses in areas of nonendemicity [76, 77]. In addition, the geometric mean titers are lower in subjects in areas of nonendemicity, and protective antibody titers are less persistent [76, 79]. Thus, administration of 3 doses is recommended for flavivirus-nonimmune subjects, such as travellers from the United States, resulting in 90%–100% seroconversion rates among young adults (table 5) [76, 80, 81].

Table 5
Table 5

Data concerning age-related effects on immune response to Japanese encephalitis vaccine.

The protective efficacy of JE vaccine against clinical infection has also been studied, predominantly among persons in areas where JE is endemic. Two randomized, placebo-controlled trials (one in Taiwan and the other in Thailand) that involved children showed 80% and 91% efficacy rates, respectively, against infection at 1 year [82, 83]. However, these efficacy studies may not be applicable to travelers from countries where JE is not endemic.

Vaccination of elderly patients. A number of reports published in the Japanese literature have suggested that older people's capacity to respond to JE vaccination is variable and not universal. Only one study in the English-language literature has compared the immune responses of aged people with those of younger subjects (table 5) [84]. In this study, a group of people aged ⩾60 years who lived in an area in Japan where JE is not endemic were vaccinated with 1 dose of different types of JE vaccines and had neutralizing antibody levels measured before and 4 weeks after vaccination. Of those persons who had negative serological findings before vaccination, 35% had at least a 2-fold increase in antibody titer, and 2.7% had at least a 4-fold increase in titer. These results were compared with those of a study of high school students, which showed an increase in titer of at least 2-fold in 20% of subjects and an increase of at least 4-fold in 2%. The study concluded that the capacity of older people to respond to JE vaccine did not seem to be inferior to that of high school students, although the number of subjects included was small. It is difficult to extrapolate these results to nonimmune populations, but no study of age-related effects on immune responses or efficacy of the JE vaccine has specifically involved travelers.

The results of a Danish study suggested that allergic reactions were more common in individuals aged 15–30 years than they were in those aged >30 years, but this was a small study and it included few individuals aged >50 years [85].

Rabies Vaccine

Because the overall risk of rabies in travelers is low [86], vaccination should be considered predominantly for travelers planning to spend significant periods of time in remote areas of high-risk countries. There are multiple rabies vaccines available; varying preexposure and postexposure schedules have been tested, and different doses, sites of administration, and routes of injection (intramuscular, subcutaneous, or intradermal) have been used. Three different vaccines are currently licensed in the United States: a human diploidcell vaccine (HDCV; Aventis Pasteur), a rhesus diploid cell adsorbed vaccine (BioPort), and a purified chick embryo cell culture vaccine (Chiron Therapeutics). Vaccines available in other countries include a purified duck embryo vaccine, a primary hamster kidney cell rabies vaccine, and a Vero cell rabies vaccine. Nerve tissue vaccines, which are still used in many developing countries, have less efficacy and are associated with an allergic encephalomyelitis in up to 0.5% of recipients. The newer cell culture vaccines are generally well tolerated and have similar immunogenicity and protective efficacy.

Antibody responses are generally used to demonstrate immunity, although they are imperfect markers of protection. The minimum protective antibody titer has been designated as either >0.5 IU/mL (by means of the mouse neutralization test) or >1 : 5 (by means of the rapid fluorescent focus inhibition technique) [86]. Most studies have shown that serum neutralizing antibodies are detectable in ∼20%–40% of young healthy vaccine recipients by day 7 after vaccination and that close to 100% of healthy vaccine recipients have rabies antibodies by 14 days after receiving 2 doses of the HDCV or rhesus diploid cell adsorbed vaccine [87–89]. The duration of protection after vaccination is variable, but adequate antibody titers are detectable in 88%–99% of recipients for ⩾1.5–2 years after intramuscular vaccination [90]. Use of the intradermal route results in slightly lower antibody titers and less-sustained immunity than does use of the intramuscular route, and the CDC does not endorse use of the intradermal route after exposure [86].

There have been no placebo-controlled trials of vaccine efficacy, so efficacy data are mainly from case reports of “failures.” Postexposure administration of various vaccines in various countries has generally yielded excellent efficacy; most treatment failures have been associated with incomplete adherence to the treatment guidelines of the World Health Organization (WHO) [91]. The overall failure rate for cell culture vaccines is estimated to be <1 case per 80,000 treatments [89, 92].

Vaccination of elderly persons. Two studies have specifically looked at the response to vaccination in elderly individuals (table 6). In one of these studies, responses to 2 antirabies vaccines (purified duck embryo vaccine and HDCV) in 260 European subjects aged 11–25 years were compared with responses in subjects aged >50 years [93]. All patients received vaccine on a 6-dose postexposure schedule. Serological examinations were performed on day 0, on day 30 (just before the fifth dose), and on day 90 (just before the sixth dose). All subjects from both age groups had adequate responses and developed protective antibody titers after the fourth dose, but the older subjects produced antibody titer levels 52% lower than those of the younger group (95% CI, 26%–84%). It is unclear whether this equates with reduced protective efficacy. The authors suggested that a sixth dose should be considered for elderly individuals, but this is not recommended by the CDC or WHO.

Table 6
Table 6

Data concerning age-related effects on immune response to rabies vaccine.

The second study involved 60 patients who were divided into 4 age groups: 1–20 years, 21–40 years, 41–60 years, and >60 years [94]. After 2 dosings of HDCV, antibody titers were significantly lower for each successively older cohort. Comparison of the individual results for the older and younger subjects revealed that the geometric mean titers reflected a continuum of response that was uniformly lower in older patients, but recipients of all ages developed protective antibody titers. No assessment of the durability of the response was performed.

A number of other studies of rabies vaccine have included some elderly patients, but the studies were not specifically designed to analyze age-related effects. In one report on antibody titers following postexposure prophylaxis with a human diploid cell rabies vaccine (Wyeth Laboratories), it was observed that inadequate titers were seen in a group of patients with a median age of 42 years, whereas responders had a median age of 21 years [95]. Other studies that have included a few elderly vaccine recipients have either found no age-related effects or have made no comment about any differences in immunogenicity in relation to age [96–103]. Allergic reactions to the vaccine are reported to be unrelated to age [89, 104]. One consideration relevant to elderly individuals is that intradermal injections may be difficult if the dermis is thin.

Other Vaccines

Administration of additional vaccines may also be considered for travelers. There is evidence that many routine vaccines that are frequently administered before travel, including tetanus-diphtheria-toxoid, hepatitis B, pneumococcal, and influenza vaccines, are associated with decreased immunogenicity in elderly recipients. For many other vaccines, including cholera (parenteral or oral), polio (parenteral or oral), and measles-mumps-rubella vaccines, there is no published information specifically about the immunogenicity, protective efficacy, or side effects in elderly recipients. The same is essentially true regarding the meningococcal vaccine, although investigators in a study in Nigeria reported that the 1-month postvaccination antibody titers were not significantly different after administration to persons aged 6–25 years, 26–45 years, and 46–65 years [105].

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Discussion

Review of the vaccine literature shows that delayed development of immune responses, decreased peak antibody responses, more rapid waning of protective antibodies, decreased protective efficacy, and increased side effects have all been noted in elderly individuals after the administration of certain vaccines. Many vaccines currently in use—in particular, many of the vaccines given prior to travel—have never been specifically studied in elderly subjects, and many questions remain unanswered.

Previous exposure to certain antigens via natural infection is more likely in elderly persons for some pathogens, such as hepatitis A virus, so elderly individuals may already be protected. However, older people have a greater risk of complications from certain travel-related infections, including JE, yellow fever, hepatitis A, and typhoid fever; therefore, immunization against these infections may be particularly important for older travelers.

Determination of the magnitude of serological responses following vaccination does not necessarily provide adequate information on the degree of protection conferred against clinical infection. Differences in antibody avidity, other qualitative aspects of humoral responses, and variations in cellular immune responses also contribute to protection from infection. Which of these measures is most important differs for each vaccine—a circumstance that complicates assessment of age effects on immunity. Even antibody titer, the simplest of these measures, has not been systematically studied in a significant number of elderly travelers for any of the vaccines we have discussed, despite evidence suggesting that extrapolation from data obtained for young individuals and/or persons in countries of endemicity may be unreliable. In particular, there is no information regarding the immunogenicity of hepatitis A vaccine in travelers >65 years of age, and no serological studies specifically about vaccination of adult travelers of any age against typhoid, yellow fever, or JE have been performed.

The interval before development of adequate responses and the durability of responses may also affect guidelines about vaccine administration. Timing of adequate immune responses is of particular relevance to travelers, because slower development of immunoprotection implies that earlier administration of travel vaccines may be required. Antibodies to hepatitis A develop more slowly in elderly patients, yet this has not been studied prospectively for any of the other travel vaccines. There is also a potential for more-rapid waning of protective antibodies in elderly persons, particularly for vaccines associated with lower antibody titers in older individuals, such as hepatitis A and rabies vaccines.

The outcome measure of most practical importance is the degree of protection against clinical infection following vaccination. As we have shown, there is no information regarding clinical efficacy in elderly recipients of any of the travel vaccines in common use. The infrequency of disease acquisition makes such studies involving travelers very difficult. Extrapolation from responses in individuals from countries of endemicity may be unreliable because of numerous potential confounders, such as differences in number and timing of prior exposures and variations in underlying nutritional and health status.

Finally, the safety of certain vaccines in elderly individuals, particularly live vaccines, remains under question. The suggestion of increased adverse events after administration of yellow fever vaccine is particularly relevant, and this needs to be studied in a more controlled fashion.

Despite the lack of data pertaining to elderly individuals, physicians are still faced with the clinical decisions of who to vaccinate, how safe vaccination is for individual patients, and what level of protective efficacy a vaccine is likely to offer. Existing evidence suggests that immune responses are at least in part age-dependent, and this could translate into a requirement for altered vaccine schedules for elderly persons, as already are used for many vaccines administered to infants. In addition, interactions among vaccines in elderly recipients have not been adequately studied. These issues are becoming increasingly important as the number of elderly persons in the community increases, as more elderly persons travel to exotic destinations, as drug resistance to many organisms becomes more prevalent, and as new vaccines are developed. The only way to provide definitive answers is to prospectively study both immunologic responses and the protective efficacy of vaccines in different communities and in different age groups.

  • Received December 27, 2001.
  • Revision received May 4, 2001.
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  1. Clin Infect Dis. (2001) 33 (9): 1553-1556. doi: 10.1086/322968
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