Notes: Most Aetna HMO plans exclude coverage of vaccines for travel.  Most Aetna traditional plans cover medically necessary travel vaccines for members of plans with preventive services benefits.  Please check benefit plan descriptions.

The following table lists vaccines that may be required for travel, and their medically necessary indications, standard administration schedule, and contraindications:

^† Persons who are immunocompromised because of immune deficiency diseases, leukemia, lymphoma, generalized cancer, or the acquired immunodeficiency syndrome, or who are receiving immunosuppressive therapy with corticosteroids, alkylating agents, anti-metabolites, or radiation.

^†† LYMErix was withdrawn from the U.S. market in February 2002.

^* Most Aetna benefit plans exclude coverage of vaccines for work.  Please check benefit plan descriptions.

Note: Many of these vaccines may also be considered medically necessary for reasons other than travel, and may be covered when medically necessary in members with preventive benefits, regardless of whether the plan excludes coverage of travel vaccines.

Note: Malaria vaccine for travel is considered experimental and investigational because an effective malaria vaccine has yet to be developed.

Note: The Advisory Committee on Immunization Practices (1996) states that plague vaccination is not indicated for most travelers to countries in which cases of plague have been reported.

The Centers for Disease Control and Prevention (CDC)'s recommended vaccinations for travelers can be found at the following website: http://wwwn.cdc.gov/travel/contentVaccinations.aspx.

In a Cochrane review on vaccines for preventing malaria, Graves and Gelband (2006a) concluded that there is no evidence for protection by SPf66 vaccines against P. falciparum in Africa.  There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America.  There is no justification for further trials of SPf66 in its current formulation.  Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

In another Cochrane review, Graves and Gelband (2006b) concluded that the MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific.  Pre-treatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials.  The results show that blood-stage vaccines may play a role and merit further development.

Vaughan et al (2009) presented a comprehensive meta-analysis of more than 500 references, describing nearly 5,000 unique B cell and T cell epitopes derived from the Plasmodium genus, and detailing thousands of immunological assays.  This was the first inventory of epitope data related to malaria-specific immunology, plasmodial pathogenesis, and vaccine performance.  The survey included host and pathogen species distribution of epitopes, the number of antibody versus CD4(+) and CD8(+) T cell epitopes, the genomic distribution of recognized epitopes, variance among epitopes from different parasite strains, and the characterization of protective epitopes and of epitopes associated with parasite evasion of the host immune response.  The results identified knowledge gaps and areas for further investigation.  This information has relevance to issues, such as the identification of epitopes and antigens associated with protective immunity, the design and development of candidate malaria vaccines, and characterization of immune response to strain polymorphisms.

Currently, there is an ongoing phase III clinical trial of a candidate vaccine for malaria, but the study has not been completed (Birkett, 2010).

The Advisory Committee on Immunization Practices (ACIP) of the CDC provided the following recommendations regarding the prevention of plague (1996):

• Routine plague vaccination is not necessary for individuals living in areas in which plague is enzootic.
• Plague vaccination is not indicated for hospital staff or other medical personnel in such areas.
• Plague vaccination is not indicated for most travelers to countries in which cases of plague have been reported.

In a Cochrane review, Ahmed et al (2013) evaluated the safety, effectiveness, and immunogenicity of vaccines for preventing entero-toxigenic Escherichia coli (ETEC) diarrhea.  These investigators searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and http://clinicaltrials.gov up to December 2012.  Randomized controlled trials (RCTs) and quasi-RCTs comparing use of vaccines to prevent ETEC with use of no intervention, a control vaccine (either an inert vaccine or a vaccine normally given to prevent an unrelated infection), an alternative ETEC vaccine, or a different dose or schedule of the same ETEC vaccine in healthy adults and children living in endemic regions, intending to travel to endemic regions, or volunteering to receive an artificial challenge of ETEC bacteria were included for analysis.  Two authors independently assessed each trial for eligibility and risk of bias.  Two independent reviewers extracted data from the included studies and analyzed the data using Review Manager (RevMan) software.  They reported outcomes as risk ratios (RR) with 95 % confidence intervals (CI) and assessed the quality of the evidence using the GRADE approach.  A total of 24 RCTs, including 53,247 participants, met the inclusion criteria -- 4 studies assessed the protective efficacy of oral cholera vaccines when used to prevent diarrhea due to ETEC and 7 studies assessed the protective efficacy of ETEC-specific vaccines.  Of these 11 studies, 7 studies presented efficacy data from field trials and 4 studies presented efficacy data from artificial challenge studies.  An additional 13 trials contributed safety and immunological data only.  The currently available, oral cholera killed whole cell vaccine (Dukoral®) was evaluated for protection of people against “travelers' diarrhea” in a single RCT in people arriving in Mexico from the USA.  These researchers did not identify any statistically significant effects on ETEC diarrhea or all-cause diarrhea (1 trial, 502 participants; low-quality evidence).  Two earlier trials, one undertaken in an endemic population in Bangladesh and one undertaken in people travelling from Finland to Morocco, evaluated a precursor of this vaccine containing purified cholera toxin B subunit rather than the recombinant subunit in Dukoral®.  Short-term protective efficacy against ETEC diarrhea was demonstrated, lasting for around 3 months (RR 0.43, 95 % CI: 0.26 to 0.71; 2 trials, 50,227 participants).  This vaccine is no longer available.  An ETEC-specific, killed whole cell vaccine, which also contains the recombinant cholera toxin B-subunit, was evaluated in people traveling from the USA to Mexico or Guatemala, and from Austria to Latin America, Africa, or Asia.  These investigators did not identify any statistically significant differences in ETEC-specific diarrhea or all-cause diarrhea (2 trials, 799 participants), and the vaccine was associated with increased vomiting (RR 2.0, 95 % CI: 1.16 to 3.45; 9 trials, 1,528 participants).  The other ETEC-specific vaccines in development have not yet demonstrated clinically important benefits.  The authors concluded that there is currently insufficient evidence from RCTs to support the use of the oral cholera vaccine Dukoral® for protecting travelers against ETEC diarrhea.  Moreover, they stated that further research is needed to develop safe and effective vaccines to provide both short- and long-term protection against ETEC diarrhea.

Also, an UpToDate review on “Travelers' diarrhea” (Wanke, 2014) states that “Use of vaccines to protect against travelers’ diarrhea is hindered by the varied pathogens that can cause it.  Although enterotoxigenic E. coli (ETEC) predominates as an etiology of travelers’ diarrhea, vaccination strategies that have focused on this pathogen as a target have been suboptimal.  Although vaccination to protect against cholera is not routinely recommended for travelers, a number of trials suggest that the oral, killed whole-cell vaccine given with the nontoxic B subunit of cholera toxin (Dukoral) provides protection for travelers against ETEC infection.  The rationale for such protection is that the B subunit of cholera is antigenically similar to the heat-labile enterotoxin of ETEC.  In two randomized trials, the killed whole-cell vaccine combined with the B subunit of cholera toxin reduced the incidence of diarrhea caused by ETEC by 67 percent in a trial in Bangladesh and 52 percent among travelers to Morocco.  The Dukoral vaccine was approved in the United States in late 2006 for use as a travelers' diarrhea vaccine.  However, a conservative estimate that took into account the incidence of ETEC infection throughout the world and the efficacy of the vaccine suggested that it may prevent ≤7 percent of travelers' diarrhea cases.  The 2006 guidelines on travel medicine from the Infectious Diseases Society of America concluded that the decision to use the vaccine to prevent travelers' diarrhea must balance its cost, adverse effects, and limited utility against the known effectiveness and costs of self-treatment as described above.  A separate vaccination strategy for ETEC also appears to have limited utility.  Despite initial promising data on vaccination with heat-labile enterotoxin from ETEC via a skin patch, it was not effective in decreasing the incidence of moderate to severe diarrhea due to either ETEC or any cause in a randomized, placebo controlled trial that included 1,644 individuals who traveled to Mexico or Guatemala.  In a subgroup analysis, the vaccine provided modest protection against ETEC that produced only heat-labile enterotoxin (vaccine efficacy 61 percent [95 % CI, 7 to 84 percent]), but not ETEC that produced heat-stable toxin or both.  This highlights the limitations of a single-antigen vaccine for travelers’ diarrhea”.