• View in gallery

    (A) Total number of yellow fever vaccines (YF-Vax and Stamaril) administered at Global TravEpiNet (GTEN) sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil. (B) Percentage of total GTEN clinic visits where yellow fever vaccines (YF-Vax and Stamaril) were administered by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

  • View in gallery

    Total number of yellow fever vaccines (YF-Vax and Stamaril) administered to travelers to Brazil at Global TravEpiNet sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

  • View in gallery

    Total number of times a yellow fever vaccine (YF-Vax or Stamaril) was deemed indicated by a clinician, but yellow fever vaccine (YF-Vax or Stamaril) was not available at Global TravEpiNet sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

  • View in gallery

    Yellow fever vaccine (YF-Vax or Stamaril) yearly usage data at Global TravEpiNet sites (2012–2018) by proportion for travelers to countries any part of which were endemic for yellow fever by month per year. Usage categories: yellow fever vaccine administered during the encounter; the traveler had pre-existing immunity; yellow fever vaccine was indicated but there was a medical contraindication to administering the vaccine; the traveler declined vaccination; the travel was to a region of the country not endemic for yellow fever and vaccination was not indicated for that itinerary; or yellow fever vaccine was not available; or other (for instance, itinerary was not yet established, and traveler asked to return to the clinic at future date).

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    Lammert SM, Rao SR, Jentes ES, Fairley JK, Erskine S, Walker AT, Hagmann SH, Sotir MJ, Ryan ET, LaRocque RC, 2016. Refusal of recommended travel-related vaccines among U.S. international travellers in global TravEpiNet. J Travel Med 24: taw075.

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Yellow Fever Vaccine Administration at Global TravEpiNet (GTEN) Clinics during a Period of Limited Vaccine Availability in the United States, 2017–2018

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  • 1 Travelers’ Health Branch, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia;
  • | 2 Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts;
  • | 3 Department of Global Health, Boston University School of Public Health, Boston, Massachusetts;
  • | 4 Travelers’ Advice and Immunization Center, Massachusetts General Hospital, Boston, Massachusetts;
  • | 5 Harvard Medical School, Boston, Massachusetts;
  • | 6 Harvard T. H. Chan School of Public Health, Boston, Massachusetts

ABSTRACT

In 2016, Sanofi Pasteur (S-P) experienced a manufacturing disruption of YF-Vax, the only U.S.-licensed yellow fever vaccine depleting the U.S. supply by mid-2017. Sanofi Pasteur received approval to import Stamaril, S-P’s French-manufactured yellow fever vaccine, for use in 260 U.S. civilian clinics under an Expanded Access Program (EAP). The CDC also broadened its yellow fever vaccination indication in early 2018. Our objective was to assess usage at participating Global TravEpiNet (GTEN) clinics, a U.S. CDC–supported national consortium of clinical sites that administer vaccines, during this period of limited availability and changing recommendations. We analyzed 2012–2018 GTEN data for yellow fever vaccine usage, unavailability, and reasons for refusal. We also performed a brief voluntary survey of GTEN sites to better understand their experience during the shortage. YF-Vax unavailability at certain GTEN clinics was intermittent and recurrent, starting months before total depletion. Unavailability at GTEN clinics peaked weeks before the total depletion. Compared with historic norms, yellow fever vaccine usage following initial vaccine availability limitations did not change until vaccine recommendations were broadened. Refusal of recommended yellow fever vaccine also decreased during this period. Queried sites participating in the EAP felt their supply of vaccine was adequate. Our analysis suggests that in response to depletion of a travel vaccine, an EAP can make an unlicensed product available, patients will participate in such a program, and the program can respond to expanding recommendations for vaccine usage.

INTRODUCTION

Yellow fever is caused by the yellow fever virus, a flavivirus transmitted to humans by the bite of an infected mosquito. Yellow fever occurs in sub-Saharan Africa and tropical South America, where the virus is maintained in an enzootic (sylvatic) cycle involving tree-hole–breeding mosquitoes and nonhuman primates.1 Humans sporadically become infected after being bitten by infected mosquitoes when humans encroach on the sylvatic cycle during occupational or recreational activities in forested areas. Yellow fever virus is also transmitted by an intermediate cycle (Africa only) and an urban cycle.1 In the latter, yellow fever virus is transmitted between humans and Aedes aegypti mosquitoes.

Most yellow fever virus infections in humans are subclinical. Symptomatic infections range from a mild nonspecific viral illness to potentially fatal viral hemorrhagic fever.1 The case fatality ratio for severe yellow fever disease is 30–60%.2 Because there are no specific medications to treat yellow fever, treatment is limited to supportive measures.

An effective vaccine to prevent yellow fever has been available since the late 1930s. This live attenuated vaccine contains the 17D yellow fever virus.1 Vaccination produces neutralizing antibodies in 80–100% of vaccinees by 10 days after vaccination and in at least 99% of vaccinees by 28 days after vaccination.1 Vaccination is associated with induction of a high level of durable viral neutralizing antibodies.3

In the United States, yellow fever vaccine is recommended for people aged 9 months or older who are traveling to or living in areas with risk for yellow fever virus transmission (https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/yf.html). In addition, certain countries require proof of yellow fever vaccination for entry, as permitted by the International Health Regulations.4 These requirements are intended to prevent importation to and transmission of yellow fever virus within countries without yellow fever virus circulation that may have competent mosquito vectors.4 Yellow fever vaccine can be administered only by clinics designated by government authorities.

Cases of yellow fever have been imported into nonendemic countries, including the United States, by returning travelers who were unimmunized and became infected with yellow fever virus during travel to yellow fever–endemic countries.1 The importation of yellow fever virus into nonendemic countries inhabited by Ae. aegypti mosquitoes, the vector of the urban transmission cycle of yellow fever virus, presents the risk of local virus transmission, resulting in a large-scale yellow fever outbreak.

In the United States, YF-Vax is the only licensed yellow fever vaccine. This vaccine is manufactured by U.S. Sanofi Pasteur (S-P) at a single facility. In 2016, S-P was transitioning production of YF-Vax from its older manufacturing facility to a new facility, which was under construction and set to open in 2018. Manufacturing complications severely curtailed the number of vaccine doses produced such that the volume was insufficient to cover the anticipated demand during the interval between permanent closure of the old manufacturing facility and opening of the new one.5,6 When the eventual total depletion of YF-Vax supplies became apparent, S-P, in consultation with the U.S. Food and Drug Administration (FDA), concluded that an expanded access investigational new drug (eIND) application to import a different yellow fever vaccine, not licensed in the United States, would be needed to assure a continuous supply. The need was magnified by concerns about having an insufficient yellow fever vaccine supply to respond adequately should yellow fever virus be locally transmitted in the U.S. after importation by unimmunized infected travelers, particularly with Angola experiencing a large yellow fever outbreak at the time that had resulted in the exportation of cases to three countries.5 Sanofi Pasteur submitted, and the U.S. FDA accepted, an eIND application to make its French-manufactured vaccine, Stamaril, available in the United States.

In consultation with CDC, S-P identified approximately 260 registered yellow fever vaccination clinics across the United States for participation in the Stamaril eIND expanded access program (EAP)5 (https://wwwnc.cdc.gov/travel/page/search-for-stamaril-clinics). The goal of the program was to maximize Stamaril availability by including clinical sites with documented large-volume ordering of YF-Vax in the recent past and with adequate geographic distribution relative to the U.S. population. The Stamaril EAP included key components of IND programs, such as an IND protocol, an institutional review board (IRB) requirement, and an informed consent process.

After instituting ordering restrictions and months of contingency planning in consultation with CDC, S-P announced the total depletion of its YF-Vax stock for civilian use on July 24, 2017.6 Thereafter, only clinics participating in the EAP could order and administer Stamaril, and the only YF-Vax available for use was any residual stock that some clinics had left over from orders filled before total depletion. During this period, the CDC also changed its recommendations regarding indication for immunization for travelers to Brazil, based on an increased number of cases in Brazil, many reported in previously unaffected areas.5 In light of these events, our objective in this analysis was to assess the impact of YF-Vax depletion, changing recommendations, and initiation of the Stamaril EAP at participating Global TravEpiNet (GTEN) clinics. Global TravEpiNet is a CDC-sponsored national consortium of clinical sites (https://wwwnc.cdc.gov/travel/page/gten) that provide health advice and vaccinations for U.S. residents traveling internationally.7 Clinicians at participating GTEN sites use a structured online questionnaire during the pretravel clinical encounter that captures demographics, medical conditions, medications, and information on travel (itinerary, purpose, housing, and duration). The system also collects information on vaccines recommended or administered, reasons for refusal if pertinent, medications prescribed, and health advice given.815 Incomplete answers are not allowed. For this analysis, we assessed GTEN data for yellow fever vaccine usage, unavailability, and reasons for refusal. We also performed a brief voluntary survey of GTEN sites to better understand their experience during the shortage.

METHODS

We analyzed data collected by the GTEN network between March 2017 and March 2018 to assess the impact of the YF-Vax shortage and the initiation of the Stamaril EAP at the clinic level in the United States; no data were derived from the EAP itself. We compared these data with those collected in the 5 years before the period of limited vaccine availability (2012–2016). Global TravEpiNet sites represent a range of clinical practices, including academic centers, health maintenance organizations, pharmacy-based practices, public health clinics, and private practices. We analyzed yellow fever vaccine usage and the reasons for nonadministration of yellow fever vaccine to patients for whom it was indicated, and the reasons for patient refusal. In March 2018, the 28 then-active GTEN member sites were also asked to complete a brief, self-administered, voluntary, on-line survey regarding their experience during the period of limited vaccine availability (Supplemental Material). IRB approval was obtained at all participating GTEN sites.

Of note, for the purposes of this analysis, we used a number of definitions. This article describes a complex and evolving timeline of limited yellow fever vaccine availability in the United States, which occurred in three overlapping phases. We use the terms “YF-Vax shortage,” “YF-Vax total depletion,” and “Stamaril EAP” to refer to these phases. A shortage of YF-Vax began at the end of 2015; a total depletion of the manufacturer’s YF-Vax stock was announced on July 24, 20176; because S-P began filling vaccine orders under the Stamaril EAP in May 2017, which was ongoing as of December 2020,5 these time periods are not mutually exclusive. The term “period of limited vaccine availability” is used to refer to the entire time comprising all three phases. The CDC also broadened its recommendations of indications for yellow fever vaccination for travelers to Brazil in January 2018.

We performed bivariate analyses using two-sided chi-square tests to compare the number of vaccines “administered,” “declined by patient,” or “not administered because of medical contraindication” during the various time periods: pre-EAP (before May 1, 2017), post-EAP initiation and pre-depletion (May 1, 2017–July 23, 2017), post-depletion to pre-Brazil broadened recommendations (July 24, 2017–January 25, 2018), and post-Brazil broadened recommendations (after January 25, 2018). Only data during the relevant time periods were used when comparing group differences. For example, to compare the distribution of vaccine administration between pre-EAP and post-EAP initiation, all data between May 1 and December 31 each year between 2012 and 2017 were included for the pre-EAP group; for pre-EAP versus post-EAP initiation/pre-depletion, only data between May 1 and July 23 of each year was included in the pre-EAP group. We used Benjamini and Hochberg’s control for the false discovery rate approach to adjust for the multiple comparisons.16

RESULTS

The GTEN network captured a total of 95,976 clinical encounters during 2012 through 2018. Of these, 25,751 (26.8%) involved administration of yellow fever vaccine Yellow fever vaccination had a yearly cyclical pattern (Figure 1). Overall, across the GTEN Consortium, the total number and proportion of all clinic visits in which yellow fever vaccine was administered not only did not decrease during the national vaccine shortage but actually increased (yellow fever vaccine was administered to 25% of GTEN attendees pre-EAP versus 33.6% post-EAP initiation; P < 0.0001). This increase particularly corresponded to the broadened recommendations for vaccination for Brazil (yellow fever vaccine was administered to 25% of GTEN attendees pre-EAP versus 24.8% after post-EAP initiation but pre-Brazil-broadened recommendations; P = 0.85; but the proportion of vaccinated increased to 39.6% following the broadened recommendations for Brazil [P < 0 .0001]). Both the total number of yellow fever vaccinations administered (Figure 1) and the total number of vaccinations for travelers going to Brazil (Figure 2) in GTEN increased starting in January 2018, coinciding with the expansion in areas covered by the CDC’s yellow fever vaccine recommendations for travel to Brazil. Yellow fever vaccine was administered to 58% of travelers to Brazil pre-EAP/pre-broadened recommendations, increased to 75% post-EAP initiation (P < 0.0001), and then 84% following broadened Brazil recommendations (P < 0.0001).

Figure 1.
Figure 1.

(A) Total number of yellow fever vaccines (YF-Vax and Stamaril) administered at Global TravEpiNet (GTEN) sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil. (B) Percentage of total GTEN clinic visits where yellow fever vaccines (YF-Vax and Stamaril) were administered by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.19-0859

Figure 2.
Figure 2.

Total number of yellow fever vaccines (YF-Vax and Stamaril) administered to travelers to Brazil at Global TravEpiNet sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.19-0859

The most frequent destinations for those seeking yellow fever vaccination from 2012 through 2018 in GTEN were Kenya (17%), Ghana (13%), Brazil (12%), Peru (11%), and Tanzania (9%). Half of the travelers to Tanzania were also visiting other countries for which CDC recommended YF-Vax. The most frequent destinations for those seeking yellow fever vaccination pre-EAP (2012 through May 2017) were Kenya (16%), Ghana (14%), Peru (11%), Tanzania (8%), and Brazil (8%). The most frequent destinations for those seeking yellow fever vaccination post-EAP initiation (June 2017 through December 2018) were Brazil (21%), Kenya (19%), Ghana (12%), Peru (11%), and Tanzania (9%).

Even before the total depletion in mid-2017, availability of YF-Vax was intermittent at GTEN clinics (Figure 3). Unavailability of any yellow fever vaccine at GTEN clinics peaked from April 3 to June 4, 2017. Stamaril became available for order in May 2017, and the use of Stamaril for yellow fever vaccinations began at limited GTEN sites in June 2017. The frequency of patient refusal of recommended immunization with any yellow fever vaccine decreased from pre-EAP to post-EAP initiation (Figure 4; 3.6% refusal before EAP versus 2.7% after post-EAP; P < 0.0001); the reasons for refusal did not change (Supplemental Figure 1). Analysis also did not disclose an increase in clinician-perceived contraindications to vaccination (Figure 4 and Supplemental Figure 2; 1.4% contraindication pre-EAP versus 1.5% post-EAP initiation; P = 0.3).

Figure 3.
Figure 3.

Total number of times a yellow fever vaccine (YF-Vax or Stamaril) was deemed indicated by a clinician, but yellow fever vaccine (YF-Vax or Stamaril) was not available at Global TravEpiNet sites by week per year, 2012–2018. Hatched arrow: EAP began filling orders. Black arrow: Total manufacturer depletion of YF-Vax. Open arrow: CDC broadened indications for vaccination against yellow fever virus for travelers to Brazil.

Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.19-0859

Figure 4.
Figure 4.

Yellow fever vaccine (YF-Vax or Stamaril) yearly usage data at Global TravEpiNet sites (2012–2018) by proportion for travelers to countries any part of which were endemic for yellow fever by month per year. Usage categories: yellow fever vaccine administered during the encounter; the traveler had pre-existing immunity; yellow fever vaccine was indicated but there was a medical contraindication to administering the vaccine; the traveler declined vaccination; the travel was to a region of the country not endemic for yellow fever and vaccination was not indicated for that itinerary; or yellow fever vaccine was not available; or other (for instance, itinerary was not yet established, and traveler asked to return to the clinic at future date).

Citation: The American Journal of Tropical Medicine and Hygiene 104, 3; 10.4269/ajtmh.19-0859

In March 2018, we queried the members of the GTEN Consortium on challenges during the period of limited vaccine availability, including whether they were participating in the EAP and their date of initiation in the program. Of 28 queried GTEN sites, 17 responded to the brief, voluntary, on-line survey (Supplemental Material), with 15 completing the survey regarding participating in the EAP. Of these 15, 14 responded with a previous or anticipated date of YF-Vax depletion; 10 sites had run out of YF-Vax, but four sites still had YF-Vax available 10 months into the EAP. Of these 15, seven sites had not been selected to participate. Of the eight sites responding that they had been selected to participate in the EAP, seven had already joined the EAP, with one site planning to join. Of these eight EAP sites, seven were academic medical centers in six major metropolitan areas and one was a multisite health maintenance organization. Three of the EAP sites were still administering YF-Vax 10 months into the EAP, but five had no YF-Vax doses left. Of the eight sites planning or actively participating in the EAP, five reported pursuing local IRB approval to join the program, one reported using the EAP central IRB, and two did not respond to this query. Four of five EAP sites that responded reported receiving adequate Stamaril to meet yellow fever vaccine demand once they joined the EAP. Four of five EAP sites that responded reported that EAP participation increased staff morale. In our survey, we did not ask GTEN site–specific financial details regarding their participation in the EAP; however, two sites reported having to reassign staff to participate in the program, and one site felt that EAP participation came at a financial cost.

DISCUSSION

Our analysis includes a number of important findings. We found that yellow fever vaccine usage by the GTEN Consortium did not decrease during a period of nationally limited vaccine availability. The level of usage remained high, despite the fact that a number of GTEN clinical sites were not invited to participate in the EAP. Indeed, the data from 2018 suggest that the use of yellow fever vaccine across the GTEN Consortium actually increased in comparison to historical norms. The timing corresponded with a broadened recommendation by the CDC in January 2018 advising that travelers to most parts of Brazil should receive yellow fever vaccination because of a large outbreak, and Brazil was the leading destination for recipients of yellow fever vaccine following the total depletion of YF-Vax in our analysis. It is uncertain whether the increased usage in 2018 also reflected a channeling of travelers who would ordinarily have gone to clinics not invited to participate in the EAP to GTEN sites participating in the EAP. Our results suggest that the use of yellow fever vaccine is cyclical in the United States, peaking in the summer, presumably reflecting travel patterns of U.S. residents to areas endemic for yellow fever. Even before the final YF-Vax depletion, YF-Vax shortages were well documented and recurrent in the GTEN network. Our analysis did not identify the reasons for these previous shortages; however, the fact that there is only one yellow fever vaccine licensed for use in the United States (YF-Vax), produced by only one manufacturer, may be a significant contributor. During single-dose vial vaccine shortages, the use of multidose yellow fever vaccine vials is required. The use of multidose vials can be problematic and burdensome for clinical sites and travelers because vaccine doses distributed from multidose vials need to be administered within 60 minutes of vaccine reconstitution or disposed of. The inability of clinicians to vaccinate due to unavailability of yellow fever vaccine peaked before sites were able to join the EAP, suggesting that future public health responses should be initiated as soon as possible. Our results suggest that participation in the EAP was burdensome on some participating clinical sites, including the need to reassign staff. Burden was shared by yellow fever vaccination sites that were not asked to participate, as their lack of yellow fever vaccine hampered their ability to provide thorough pre-travel clinical care for their patients.

We were surprised to find that a number of sites were still administering YF-Vax months after the total depletion of manufacturer’s stock. These sites may have had lower vaccine usage than they had anticipated, or they may have stockpiled YF-Vax while it was still available. Because S-P restricted sites’ monthly orders in the months leading up to the depletion, some GTEN clinics were unable to meet their demand before the EAP. It should be noted that consideration of targeted use of residual YF-Vax for select patients during the Stamaril EAP would allow vaccination of individuals who did not meet the inclusion criteria in the EAP. For instance, YF-Vax could be used to desensitize and subsequently vaccinate a traveler allergic to yellow fever vaccine or any of its components; such individuals would not have been enrollable in the Stamaril EAP. Having access to such non-IND resources might be part of plans for future responses to vaccine depletions. Despite strict inclusion and exclusion criteria, we did not find a proportional increase in clinicians not administering yellow fever vaccine during the Stamaril EAP because of perceived medical contraindications.

Selection of clinical sites for participation in the EAP was performed by S-P in consultation with the CDC and reflected previous YF-Vax usage and geographic distribution, with the goals of maximizing vaccine distribution, administrative efficiency, and geographic availability. Overall, roughly, only 6% of U.S. yellow fever vaccination clinics were invited to participate in the EAP.5 With regard to vaccine recipient acceptance, it was noteworthy that our analysis suggested a decrease in vaccine refusal for Stamaril, although it was an unlicensed product requiring an informed consent process in the United States. Indeed, acceptance of yellow fever vaccination could be expected in those travelers who identified clinics participating in the EAP and went there to receive vaccine.

Participation by clinics in the Stamaril EAP required prior IRB approval and an informed consent process for all vaccinated patients because Stamaril is unlicensed for use in the United States. Only one GTEN site used the central IRB process included as part of the EAP. Global TravEpiNet sites selected for EAP participation who agreed to join were predominantly large urban academic health facilities associated with organizational IRBs. Although we did not ask GTEN members their reason for choosing their institutional option, it may reflect familiarity with their institutional processes and administrative requirements. For clinical sites not associated with IRBs, having a central program-associated IRB would be required for program participation and would be essential for future EAPs to maximize vaccine availability.

We were concerned to see that Tanzania was a common destination for recipients of yellow fever vaccine at GTEN clinical sites both before and after depletion of YF-Vax. Before 2012, the CDC recommended yellow fever vaccination for travel to Tanzania. However, in 2012, the CDC changed its yellow fever vaccination recommendation to “generally not recommended” for travelers to Tanzania, based on a WHO working group’s reclassification of the risk in Tanzania to “low potential for exposure” to yellow fever virus.17,18 Approximately half of the travelers to Tanzania in our analysis who received yellow fever vaccine were also traveling to another country for which CDC recommended vaccination; the other half were traveling only to Tanzania. Vaccination of travelers to Tanzania occurred, despite a period of nationally limited yellow fever vaccine availability, and CDC recommendations stating the vaccination would generally not be indicated for such travel. This finding requires further investigation but may suggest that clinicians may find it hard to define when “generally not recommended” applies to individual travelers for a usually well-tolerated intervention to prevent a potentially life-threatening infection.

The period of nationally limited yellow fever vaccine availability in the United States has occurred coincidentally to a significant global shortage of yellow fever vaccine although these situations are unrelated causally because YF-Vax is not part of the global yellow fever vaccine supply. At present, there are only four manufacturers of yellow fever vaccines approved by the WHO for global use. Although their yearly production is adequate to meet routine vaccination goals, it has occasionally been insufficient to supply the needs of large preventive vaccination campaigns in response to outbreaks (Angola outbreak stockout). Indeed, fractional dosing is being investigated to help regions and countries respond to yellow fever.19 The fact that the global yellow fever vaccine supply is limited is disheartening in light of the global importance of yellow fever, its outbreak potential, its high mortality, its potential for geographic spread, and the absence of effective targeted therapy.

Our analysis has some limitations. Global TravEpiNet involves a limited number of clinical sites, and GTEN sites may not be representative of all sites providing pre-travel clinical care. Travelers who visited EAP participating sites may also not be representative of all travelers to regions endemic for yellow fever, and our survey cohort size was small and voluntary. Despite these limitations, our data offer a unique perspective into vaccine usage during a period of nationally limited vaccine availability and changing recommendations. Our analysis suggests that during a total depletion of a travel vaccine, an expanded access IND program can be used to make unlicensed product available, that patients will participate in such a program, and that the program can even respond to expanding and evolving recommendations for vaccine usage, at least at participating sites. These data can be used to inform contingency planning for future shortages of yellow fever and other travel vaccines and suggest that such responses require coordinated efforts among manufacturers, public health authorities, and clinical sites.

Supplemental material and figures

ACKNOWLEDGMENTS

Members of the Global TravEpiNet Consortium (in alphabetical order) include George M. Abraham, Saint Vincent Hospital (Worcester, MA); Salvador Alvarez, Mayo Clinic (Jacksonville, FL); Vernon Ansdell and Johnnie A. Yates, Travel Medicine Clinic, Kaiser Permanente (Honolulu, HI); Elisha H. Atkins, Chelsea HealthCare Center (Chelsea, MA); Holly K. Birich and Dagmar Vitek, Salt Lake Valley Health Department (Salt Lake, Utah); John Cahill, Travel and Immunization Center, St. Luke’s-Roosevelt (New York, NY); Lin Chen, Mount Auburn Hospital (Cambridge, MA); Bradley A. Connor, New York Center for Travel and Tropical Medicine, Cornell University (New York, NY); Roberta Dismukes, Jessica Fairley, Phyllis Kozarsky, and Henry Wu, Emory TravelWell, Emory University (Atlanta, GA); Ronke Dosunmu, JourneyHealth (Maywood, NJ); Jeffrey A. Goad and Edith Mirzaian, International Travel Medicine Clinic, University of Southern California (Los Angeles, CA); Nelson Iván Agudelo Higuita, University of Oklahoma Health Sciences Center (Oklahoma City, OK); Karl Hess, Hendricks Pharmacy International Travel Clinic (Claremont, CA); Noreen A. Hynes, Johns Hopkins Travel and Tropical Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine (Baltimore, MD); Frederique Jacquerioz and Susan McLellan, Tulane University (New Orleans, LA); Jenn Katsolis, Jacksonville Travel Clinic-St. Vincents (Jacksonville, FL); Paul Kelly, Bronx Lebanon Medical Center (New York, NY); Mark Knouse, Keystone Travel Medicine, Lehigh Valley Health Network (Allentown, PA); Jennifer Lee, Northwestern Medical Group-Travel Medicine, Northwestern Memorial Hospital (Chicago, IL); Daniel Leung, Brian Kendall, and DeVon Hale, International Travel Clinic, University of Utah (Salt Lake City, UT); Alawode Oladele and Hanna Demeke, DeKalb County Board of Health Travel Services-DeKalb North and Central-T.O. Vinson Centers (Decatur, GA); Alawode Oladele and Althea Otuata, DeKalb County Board of Health Travel Services-DeKalb East (Decatur, GA); Roger Pasinski and Amy E. Wheeler, Revere HealthCare Center (Revere, MA); Adrienne Showler, Laura Coster, and Jessica Rosen, Infectious Diseases and Travel Medicine, Georgetown University (Washington, DC); Brian S. Schwartz, Travel Medicine and Immunization Clinic, University of California (San Francisco, CA); William Stauffer and Patricia Walker, HealthPartners Travel Medicine Clinics (St. Paul, MN); Joseph Vinetz, Travel Clinic, Division of Infectious Diseases, Department of Medicine, University of California-San Diego School of Medicine (La Jolla, CA); and Julian Ritchey, Sanofi Pasteur Inc. (Swiftwater, PA).

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Author Notes

Address correspondence to Allison Taylor Walker, Travelers’ Health Branch, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, 1600 Clifton Rd., MS V18-2, Atlanta, GA 30333. E-mail: eie7@cdc.gov

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. CDC.

Financial support: The GTEN Consortium is supported by U.S. CDC Grant U01CK000490.

Authors’ addresses: Allison Taylor Walker and Mark D. Gershman, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: eie7@cdc.gov and dvj8@cdc.gov. Sowmya R. Rao, Biostatistics Center, Massachusetts General Hospital, Boston, MA, and Department of Global Health, Boston University School of Public Health, Boston, MA, E-mail: srrao@mgh.harvard.edu. Regina C. LaRocque, Travelers’ Advice and Immunization Center, Massachusetts General Hospital, Boston, MA, E-mail: rclarocque@mgh.harvard.edu. Edward T. Ryan, Harvard T. H. Chan School of Public Health, Boston, MA, Travelers’ Advice and Immunization Center, Massachusetts General Hospital, Boston, MA, and Harvard Medical School, Boston, MA, E-mail: etryan@mgh.harvard.edu.

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