In 2016, Sanofi Pasteur (S-P) experienced a manufacturing disruption of yellow fever vaccine (YF-Vax), the only U.S.-licensed YF-Vax, depleting the U.S. supply by mid-2017. Sanofi Pasteur received approval to import Stamaril, S-P's French-manufactured YF-Vax, for use in 260 U.S. civilian clinics under an expanded access investigational new drug program (EAP). The CDC also broadened its YF-Vax 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 YF-Vax usage, unavailability, and reasons for refusal. We also performed a brief voluntary survey of GTEN sites to better understand their experience during the shortage. Yellow fever vaccine 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, YF-Vax usage following initial vaccine availability limitations did not change until vaccine recommendations were broadened. Refusal of recommended YF-Vax 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.

Sanofi Pasteur, the manufacturer of the only yellow fever vaccine (YF-VAX) licensed in the United States, has announced that their stock of YF-VAX is totally depleted as of July 24, 2017. YF-VAX for civilian use will be unavailable for ordering from Sanofi Pasteur until mid-2018, when their new manufacturing facility is expected to be completed. However, YF-VAX might be available at some clinics for several months, until remaining supplies at those sites are exhausted. In anticipation of this temporary total depletion, in 2016, Sanofi Pasteur submitted an expanded access investigational new drug application to the Food and Drug Administration to allow for importation and use of Stamaril. The Food and Drug Administration accepted Sanofi Pasteur's application in October 2016.

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices.

IMPORTANCE: Travelers from around the globe will attend the 2014 Federation Internationale de Football Association (FIFA) World Cup and the 2016 Olympic and Paralympic Games in Brazil. Travelers to these mass gathering events may be exposed to a range of health risks, including a variety of infectious diseases. Most travelers who become ill will present to their primary care physicians, and thus it is important that clinicians are aware of the risks their patients encountered. OBJECTIVE: To highlight health and safety concerns for people traveling to these events in Brazil so that health care practitioners can better prepare travelers before they travel and more effectively diagnose and treat travelers after they return. EVIDENCE REVIEW: We reviewed both peer-reviewed and gray literature to identify health outcomes associated with travel to Brazil and mass gatherings. Thirteen specific infectious diseases are described in terms of signs, symptoms, and treatment. Relevant safety and security concerns are also discussed. FINDINGS: Travelers to Brazil for mass gathering events face unique health risks associated with their travel. CONCLUSIONS AND RELEVANCE: Travelers should consult a health care practitioner 4 to 6 weeks before travel to Brazil and seek up-to-date information regarding their specific itineraries. For the most up-to-date information, health care practitioners can visit the Centers for Disease Control and Prevention (CDC) Travelers' Health website (http://wwwnc.cdc.gov/travel) or review CDC's Yellow Book online (http://wwwnc.cdc.gov/travel/page/yellowbook-home-2014).

Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27-5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37-6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk-benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations.

Viscerotropic disease (VTD) is defined as acute multiple organ system dysfunction that occurs following vaccination. The severity of VTD ranges from relatively mild multisystem disease to severe multiple organ system failure and death. The term VTD was first used shortly after the initial published reports in 2001 of febrile multiple organ system failure following yellow fever (YF) vaccination [1–7]. To date, VTD has been reported only in association with YF vaccine and has been thus referred to as YF vaccine-associated viscerotropic disease (YEL-AVD). | YF vaccine is manufactured from the live attenuated 17D virus substrain. It is considered relatively safe and effective in preventing YF disease, which results from YF virus transmission through the bite of an infected mosquito [8]. YF virus circulates in sub-Saharan Africa and tropical South America, where it causes endemic and intermittently epidemic disease. Most YF disease in these areas is attributable to jungle (sylvatic) or savanna (intermediate) transmission cycles, which occur predominantly in sparsely populated forested areas and rural villages, respectively [8]. To protect vulnerable populations, endemic countries target YF vaccination efforts towards their residents, who reside in both rural and urban settings with varying resources.

The changing epidemiology of yellow fever and continued reports of rare but serious adverse events associated with yellow fever vaccine have drawn attention to the need to revisit criteria for the designation of areas with risk for yellow fever virus activity, and to revise the vaccine recommendations for international travel. WHO convened a working group of international experts to review factors important for the transmission of yellow fever virus and country-specific yellow fever information, to establish criteria for additions to or removal from the list of countries with risk for yellow fever virus transmission, to update yellow fever risk maps, and to revise the recommendations for vaccination for international travel. This report details the recommendations made by the working group about criteria for the designation of risk and specific changes to the classification of areas with risk for transmission of yellow fever virus.