TY - JOUR
AU - Visser, Leo, G
AB - Abstract Yellow fever outbreaks have continued to occur and caused infection and deaths in travelers from non-endemic regions. Yellow fever vaccine has proven effective, but vaccination decisions require balancing benefits with risks. Of concern is the continued vaccine shortage worldwide, including of the YF-VAX® stockout in North America, which has presented many challenges. yellow fever, vaccine, shortage, outbreak, expanded access program In the wake of Zika virus outbreaks in the Americas, another mosquito-transmitted infection is stirring up trouble again: yellow fever (YF). Throughout history, YF has caused countless epidemics. YF was imported with the slave trade from tropical Africa to the Western hemisphere, and subsequently to cities in North America, the Caribbean, and Western Europe [1]. YF decimated populations during outbreaks in Philadelphia, New York, New Orleans, and along the Mississippi River, and led to the relocation of the US capital from Philadelphia to Washington D.C. [1]. Recognition of mosquitoes as vectors for YF and malaria and the efforts that ensued towards mosquito control finally culminated in the successful construction of the Panama Canal [1]. Currently, 47 countries in Africa and Central and South America have at least some regions where there is risk for YF, with about 200 000 severe cases of YF worldwide each year and up to 60 000 deaths [2]. In 2015 and 2016, large outbreaks occurred in Angola and the Democratic Republic of the Congo, followed by outbreaks in Brazil and Nigeria in 2017 and 2018. Of particular concern is Brazil, where an ongoing YF epizootic has expanded endemic zones, encroaching on Rio de Janeiro and Sao Paulo. Recently, GeoSentinel, a global surveillance network of 70 travel and tropical medicine clinics, recorded 5 cases of YF in unvaccinated travelers returning from Brazil to Europe during January–March 2018, including 2 deaths; additional YF cases and deaths have been reported in travelers from Argentina and Chile, also with exposure in Brazil [3]. Exposures occurred near major cities in the states of Sao Paulo, Minas Gerais, and Rio de Janeiro, and particularly in Ilha Grande. YF is caused by a flavivirus related to Zika, West Nile, and dengue. Infected persons may develop symptoms that include fever, nausea, vomiting, and abdominal pain, which may progress in 1 out of 5 cases to jaundice, liver and kidney failure, and bleeding. Unlike the typically mild Zika presentation, the death rate from symptomatic YF can reach 40–60% [2]. The YF vaccine was developed in the 1930s and its use can achieve disease control in at-risk countries if more than 80% of the population is vaccinated. The vaccine provides protection to >95% of those who are vaccinated and the immunity lasts a lifetime for many [4]. The YF vaccine has been associated with rare occurrences of severe viscerotropic and neurologic adverse events, estimated to occur at the rates of 0.3 and 0.8 per 100 000 doses distributed, respectively [5]. The risk rises with increasing age and has led to a hesitancy to administer the YF vaccine to persons aged 60 years and older [6]. In the setting of the current Brazilian outbreaks, many more travelers, including those ≥60 years old, need to be vaccinated. In addition to age and destination, the decision requires consideration of other factors, such as the traveler’s health status, their immune competency, and whether their future travel may benefit from YF vaccination (cumulative risk assessment) [6, 7]. Typically, there is a global stockpile of 6 million YF vaccine doses, because of the potential for YF epidemics to erupt. However, recent epidemics exhausted the vaccine stockpile, resulting in a global shortage [2]. Fractional dosing, a dose-sparing strategy, was utilized successfully to control the outbreak in the Democratic Republic of the Congo [8]. Brazil manufactures its own yellow fever vaccine, although the need far outweighs the supply; thus, Brazil will require fractional dosing in its plans to vaccinate the entire population of 77 million people by April 2019 [9]. The Global Alliance for Vaccines and Immunization, the World Health Organization (WHO), the United Nations International Children's Emergency Fund, and other partners plan to vaccinate 1 billion Africans by 2026 [10]. Although the 4 manufacturers of the YF vaccine are investing in increases to their supply capacity, there is no room for unpredictable surges in demand for the next 5 years [11]. In North America, the vaccine supply was recently depleted because the manufacturer, Sanofi Pasteur, is building a new plant that will not be able to supply YF-VAX until mid 2019. In order to protect travelers going to YF risk areas, Sanofi Pasteur worked with the US Food and Drug Administration and the Centers for Disease Control and Prevention (CDC) to establish an Expanded Access Program (EAP) under an Investigational New Drug Protocol using a French-made vaccine, Stamaril. Despite the successful use of Stamaril in >70 countries and its status as a WHO-prequalified and European Medicine Agency–approved vaccine, such a program has been required to legally deploy the vaccine in the US. Although over 4000 licensed clinics in the US provide the vaccine to travelers, only ~250 can administer Stamaril, as listed on the CDC Travelers’ Health website (www.cdc.gov/travel/page/search-for-stamaril-clinics). Travelers now require much more advance planning and some have reported hours of driving to obtain pre-travel consultations and vaccinations. The YF vaccine shortage and EAP demonstrate the challenges of ensuring a vaccine supply when there is a sole manufacturer. EAP sites have reported significant efforts to organize and implement the program, including Institutional Review Board approvals, contractual arrangements, staff training, and continued monitoring. Reasons to limit the number of EAP sites include budgetary constraints and managing the clinical trial. Enrolling larger-volume clinics to participate in a Stamaril EAP conserved the YF-VAX that would have been used by these sites, and allowed for the extension of the YF-VAX supply to non-EAP sites. With the depletion of YF-VAX, non-EAP sites have been frustrated about needing to refer patients elsewhere for YF vaccination. There has also been concern that some clinics with Stamaril may inflate their fees. If a YF vaccine shortage should occur again in the United States, we urge the Food and Drug Administration to consider the current EAP as an adequate clinical trial and to waive the need for an Investigational New Drug investigation for Stamaril. Canada also faces the YF vaccine shortage, and the Committee to Advise on Tropical Medicine and Travel recommends a fractional dosing approach using their remaining YF vaccine (YF-VAX) [12]. Because the WHO does not consider YF fractional dosing to satisfy International Health Regulations [13], the Committee to Advise on Tropical Medicine and Travel recommends using the Certificate of Medical Contraindication to Vaccination provided by the Public Health Agency of Canada, with an explanation that a YF fractional dose of 0.1 ml was administered due to the vaccine shortage. Western Europe has also experienced YF vaccine shortages at times. With the recent Zika and chikungunya outbreaks and the long-standing presence of dengue in the Americas, mosquito-borne infections are occurring in areas that were previously unaffected and in areas where these diseases have been absent for many years. The CDC now recommends YF vaccination for travel to regions of Brazil where travlers were previously not considered to be at risk. Like Zika, chikungunya, and dengue, day-biting mosquitoes transmit YF. Unlike with these other viruses, YF can be prevented by a vaccine. Medical providers have the obligation to educate and members of the public—if they plan to travel—should make an effort to educate themselves about health risks and to seek medical expertise prior to travel. It may be a challenge to locate a clinic and to find a vaccine in the setting of the current outbreaks and vaccine shortages, but being vaccinated prevents illness and death. All travelers need to heed the alerts about YF. It is not gone and not forgotten. Note Potential conflicts of interest. L. H. C. reports advisor fees from Shoreland Inc. outside of the submitted work and directs a Stamaril Expanded Access Program site. L. G. V. reports grants from the International Society of Travel Medicine and non-financial support from GSK outside the submitted work. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. References 1. Moreno-Madriñán MJ , Turell M . History of mosquitoborne diseases in the United States and implications for new pathogens . Emerg Infect Dis 2018 ; 24 : 821 – 6 . Google Scholar Crossref Search ADS PubMed 2. Chen LH , Hamer DH . Vaccination challenges in confronting the resurgent threat from yellow fever . JAMA 2017 ; 318 : 1651 – 2 . Google Scholar Crossref Search ADS PubMed 3. Hamer DH , Angelo K , Caumes E , et al. Fatal yellow fever in travelers to Brazil, 2018 . MMWR Morb Mortal Wkly Rep 2018 ; 67 : 340 – 1 . Google Scholar Crossref Search ADS PubMed 4. Staples JE , Bocchini JA Jr , Rubin L , Fischer M ; Centers for Disease Control and Prevention (CDC) . Yellow fever vaccine booster doses: recommendations of the advisory committee on immunization practices, 2015 . MMWR Morb Mortal Wkly Rep 2015 ; 64 : 647 – 50 . Google Scholar PubMed 5. Lindsey NP , Rabe IB , Miller ER , Fischer M , Staples JE . Adverse event reports following yellow fever vaccination, 2007–13 . J Travel Med 2016 ; 23 : 1 – 6 . Google Scholar Crossref Search ADS 6. Lown BA , Chen LH , Wilson ME , et al. Vaccine administration decision making: the case of yellow fever vaccine . Clin Infect Dis 2012 ; 55 : 837 – 43 . Google Scholar Crossref Search ADS PubMed 7. Leder K , Chen LH , Wilson ME . Aggregate travel vs. single trip assessment: arguments for cumulative risk analysis . Vaccine 2012 ; 30 : 2600 – 4 . Google Scholar Crossref Search ADS PubMed 8. Ahuka-Mundeke S , Casey RM , Harris JB , et al. Immunogenicity of fractional-dose vaccine during a yellow fever outbreak - preliminary report . N Engl J Med 2018 . doi: 10.1056/NEJMoa1710430. [Epub ahead of print]. 9. ProMED . Yellow fever – Americas: Brazil, MOH. Archive 20180430.5774384 . Available at http://www.promedmail.org. Accessed 30 April 2018 . 10. World Health Organization . News release: nearly one billion people in Africa to be protected against yellow fever by 2026 . Available at http://www.who.int/mediacentre/news/releases/2018/yellow-fever-africa/en/. Accessed 1 June 2018 . 11. Global Alliance for Vaccines and Immunization. Yellow fever supply and procurement roadmap update, 20th March 2017 . Available at https://www.gavi.org/library/gavi-documents/supply-procurement/. Accessed 1 July 2018 . 12. Committee to Advise on Tropical Medicine and Travel . Interim Canadian recommendations for the use of a fractional dose of yellow fever vaccine during a vaccine shortage . Available at https://www.canada.ca/en/public-health/services/publications/diseases-conditions/interim-recommendations-fractional-dose-yellow-fever-vaccine-shortage.html. Accessed 1 June 2018 . 13. World Health Organization . Yellow fever vaccine: WHO position on the use of fractional doses – June 2017 . Weekly Epidemiol Rec 2017 ; 25 : 345 – 56 . © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - What’s Old Is New Again: The Re-emergence of Yellow Fever in Brazil and Vaccine Shortages
JO - Clinical Infectious Diseases
DO - 10.1093/cid/ciy777
DA - 2019-05-02
UR - https://www.deepdyve.com/lp/oxford-university-press/what-s-old-is-new-again-the-re-emergence-of-yellow-fever-in-brazil-and-IlVpgmS0gx
SP - 1761
VL - 68
IS - 10
DP - DeepDyve
ER -