This statement outlines interim recommendations intended for use during yellow fever vaccine shortages only. The recommendations differ from the standard recommendations for yellow fever vaccination in the Canadian Immunization Guide and in the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement for Travellers and Yellow Fever.
Suggested citation: Yellow Fever Working Group on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT). Interim Canadian Recommendations for the use of a fractional dose of yellow fever during a vaccine shortage. Can Comm Dis Rep 2016;42:158-60.
Yellow fever vaccine shortages pose a challenge. Travel clinics may be allotted a small fraction of the number of vaccines typically ordered, or in some cases, travel clinics will not have access to the yellow fever vaccine until a new supply of the vaccine is available. There is currently only one licensed marketer of the vaccine in Canada.
In 2016, there have been calls for the use of a fractional dose of yellow fever vaccine to address a global yellow fever vaccine shortage, a measure which would allow for immunization of a greater number of people during the vaccine shortageFootnote 1,Footnote 2,Footnote 3. This suggestion is primarily based on three studies which have shown that doses in the range of 1/10 to 1/5 of the usual 0.5 ml subcutaneous dose are protective based on laboratory criteria.
On 17 June 2016, the World Health Organization (WHO) released a statement that the WHO Strategic Advisory Group of Experts (SAGE) on Immunization found that the use of a fifth of a standard vaccine dose (0.1 ml instead of 0.5 ml) would provide protection against yellow fever for at least 12 months based on a review of existing evidenceFootnote 4. The WHO states that the fractional dose of yellow fever vaccine can be considered a safe and effective approach to control an urban outbreak in case of vaccine shortages.
CATMAT formed a working group to review the evidence and make interim recommendations on the use and documentation of fractional doses of yellow fever vaccine in Canada intended for use during yellow fever vaccine shortages only. Each member was a volunteer, and none declared a relevant conflict of interest. The recommendations differ from the standard recommendations for yellow fever vaccination in the Canadian Immunization GuideFootnote 5 and in the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement for Travellers and Yellow FeverFootnote 6.
A literature search for evidence related to the immunogenicity of a fractional dose of yellow fever vaccine was conducted. Evidence was retrieved by performing searches in electronic databases (Ovid MEDLINE, Embase, Global Health and Scopus). The search spanned the initial date for each database until June 2016 and 49 results were identified. Titles and abstracts of these results were reviewed and selected for inclusion based on relevancy to the research question.
In 2008, Roukens et al studied the effect of a one-fifth dose of yellow fever vaccine administered intradermally. All subjects developed titres of neutralizing antibody considered to be protectiveFootnote 7. The average subject age was 27 years with a wide adult age range (18 to 70 years).
In 2013, Martins et al studied seroconversion and viremia responses to the use of full dose and five different dilutions of the usual human dose of 17-DD yellow fever vaccine administered subcutaneouslyFootnote 8. There was little difference in immune response down to a dilution of 1:50.
In a 2014 extension of the Martins study (using the same patient data and collected blood), Campi-Azevedo studied serum biomarkers of cellular immunity responses using fractional dosesFootnote 9. There was evidence of protection at dilutions down to 1:50. However, consistent findings of equivalency to a full dose across all markers of immunity (serology, viremia and cellular immunity) were found down to a 1:10 dilution. In the Martins and Campi-Azevedo investigations, all subjects were healthy young males with an average age of 19 years.
Although the results of these studies are encouraging, this constitutes a limited evidence base. Further research is needed to determine the effectiveness of fractional doses, especially in young children.
Under normal circumstances, a recommendation for use of fractional dose of yellow fever vaccine would not be made for travellers. However, some travellers going to yellow fever endemic or epidemic regions may not have access to a full dose of yellow fever vaccine, and as such, these travellers face the choice of not receiving a vaccine or receiving a fractional dose of vaccine.
In view of this situation, CATMAT makes the following recommendations, applicable to individuals for whom the standard yellow fever vaccine recommendations apply, including young children:
The WHO states that a fractional dose of the yellow fever vaccine would not qualify for a yellow fever certificate under the International Health Regulations (IHR)Footnote 4. Therefore CATMAT does not recommend that practitioners use the official International Certificate of Vaccination or Prophylaxis (ICVP) card to document a fractional dose.
One option for documentation is the use of the Certificate of Medical Contraindication to Vaccination provided by the Public Health Agency of Canada. An explanation can be written inside informing that a fractional dose of 0.1 ml of the yellow fever vaccine was administered subcutaneously due to a severe vaccine shortage.
This statement was developed by the Yellow Fever Working Group: Teitelbaum P (Chair), Bui Y, Libman M, Pernica J and Abdel-Motagally M.
CATMAT members: McCarthy A (Chair), Acharya A, Boggild A, Brophy J, Bui Y, Crockett M, Greenaway C, Libman M, Teitelbaum P and Vaughan S.
Liaison members: Audcent T (Canadian Paediatric Society), Gershman M (United States Centers for Disease Control and Prevention) and Pernica J (Association of Medical Microbiology and Infectious Disease Canada).
Ex officio members: Marion D (Canadian Forces Health Services Centre, Department of National Defence), Rossi C (Directorate of Force Health Services Group, Department of National Defence), McDonald P (Division of Anti-Infective Drugs, Health Canada) and Schofield S (Pest Management Entomology, Department of National Defence).