Interim Canadian recommendations for the use of fractional dose of yellow fever vaccine during a vaccine shortage

Last updated: April 14, 2026

Notice to reader

Updated in April 2026: This statement has been rescinded and is no longer valid as the shortage of Yellow Fever vaccine has been resolved. CATMAT recommends that anyone who received a fractional dose of Yellow Fever vaccine while the shortage was in effect should now get a regular dose of the vaccine, if travelling to an area where yellow fever vaccination is recommended or required.

Note: This statement might be put back into effect should any shortages occur again in the future.

On this page

• Preamble
• Summary
• Introduction
• Methods
• Results
• Recommendations
• Documentation of fractional dose yellow fever vaccination
• Additional resources and useful links
• Acknowledgements
• Conflict of interest
• References

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. The Agency acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Summary

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.

Introduction

Yellow fever vaccine shortages pose a challenge. During shortages, 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. In Canada, there is only one licensed marketer of the yellow fever vaccine.

In 2016, there were 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 shortage. 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^{Note de bas de page 1Note de bas de page 2Note de bas de page 3}. Consequently, on 17 June 2016, the World Health Organization (WHO) released a statement that the WHO Strategic Advisory Group of Experts (SAGE) on Immunization concluded 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 evidence^{Note de bas de page 4}. The WHO now 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 convened a working group to review the evidence and develop 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 Guide^{Note de bas de page 5} and in the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement for Travellers and Yellow Fever^{Note de bas de page 6}.

Methods

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 original search conducted in 2017 spanned the initial date for each database until December 2016. Titles and abstracts of these results were reviewed and selected for inclusion based on relevancy to the research question. In March 2026, the working group completed a targeted update to identify and include key publications relevant to the evidence base.

Results

In 2008, Roukens et al. studied the effect of a one-fifth dose of yellow fever vaccine administered intradermally. All subjects developed titers of neutralizing antibody considered to be protective^{Note de bas de page 7}. The average subject age was 27 years with a wide adult age range (18 to 70 years). A subsequent 10-year follow-up study of a subset of participants (n = 75) demonstrated persistence of neutralizing antibody titres, with 98% (39/40) of those who received a one-fifth intradermal dose and 97% (34/35) of those who received a full subcutaneous dose maintaining seroprotective levels, with no significant difference in geometric mean titres between groups, suggesting durable immune response over the longer term despite the limited sample size^{Note de bas de page 8}.

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 subcutaneously^{Note de bas de page 9}. 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 et al. studied serum biomarkers of cellular immunity responses using fractional doses^{Note de bas de page 10}. 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. A 2020 systematic review corroborates these findings, indicating that fractional doses (at least one-fifth of the standard dose) produce similar serological responses to full doses in healthy populations^{Note de bas de page 11}.

More recent immunogenicity and safety studies in children aged 9 to 59 months and in HIV positive individuals with CD4 counts above 200 cells/mm³, and long-term follow-up studies in Brazil and the Democratic Republic of the Congo support the earlier evidence that fractional dosing may provide protection similar to a regular dose^{Note de bas de page 12Note de bas de page 13Note de bas de page 14Note de bas de page 15Note de bas de page 16}. While a 2021 Brazilian study reported rare cases of neurotropic disease during a large-scale fractional-dosing campaign^{Note de bas de page 17}, these findings should be interpreted in the context of broader evidence demonstrating comparable immunogenicity of fractional dosing to full dosing in healthy populations.

Although the results of these studies are encouraging, this constitutes a limited evidence base. Further research is needed to confirm the long-term efficacy of fractional dosing.

Recommendations

Under normal circumstances, a recommendation for use of fractional dose of yellow fever vaccine would not be made for travellers. In the event of a shortage, 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 recommendation, applicable to individuals for whom the standard yellow fever vaccine recommendations apply, including young children:

• For travel to a region of a country with risk of yellow fever, health care professionals should first emphasize the importance of receiving a full dose of vaccine or otherwise postponing the trip. This is especially critical for travel to areas experiencing an ongoing outbreak of the disease.
• If a traveller must travel to an endemic area, especially to areas experiencing an ongoing outbreak of yellow fever, and a full dose cannot be located after reasonable efforts, a fractional dose may be administered. The dose should be one-fifth of the usual dose (0.1 ml instead of 0.5 ml) administered by the traditional subcutaneous route. As with full dose, a fractional dose is considered protective 10 days after it is administered to a person who has never before received the yellow fever vaccine.
  • A fractional dose should not be documented in the official International Certificate of Vaccination or Prophylaxis (ICVP) card (see Documentation of fractional dose yellow fever vaccination)
• If a traveller planning a high-risk itinerary receives a fractional dose of yellow fever vaccine, and then later finds that a full dose has become available, the full dose may be administered and the International Certificate of Vaccination or Prophylaxis (ICVP) may be issued.
• Once reconstituted, the vaccine vial should be stored between 2° and 8° Celsius, and used within one hour. Thus, it will be necessary to vaccinate several people within that hour in order to efficiently use the contents of the vial in the allotted time. The health care professional may find that the use of disposable 1 cc insulin syringes with a non-detachable needle wastes less vaccine. Four, possibly five, doses may be obtained from one vial. Strict aseptic technique should be observed.
• If fewer than five doses are being administered, it is recommended that the entire contents of the vial be used, equally distributed among those being immunized. This will allow for the administration of somewhat more than 0.1 ml per person.
• Based on available data, a fractional, one-fifth dose (0.1 ml instead of 0.5 ml) should be considered protective for at least one year. Protection may be longer; however, more long-term data are needed. No recommendation is made at this time regarding repeat fractional dose immunization for subsequent travel.
• Once the supply of yellow fever vaccine is restored in Canada, the use of fractional doses should be discontinued. Shortage status can be confirmed on the Health Product Shortages website.
• Practitioners are reminded that the WHO now considers a single full dose of yellow fever vaccine protective for life regardless of when it is administered.
• There are limited data on seropositivity using fractional doses in travellers who are HIV positive, pregnant (and in whom a risk evaluation concludes immunization is appropriate) or under 2 years of age. However, the potency of a one-fifth dose of yellow fever vaccine would still exceed the minimum vaccine potency recommended by WHO. The clinician should in all cases weigh the risk of yellow fever exposure and availability of vaccine when deciding whether or not to use fractional dosing in these populations.
• Practitioners should provide the same counselling on the risks and benefits of vaccination for a fractional dose as they would for a full dose.
• Practitioners should presume that the adverse events associated with a full dose are likely to be similar when a fractional dose is administered.

Documentation of fractional dose yellow fever vaccination

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)^{Note de bas de page 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.

Additional resources and useful links

• Yellow fever vaccinations centres in Canada
• Vaccination requirements and recommendations for international travellers (World Health Organization)

Acknowledgements

This statement was prepared by the CATMAT Yellow Fever Working Group: YG Bui (lead), A Khatib, M Libman, J Pernica, and approved by CATMAT.

CATMAT gratefully acknowledges the contribution to this statement of: P Teitelbaum, M Abdel-Motagally and E Payne.

CATMAT members: M Libman (Chair), YG Bui (Vice-Chair), K Plewes (Malaria Sub-Committee Chair), I Bogoch, C Hogan, K Kazmi, A Khatib, P Lagacé-Wiens, J Lee and C Yansouni.

Liaison representatives: J Pernica (Association of Medical Microbiology and Infectious Disease Canada) and K O'Laughlin (Centers for Disease Control and Prevention, United States).

Ex officio representatives: V Donici (National Defence and the Canadian Armed Forces [ND-CAF], C Jensen (National Advisory Committee on Immunization [NACI] Secretariat, PHAC), D Marion (ND-CAF), S Schofield (ND-CAF), M Tunis (NACI Secretariat, PHAC), and R Zimmer (Biologic and Radiopharmaceutical Drugs Directorate, Health Canada).

Conflict of interest

None declared.