Our math model found tradeoffs in MPOX vaccination strategies and supports smaller doses to protect a larger population at risk
When there is a shortage of vaccine available in a public health crisis, one policy option is to offer the full dose to a small population or alternatively offer a smaller dose to a larger population. There can be uncertainty in which policy option will produce better health outcomes for the community.
The Policy Decision Dilemma
The spring-summer 2022 MPOX (aka monkeypox or MPX) outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM).
Will low-dose vaccination stretch the monkeypox vaccine supply, or backfire?
In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching each single full-dose vaccine vial to cover 3-4 people.
The dilemma was that no scientists knew for sure yet if a smaller dose would effectively protect people from MPOX infection. Media reported heavily on rationing, dose-sparing protocols, and criticisms by activists. Luciana Borio and Philip Krause shared their clear opinion on the benefits and risks:
“If the vaccine can be administered at lower doses at no risk to effectiveness, lower-dose intradermal injections make sense. But this strategy could also backfire. If there is a risk to effectiveness, it may be better to focus the available full doses of vaccine on individuals at highest risk — men who have sex with multiple male partners — to provide the best chance of getting the outbreak under control.”Philip Krause and Luciana Borio | 8 Aug 2022 STAT
Key differences in the MPOX vaccine dose-sparing strategy included:
- one-fifth the vaccine dose per shot
- given in forearm instead of upper arm
- injected at surface of skin (intradermal) rather than subcutaneous
- leaves a noticeable scar the size of a dime on the arm
- one vaccine vial can be used for 3-4 people instead of 1
A smaller dose for more people is best when supply is limited
Research findings from our new study, presented at CROI 2023 with full paper available as pre-print on medRxiv, generated this much-needed evidence. We used mathematical modeling to compare the different approaches and identify what would be the most responsible strategy.
Our study found dose-sparing vaccination to be a viable public-health policy when MPOX vaccine supply is limited and the smaller dose retains at least moderate effectiveness
Even with uncertainty in the real world effectiveness of a smaller dose, the benefits of protecting a larger number of high-risk people produced better health outcomes at the community level and fewer total MPOX infections over the next six months compared to the alternative approach that would offer a limited supply of full dose vaccine to fewer people.
When a limited number of vaccine vials were available (2,500 vaccine vials), sufficient to vaccinate 31% of the high-risk population, then a dose-sparing strategy prevented more infections compared to full-dose vaccination as long as the smaller dose retained >40% of the effectiveness of a full dose.
The community experience of a visible scar wasn’t great
A full MPOX dose injected into muscle of the upper arm does not leave a scar. A smaller 1/5 dose injected under the surface of the skin in the forearm leaves a round coin-sized scar. Many people complained about the scar.
When providing protection services to Broadway theaters, my team at Infectious Economics had several risk-reduction counseling conversations with gay men who were afraid that the scar was a permanent branding by the government that would visibly identify them as a person who had high-risk sexual activity with other men in the summer of 2022 (based on criteria of eligibility for vaccination). This is an ethical consideration that warrants more conversation and highlights the importance of informed consent.
The differential equations that capture MPOX transmission dynamics
To test the hypothesis that a smaller dose of MPOX vaccine in a larger population may produce better outcomes than a full dose in fewer people, we designed an experiment to simulated and compared the health outcomes of each scenario. The 2021 MPOX outbreak was primarily attributed to spread through sexual activities of men who have sex with men.
We were fortunate to benefit from having defined the probabilities for a sexual mixing matrix of this population back in 2018. Our new model of MPOX transmission among sexually active MSM population (age 15-65) was developed on the basis of a model I previously published on for the prevention of HIV. This allowed us to move quickly with modifications rather than starting from scratch in the MPOX emergency.
Here is the system of differential equations we designed and solved:
As a result, the force of infection on a susceptible individual who is not vaccinated is defined aswhile and the force of infection on a susceptible individual who is vaccinated is defined as
Follow this treasure map to de-code the symbols above and solve the puzzle.
Support for this research was provided by the HIV Vaccine Trials Network (HVTN), HIV Prevention Trials Network (HPTN), and Infectious Economics. Header photo credit to Mario Tama, Getty Images.
- Dobromir Dimitrov, Blythe Adamson, Laura Matrajt. Evaluating the use of dose-sparing vaccination strategies for Monkeypox. medRxiv 2022.11.04.22281966; doi: https://doi.org/10.1101/2022.11.04.22281966
- Dobromir Dimitrov, Blythe Adamson, Laura Matrajt. Conference on Retroviruses and Opportunistic Infections (CROI) 2023. Poster Presentation, 21 Feb 2023.