An expert panel voted Thursday to advise that the Centers for Disease Control and Prevention recommend use of a controversial dengue vaccine, despite the fact that it can only be given to a small fraction of U.S. children and requires a pre-vaccination test in order to be used safely.
The 14-0 vote by the Advisory Committee on Immunization Practices clears the way for rollout of Sanofi’s three-dose Dengvaxia vaccine, assuming the CDC accepts the advice. The CDC very rarely overrides recommendations from the group, known as ACIP.
Even members of the ACIP’s dengue work group — which conducted an in-depth review of the feasibility of using the vaccine — acknowledged deploying Dengvaxia won’t be easy.
“This is a very challenging implementation and nothing that there is any precedent [for], in terms of doing a lab test before vaccinating,” said Gabriela Paz-Bailey, of the CDC’s dengue branch, which is located in San Juan, Puerto Rico.
As licensed by the Food and Drug Administration, the vaccine can only be given to children aged 9 to 16 who live in areas where dengue is endemic and who have laboratory confirmation of having had at least one previous dengue infection. In the U.S. context, that means Puerto Rico and a few other offshore territories and protectorates.
Dengvaxia is the first and to date only vaccine commercially available to protect against dengue, a significant global health threat. But after the vaccine was first put into use abroad — it was used most widely in the Philippines — it became apparent that Dengvaxia use carries a significant risk. It is protective for people who have had at least one previous dengue infection. But in those who are dengue-naïve, the vaccine raises the risk that an individual will have a severe case of dengue if the vaccine doesn’t block infection.
There are four serotypes of dengue viruses, numbered 1 through 4. Infection with any one of them does not protect against the others and actually appears, for a time, to increase the risk that a subsequent dengue infection will trigger a severe form of the disease that can be life-threatening. That phenomenon is called antibody-dependent enhancement, or ADE. The vaccine’s use in the Philippines indicated that in children who had never had a dengue infection, the vaccine acted in the way that a first infection did — raising the risk of severe dengue requiring hospitalization if the vaccinated child went on to contract the virus.
Based on those findings, the World Health Organization’s vaccine advisory panel recommended that Dengvaxia only be given to people with a medically confirmed history of dengue infection, a limitation the FDA later included in its license for the product. But that requirement came with complications, given that at the time there were no approved tests to use to check a person’s previous dengue-infection status before vaccination.
During its meeting Thursday, the ACIP was informed that CDC has identified three commercial tests that are sufficiently accurate to use for pre-vaccination screening. But Iris Cardona, chief medical officer for the Puerto Rico Department of Health, told the committee only about one-quarter of health care providers who give vaccines on the island have the in-house capacity to conduct the test on children who come forward for vaccination. She said a phased-in rollout of the vaccine in Puerto Rico will likely be needed.
There are other challenges. Cardona told the committee that while vaccination rates among teenagers in Puerto Rico are reasonably high, uptake of the second dose of the vaccine for human papillomavirus is substantially lower — 58% — than it is for the first dose, which is 84%. That raises questions about whether children eligible for Dengvaxia will return for all three doses, which are given at six-month intervals.
But the committee was also told about the potential benefits. Modeling work used to assess the public health impact of using the vaccine suggested that if a cohort of 9-year-olds was vaccinated and followed for a decade, between 1,262 and 4,295 fewer children would be hospitalized for severe dengue infections, depending on how much transmission of the virus was occurring over that time. During that same timeframe, between 28 and 112 children who should not have received the vaccine because they were dengue-naïve might end up with an infection that required hospital care.
Yvonne Maldonado, a nonvoting liaison to the committee representing the American Academy of Pediatrics, said her organization supports use of the vaccine.
“We don’t believe that this is going to be an easy process. There are a lot logistical issues to be dealt with,” she said. “But if Covid-19 taught us one thing, it’s that you have to weigh the risks and the benefits. And I understand that the risks sound uncomfortable, but the risks here are extremely manageable, albeit there will be a number of administrative obstacles to move through.”