The CDC’s Advisory Committee on Immunization Practices (ACIP) has now recommended using Sanofi’s dengue vaccine, Dengvaxia, in the US, with specific restrictions. The vaccine is only to be used for children aged 9–16 who live in endemic areas and who have evidence with a specific diagnostic test of prior dengue infection.
Dengue is a mosquito-borne virus found throughout the world, primarily in tropical or subtropical climates. Cases had steadily been increasing to 5.2 million in 2019, and the geographic distribution of cases is broadening with climate change and urbanizatio n. About half of the world’s population is now at risk.
The dengue virus has four serotypes. The first infection may be mild or asymptomatic, but the second one can be life-threatening because of a phenomenon called antibody-dependent enhancement.
The lead author of the new recommendations is Gabriela Paz-Bailey, MD, PhD, Division of Vector-Borne Diseases, Dengue Branch, CDC. She told Medscape Medical News that during the second infection, when there are “low levels of antibodies from that first infection, the antibodies help the virus get inside the cells. There the virus is not killed, and that results in increased viral load, and then that can result in more severe disease and the plasma leakage” syndrome, which can lead to shock, severe bleeding, and organ failure. The death rate for severe dengue is up to 13%.
Previous infection with Zika virus, common in the same areas where dengue is endemic, can also increase the risk for symptomatic and severe dengue for subsequent infections.
In the US, Puerto Rico is the main focus of control efforts because 95% of domestic dengue cases originate there — almost 30,000 cases between 2010 and 2020, with 11,000 cases and 4000 hospitalizations occurring in children between the ages of 10 and 19..
Because Ae aegypti, the primary mosquito vector transmitting dengue, is resistant to all commonly used insecticides in Puerto Rico, preventive efforts have shifted from insecticides to vaccination.
Antibody Tests Prevaccination
The main concern with the Sanofi’s dengue vaccine is that it could act as an asymptomatic primary dengue infection, in effect priming the body for a severe reaction from antibody-dependent enhancement with a subsequent infection. That is why it’s critical that the vaccine only be given to children with evidence of prior disease.
Paz-Bailey said, “The CDC came up with recommendations of what the performance of the test used for prevaccination screening should be. And it was 98% specificity and 75% sensitivity…. But no test by itself was found to have a specificity of 98%, and this is why we’re recommending the two-test algorithm,” in which two different assays are run off the same blood sample, drawn at a prevaccination visit.
If the child has evidence of prior dengue, they can proceed with vaccination to protect against recurrent infection. Dengvaxia is given as a series of three shots over 6 months. Vaccine efficacy is 82% — so not everyone is protected, and additionally, that protection declines over time.
There is concern that it will be difficult to achieve compliance with such a complex regimen. Paz-Bailey said, “But I think that the trust in vaccines that is highly prevalent for [Puerto] Rico and trusting the healthcare system, and sort of the importance that is assigned to dengue by providers and by parents because of previous outbreaks and previous experiences is going to help us.” She added, “I think that the COVID experience has been very revealing. And what we have learned is that Puerto Rico has a very strong healthcare system, a very strong network of vaccine providers…. Coverage for COVID vaccine is higher than in other parts of the US.”
One of the interesting things about dengue is that the first infection can range from asymptomatic to life-threatening. The second infection is generally worse because of this antibody-dependent enhancement phenomenon. Eng Eong Ooi, MD, PhD, professor of microbiology and immunology, National University of Singapore, told Medscape Medical News, “After you have two infections, you seem to be protected quite well against the remaining two [serotypes]. The vaccine serves as another episode of infection in those who had prior dengue, so then any natural infections after the vaccination in the seropositive become like the outcome of a third or fourth infection.”
Vaccination alone will not solve dengue. Ooi said, “There’s not one method that would fully control dengue. You need both vaccines as well as control measures, whether it’s Wolbachia or something else. At the same time, I think we need antiviral drugs, because hitting this virus in just one part of its lifecycle wouldn’t make a huge, lasting impact.” Ooi added that as “the spread of the virus and the population immunity drops, you’re actually now more vulnerable to dengue outbreaks when they do get introduced. So, suppressing transmission alone isn’t the answer. You also have to keep herd immunity levels high. So if we can reduce the virus transmission by controlling either mosquito population or transmission and at the same time vaccinate to keep the immunity levels high, then I think we have a chance of controlling dengue.”
Paz-Bailey concluded, “I do want to emphasize that we are excited about having these tools, because for years and years, we have had really limited options to prevent and control dengue. It’s an important addition to have the vaccine be approved to be used within the US, and it’s going to pave the road for future vaccines.”
Paz-Bailey and Ooi report no relevant financial relationships.
MMWR Morb Mortal Wkly Rep. Published online December 17, 2021. Full text
Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.