The World Health Organization says use of the world’s only licensed dengue vaccine should be restricted because of concerns it increases the risk of severe disease in people who have never previously had dengue.
In a new interim recommendation released Friday, the global health agency said it based the decision on new data from the vaccine’s manufacturer, Sanofi (SNY) Pasteur, that was released in late November.
Until a full review can be conducted, “WHO recommends vaccination only in individuals with a documented past dengue infection, either by a diagnostic test or by a documented medical history of past dengue illness,” the WHO said. The recommendation was embedded in a revised Q&A about the vaccine.
The review is not expected before April at the earliest, the agency said.
Some experts have been calling for this advice. Several told STAT recently that restricting use of Dengvaxia, as the vaccine is called, to people who have previously been infected is the precautionary thing to do at this time.
“If you’re negative, it’s a no. If you’re positive, you should be offered it. If you’re unsure or unknown, probably the best advice would be to not have it,” Dr. Jeremy Farrar, director of the Wellcome Trust and co-chair of the WHO technical advisory group on Dengvaxia, told STAT.
Farrar expressed concern, though, about what this approach would do to the commercial viability of the vaccine.
Dengvaxia has been licensed in 19 countries, but has only been used in large immunization programs in two — the Philippines and Brazil. The vaccine has not yet been approved in Europe or the United States.
In an emailed response to a request for comment, Sanofi said it has asked drug regulators in all countries where Dengvaxia is either licensed or under evaluation for licensure to update the product’s label to instruct health care professionals to assess the likelihood of prior dengue infection before giving the vaccine.
“For individuals who have not been previously infected by the dengue virus vaccination should not be recommended,” the company said, adding that where testing is available, doctors could use it to determine whether a patient is a candidate for the vaccine.
The problem is there is no rapid point-of-care test that would allow doctors to identify to whom it is safe to give the vaccine. Tests that are available would take some time to come up with an answer. While it is likely rapid tests can be developed, it will take time.
And few people would have medical records confirming their dengue status. As many as three-quarters of infections are symptom-free; many other cases are mild and those people are unlikely to be tested.
News that the vaccine can increase the risk of severe disease in people who have not previously been infected with dengue has caused great consternation in the Philippines, where government officials have demanded an investigation into how Sanofi marketed Dengvaxia.
There have long been concerns that a vaccine for the disease could be risky for certain people, because of an unusual phenomenon seen with dengue infection.
Dengue is caused by four related viruses, named dengue 1 through 4; infection with one does not protect against the others.
A small portion of people who contract the disease — which is transmitted by Aedes aegypti mosquitoes — develop a severe form, known as dengue hemorrhagic fever. It can be fatal. It’s estimated that about 500,000 people develop severe dengue each year and about 22,000 die.
People are more likely to suffer severe disease on their second dengue infection — a result, it is believed, of a phenomenon called antibody dependent enhancement, or ADE.
And it appears that in people who had not previously contracted dengue, the vaccine acts like a first infection, setting them up to be at higher risk of severe disease if they become infected later. The vaccine is only partially protective.
Two mathematical modelers who have been warning that this vaccine poses a risk to some of the people who have been getting it were critical of how long it has taken for the problem to be recognized and addressed.
Maíra Aguiar and Nico Stollenwerk of Nova University and the University of Lisbon, both in Portugal, said the information from Sanofi and the advice from the WHO “are inexcusably late,” given that the problem was spotted in a clinical trial which was published more than a year ago.
“Even with controversial modeling results indicating that the use of Dengvaxia in highly endemic settings could be beneficial at the population level, ethically no one should have been put under risk by receiving this vaccine,” Aguiar and Stollenwerk wrote in a letter to the journal Lancet Infectious Diseases.
An earlier version of this story incorrectly suggested that Sanofi has sought to license Dengvaxia in the U.S.