Sanofi, the multinational vaccine powerhouse, recently issued a warning about one of its newest vaccines, called Dengvaxia, a vaccine developed to prevent infection with dengue virus. The vaccine was put into large-scale use in children in the Philippines in early 2017 and did in fact prevent severe Dengue infection, but soon afterwards was found to have a more complicated efficacy profile. It prevented severe dengue in those having been previously infected with the virus, but was found to cause more severe disease in those previously uninfected. The vaccine acted as a “primer” for a more severe reaction from infection with different dengue strains later on. So even though overall the vaccine would be considered a success, with less cases of dengue and less severe cases requiring hospitalization, the Philippines has withdrawn the vaccine. Additionally, the WHO now recommends that the vaccine only be used in those known to have already been infected with at least one strain of Dengue in the past. Ironically, there are currently no commercially available rapid tests to determine if one was infected in the past, which pretty much means that almost no one should get the vaccine unless they have been diagnosed with acute Dengue already.
As it turns out, there were warning signs in the clinical trials for Denvaxia – younger children, who by virtue of being alive for less time were also less likely to have been previously infected with Dengue, showed higher infection and complication rates when vaccinated and exposed to Dengue when compared with older children. Despite this clue, multiple countries approved the vaccine for children 9 and older. The Philippines spent about $68 million dollars on the vaccination program in 2017 before suspending the vaccine’s use.
The reaction in the Philippines has predictably been fierce, with many claiming that the children of the country had been experimented on, despite the vaccine’s net decrease in total cases of dengue, as well as decreasing severe cases and hospitalizations.
The company tried to put a positive spin on the new study, with one of its vaccine unit chiefs, Dr. Su-Peing Ng, quoted as saying “With the new data, we now know what is the best way to utilize the dengue vaccine.” That is to say, the best way to use it is not to use it in resource-poor countries, where there is little money for testing to see who would benefit (or suffer) most from getting the vaccine.
The June 13, 2018 issue of the New England Journal of Medicine ran an article on the vaccine’s unintended consequences. In an accompanying editorial, Lisa Rosenbaum, MD, writes:
Of course, the vaccine does protect children from dengue; thanks to the vaccination campaign, there are far fewer severe cases than there would otherwise have been. But the story of illness averted doesn’t stand a chance against the one involving innocent children, a pharmaceutical giant, and a disease that takes a brutal, bloody toll on its victims. At the core of the outrage lies the challenge plaguing all prevention efforts: the faces of the children who were vaccinated and in whom a severe case of dengue subsequently developed will be highly visible in media coverage, while the many more vaccinated children who were spared severe illness will remain unseen.
The real tragedy, of course, is that although the vaccine may “work,” the need for special testing before deciding if a particular patient will benefit from it means that the poorest regions that need it the most, such as the Philippines, will not have the money to use it to save the most vulnerable.
-Read the complete Medscape story here.
-See the original article in the New England Journal of Medicine here.
-Find the NEJM’s insightful editorial by Lisa Rosenbaum, MD, here.