Parents brought pictures of children immunized with Dengvaxia to a 2018 hearing at the Philippine Senate.
NOEL CELIS/AFP/GETTY IMAGES
By Fatima Arkin
A prominent pediatrician and medical researcher in the Philippines has been indicted over the failed—and many say premature—introduction of Dengvaxia, a vaccine against dengue that was yanked from the Philippine market in 2017 because of safety issues. If convicted of accusations leveled at her by the national Department of Justice (DOJ), Rose Capeding, 63, former head of the dengue department of the Research Institute for Tropical Medicine (RITM) here, could face up to 48 years in prison.
In February, prosecutors concluded there is probable cause to indict Capeding and 19 others for “reckless imprudence resulting [in] homicide,” because they “facilitated, with undue haste,” Dengvaxia’s approval and its rollout among Philippine schoolchildren.
Capeding, through her family, declined to comment, but her son Juhani Capeding says his mother “couldn’t have imagined” that submitting research to top medical journals could have led to “this point.” Some of Capeding’s colleagues agree. “As a scientist, I really feel so disgusted, dismayed, [and] heartbroken about the whole situation,” says Lulu Bravo, executive director of the Philippine Foundation for Vaccination here.
Also charged are Capeding’s former boss, former RITM head Socorro Lupisan; former Department of Health (DOH) Secretary Janette Garin; other officials at DOH and the Philippines Food and Drug Administration (FDA); and current and former officials of Sanofi Pasteur, the French company producing the shots. The first of eight criminal cases—which could be consolidated—are now pending in five courts throughout the northern island of Luzon, where the vaccination campaign took place.
Dengvaxia consists of an attenuated yellow fever virus that expresses genes of each of the four types of dengue virus. The Philippine FDA greenlighted the vaccine in December 2015, based on research funded by Sanofi Pasteur in which Capeding played an important role. For example, she was the first author on a 2014 paper in The Lancet detailing a study among more than 10,000 children in five Asian countries that showed Dengvaxia worked and had a good safety profile. In April 2016, the Philippine government launched a $67 million public school–based immunization program for Dengvaxia.
That alarmed some scientists, because the dengue virus is peculiar: A first infection is rarely fatal, but a second one with a different virus type can lead to much more serious disease, because of what is called antibody-dependent enhancement (ADE), in which the immune response to the first virus amplifies the effect of the second type. Scott Halstead, who studies dengue at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, argued that dengue vaccines could have the same effect, and warned that Dengvaxia should not be given to children never infected with dengue. But a vaccine panel at the World Health Organization (WHO) concluded in 2016 that Dengvaxia was safe for children aged 9 and older.
Halstead’s concerns proved valid. In November 2017, Sanofi Pasteur announced that the vaccine could indeed exacerbate cases of dengue in children never previously infected, and the Philippines halted the campaign immediately. (WHO now recommends the vaccine be used only after a test to be sure children have had at least one brush with dengue.)
The news enraged and frightened the parents of some 830,000 schoolchildren who had already received one or more Dengvaxia shots. Given the high prevalence of dengue in the Philippines, most probably already had the disease at least once, and thus are not at risk of ADE—but some had not. In September 2018, DOH Undersecretary Enrique Domingo told reporters that 130 vaccinated children had died; 19 of those had dengue, meaning ADE possibly played a role. The case triggered “mass hysteria,” says Edsel Salvaña, an infectious disease physician at the University of the Philippines here. “Parents thought their kids were all going to die.”
What prosecutors think Capeding—or any of the other accused—is responsible for remains unclear, because the full report about the case has not yet been released. But other scientists have come to Capeding’s defense. “[If] you’re going to say that a scientist doing a clinical trial is actually liable for anything bad that happens once the product is approved, then that’s just crazy,” Salvaña says. “The indictment of Rose Capeding is an egregious, unjust, and highly disturbing act,” adds Tikki Pangestu, a Singapore-based adviser to the Asia Dengue Vaccine Advocacy Group who has written policy and advocacy papers with Capeding.
But Halstead says the trials Capeding helped conduct were not well designed; if the researchers had looked separately at outcomes for children who did and didn’t have dengue before the shot, they would have identified the ADE risk, he says. He notes that Sanofi and WHO committees designed the trials, however, not Capeding. He declined to say whether criminal charges are warranted: “This is a very complex ethical and scientific question that needs to be handled carefully.”
Sanofi, in a statement to Science, says the company “strongly disagrees with the DOJ’s findings made against its officials (current and past) and we will vigorously defend them.” It’s not yet clear when the criminal trials will start.
Source: Science Mag