https://www.npr.org/sections/goatsandsoda/2019/05/03/719037789/botched-vaccine-launch-has-deadly-repercussions"Rush To Produce, Sell Vaccine Put Kids In Philippines At Risk
May 3, 20192:53 PM ET
Michaeleen Doucleff
The U.S. Food and Drug Administration just approved one of the most sought after vaccines in recent decades. It's the world's first vaccine to prevent dengue fever — a disease so painful that its nickname is "breakbone fever."
The vaccine, called Dengvaxia, is aimed at helping children in Puerto Rico and other U.S. territories where dengue is a problem.
But this vaccine has a dark — and deadly — history. One that has led to criminal charges in the Philippines, sparked national panic and fueled a massive measles outbreak that has already killed more than 355 people.
The concern
That story begins on a stage in Manila in 2016.
A young girl, about age 9 or 10, sat on a chair surrounded by health officials. She wore a bright yellow T-shirt with the words "Dengue is dangerous" across it. She squeezed her eyes and bit her lip as the health secretary of the Philippines, Dr. Janette Garin, gave her a shot in the arm.
That shot launched a massive vaccine campaign to inoculate nearly 1 million schoolchildren with Dengvaxia. The goal was to save thousands of kids' lives and prevent an estimated 10,000 hospitalizations over a five-year period.
But in the end, estimates are that more than 100,000 Philippine children received a vaccine that health officials say increased their risk of a severe and sometimes deadly condition. In addition, other children who received the vaccine may have been endangered because, their parents alleged, they were not in good health.
The French pharmaceutical company Sanofi Pasteur spent 20 years — and about $2 billion — to develop Dengvaxia. The company tested it in several large trials with more than 30,000 kids globally and published the results in the prestigious New England Journal of Medicine.
But halfway around the world from the Philippines, in a Washington, D.C., suburb, one scientist was worried about the new vaccine.
"When I read the New England Journal article, I almost fell out of my chair," says Dr. Scott Halstead, who has studied dengue for more than 50 years with the U.S. military. When Halstead looked at the vaccine's safety data in the clinical trial, he knew right away there was a problem.
For some children, the vaccine didn't seem to work. In fact, Halstead says, it appeared to be harmful. When those kids caught dengue after being vaccinated, the vaccine appeared to worsen the disease in some instances. Specifically, for children who had never been exposed to dengue, the vaccine seemed to increase the risk of a deadly complication called plasma leakage syndrome, in which blood vessels start to leak the yellow fluid of the blood.
"Then everything gets worse, and maybe it's impossible to save your life," Halstead says. "A child can go into shock."
"The trouble is that the disease occurs very rapidly, just in a matter of a few hours," he adds. "And there's nothing on the outside of the body to signify the person is leaking fluid on the inside."
The complication is rare, says Halstead. Still, he was so worried about the safety concerns that he wrote at least six editorials for scientific journals. He even made a video to warn the Philippine government about the problem.
"I just think, 'No, you can't give a vaccine to a perfectly normal, healthy person and then put them at an increased risk for the rest of their lives for plasma leakage syndrome,' " Halstead says. "You can't do that."
The vaccine manufacturer disagreed with Halstead's interpretation of the study's results. The company wrote a rebuttal, asserting that regulatory agencies had approved Dengvaxia "on the basis of the vaccine's proven protection and acceptable safety profile."
The company also said it would perform additional studies to "further access the safety, efficacy and effectiveness" of the vaccine.
Despite these concerns, in July 2016, the World Health Organization went ahead and recommended the vaccine for all children ages 9 to 16.
"Yes, we did. It was what we call a 'conditional recommendation' with the emphasis to minimize potential risks," says Dr. Joachim Hombach, who led WHO's review of the vaccine. "We saw the problems. We also clearly pointed to the data gaps."
WHO recommended that Sanofi do more experiments to better understand the vaccine's safety issues. In its assessment, WHO pointed out that the vaccine "may be ineffective or may theoretically even increase the future risk of [being] hospitalized or severe dengue illness" in people who have never been exposed to dengue — which is about 10% to 20% of Philippine children.
WHO's recommendation came three months after the Philippines launched its mass vaccination campaign in April 2016.
A year and half later, that campaign came to a screeching halt."
Much more
https://www.npr.org/sections/goatsandsoda/2019/05/03/719037789/botched-vaccine-launch-has-deadly-repercussions______________________________________________
"Dengue vaccine fiasco leads to criminal charges for researcher in the Philippines
By Fatima ArkinApr. 24, 2019 , 3:55 PM
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."
"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, a retired dengue expert formerly 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.""
https://www.sciencemag.org/news/2019/04/dengue-vaccine-fiasco-leads-criminal-charges-researcher-philippines
