health & science
Dengue: The centre of a vaccine disaster story
In the midst of a measles outbreak, Farah Hancock looks at the disastrous roll-out of a dengue vaccine in the Philippines and the measles flow-on effect as part of a series on vaccines.
For most New Zealanders, dengue is a vague worry when holidaying in tropical countries. For locals of those countries, it’s a growing daily threat.
The mosquito-borne disease nicknamed “breakbone fever” due to its painful symptoms can be unpleasant and - for some - fatal.
Rates of dengue are skyrocketing. In just one day this week, 1000 new cases were diagnosed in Bangladesh, mostly in children. In the Philippines 100,000 cases have been reported this year, an 85 percent increase from the same time period last year.
There’s no cure for dengue but there is a vaccine.
The bad news is it’s at the centre of a vaccine disaster story. In 2016 its world-first mass roll-out in the Philippines caused political scandal, the exhumation of children’s bodies, and an ongoing court case.
Indirectly it’s been blamed for a distrust of vaccines, muddying the waters of scientific consensus on vaccine safety, and a measles outbreak which has even reached New Zealand shores.
The vaccine, Dengvaxia, was given to more than 830,000 Filipino children. For many of the children it would have been safe and provided protection against dengue fever. For others it could make getting dengue dangerous.
Following vaccination, 154 children died. Most of these deaths were unrelated to the vaccine, but 19 of those who died had severe dengue fever. Exhumations have shown excessive bleeding, a hallmark of dengue haemorrhagic fever, in some of the children.
A criminal suit has been filed over the deaths of 11 of those children.
Since the scandal erupted, Filipinos' confidence in vaccines plummeted from 93 percent to less than 33 percent. Vaccination rates have dropped, and measles has spread. In 2019 alone there have been at least 477 deaths caused by measles.
What went wrong with Dengvaxia
The drug trials conducted by the maker of Dengvaxia, French drug company Sanofi Pasteur, did not screen all participants for previous dengue infection. When it comes to dengue, previous infection matters.
There are four types of dengue virus, and getting one type doesn’t give you immunity from getting the other three types, and each infection has a different effect on the body.
The first infection can make you feel awful, the second can kill, but the third and fourth infections are mild.
When asked why the body reacts differently each time, The Malaghan Institute’s Professor Graham Le Gros said it’s a tricky disease.
“These particular viruses play with us. They play with our immune system.”
After a first infection the body makes an immune response to that type of dengue. If you then get bitten by a mosquito carrying a different strain of dengue, the body thinks it’s the same as the first virus.
The result is like turning up to a gun fight with a water pistol.
“The partial immune response helps the immune cells become super infected with the virus,” said Le Gros.
The result can be dengue haemorrhagic fever, where the body internally leaks blood, sometimes lethally. Around 10,000 to 20,000 people die from dengue each year.
Prior to the $88 million roll-out of Dengvaxia in the Philippines, concerns from scientists about the risks showing in the drug company’s own data from trials went unheeded.
The data showed children vaccinated between the ages of two and five were seven times more likely than unvaccinated children to be hospitalised for dengue.
By not screening all trial participants for prior exposure to dengue fever, Sanofi Pasteur saw results which showed older children had a reduction of hospital admissions due to severe dengue fever of 93 percent. For younger children the hospitalisation rate increased.
They put this down to age, thinking the vaccine didn’t work for younger children and recommended the vaccine for those aged nine and over.
This was incorrect. Older children were more likely to have been exposed to dengue than younger children.
Giving the vaccine to a nine-year-old who hadn’t had dengue meant there was a chance they might skip the unpleasant but less deadly first infection and get the second, life-threatening infection.
When the programme went ahead without screening, vaccinated children started dying from severe dengue.
The programme was halted and the vaccine-maker did an about-face. Dengvaxia is now recommended only for people who have had dengue previously.
Results from a five-year period show for those who have had dengue and been vaccinated, the risk of severe dengue is one in 1000.
Without vaccination, 1.7 in every 1000 people would get severe dengue.
For people who haven’t had dengue previously, vaccination put four in every 1000 people at risk of getting severe dengue.
An ethical decision
University of Auckland's Dr Nikki Turner is the director of the Immunisation Advisory Centre. She’s also a member of the World Health Organisation's Strategic Advisory Group of Experts which made recommendations regarding Dengvaxia.
She said the group suggested the vaccine only get rolled out in areas where there was already a high rate of dengue.
“The Philippines chose to roll it out in parts of the Philippines in areas where there probably wasn’t that very high endemicity. So probably a higher percentage who hadn’t already been exposed to dengue.”
Turner said at a community-wide level the vaccine shows benefits, but the ethical decision is whether community benefits should be pursued when it can put individuals at high risk.
The current WHO recommendation is for screening.
Sadly, there’s no cheap, effective screening method currently available. This means the vaccine will likely not be used in mass vaccination programmes in countries who most need it.
In some ways this makes the Filipino roll-out of the dengue vaccine a triple tragedy. Children died, a vaccine which works when targeted to the right people isn’t reaching those who need it most, and thirdly, there’s measles.
New Zealand eliminated measles in 2012. Since then, every outbreak of measles in New Zealand has been imported from other countries.
So far this year 407 measles cases have been confirmed in New Zealand and 161 people hospitalised. As of the end of June, 54 cases of measles had been linked to cases from the Philippines.
If the cases continue to spread for more than a year New Zealand will lose its status of having eliminated measles.