DENGUE IN THE PHILIPPINES WAS CAUSED BY THE DENGUE VACCINE

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32525-5/fulltext

ORRESPONDENCE| VOLUME 394, ISSUE 10215, P2151-2152, DECEMBER 14, 2019

Vaccine-attributable severe dengue in the Philippines

Published:December 14, 2019DOI:https://doi.org/10.1016/S0140-6736(19)32525-5

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In 2016, WHO

recommended that the dengue vaccine CYD-TDV (Dengvaxia; Pasteur, Lyon, France), the first dengue vaccine, licensed for use in adults and children aged 9 years or older, be considered for use in highly endemic regions where at least 70% of 9-year-old children had previously been infected with dengue. The Philippines was the first country to introduce Dengvaxia on a large scale in selected highly endemic regions, targeting about 1 million children aged 9–10 years. In November, 2017, an excess risk of hospitalisation for dengue and severe dengue in vaccinees who had not had a previous dengue infection at the time of vaccination was reported,

on the basis of retrospective analyses

of data from the Dengvaxia phase 3 trials, using a novel non-structural protein 1 (NS1) based antibody assay. Following a reanalysis of these data,

the Philippine Dengvaxia programme was suspended. However, by the time the programme had been suspended, more than 830 000 children had received at least one of the three recommended Dengvaxia doses. The news about the safety concerns in dengue-naive vaccinees led to major public outcry, with loss in vaccine confidence that extended to routine childhood vaccines.

⁴

Parents whose children had received Dengvaxia were understandably alarmed by the reported adverse effect of the vaccine, especially because most parents will not have known whether their child had been infected by the dengue virus previously, and any cases of severe dengue in vaccinees might have been attributed to the disease-enhancing properties of the vaccine in seronegative children. Similarly, clinicians looking after vaccinated children admitted with severe dengue were also tempted to attribute every episode to vaccine-enhanced disease. However, in reality a minority of cases are likely to be attributed to vaccine-enhanced disease.

No vaccine is 100% efficacious and cases of breakthrough disease arise through vaccine failure. For the first licensed dengue vaccine, the issues of efficacy and safety are complex because both are driven by serostatus. Serostatus refers to whether a person has had a previous dengue infection; a seropositive person will have had at least one dengue infection in the past, whereas a seronegative person is dengue-naive. The efficacy of Dengvaxia against severe dengue in seropositive vaccinees in the phase 3 trials was 84% (95% CI 63–93).

Most vaccinees in the Philippine programme, possibly around 85%, were likely seropositive.

⁵

Hence, we would expect to see breakthrough disease in seropositive vaccinees when exposed to natural infection, especially in light of the current outbreak of dengue in the Philippines. Cases of severe dengue would be a mixture of breakthrough cases and of enhanced disease in seronegative children.

⁶

The risks associated with Dengvaxia must be put into perspective. First, many cases of hospitalisation and severe dengue following vaccination are likely to be attributable to vaccine breakthrough cases in seropositive vaccinees because a high proportion of vaccinees are dengue seropositive, in whom the vaccine protects but does not give total protection. Second, in all children vaccinated, the overall incidence of hospitalised dengue is likely to be substantially lower in the 5 years following vaccination than would have been the case had no one been vaccinated.

⁶

On a population level, in highly endemic regions, like the selected regions of the Philippines, the number of dengue cases averted by Dengvaxia is likely to substantially outweigh the number of vaccine-induced cases, and vaccination with Dengvaxia has an overall net benefit to the population.

⁷

Vaccinating only those testing seropositive would be the preferred strategy for future use of the vaccine, but this depends on the development of sensitive and specific rapid point-of-care tests to identify this group.

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Figure thumbnail fx1 — View Large Image
Copyright © 2019 Noel Celis/Contributor/Getty Images

AW-S serves as a consultant to WHO. PGS reports personal fees from Sanofi Pasteur and Takeda. SF and PGS were members of the WHO SAGE Working Group on dengue vaccines. The views expressed in this Correspondence are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the agencies or organisations with which the authors are affiliated.

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Published: 14 December 2019

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DOI: https://doi.org/10.1016/S0140-6736(19)32525-5

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THE "ERROR": THREATENING SANOFI WITH PROSECUTION WITHOUT PROSECUTION, OTHERWISE THE COMPLICITY OF PHILIPPINES GOVERNMENT AND MEDICAL ESTABLISHMENT WOULD HAVE EMERGED - TIME FOR TAKING NOT JUST THE PHILIPPINES GOVERNMENT BUT ALSO THE PHILIPPINES PEOPLE BY THEIR BALLS

Philippines to charge officials of Sanofi, government over dengue vaccine

By Karen Lema, Matthias Blamont

MANILA/PARIS (Reuters) - The Philippine Department of Justice on Friday said it had found probable cause to indict officials from French drugmaker Sanofi and former and current Philippine health officials over 10 deaths it said were linked to use of a dengue vaccine.

The logo of Sanofi is pictured during the Viva Tech start-up and technology summit in Paris, France, May 25, 2018. REUTERS/Charles Platiau

It recommended charges be filed in court for multiple counts of reckless imprudence resulting in homicide, due to what it said were procedural lapses and irregularities in implementing a Philippine dengue immunization program using Sanofi’s Dengvaxia.

The prosecutors said six Sanofi officials, mostly country representatives of the firm, and 14 current and former Philippine health officials should be charged, including former Health Minister Janette Garin.

Sanofi has repeatedly said Dengvaxia is safe and effective and, on Friday, rejected the justice department’s recommendations.

“We strongly disagree with the findings made against Sanofi and some of its employees and we will vigorously defend them,” a spokesman said in an emailed statement, adding it was not appropriate to comment further as proceedings were ongoing.

Dengue is a mosquito-borne tropical disease that kills about 20,000 people a year and infects hundreds of millions.

Approved in late 2015 as the world’s first vaccine to treat the condition, Dengvaxia has rapidly become Sanofi’s most problematic program to date.

The company acknowledged two years ago its use could, in some cases, increase the risk of severe dengue in people who had not been previously exposed to the disease, limiting access to vaccine after deaths of children were reported in the Philippines.

“INEXCUSABLE”

The World Health Organization (WHO) advises the vaccine should only be used after testing individuals to assess whether they have ever been exposed to the disease.

Despite concerns around its use, the European Medicines Agency has approved Dengvaxia and the U.S. Food and Drug Administration has granted priority review with a decision expected in May.

However, the Philippines has permanently halted the sale, distribution and marketing of Dengvaxia, which was initially seen as a potential $1-billion-a-year-plus product.

Net sales of the vaccine stood at 3 million euros ($3.42 million) in 2017. Sanofi did not provide a figure for 2018.

The Philippines justice department statement did not say Dengvaxia had caused the deaths, but it quoted excerpts from a resolution by prosecutors that said the 20 individuals had exhibited an “inexcusable lack of precaution and foresight”.

It said the government registered and bought Dengvaxia for its immunization program with undue haste.

The Philippines started rolling out the vaccination program in 2016 in a bid to dramatically reduce as many as 200,000 domestic dengue cases a year. It spent 3.5 billion pesos ($67.7 million) on the program during which it immunized 800,000 children with Dengvaxia.

But that drive came under heavy scrutiny the following year, with critics and some lawmakers voicing concerns about the speed at which the government sought to register, procure and distribute Dengvaxia among schools and clinics.

SAFETY CONCERNS

A criminal investigation and two congressional inquiries have already taken place and the Philippines last month revoked the product’s license after concluding Sanofi had failed to meet directives issued by regulators.

Justice undersecretary Markk Perete told Reuters that there were 35 deaths under investigation, 10 of which were the basis for the charges announced on Friday.

Perete said the 20 individuals faced up to six years in prison for each of the alleged offences. All but two officials could be charged with eight counts of reckless imprudence resulting in homicide, he said.

A Sanofi source with knowledge of the situation said the Philippine prosecutors’ criticism was vague and they were mostly interested in the processes by which the product was approved.

Separately to the case announced on Friday, the Philippines has tasked a panel of medical experts to investigate the deaths of scores of children who received the vaccine, to establish whether or not Dengvaxia was a contributing factor.

The panel’s head, Juliet Aguilar, told Reuters that medical records of 119 victims were being looked into as of Friday.

The 20 officials named by the justice department on Friday had shown neglect in having “totally disregarded the identified risks and adverse effects of the vaccine”, the resolution said.

The department said those risks “materialized with the death of the victims”.

It also said Sanofi had failed to closely monitor the recipients of Dengvaxia, nor did it extend medical assistance to victims or their families, even after reports of “serious adverse reactions” surfaced.

Additional reporting by Neil Jerome Morales in Manila; Editing by Nick Macfie and Kirsten Donovan

Our Standards: The Thomson Reuters Trust Principles.

WHEN SANOFI WAS CAUGHT IN FRAUDING THE PHILIPPINES GOVERNMENT, THE OFFICIALS INVOLVED IN THE PROCUREMENT WENT INTO HIDING, TOGETHER WITH SANOFI

Dengue vaccine not deadly: Sanofi, Philippines

Su-Peing Ng, global medical head for Sanofi Pasteur, addresses a press conference in Manila on the dengue vaccination programme (AFP Photo/TED ALJIBE) (AFP)

December 4, 2017

Manila (AFP) - A world-first dengue vaccination programme in the Philippines that was suspended over safety concerns will not cause anyone who was immunised to die, drug manufacturer Sanofi and local authorities said on Monday.

The Philippines on Friday suspended the programme, after more than 733,000 people had been immunised, in response to a statement from Sanofi that its vaccine could cause "more cases of severe disease" for people who had not previously had the mosquito-borne ailment.

After news outlets and some politicians in the Philippines expressed concern about the welfare of those immunised, the French pharaceutical giant held a press conference in Manila to state the potential cases of "severe dengue" would not be fatal.

"What is this severe (dengue)? When people think of 'severe', this already includes dengue shock that could lead to death, but no," Sanofi Pasteur regional head for dengue Joselito Sta. Ana told reporters.

Sta. Ana said Sanofi's definition of "severe dengue" merely referred to symptoms including two days of fever, a lower platelet count and bruising.

Philippine presidential spokesman Harry Roque also sought to allay fears, stating there was "no danger" with the Dengvaxia vaccine.

"The worst that can happen is for those who have not had dengue before -- which is one out of 10 (Filipinos) -- they may get infected with dengue but falling under our previous classification of 'mild', having fever and bruises," Roque said.

Nevertheless, the justice department announced Monday that the National Bureau of Investigation would investigate the vaccination programme "over the alleged danger to public health". It warned in a statement that charges could follow.

The previous administration of president Benigno Aquino launched the vaccination programme last year, making the Philippines the first nation to use Dengvaxia on a mass scale.

Although the Philippine programme has been suspended, Dengvaxia remains available on an individual basis in consultation with doctors, the health department said.

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