February 20, 2018

#DengGate: Sanofi, DoH turned Pinoy kids into guinea pigs? No, a lot worse than that

The Department of Health and Sanofi's collective strategy in three words: "INJECT AND FORGET".

NOTES: 

  • A Table of References is included at the end of this article.
  • I'll just proofread a little later. I'm already exhausted.

In November 2017, Sanofi Pasteur in a press release admitted that its anti-dengue drug Dengvaxia (CYD-TDV) may enhance dengue symptoms for seronegative recipients, or those who have never had dengue prior to vaccination [1]. Two weeks later, the World Health Organization (WHO) seconded [2] Sanofi’s new contraindication as it advised against vaccinating seronegative individuals with the said drug.

Sanofi Dengvaxia’s flaw is in its ability to serve as a first-time infection for seronegative recipients, so that they immediately develop severe dengue right after their first real-life infection, as opposed to just mild or even asymptomatic dengue fever for seronegatives who’ve never received the vaccine[3].

This phenomenon is called Antibody-Dependent Enhancement (ADE). Seronegative individuals infected for the first time with dengue develop lifelong immunity against the dengue strain that infected them. Should they be subsequently infected with a different strain, however, severe dengue hemorrhagic fever or dengue shock syndrome occurs [4].
The confirmation of ADE in Dengvaxia Recipients would not have been much of an issue if not for the fact that Sanofi willfully neglected to conduct pertinent studies about this potential issue prior to launching the Aquino-era anti-dengue mass vaccination program in April 2016.
The Basic WHO Guidelines

A report delivered by Peter Smith of London School of Hygiene & Tropical Medicine[5] during the April 2016 WHO-SAGE meeting indicated that seronegative children 9 years and up are at risk of ADE. The 17 March 2016 WHO-SAGE background paper [6] reflects the results Smith’s report as it, and so does a subsequent April 2016 WHO-SAGE paper [7].

The recommendations are as follows:
  • If 90% or more of a target population is seropositive, mass vaccination at 9 years of age offers optimal impact.
  • If over 50% but below 90% of a target population is seropositive, mass vaccination at 11 to 14 years of age is preferable.
  • If less than 50% of a target population is seropositive, mass vaccination is not recommended.
Using these WHO guidelines, the Philippine Department of Health (DOH), headed by Sec. Janette Garin, launched a mass vaccination program in April 2016 that targeted 1,000,000 4th graders in Luzon, most of whom are 9 years old. Almost half of this number were vaccinated before Garin left office in June 2016.

Per WHO guidelines, the decision to mass vaccinate 9-year-olds could only be justified if 90% of them are seropositive. And this is exactly what Garin claimed when she, in defense of the program, said[8], “the DOH officials will be vindicated because we did something that will save 90 percent of Filipino children”.

Garin bastardizes WHO Guidelines

Garin based her claim on the Alera Paper[9], a survey of dengue seroprevalence published February 2016, about two months before she mass-vaccinated the kids. A closer look at the paper, however, shows that either Garin intentionally misrepresented the paper, or she’s just plain stupid, for the following reasons:

First, all the 1,000 survey respondents come from the Punta Princesa, a small village of 27,000 in Cebu City, so that the paper should apply to Punta Princesa alone. Even generalizing the findings to the entirety of Cebu City with a population of 923,000 [10] would still qualify as terrible mathematics due to selective sampling.

But Garin did even worse: she used the seroprevalence rate of a small village in Cebu as a basis of the seroprevalence rate of a target population in the island of Luzon. This goes totally against the WHO recommendation that decisions should be supported by geographically relevant seroprevalence studie s[11]. How in the world can a seroprevalence study in Cebu be applicable to Luzon?Second, Figure 2 of the Alera Paper (shown below) indicates only 80% seroprevalence among those within the 6-15 age bracket, with no specific information pertaining to 9-year-olds. Per WHO guidelines at the time, 80% seroprevalence implied that mass vaccinations are recommended only for those 11 years and up and not 9-year-olds.


In short, Garin had no basis for her claim that 9-year-old kids in Luzon are 90% seropositive. Garin should not have greenlighted the April 2016 mass vaccination program at all.

But the Bad Science doesn’t end there: aside from severe dengue, another side effect may also be multi-organ system failure. To make matters even worse, this multi-organ system failure may occur with or without a dengue infection.

Dengvaxia and Multi-Organ Failure

Tasked by the Justice Department with providing legal assistance to Dengvaxia victims, the Public Attorney’s Office has autopsied 22 bodies[12] as of 20 February 2018, with a lot more in line.

According to PAO Forensic Laboratory Dr. Erwin Erfe, these deaths seem to reveal a pattern: a vast majority of the autopsied remains show strong signs of Viscerotropic-Like Disease (VLD)[13], characterized by the swelling and/or bleeding of multiple internal organs, which may have led to organ failure and eventually, death.

Some experts may dismiss Erfe’s claims as wild. However, no less than Bruno Guy of Sanofi’s Research and Discovery Department[14] repeatedly admitted that VLD is a potential side effect of Dengvaxia. He admitted this in scientific papers he co-authored in 2010[15], 2014[16], 2015[17], and 2016[18].

Despite lacking further studies on the incidence rate of VLD among Dengvaxia recipients, the Department of Health, along with its enabler Sanofi, greenlighted the Dengvaxia Program involving one million kids. The bad science on DOH’s part is already a given, but adding the fact that Sanofi willfully sold DOH 1 million Dengvaxia regimens, despite the lack of data supporting such a massive requirement, suggests that Sanofi was complicit[19].

To make matters worse, many of these kids were never screened for pre-existing conditions that could have increased their risk for contracting not only VLD, but also severe dengue. Many of them even got vaccinated without consent from the kids’ parents[20].

Briefly Dissecting the Organ Failure Issue

There are two possibilities here: (1) VLD was due to the vaccine, or (2) VLD was due to some pre-existing condition. If the first is true, then we’re done. If the second was true, the absence of due diligence on the part of the DOH – in this case the sufficient pre-screening of vaccine recipients – puts the burden of evidence on DOH. That is, it may be presumed – at least in legal terms – that Dengvaxia caused VLD until the DOH or Sanofi proves otherwise.

For argument’s sake, however, let’s assume that a given casualty had a pre-existing condition that could have caused VLD. Would the victim remain alive if Dengvaxia wasn’t around? Again, the fact that DOH and Sanofi agreed to administer Dengvaxia without sufficient pre-screening smacks of willful negligence on their part.

Again, there was no study to confirm the incidence rates of VLD – of multi-organ failure – among Dengvaxia recipients. Instead of conducting one, DOH and Sanofi decided to proceed with injecting a million kids with the experimental drug.

There are at least 22 casualties right now, and the figure is a very modest estimate at that.

Whichever way it goes, the collective criminal negligence of Sanofi and the Department of Health resulted into innocent kids of trusting parents being hospitalized, possibly with some of them ending up dead.

Sanofi thinks Filipino lives are less valuable?

The first step towards confirming the VLD risk among Dengvaxia recipients should be an attempt at benchmarking VLD incidence rates prior to the introduction of Dengvaxia.

After getting a suitable benchmark, i.e. an area’s pre-Dengvaxia VLD incidence rate, it can then be compared to the ensuing post-Dengvaxia VLD incidence rate. That is, testing for statistical significance, the presence (or absence) of a considerable increase in VLD incidence rates after Dengvaxia’s introduction to a target population would confirm (or refute) the hypothesis that Dengvaxia may cause VLD.

Interestingly, Sanofi did sponsor a “Step One (VLD Benchmarking) Study”. With funding from Sanofi, RTI Health Solutions’ December 2017 paper entitled “Incidence Study of Viscerotropic-Like and Neurotropic-Like Disease in Three Dengue-Endemic Countries[21]”, did exactly that. That is, the study attempted to estimate the incidence rate of multi-organ dysfunction prior to Dengvaxia’s market release.

The 2017 Sanofi Paper’s cover page is shown below:

Sanofi then acknowledged the paper’s receipt in December 2017.

Given this paper, checking for significant increases in post-Dengvaxia VLD incidence rates would be relatively easy, as we now have a figure to compare to.

But….


No Philippines?

Unfortunately, the study DID NOT include the Philippines: it includes only Malaysia, Brazil, and Mexico. After, the paper itself admits that making direct comparison of results among the three countries is difficult, let alone comparing it to another country that wasn’t included in the study, such as the Philippines.

That is, should the Malaysian, the Brazilian, or the Mexican governments can more easily check for significant increases in VLD cases should they decide to mass vaccinate kids with Dengvaxia.
That way, should multiple multi-organ system failure cases after Dengvaxia vaccination be reported, the government can more easily check if Dengvaxia did cause increased VLD incidence, or whether the number of such new VLD cases are too small to justify widespread alarm.

BUT THAT CANNOT BE DONE IN THE PHILIPPINES BECAUSE THE PHILIPPINES IS NOT IN THAT SANOFI PAPER.

DOH and Sanofi is hiding something

ThinkingPinoy has discovered a DoH-led coverup of the Dengvaxia Scandal in as early as December 2017[22], but it appears that there’s more to in that just that.

Despite being the country with the greatest number of Dengvaxia recipients to date, Sanofi seems to have excluded the Philippines in the said VLD benchmarking effort. Why did Sanofi exclude the Philippines? Why did it choose Malaysia, Brazil, and Mexico, when the fact of the matter is that the Philippines is the single biggest Dengvaxia buyer?

Did Sanofi think that Filipino lives are worth less than that those of Malaysians, Brazilians, and Mexicans… or was Sanofi confident that Philippine regulators will greenlight Dengvaxia despite this glaring detail?

Well, based on the leaked DOH emails later confirmed to be authentic per the early February Senate Hearing on Dengvaxia, conflicted health officials were indeed overeager to launch Dengvaxia in Philippines.

For one, Health Undersecretary Kenneth Hartigan-Go was even volunteered to create new regulations[23] to ease Dengvaxia’s entry into the country. Hartigan-Go has been a Zuellig beneficiary for most of his professional life. Zuellig is Dengvaxia’s exclusive distributor in the Philippines.

But wait, there’s more.

Inject and Forget

A look at the fifth page of Sanofi’s Registration Application[24] submitted to the Philippine Food and Drug Administration shows that Sanofi never intended to include the Philippines in the said benchmarking paper, as it declared that the study to measure background incidence rates of viscerotropism was being conducted in the three countries mentioned, with zero indication that Sanofi intends to include the Philippines in it.

Despite this, Sanofi promised FDA that it will conduct a 5-year monitoring of adverse events of special interest (AESI), such as when a recipient gets sick shortly after vaccination. The said AESI monitoring supposedly commenced right after the government starts injecting Dengvaxia.

Sources from both DOH and FDA informed ThinkingPinoy that Sanofi has yet to submit preliminary results of AESI monitoring to the government.

While it can be argued that the final report won’t be there until five years after Dengvaxia’s launch, it must be noted that Sanofi promised in the same Registration Application to submit Period Benefit Risk Evaluation Reports (PBRER) every six months.

Unfortunately, almost 24 months have already elapsed since Dengvaxia’s Philippine Debut, yet not a single PBRER has been submitted to the DOH, suggesting either Sanofi is either willfully neglecting its statutory obligations… or that the initial three PBRER’s looks so bad, Sanofi doesn’t want to give the DOH a copy.

Suffice it to say, DOH and Sanofi rushed the procurement, approval, and administration of the highly experimental drug Dengvaxia with little to no care about the side effects that Dengvaxia may cause.

To put it simply, Filipinos were indeed treated as if their bodies and souls are worth less than Malaysia, Brazil, and Mexico.

Less than Guinea Pigs

ThinkingPinoy suddenly recalled Senator Dick Gordon’s accusation that Sanofi and DOH used Filipino kids as guinea pigs. Gordon's a little wrong: Guinea pigs are test subjects, but THERE ARE NO TESTS.

So… if the hundreds of thousands of 9-year-olds who received Dengvaxia weren’t treated as guinea pigs, how exactly were they treated?

By the looks of it, Sanofi and DOH saw the 4th graders as disposable money machines, nothing more and nothing less.

At least twenty-two of those money makers have died so far, and we’re far from the end of this healthcare disaster of intercontinental proportions.

How many more deaths are needed for Sanofi to honestly address the crisis? And more importantly, how many more are needed for DoH to realize that it must advocate not for Big Pharmaceutical Companies, but for the Filipino People?

The answers to these questions, I do not know. [ThinkingPinoy]

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REFERENCES:

[1] Sanofi. Sanofi updates information on dengue vaccine. Press Release. 29 November 2017.

[2] World Health Organization. WHO advises Dengvaxia be used only in people previously infected with dengue. Press Release. 13 December 2017.

[3] Nieto, R. Aquino’s Garin ignores WHO warnings, risks 700k Filipino kids’ lives. ThinkingPinoy. 03 December 2017.

[4] Guzman, M. et Al. “The Complexity of Antibody-Dependent Enhancement of Dengue Virus Infection”. Viruses. 08 December 2010.

[5] Smith, P. Dengue Vaccine (CYD-TDV “Dengvaxia®”) Clinical Trial Results. London School of Hygiene & Tropical Medicine. 14 April 2016.

[6] Strategic Advisory Group of Experts on Immunization. Background Paper on Dengue Vaccines. World Health Organization Weekly Epidemiological Record. 17 March 2016.

[7] Strategic Advisory Group of Experts on Immunization. Summary of the April 2016 meeting of the Strategic Advisory Group of Experts on immunization (SAGE). World Health Organization Weekly Epidemiological Record. 14 April 2016.

[8] Davila, K. 'My conscience is clear': Garin ready to face raps over Dengvaxia. ANC Headstart. 06 February 2018.

[9] Alera, M. et Al. Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines. PLOS Neglected Tropical Diseases. 04 February 2016.

[10] Philippine Statistics Authority. Population of Region VII - Central Visayas (Based on the 2015 Census of Population). 06 June 2016.

[11] See [6]

[12] Nieto, R. Dengvaxia Victim No. 22. ThinkingPinoy. 16 February 2018.

[13] Gaston, C. Parents with children vaccinated with Dengvaxia troop to PAO building. GMA News. 06 February 2018.

[14] Sanofi. Bio: Bruno Guy. Retrieved 20 February 2018.

[15] Guy, B. et Al. Development of Sanofi Pasteur tetravalent dengue vaccine. Human Vaccines. Human Vaccines. September 2010.

[16] Guy, B. et Al. Live virus vaccines based on a yellow fever vaccine backbone: Standardized template with key considerations for a risk/benefit assessment. Vaccine. 27 October 2014.

[17] Guy, B. et Al. Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward. Vaccine. 10 December 2015.

[18] Guy, B. et Al. Vaccination Against Dengue: Challenges and Current Developments. Annual Review of Medicine. 10 October 2015.

[19] Nieto, R. DoH and Sanofi's Secret: Dengvaxia may cause multiple organ failure. ThinkingPinoy. 07 February 2017.

[20] Nieto, R. Kid in ICU for dengue only 3 months after 3rd dose -- Tarlac Mom. ThinkingPinoy. 05 December 2017.

[21] Johannes, C. et Al. Incidence of Viscerotropic-Like and Neurotropic-Like Disease in Three Dengue-Endemic Countries. RTIHS Health Solutions. 06 December 2017.

[22] Nieto, R. Botched Tarlac Dengvaxia case hints DoH-led coverup. ThinkingPinoy. 05 February 2018.

[23] Nieto, R. Leaked emails show PNoy, Garin, Hartigan-Go intentionally bent rules for Sanofi. ThinkingPinoy. 05 February 2018.

[24] Sanofi. Sanofi Pasteur Dengue Vaccine Initial Marketing Authorization Application. 22 December 2015.

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