The Dengvaxia Controversy Explained

The Dengvaxia Controversy Explained

The Philippine government, under the administration of former president Benigno Aquino III, launched a dengue immunization program on 11 February 2016 using the Dengvaxia vaccine developed by France-based pharmaceutical company Sanofi.

Primarily spearheaded by the Department of Health or DOH under the leadership of former health secretary Janette Garin, the program aimed to vaccinate elementary students in public schools beginning in Metro Manila and continuing in Southern and Central Luzon, before launching it further across the country.

The school-based dengue immunization program specifically kicked off on 4 April 2016 with the purchase of Dengvaxia vaccines worth PhP 3.5 billion. The DOH noted that the recipients would be given three doses, which would be administered every six months.

In late November 2017, the DOH temporarily suspended the program after Sanofi issued a statement explaining that its vaccine could pose higher risks of developing a severe case of dengue, particularly to those individual recipients who do not have prior dengue infection.

Reports emerged that several children died from various complications allegedly attributed to Dengvaxia vaccine. The Senate of the Philippines launched an investigation to determine if there was an irregularity in the procurement of the vaccine. The Department of Justice also conducted an investigation to determine the liability of relevant parties.

Note that about 700,000 school-aged children received at least one dose of the vaccine since the program kicked off in April 2016.

Risk of Dengvaxia Vaccination: Findings from Sanofi

Sanofi spent 20 years in developing what has been deemed as the first-ever dengue vaccine in the world. It conducted clinical trials in five Asian countries, including the Philippines, and Latin American countries. The Philippines was the only country that completed all three phases of the clinical trial.

However, on 29 November 2017, the France-based pharmaceutical company issued a statement warning about the risks of its dengue vaccine. To be specific, based on six years of clinical data collected and analyzed to evaluate the safety and efficacy of Dengvaxia, Sanofi arrived at two conclusions.

The first is that the vaccine provides persistent and protective benefit against dengue infection, particularly to those who had prior dengue infection. However, the second conclusion is that Dengvaxia may result in a severe case of dengue infection in the long term in those who are seronegative at the time of first vaccination.

In the context of dengue infection, a seronegative individual is a person who has not yet contracted the disease. Hence, based on the clinical data, a considerable portion of seronegative individuals who received Dengvaxia immunization developed a severe case of dengue infection.

Nevertheless, the aforementioned results compelled Sanofi to issue a statement urging national governments, especially their respective regulatory agencies, to update the prescribing information about Dengvaxia and to determine first prior dengue infection in an individual before vaccinating.

Other Studies: Explaining the Dangers of Dengvaxia

Remember that the risk of Dengvaxia vaccination is only applicable to seronegative individuals or to those who have not yet contracted dengue infection prior to vaccination. This risk is related to a phenomenon in which individuals who got infected by the dengue virus for the second time usually suffer severe to fatal cases of dengue disease such as dengue hemorrhagic fever and dengue shock syndrome.

For decades, medical researchers tried to solve a dengue mystery: why the second infection is worse than the first. Dr. Scott Halstead has been insisting a biological mechanism called antibody-dependent enhancement or ADE as the reason behind the phenomenon. His more recent findings, as well as the findings by other researchers, have validated this theory.

The ADE theory explains that antibodies generated by a previous bout of dengue could actually put an individual at risk of more severe disease if he or she contracted the virus a second time.

As explained, initial infection from either one of the four serotypes of dengue virus would trigger a unique antibody response. During the second infection from another one of these serotypes, the antibodies from the first infection would still bind to the dengue virus but would not be strong enough to neutralize the viral infection.

The resulting antibody-virus complex permits easier entry to the host cells, thus enabling the dengue virus to replicate at even higher rates. In other words, the antibodies from the first infection seemingly team up with the dengue virus from the second infection and serve as a “trojan horse” that allows more virulent activity.

An increase in the dengue viral load triggers the immune system to produce large amounts of chemical messengers called cytokines that in turn, would result in a cytokine storm. These cytokines activate more immune cells, produce more cytokines, trigger inflammations, and increase the likelihood of blood vessels leaking, thus causing hemorrhage and shock.

Halstead noted that the same ADE mechanism transpires in seronegative recipients of Dengvaxia vaccine. Specifically, upon receiving the vaccine, these individuals develop antibodies against the dengue virus that, in turn, would later enhance the virulent activity of the virus upon contracting a dengue infection for the first time.

Simply put, for the seronegative individuals who have received the dengue vaccine, an initial infection form the dengue virus is identical to a second dengue infection. Note that other findings by Halstead noted that Dengvaxia sensitizes seronegative individuals to vaccine-enhanced disease regardless of age.

Alleged Deaths and Other Consequences in the Philippines

The House of Representatives published a draft report in November 2016 that included a report from the DOH. Accordingly, there were 30 serious cases from 18 March to 20 August 2016 involving vaccinated children that needed hospitalization. However, none of these cases were confirmed to be linked directly to the administration of Dengvaxia.

Since Sanofi issued the controversial statement and the DOH issued the temporary suspension of its dengue immunization program in November 2017, further reports have surfaced claiming that there have been deaths associated with Dengvaxia immunization.

The Public Attorney’s Office or PAO headed by Persida Acosta spearheaded the collection and dissemination of fatalities allegedly due to the vaccine. Note that the office conducted its own autopsies of bodies of children who allegedly died due to the vaccine as part of its effort to file cases against relevant individuals.

Results of the investigation conducted by the University of the Philippines-Philippine General Hospital or UP-PGH Dengue Investigative Task Force revealed that three out of the 14 kids died of dengue despite receiving Dengvaxia vaccine. However, although the report noted that these deaths might have been due to vaccine failure, further validations are needed.

A group of doctors called Doctors for Truth and Welfare led by former health secretary Esperanza Cabral criticized PAO for spreading unproven claims, as well as for conducting autopsies on its own accord.

Nevertheless, no deaths due to Dengvaxia have been scientifically proven. However, the controversy surrounding this vaccine and the dengue immunization program has created a public scare that in turn, purportedly resulted in a measles outbreak in 2019. Note that the Dengvaxia debacle remains one of the top controversies associated with the administration of former President Aquino.

FURTHER READINGS AND REFERENCES

  • Cepada, M. 2 February 2018. “3 Out of 14 Kids Died of Dengue After Dengvaxia Shot – UP-PGH Panel.” Rappler. Available online
  • Halstead, S. B. 2017. “Dengvaxia Sensitizes Seronegatives to Vaccine Enhanced Disease Regardless of Age.” Vaccine. 35(47): 6355-6358. DOI: 10.1016/j.vaccine.2017.09.089
  • Katzelnick, L. C., Gresh, L., Halloran, M. E., Mercado, J. C., Kuan, G., Gordon, A., Balmaseda, A., and Harris, E. 2017. “Antibody-Dependent Enhancement of Severe Dengue in Humans.” Science. 358(6365): 929-932. DOI: 10.1126/science.aan6836
  • Sanofi Pasteur. 29 November 2017. “Sanofi Updates Information on Dengue Vaccine.” Sanofi Pasteur. Available online
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