CLINICAL MATTERS

A clandestine US operation during the Covid-19 pandemic to discredit Chinese vaccines in the Philippines was confirmed by official communication between the two governments last June 25, 2024. This was according to a followup report by Reuters on the initial controversy, after it reviewed a document referencing information sent from the US Defense Department to the Philippine Department of Foreign Affairs and Department of National Defense.

In the original report, Reuters stated that the US Department of Defense admitted that it had questioned the safety of the Chinese vaccines through social media messaging with the aim of discrediting China’s vaccine diplomacy push. Anti-vaxxers and some political operators jumped on this campaign and amplified the misinformation, resulting in the decreased uptake of Chinese vaccines which, for months, was the only available vaccine for Covid-19 locally. This intentional tampering with vaccine confidence during a public health emergency is unconscionable, and likely cost thousands of Filipino lives.

While it won’t bring back the dead or repair the damage to our public health programs, an admission of guilt is the first step towards accountability. The program, which started during the Trump administration, continued into the early months of the Biden presidency but was subsequently banned in early 2021. One positive note in the document is that, aside from acknowledging its missteps, the US assured the Philippines that its military “has vastly improved oversight and accountability of information operations” since 2022. We hope that they remain true to their word, especially if there is a change in administration anew.

Out of all the countries in the world, the Philippines is particularly susceptible to vaccine misinformation following its disastrous experience with the Dengvaxia controversy in 2017. Up to that point, the Philippines was performing adequately in vaccine campaigns especially for children. This reached a zenith during the term of health secretary Dr. Juan Flavier, when national vaccination rates for common diseases like polio went as high as 98 percent thanks to a savvy public media campaign and partnership with civil society. Since then, vaccine coverage has gradually declined because of several factors, including increasing vaccine misinformation. One particularly damaging item was the publication of the now-discredited paper of Andrew Wakefield, which falsely linked autism to MMR (measles, mumps, and rubella) vaccines. While it has been shown that the data he gathered was fraudulent and manipulated, the damage to vaccines from that initial paper continues despite its retraction. Nevertheless, vaccine confidence in the Philippines remained as high as 93 percent in 2015 and vaccine coverage for common diseases such as measles remained above 70 percent in subsequent years as the government and public health workers tried their best to combat misinformation.

This all changed in 2016 when the Philippine government decided to launch a mass vaccination program using a newly approved dengue vaccine from Sanofi. Known as Dengvaxia, the vaccine was shown to decrease the risk of hospitalization due to severe dengue in children by more than 90 percent. In a country that sees over 200,000 cases of dengue each year, this sounded like a godsend.

Dengvaxia is not a traditional vaccine since it is not meant to prevent dengue infection. Instead, its major utility lies in decreasing the risk of severe dengue that usually occurs on the second dengue infection. There are four dengue serotypes, all of which are present in the Philippines. Infection with one serotype confers immunity to that serotype but not to the others, and so up to four lifetime infections are possible.

The first dengue infection is typically mild, along with the third and fourth infections. It is the second infection that is at highest risk for severe dengue, which manifests as uncontrolled bleeding and a dangerous drop in blood pressure. The increase in severe dengue risk with the second infection is thought to bedue to a phenomenon known as antibody-dependent enhancement. This was always seen as the biggest hurdle with the development any dengue vaccine - the inherent risk of inadvertently setting people up for a second dengue infection and its increased risk of severe disease.

Dengvaxia, which targets all four serotypes with varying degrees of efficacy, was meant to induce enough immunity to skip the risk of severe disease from a second natural dengue infection. If given to a population who have already had at least one natural dengue infection, then even if just one serotype induces immunity, the risk of severe dengue with a second natural dengue infection is mitigated. In the target population of the vaccine consisting of Filipino schoolchildren in Grade 4 or older, the dengue seropositivity from previous studies for at least one dengue infection was 87 percent. With strong evidence of protection in both seronegative and seropositive childrenand no clear evidence of harm among seronegative subjects after one year of follow-up in the clinical trials, the vaccine received approval without requiring a test for previous dengue infection.

In November 2017, more than a year into the mass vaccination program, Sanofi abruptly announced that new follow-up clinical trial data three years after vaccination showed that seronegative patients were no longer protected from severe dengue from a second natural infection and that Dengvaxia should not be used in this population. Moreover, there was a safety signal that indicated Dengvaxia may mimic a primary dengue infection in seronegative recipients and that a first natural infection in a seronegative vaccine recipient may act like the dreaded second infection. What it failed to clarify was that there were no attributable direct deaths due to Dengvaxia in the extended safety study, and the risk of severe disease in seronegative patients was no higher than that of a second natural infection. The vaccine continued to protect seropositive children from severe infection at a high rate. However, this was not properly communicated by Sanofi. An information vacuum and sensationalist reporting resulted in widespread panic when parents thought that their children might die from a potentially harmful vaccine.

Worse, the mass vaccination program was pushed prematurely, even before the WHO SAGE vaccine experts panel had made their recommendation, and so the government had no cover from a globally respected authority despite similar conclusions on the use of Dengvaxia. What followed was a political witch hunt with exaggerated and unsubstantiated claims of harm and the unwarranted indictments of innocent scientists who had nothing to do with the implementation of the program. It is true that the program was ill-conceived and those most responsible for the fiasco should be investigated, but the aftermath of the highly political persecution cratered the government’s vaccine programs. Vaccine coverage dangerously fell to 32 percent in 2018, predictably followed by deadly outbreaks of measles, chicken pox and polio. The dengue vaccine was banned despite its usefulness in children with known previous dengue infection, and only those who could afford to get it from other countries were able to benefit resulting in denial of an effective vaccine for the vast majority of seropositive children. Vaccine confidence had only begun to recover and was increasing in the months leading up to Covid-19 vaccination when the anti-Chinese vaccine propaganda hit.

The double whammy of the Dengvaxia controversy followed by the tampering of vaccine confidence against Chinese-made Covid-19 vaccines by an ally is a cautionary tale for anyone who wants to target vaccines for propaganda.Vaccines are a common good and should be off-limits from partisan politics. Otherwise, people will continue to needlessly die from vaccine-preventable diseases. The WHO has said as much, but there remains little accountability for the perpetrators who think little of the public health consequence of their actions. Stronger mechanisms for deterring these bad actors should be instituted, perhaps through legislation. In the meantime, the long-term solution for improving vaccine uptake and maximizing its public health benefits is properly educating our people not just against anti-vaccine rhetoric, but misinformation in general. Getting people to recognize fake news and learning to properly fact check may yet prove to be the best vaccine against anti-vaxxers, political or otherwise.