The Dengvaxia affair

In 2016 the Philippines started a vaccination campaign against Dengue, a mosquito-borne tropical disease, infecting worldwide hundreds of millions people,  whose seriousness is however usually limited, “Dengue fever is a severe, flu-like illness that affects infants, young children and adults, but seldom causes death”. The Philippines’ immunization programme was based on Dengvaxia, a vaccine produced by Sanofi Pasteur, which was known to provide an effective prevention in subjects who had prior infection. Since early 2016, however, Scott Halstead, the leading scientist in dengue research, had denounced that Dengvaxia could cause a phenomenon that he first described in 1977  calling it ADE, or antibody-dependent enhancement.  ADE, which implies that antibodies increase viral infectivity and consequently severity of an infection, is not rare in lab cell cultures, but it has been rarely demonstrated in vivo, although it has been suspected in some cases. In March 2016, Halstead and Russel published a short paper whose conclusion read “hospitalized cases among vaccinated seropositives (…) were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were (…) at increased risk of developing hospitalized disease during a subsequent wild type DENV infection”.  Sanofi Pasteur contested this  conclusion, arguing that  it was not enough supported by data.  Halstead went on warning Sanofi and  the WHO to be cautious before launching any mass vaccination campaign. " We have a vaccine that enhances dengue"  he declared  in a 2016 interview “It's clear as the nose on my face: Vaccine recipients less than 5 years old had five to seven times more rates of hospitalizations for severe dengue virus than placebo controls”. In response, the World Health Organization convened a Strategic Advisory Group of Experts (SAGE) who reviewed the evidence. SAGE’s conclusions, published on July 2016, recommended that “countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease (…) seroprevalence, should be approximately 70% or greater in the age group targeted for vaccination in order to maximize public health impact and cost-effectiveness. Vaccination of populations with seroprevalence between 50% and 70% is acceptable (…) the vaccine is not recommended when seroprevalence is below 50%”.  These conclusions were puzzling  because they were based on the concept that an immunization campaign – addressing  a serious disease, however, rarely deadly – could be legitimate even if  public health authorities suspect that a percentage of vaccinated subjects not only will not benefit from vaccination, but they will be exposed to increased risks.  WHO position paper gave in fact the green light for the Philippines vaccination campaign. Now - on November 29, 2017 - Sanofi Pasteur released a new statement, admitting that-  after analysing data from a six-year study -  Halstead was not probably so wrong because  “the analysis found that in the longer term, more cases of severe disease could occur following vaccination”.  This is particularly worrisome in the case of children vaccination, given that a child is less likely to have had a previous dengue infection. A few days after Sanofi’s release, the Philippines department of health took the decision – soon corroborated by of the World Health Organization  - to suspend the Dengue vaccination programme. Probably a bit too late, however, given that some 830,000 children in the Philippines, and around 300,000 in Brazil, where an analogous programme was running, were already vaccinated. We don’t know how many of them were seronegative, and consequently it is  impossible to predict the impact that Dengvaxia could have on them.

From a risk communication perspective this story incites to make two points and a final reflection.

The first point concerns the “storyline”. Once again, the public is faced with a plot made of a honest scientist, whose alerts are overlooked by public authorities and institutions, and a villain played by pharma industry. Can it be possible that we are still repeating this plot for the umpteenth time? Why people don’t learn the lesson? How could one hope that public authorities, health institutions, the WHO, pharma industry, are trusted if they are so stupid to start an immunization campaign -  addressing a non-mortal disease (at least in most cases), and involving children - when there are concrete risks to be obliged to discontinue it very soon? Both Sanofi Pasteur and the WHO were indeed aware since July 2016 that Halstead was likely to be right, otherwise WHO Position Paper of July 2016 would not make any sense. Could they realistically imagine that political authorities could put up with an immunisation campaign threatening to increase risks in a category – be it large or small – to which each citizen could fear to belong, if she does not take a blood test?

The second point concerns “money”. It has been told again and again that pharma companies do not make money with vaccines,  this is one of the tritest arguments used to challenge conspiracy theory on vaccination. It is probably time to say that this argument is misleading. The global economy is hardly the traditional market economy, and money is not made – if not marginally – by selling items. In a financialized economy, one should  look at the financial market to understand what is going on. In the last five two years, Sanofi share increased its value from a lower bound at 67 Euro in 2016, to around 83 Euro in May 2017. After the Dengvaxia affair, Sanofi share is losing about 0,8 %.  Repeating the tale that industry does not gain money with vaccines is offensive to people’s intelligence, and once again it is a stupid move in communication terms.

The final reflection concerns anti-vaccination movements. In principle, the Dengvaxia affair could have been written by them, it seems the almost perfect case to be used to attack vaccines and vaccination, yet anti-vaccination activists are surprisingly absent, at least till today. Google trends shows that impressions concerning this affair are largely concentrated in the Philippines, and, much less, in a few other Asian countries and in Brazil. Industrialized countries, where anti vaccination movements are mostly active, don’t show to be interested in Dengvaxia. The U.S. as well as E.U. countries show a rate of impressions lower than 1% than the Philippines. Even France appears to be not interested, notwithstanding Sanofi is French and France is the country hosting the world largest group of people hesitant to vaccination. This is confirmed by  social conversation. The Dengvaxia affair is having a very low social penetration, geographically concentrated in the Philippines and a few other countries. Maybe this scenario will change in the next weeks, hopefully not, but for now it is difficult to escape the sensation that anti vaccination activists are hardly interested in people's health. This seems to confirm once again that anti vaccination is a symbolic war, which mostly concerns  fantasies on purity and impurity, collective dreams and, unfortunately, also nightmares, but has little to do with facts.