The problem with complexity

The dangers of technological complexity were highlighted after authorities in the Philippines suspended the administration of the dengue fever vaccine Dengvaxia when manufacturer Sanofi announced that while it would help those who once had the disease it might produce an even more severe attack in those who were infected for the first time.  The company said:

Based on up to six years of clinical data, the new analysis ...  confirmed that Dengvaxia provides persistent protective benefit against dengue fever in those who had prior infection. For those not previously infected by dengue virus, however, the analysis found that in the longer term, more cases of severe disease could occur following  vaccination upon a subsequent dengue infection.

“These findings highlight the complex nature of dengue infection. We are working with health authorities to ensure that prescribers, vaccinators and patients are fully  informed of the new findings, with the goal of enhancing the impact of Dengvaxia in dengue- endemic countries.” said Dr. Su-Peing Ng, Global Medical Head, Sanofi Pasteur.

Unfortunately the warning came too late.  Health authorities had already vaccinated 733,000 children with Dengvaxia before the warning. Philippine authorities had eagerly jumped at a "landmark" program to become "the first country to start using it on a mass scale" after it had been clinically trialed in 10 countries -- 5 in Asia and 5 in Latin America -- with apparent success. Now all the chastened bureaucrats could belatedly do was glumly announce preparations for a "worst-case scenario" should a spike in the disease occur.

The bureaucrats had understandably relied on rational ignorance, in this case the prestige of the WHO and French pharmaceuticals, to reach a decision about the safety of a technology.  But what rational ignorance hides is complexity.  Behind the scenes there was dissent over the mechanism by which vaccine worked of which the bureaucrats were unaware.  Even as Dengvaxia passed its trials some researchers feared the vaccine could trigger antibodies in a "naïve subject" that would weaken them against a second exposure, a process called ADE. "Protective antibodies can turn double agent, teaming up with the dengue virus to make an infection more severe, even life-threatening." Those fears might have proved correct.

What the vaccine might actually have done was kick in the door for those who have never had dengue before.  "In an email correspondence, Sanofi Pasteur spokesperson Laurence Bollack held back from admitting the vaccine caused ADE. ... Halstead and Russell disagreed. Using Sanofi's phase 3 data, they published a study in Vaccine last February showing that during the 3 years following immunization among seronegative children, dengue hospitalization rate was significantly higher among vaccinees than controls. For children without prior dengue exposure, the vaccine acts as a priming dose of the virus." No one imagines Sanofi knew this would happen.  It was just one of those things humans cannot foresee.