Vaccines, Public Policy, and the Monetary Value of a Human Life.

My first encounter with meningococcus made a deep impression on me.

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By the time EMS got him to the Hood River ER, he was nearly dead. But they pumped him full of antibiotics, vasopressors, and normal saline, and evacuated him via life flight helicopter to OHSU, where he became my patient for the next month in the ICU. Categorically, I have never since seen an infectious disease that progressed with such catastrophic rapidity as this. By the time he arrived at our unit, the scattered skin lesions that alerted his mother had merged into confluent black patches that we watched blossom and spread at the rate of centimeters per hour. What had been a dusky tone at the tips of his fingers and toes on arrival was now jet black by midnight, and that sinister dusky blue tone had crept up to his wrists and knees. Cultures drawn from his blood and spinal fluid confirmed what we already suspected: The pathogen was Neisseria meningitidis.

Over the ensuing weeks, we did everything we had been taught in the management of severe sepsis, plus any number of innovations motivated by sheer desperation. And he survived. He was, after all, young and healthy, and his youth more than anything allowed him to cling to life. But he left the ICU much diminished by his encounter with the meningococcus: permanently wedded to a dialysis machine, missing his nose, ears, and fingers, and without both legs below the knees. Like the proverbial Humpty Dumpty, the best medical science had to offer at the time was to try and pick up the pieces after the catastrophe, with no hope of making our patient whole again. But I became persuaded that prevention was the only real solution.

Fast forward to 2008. I was then an assistant professor of global health at the School of Public Health, when the opportunity arose to take a director position leading the clinical development of a meningococcal vaccine at Novartis Vaccines and Diagnostics (NVD). I took that job, a major factor in that decision being the memory of my patient. And for the next three years, working alongside about 600 colleagues at NVD, I lived and breathed meningococcal vaccines for the next three years in pursuit of a prevention.

Did we succeed? Officially, yes, but effectively, no.

While the vaccine worked, and was licensed and in is now available in much of the world, we failed to persuade key policy makers that the vaccine was worth endorsing as routine preventive care for infants, the age group most vulnerable to meningococcal disease.

But why?

Vaccines generally work in two ways, and ideally (but not necessarily) by both: indirect and direct protection. “Indirect protection” as analogous to cutting firewalls in a dry forest that suffers frequent lightning strikes and is prone to forest fires. Since we cannot know where lightning will hit, we try to build enough firewalls to prevent a conflagration stemming from lighting hitting anywhere in our forest. The key is to figure out how many firewalls you need and to be vigilant about maintaining them year after year. Vaccinating a high enough proportion of individuals in a population to create immunologic fire walls impedes person to person spread and make it impossible for the epidemic to propagate. When this critical threshold of protection has been reached, we have achieved “herd immunity.”

By contrast, “direct protection” is analogous to clearing the brush away from selected houses every few years or so, in the hopes that if a fire comes along, that structure may yet survive. This strategy does nothing to stop the spread of forest fires in general and does nothing to protect the neighbor’s house. Plus, one has to be vigilant about keeping the brush from re-accumulating each year.

The policy we had hoped to receive from ACIP was a so-called “general recommendation,” such that our vaccine would be added to the standard infant immunization schedule, would be given to all infants as part of routine well-child care, and would reach high enough population coverage to achieve herd immunity. But what ACIP granted instead was a “permissive recommendation” that the vaccine be administered only to certain high-risk infants, mainly consisting of children born with certain genetic or acquired immunodeficiency states (including HIV) that increased their personal risk of meningococcal disease. Even if all such children were identified, it would total only a few thousand children each year, well below the threshold required for herd immunity.

ACIP’s decision reflected a variety of factors, was well-reasoned, and, I will grudgingly admit, probably correct. Chief among these was that meningococcal disease is very rare, so preventing it by vaccinating all 4 million infants born each year would obviously be very expensive on a per-case prevented basis. In short, they felt that the problem was not sufficiently common to warrant a broad-based solution of that kind. Putting this into metaphorical terms, this meant that the ACIP endorsed the brush clearing strategy over building firewalls, and only for those few houses seen as most vulnerable to forest fires.

In ethical terms, ACIP’s decision represented some pretty hard calculus. It meant that we had decided to allow those meningococcal cases and deaths to occur, while knowing that we had the tools to prevent them. I can only imagine how the ACIP members (many of whom are pediatricians, and all of whom know personally what meningococcal disease can do) must have struggled with this particularly as their meetings and discussions were always attended by meningitis vaccine advocacy groups, comprised of meningococcal survivors or the families of those who had died, who advocated passionately and often tearfully at these meetings.

All of this affected me very personally, leaving me disappointed, frustrated, and indignant. I wanted to feel that I had, in some small way, contributed to eliminating a disease that was unambiguously horrendous. I wanted to be able to say “never again” to someone having to go through what my 19-year-old patient did. It begged the question that occupied the recesses of my mind for years after leaving Industry and returning to academic life: If preventing meningococcal disease was not deemed worthy of doing, what would be?

Several years later, the opportunity came to try and answer this question, or at least to work through some catharsis. Using an online database hosted by CDC, myself and several academic colleagues with expertise in vaccinology, plus a talented MPH student who was interested in vaccines, tabulated all of the causes of death in US infants over a five-year period to try and put some numerical context around meningococcal deaths and other vaccine preventable deaths relative to all infant deaths in this country. What we found was interesting, and in some cases quite surprising.

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In the US, it appears that we have reached a transition point. Collectively we have been quite successful at preventing preventable deaths. But that success means that further improvements will more ever more difficult to achieve, not to mention more costly. Simply put, the days when cheap vaccines could achieve major reductions in infant deaths are over. Appreciably reducing the total US infant deaths using new vaccines is now mathematically impossible. But if our goal is to prevent preventable deaths, then all of these vaccines become far more appealing. Which denominator should we choose?

Twenty years have passed since I cared for that young man. If he is still alive, that means that he has now spent the majority of his life living with the consequences of that fateful, unanticipated, and very unlikely encounter with meningococcus. We have since developed a vaccine to prevent it happening again. The question then becomes: How much should we be willing to pay to prevent disease? And how do we value a death averted versus a life saved? The impact of the meningococcal vaccine may be immeasurably small, but the impact on those individuals with this disease, not to mention their families and communities, is anything but insignificant.

Christopher Gill is an associate professor of global health.