The Red Queen & Pneumococcus

What does Alice in Wonderland have to do with infectious disease? It's not the risk of contracting tularemia from the rabbit but it's a very important quote from the Red Queen. Her statement below to Alice provided the basis for an important hypothesis.

"Now, here, you see, it takes all the running you can do, to keep in the same place."

This statement about Wonderland was taken up evolutionary biologist Leigh Van Halen to formulate the "Red Queen Hypothesis". According to this hypothesis, species constantly evolve to adapt to a world teeming with other evolving species just to keep up and survive, let alone reproduce.

Important evidence that illustrates that the Red Queen Hypothesis is more than a hypothesis was recently published in Clinical Infectious Diseases and revolves around the introduction of pneumococcal vaccines for children. Pneumococcus causes many important infections including those of the ears and sinuses as well as pneumonia. In 2000, the 7-valent version of the pneumococcal (Streptococcus pneumoniae) conjugate vaccine was released and became a universal vaccine recommendation in the US. The 13-valent version supplanted the 7-valent formulation 10 years later (Prevnar). Shortly, thereafter infections from non-vaccine types began to become more frequent, i.e. serotype replacement occurred.

This phenomenon led to discussion focused on whether "Red Queen dynamics" were at play. A new study provides fascinating evidence of the Red Queen's insight at work. In this study, conducted in Utah, specimens from 641 children who were hospitalized with invasive pneumococcal disease (IPD) between 1997 and 2014 were studied.

The results are striking. Not surprisingly, once the vaccines were introduced serotype diversity increased as serotypes that were, pre-vaccine, outcompeted by other serotypes got a chance to cause infection as the big 7 (and the big 13) were rendered obsolete, alone in a world that was too vaccinated for them to flourish.

However, after a period of time, that diversity decreased as certain serotypes began to dominate others and became the main causes of IPD in the post-Prevnar era. What transpired was the establishment of a new evolutionary paradigm in response to changing world conditions that came in the form of potent vaccines that brought about a great culling of the pneumococcal species. Ever resilient, the pneumococcus quickly adapted, on the species levels, to this new normal.

Serotype replacement and Red Queen dynamics make vaccine development a very difficult proposition when there is a pathogen swarm waiting for their turn to wreak havoc.