Man contracts Plague - E.M. Ward
“A terrified man realizing he has just contracted the plague, surrounded by a group of people.”
By E.M. Ward, 1848.

Even the most lethal pathogens we know of don’t kill every single infected individual.1. Sometimes this is because the pathogen that infects the person is relatively weak. Sometimes it’s because the dose was low. And sometimes it’s because of something intrinsic to the patient. Some people are genetically resistant to HIV, because they have a mutated receptor, for example.

The opposite is also true. Sometimes people are more intrinsically susceptible to a pathogen. That became terribly clear during the AIDS epidemic, when quite innocuous agents started killing people, but there are probably many, many natural genetic variants that make us susceptible to some pathogens, just as some make us resistant. When epidemiologists look for “risk factors” that increase mortality or disease severity, this is part of the information they’re trying to tease out, in a rather crude way Sorting this out is part of the goal of the whole personalized medicine movement.

A fascinating example was just documented in MMWR. 2 Here a researcher was working with a genetically modified form of Black Plague bacteria (Yersinia pestis). This bacteria should have been harmless, because it had had its ability to grab iron from the host removed. 3. But the researcher became infected, and died, of an infection with the weakened strain.

We now learn that this was probably because the researcher had his own genetic mutation, hereditary hematochromatosis, which leads to increased levels of iron in the blood. He may4 have been uniquely susceptible to this strain,5 which could only infect people who conveniently made extra iron available to it:

Conceivably, hemochromatosis-induced iron overload might have a similar effect, enhancing the virulence of the infecting KIM D27 strain by compensating for its iron-acquisition defects6

Patients and pathogens are ecosystems; you need to understand both of them, or you don’t understand either.

  1. Even rabies virus, for example, which kills well over 99.999% of the people it infects, has had a half-dozen people survive. Myxomatosis virus let a few rabbits survive, and their progeny became relatively resistant; there are a handful of long-term survivors of HIV treatment; and when we get down to things like ebola and smallpox, 10-30% of infected people survive.[↩]
  2. Steve Silberman’s twitter account first drew my attention to the report.[↩]
  3. The quest for iron is a constant struggle for pathogenic (and other) bacteria, and they have evolved all kinds of mechanisms to seize it from the host, while at the same time animals have evolved more and more ways to keep iron away from invading bacteria.[↩]
  4. Note that this is speculation, not proven![↩]
  5. He also had diabetes, which may have made him more susceptible as well[↩]
  6. Centers for Disease Control and Prevention (CDC) (2011). Fatal Laboratory-Acquired Infection with an Attenuated Yersinia pestis Strain — Chicago, Illinois, 2009. MMWR. Morbidity and mortality weekly report, 60 (7), 201-5 PMID: 21346706[↩]