Infectious Disease and the Evolution of Virulence

Friday, June 11th, 2010

Diseases often become less virulent over time, but not always, Paul Ewald warns:

I would say that disease organisms are selected to compete with other disease organisms, that’s the bottom line. So if a disease organism is transmitted in a way that requires a healthy host, the best competitors will be those disease organisms that are mild enough to keep their host healthy to allow themselves to be transmitted.

By focusing on the mode of transmission for disease organisms we can gain a lot of insight into why some disease organisms are harmful and other disease organisms are mild. For example, a disease organism like the rhino virus that causes a common cold really does depend on fairly healthy people to be transmitted. So, not surprisingly, the rhino virus is one of the mildest viruses that we know about. In fact, nobody has ever been known to die from a rhino virus, and that’s not true for almost any other disease organism of humans for which we have ample information. Almost all the other disease organisms will cause enough damage so that some people might die, if they’re particularly vulnerable.

So, in the case of these mild organisms like the rhino virus, if a person happened to be housing a virulent mutant — these mutants are happening all the time, even in the mild organisms, mutations that might make it a little more harmful or a little less harmful — then you can ask the question, “Will that organism spread?”

The rhino virus is transmitted when people sneeze on other people, or maybe people sneeze in their hands and then they shake hands with other people, and those people then may touch their nose with those contaminated hands. Given that those are the main routes of transmission, it’s clear that if we had somebody who is infected with a particularly harmful variant of the rhino virus, a variant that was so harmful that the person would have to stay in bed, that even though that virus might be reproducing a lot more in the short run, in the long run that organism would lose out in competition. A person who is stuck at home in bed is not going around sneezing on their friends. An immobilized person is not going to be a major source of transmission for something like the rhino virus. That explains why the rhino virus has evolved to be fairly mild.

At the other extreme we’ve got disease organisms like the protozoan that causes malaria, which can be very harmful. What’s especially important in this context is that if the organism is harmful, so harmful that the person can’t move from bed, the organism, at least in many parts of the world, can [still] be readily transmitted to other people because a person who’s sick, maybe delirious in bed, is a sitting duck for mosquitoes.

Mosquitoes can bite that person more effectively than a person who’s feeling very healthy. So in this case we expect that natural selection would actually favor those variants of the malaria organism that exploit the host fairly ruthlessly. A sick person’s less likely to swat a mosquito. So, in that case we expect that these disease organisms that are transmitted by vectors, things like mosquitoes, should evolve to be among the most nasty of human pathogens and that’s, in fact, what we find.

We find that the vector-borne disease organisms, disease organisms transmitted by things like mosquitoes or sand flies, tend to be much more damaging than the disease organisms that are transmitted by people walking around sneezing or coughing on other people.

Diarrheal disease organisms can be transmitted in several different ways, and at least one of those ways also allows the organism to be transmitted from very sick people — that way is waterborne transmission. If a diarrheal organism is transmitted by water, then even a very sick person can serve as a source of infection for hundreds or even thousands of other people.

How does that work? If you were living in a place like Bangladesh or Ecuador, a place in which water supplies are not well protected, and you imagine somebody who is infected with a particularly ruthless strain of a diarrheal bacterium, that bacterium may be reproducing to a very high level and thereby causing the negative effects that we see in the sick person. In the process of reproducing, it’s gaining competitive advantages against other organisms by shedding tremendous numbers, maybe as many as a billion organisms from a single infected individual. And because that person’s not moving, those organisms are released into clothing or bed sheets, and they don’t stay there — somebody else will come along, take that contaminated material, maybe wash it in a canal. The canal water may drain into drinking water, or people may come to the contaminated water and gather that water and bring it back in the house. Maybe some system for distributing water will go to a contaminated source and distribute it to large numbers of people. That whole process is analogous to a swarm of mosquitoes moving from one infected individual to large numbers of susceptible individuals.

[We] refer to those cultural analogs of vectors like mosquitoes as “cultural vectors.” Waterborne transmission is part of a cultural vector that allows transmission to occur from very sick people, and, in so doing, would tip the competitive balance in favor of the more nasty exploitative variance in the disease organism population. As a consequence, if you have contaminated water allowing transmission of disease organisms, we expect those disease organisms to evolve to a particularly high level of harmfulness, and that’s exactly what we see.

If we look at the bacteria that cause diarrhea and we quantify how dependent they are on water as a mode of transmission, we find that the more waterborne bacteria are much more harmful. The worst of all of the diarrheal bacteria that we know of have been waterborne bacteria. [For] example, the bacteria that cause cholera are often waterborne. Bacteria that cause typhoid fever are often waterborne. Bacteria that cause the worst of the bloody diarrheas that we call dysentery are waterborne.

As a consequence, if waterborne transmission [is] very prevalent in an area, then we expect that the diarrheal disease organism should evolve to become more exploitative, using us more extensively as their food sources, and thereby become more harmful to us. If, instead, we clean up the water supplies, then we force the disease organisms to be transmitted only by routes that require healthy people. So what we should be finding if we clean up water supplies is that we drive the organisms to evolve toward mildness.

And that’s a very powerful idea, because when you clean up the water supply, the only routes that are left for transmission are routes that require people to be fairly healthy. So the new view would say if you clean up the water supply, we’ll get far more benefit than we’d expect, because in addition to reducing the frequency of infection, we’ll also mold the organisms — evolutionarily, we’ll force them to evolve to mildness.

The evidence from the literature indicates that, in many cases, we could have forced them to evolve to be so mild that almost nobody would be killed. In fact, most people wouldn’t even know they’re infected. They would have infections that are asymptomatic; that is, people are carrying around the organism and the organism’s generating some immunity in them and so it’s providing some protection against the other organisms, but the person who’s carrying the organism around doesn’t even know that he or she’s infected.

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