Exam 3 (The Evolution of Virulence)

Infection virulence

the severity of disease caused by an infection; a spectrum term; influenced by susceptibility of the host and inherent virulence of the pathogen

Previous conventional wisdom of pathogens' existence

the harmful pathogens we see today simply haven't had enough time to adapt to their host

Previous conventional wisdom supporting example

Myxoma virus was intentionally introduced to rabbit populations in Australia for population control, 99% infection fatality ratio (IFR), transmitted by mosquitos, fleas, and skin lesions, but sharp drop in IFR after introduction (99% IFR to 30% IFR in only two years, due to evolutionary (genetic) changes in inherent virulence of pathogen, not acquired immunity of the rabbits)

Problems with conventional wisdom

1. In the classic Myxoma example, the circulating strain remained highly virulent (dropped to 30% IFR but remained there)

2. Many pathogens have circulated and evolved in humans for centuries to millennia but remain harmful; P. falciparum (malaria), Mycobacterium tuberculosis, Variola major and minor viruses (smallpox).

3. Many examples of pathogens evolving to be more virulent

Virulence Tradeoff

Evolution can favor virulence if the increase to transmission (R0) from producing many copies of itself outweighs the risk of reducing transmission from increased disease severity

Later evidence from Myxoma virus

The optimal level of virulence was favored by evolution; Initial strains (99% mortality) killed too quickly and were never transmitted to next rabbit, very mild strains weren't contagious enough, intermediate strains (30% mortality) had highest transmission success (high enough density to transmit but didn't kill host too quickly)

Virulence Tradeoff example: Plasmodium falciparum

P. falciparum expresses a specific surface protein (virulence factor) that causes infected RBCs to stick to uninfected red blood cells (RBCs), creating a cluster of cells, enabling P. falciparum to quickly infect new RBCs, but those same virulent variants were more likely to infect mosquitoes during feeding; because of this, evolution has favored relatively high virulence (1-3% IFR)

Vector-borne vs non vector-borne pathogens

vector-borne more virulent (does not rely on healthy, living host for transmission); but some non vector-borne still highly virulent--can remain infectious in environment for long periods of time, not depending on healthy mobile host (e.g., smallpox, mycobacterium TB, etc.)

Highly Pathogenic Avian Influenza Virus (HPAIV)

doesn't spread in nature, in instances where it has infected wild birds, the source is always a domestic population; alternatively, genetic evidence shows that Low-PAIV enters domestic high-density populations, and then evolves into HPAIV (the close, unavoidable contact of birds in these settings selects for harmful variants)