Also pain, nausea, vomiting, diarrhea, anxiety, fatigue, sneezing, inflammation, anaemia, morning sickness Do we do a disservice by blocking these defenses? Smoke-detector principle

(6) Host defenses Expel, destroy, or sequester the pathogen e.g. cough, sneeze, runny nose, vomiting, and diarrhea expel pathogens e.g. fever and inflammation expel and destroy foreign matter e.g. immune system recognizes and destroys e.g. some pathogens are sequestered

(11) Manipulation Pathogens often manipulate host adaptations for their own purposes e.g.intensification of coughing and sneezing e.g.cholera toxin interferes with reabsorbtion of liquid from the bowel e.g.rabies virus alters aggression e.g.lancet flukes in ants and sheep

The conventional wisdom In the 1980s, evolutionary biologists realized that if transmission and virulence were positively coupled, natural selection acting on individuals could favor the evolution and maintenance of some level of virulence It comes down to elucidating the relationship between the rate of parasite-mediated mortality and the rate of transmission. If the relationship is positive, some level of virulence may be favored In other words, if killing your host is correlated with higher transmission, natural selection may well favor virulence

R0: The basic reproductive rate If all parameters were independent, benign parasites would evolve Natural selection would favor highly transmissible, incurable commensals or symbionts On the other hand, if transmission and virulence were positively coupled, some level of virulence will be favored

Myxoma virus Pox virus introduced into Australia to control European rabbit populations Vectored by mosquitos and fleas, skin lesions Initially the virus was extremely virulent (99%) mortality A sharp drop in virulence was initially observed Positive coupling between transmission and virus-induced mortality

Myxoma virus Trade-off between virulence and transmission: highly virulent forms killed too quickly, reducing chance of being picked up by vector Viruses that were too attenuated (mild) had fewer lesions and lower viral load, again translating into less chance of being picked up by vector Happy medium selected for, rather than ever-more benign forms

Paul Ewald’s view All else being equal, vectored diseases ought to have a higher optimal virulence than directly-transmitted ones since immobilizing the host does not prevent (and may even enhance) transmission There does seem to be some support for the idea that insect-vectored diseases are more virulent

Paul Ewald’s view Diseases that spread by “cultural vectors” should also tend to high virulence. Cultural vectors are simply amalgams of behavior and environmental conditions that allow immobilized hosts to transmit infections Diarrheal pathogens, for example, can be passed through drinking-water systems. An immobilized victim can still infect lots of people if contaminated materials get into drinking water

Paul Ewald’s view Sexually transmitted diseases can be expected to modulate their virulence in relation to the frequency of sexual activity Consider a population of fairly monogamous couples, where, on average, EPCs take place once every three years How might this shape the natural history of the parasite? How well would a typical cold virus survive if it was being transmitted sexually? What might happen if sexual activity increases dramatically?