Establishment+Virulence

=Establishment and Virulence=

Blumenthal 25 Aug 2008, 11-12 PM

=Objectives (2007)=

The interaction between infectious agents, host defenses, and health interventions is a co-evolution arms race where one agent develops a strategy, and the other agent develops counter-strategies. For example, the host response to a pathogen may to be sequester iron to prevent microbial growth; however, the pathogen may develop a mechanism to steal iron. Another example may be the development of antibiotics and the subsequent development of antibiotic-resistant strains of pathogens. Host response, infectious agents, and treatments are never static, but dynamically changing all the time, and have been doing so for a long time.
 * 1. Recognize that host response, infectious agent, and treatment all respond to one another dynamically.**

Host damage and disease symptoms are often thought to be caused by infectious agents; however, the host immune response can cause damage too. Damage in hosts that mount a weak immune response is usually pathogen-related; damage in hosts that mount a very strong immune response is usually host-mediated. Disease is a complex outcome that can arise because of of pathogen-mediated damage, host-mediated damage, or both.
 * 2. Recognize that host response and infectious agent can act together in generating disease symptoms.**

One theory as to why genetic disease persist in the human population and aren't selected out eons ago is that the diseased alleles provide some sort of antimicrobial activity against pathogens. The premise is that the selective pressure exerted by microbial pathogens is so strong that it has favored the spread of infection-resistance genes, even when those genes are associated with genetic disease. This is most evident in alleles that provide a heterozygous advantage, where a heterozygous individual can carry the protection of the resistance gene without the full burden of genetic disease. Evidence for this theory is very strong for some diseases, but mixed in others.
 * 3. Explain how some common genetic diseases are associated with resistance to microbial pathogens.**

A highly successful pathogen can have relatively low virulence because it can use a relatively asymptomatic host as a modality for transmitting and spreading itself. For example, tuberculosis infects about 30% of exposed individuals, of which only 5% may develop acute symptoms. The remaining 95% can remain latent carriers that can spread the infection to other individuals, often without the infected hosts knowing that they have been infected.
 * 4. Recognize that successful pathogens can have relatively low virulence.**

Changes in virulence are related to the life history of the infectious agent and its mode of transmission. Infections requiring direct contact usually selects for lower virulence, allowing the host to remain mobile and interact with others. Infections that use intermediaries to spread can select for higher virulence, because the infectious agent can spread even from a totally incapacitated host -- in this case, rapid production of a high number of infectious agents improves spread. This trade off model for the evolution of virulence has mixed evidence and relies on the assumption that the parasite-induced host mortality is costly for the parasite, and transmission is inextricably linked to virulence. However, virulence is not always a simple function of parasite reproduction, and has many causes, including host immune response.
 * 5. Explain how the transmission mechanism of an infectious agent may affect its extent of virulence (“trade off” model).**

(1) The organism is routinely found in the lesions of the disease. (2) The organism can be isolated in pure culture on laboratory media. (3) Inoculating experimental animals with the isolated organism produces disease. (4) The organism can be recovered from the lesions of the inoculated experimental animals.
 * 6. List the “gold” standards of proof for causal relationships (Koch’s postulates) between:**
 * a. a microbe and a disease.**

(1) The gene/product is routinely found in virulent isolates of the organism and mutants lacking the gene/product have reduced virulence. (2) The gene can be cloned and the purified gene product has the expected activity. (3) Putting the cloned gene into a mutant lacking that gene restores virulence. Alternatively, putting the cloned gene into a nonvirulent species gives the relevant properties. (4) The isolate with restored virulence can be recovered from infected animals/tissue cultures and contains the cloned gene.
 * b. a microbial product and virulence.**

(1) In some disease, the organism is gone by the time symptoms appear. (2) Some organisms have never been cultured on lab media or on cell lines while others rapidly lose virulence factors when cultured on lab media. (3) Some organisms only cause disease in humans. Relman's Alternatives are generally used in these cases.
 * 7. Describe situations under which Koch’s postulates cannot be used, and the approach used in such cases.**

Correlation does not prove causation. The size and damage of a fire can be correlated with the number of fire trucks arriving at the scene, but the number of fire trucks arriving does not cause the size or damage of the fire.
 * 8. Recognize that correlation is an important first step in proving causality, but it is only a first step.**