1. Microbiology Koch and establishing causal links between microrganisms and disease.

2. History of linking organisms to disease Spontaneous generation – Originally it was thought that living organism might arise spontaneously from non-living matter. E.g. maggots forming from decaying meat. – This theory was discredited in experiments by Louis Pastuer.

3. Koch's Postulates Establishing a specific microbe as the cause of an infective disease: The Koch - Henle postulates: – Isolate the organism from every case – Propagate in pure culture in vitro – Reproduce disease by injecting the organism into a suitable recipient – Re-isolate the organism OK for major acute diseases like plague, small pox, typhoid.

4. Koch’s postulates may not apply to: Chronic or minor conditions Diseases with multiple causes When the pathogen can't be grown outside the host. – What organisms/infectous agent would this apply to? – Viruses – Prions

5. Pathogens cause infection and the establishment and outcome of infection is DOSE-RELATED: ID 50 (dose required to produce specified outcome in 50% of target population) is shifted : by increased virulence - or decreased host-resistance by decreased virulence - or increased host-resistance

6. In 1965 Austin Bradford Hill detailed criteria for assessing evidence of causation. None of these are evidence on their own, nor does their absence mean no causation. 1.Strength of correlation 2.Consistency of correlation. 3.Specificity: Causation is likely if a very specific population at a specific site and disease are linked with no other likely explanation e.g cholera and the Broadstreet pump. 4.Temporality: cause must precede effect.

7. Bradford criteria continued. 5.Biological gradient. – Often more exposure  greater effect – or less exposure –> greater e.g. mineral deficiency. – Sometimes just the presence of a factor can lead to disease. 6.Plausibility: A plausible mechanism. 7.Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations".[12] 8.Experiment: e.g. helicobacter pylori and stomach ulcers. 9.Analogy: The effect of similar factors may be considered.[12]