This session begins our discussion of the pathogen. One unique feature of infectious diseases is the absolute requirement that a person can become infected only if that person is exposed to the pathogen. In contrast, chronic diseases such as cancers and diabetes have a multitude of causes, no one of which is absolutely required. For infectious diseases a necessary step is exposure to, and infection by, the pathogen. Although exposure to the pathogen is necessary for infection, a particular pathogen may cause no infection, asymptomatic or subclinical infection, or severe infection. The severity of infection may depend on the dose of the pathogen experienced by the host. In a previous session, we saw that Salmonella infection has a shorter incubation period when a person swallows a larger dose of the bacteria. Experiments done in the United States on prisoners in the 1970's showed that the probability of infection with cholera was higher for those who ingested a larger number of bacteria. Moreover, among those who did become infected, the ones who had swallowed more bacteria were more likely to have symptomatic disease, meaning diarrhea. For an infection like cholera, the presence of diarrhea is also associated with more shedding of bacteria and thus potentially higher transmission. In such a setting, higher dose can lead to higher infectiousness. HIV provides another example, this time for sexual transmission, where exposure dose affects the risk of becoming infected. This was shown in a study of HIV transmission within discordant couples in Uganda: couples with one HIV positive partner and one HIV negative one. The viral load, or concentration of the virus in the blood of the infected partner was measured, and the couple was followed to see if the other partner became infected. The risk to the HIV-negative partner varied significantly depending on the viral load of the positive partner. For patients with the lowest viral load, each act had only about a 1 in 10,000 chance of leading to transmission. For patients in the highest viral load category, that risk was 28 times higher, almost 1 in 400 acts. Not just the number of pathogens one is exposed to, but also the genetic properties of the pathogen can also determine severity of disease. Some strains of the bacterium E. coli live in every one of our large intestines without causing any disease. Yet particular strains of E. coli have genes encoding so called "virulence factors" proteins that make them more likely to cause disease by attaching to, invading, or poisoning our cells. Different virulence factors create a tendency to cause different types of disease: adhesins that promote attachment to the urinary tract can make urinary tract infection more likely, while toxins secreted by some strains can cause severe diarrhea and even systemic complications such as hemolytic uremic syndrome, which can be life threatening. The genetics of a pathogen can also affect the risk of disease upon exposure. Each bacterium of the species Streptococcus pneumoniae is classified as having one of over 90 different serotypes, variants that differ in the chemical composition of the sugar that coats the outside of the bacterium. This bacterium can live in the nasopharynx of healthy people without causing any symptoms. In some instances it can move from there into areas of the body that are normally sterile, such as the middle ear, the lungs, or the bloodstream, where it may cause disease. Some serotypes, such as serotype 1, cause frequent disease in some populations but much more rarely are found in asymptomatic carriage. Other serotypes, such as type 35B, are relatively common in asymptomatic carriage but only very rarely cause disease. This genetically determined property of individual bacterium, the serotype, has a major impact on the organism's invasiveness, or tendency to cause disease. It is thought that the differences are largely due to differences in the serotypes' abilities to evade host immune responses. In this session we have emphasized that for infectious diseases, exposure to the pathogen is absolutely necessary, but the dose of the pathogen one is exposed to, and the genetic properties of the pathogen, affect the risk of becoming infected and the severity of the resulting disease, if any.