• acute, chronic, or recurrent infections may be involved in pathogenesis;

  • detection and culture of microbes in a variety of tissues may be difficult;

  • a number of factors, including environmental and genetic (host and microbe) factors, may be involved in the disease etiology; and

  • adequate methods may be lacking to identify novel or rare microorganisms.

The case studies presented in this chapter were chosen to provide insight into the range of research under way in the field. The chronic diseases covered represent the full spectrum of those that have been linked in some degree, from “clearly proven” to “suspected,” with infectious agents; they are caused by a variety of microorganisms; and their association with disease is supported variously by laboratory and epidemiological studies. Although other diseases and studies might have been included, some limits were imposed by time constraints and the availability of speakers.

Eduardo Franco reviewed the evidence that human papillomavirus (HPV) infection is a cause of cervical cancer. HPV infection precedes lesion development and appears to be necessary for cervical cancer to occur. This is one of the first examples in which an infectious agent has been identified to be necessary for cancer development. This causal relationship was revealed through the use of improved diagnostic tools that enabled more accurate identification of HPV. As the role of infection by certain types of HPV is better elucidated as the cause of cervical cancer, HPV testing in cervical cancer screening programs becomes an important part of a primary prevention strategy. Another component of this strategy may be increased use of a recently developed vaccine. Clinical studies indicate that the new HPV 16 VLP vaccine was 100 percent effective in preventing acquisition of persistent infection with HPV 16, and was 90 percent effective in preventing any incident HPV 16 infection, transient or persistent. Immunization against HPV may have greatest value in developing countries, where 80 percent of the global burden of cervical cancer occurs each year.

William Mason presented the association between hepatitis B virus infection and liver disease. Infection with the virus remains a worldwide problem, with more than 350 million people chronically infected. Although a vaccine has been available for the past 20 years, its high cost prevents universal vaccination. Current research, therefore, has focused on the development of effective therapies to cure those individuals chronically infected with the virus. Mason described the research presently being conducted in a number of animal model systems, including the woodchuck. Along with clinical studies, these models have been able to characterize infections and evaluate therapies, as well as better elucidate the difficulties of treating chronic infections with nucleoside analogs.

Michael Dunne described the relationship between infection and cardiovascular disease. There is a tight association between hypercholesterolemia and atherosclerosis; recent research has examined how inflammation within the plaque



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