Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 1) Harrison's Internal Medicine > Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions Host–Pathogen Interactions: Introduction Despite decades of dramatic progress in their treatment and prevention, infectious diseases remain a major cause of death and debility and are responsible for worsening the living conditions of many millions of people around the world. Infections frequently challenge the physician's diagnostic skill and must be considered in the differential diagnoses of syndromes affecting every organ system. Changing Epidemiology of Infectious Diseases With the advent of antimicrobial agents, some medical leaders believed that infectious diseases would soon be eliminated and become of historic interest only. Indeed, the hundreds of chemotherapeutic agents developed since World War II, most of which are potent and safe, include drugs effective not only against bacteria but also against viruses, fungi, and parasites. Nevertheless, we now realize that as we developed antimicrobial agents, microbes developed the ability to elude our best weapons and to counterattack with new survival strategies. Antibiotic resistance occurs at an alarming rate among all classes of mammalian pathogens. Pneumococci resistant to penicillin and enterococci resistant to vancomycin have become commonplace. Even Staphylococcus aureus strains resistant to vancomycin have appeared. Such pathogens present real clinical problems in managing infections that were easily treatable just a few years ago. Diseases once thought to have been nearly eradicated from the developed world—tuberculosis, cholera, and rheumatic fever, for example—have rebounded with renewed ferocity. Newly discovered and emerging infectious agents appear to have been brought into contact with humans by changes in the environment and by movements of human and animal populations. An example of the propensity for pathogens to escape from their usual niche is the alarming 1999 outbreak in New York of encephalitis due to West Nile virus, which had never previously been isolated in the Americas. In 2003, severe acute respiratory syndrome (SARS) was first recognized. This emerging clinical entity is caused by a novel coronavirus that may have jumped from an animal niche to become a significant human pathogen. By 2006, H5N1 avian influenza, having spread rapidly through poultry farms in Asia and having caused deaths in exposed humans, had reached Europe and Africa, heightening fears of a new influenza pandemic. Many infectious agents have been discovered only in recent decades (Fig. 113-1). Ebola virus, human metapneumovirus, Anaplasma phagocytophila (the agent of human granulocytotropic ehrlichiosis), and retroviruses such as HIV humble us despite our deepening understanding of pathogenesis at the most basic molecular level. Even in developed countries, infectious diseases have made a resurgence. Between 1980 and 1996, mortality from infectious diseases in the United States increased by 64% to levels not seen since the 1940s. Figure 113-1 Map of the world showing examples of geographic locales where infectious diseases were noted to have emerged or resurged. (Adapted from Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States, Department of Health and Human Services, Centers for Disease Control and Prevention, 1994.) The role of infectious agents in the etiology of diseases once believed to be noninfectious is increasingly recognized. For example, it is now widely accepted that Helicobacter pylori is the causative agent of peptic ulcer disease and perhaps of gastric malignancy. Human papillomavirus is likely to be the most important cause of invasive cervical cancer. Human herpesvirus type 8 is believed to be the cause of most cases of Kaposi's sarcoma. Epstein-Barr virus is a cause of certain lymphomas and may play a role in the genesis of Hodgkin's disease. The possibility certainly exists that other diseases of unknown cause, such as rheumatoid arthritis, sarcoidosis, or inflammatory bowel disease, have infectious etiologies. There is even evidence that atherosclerosis may have an infectious component. In contrast, there are data to suggest that decreased exposures to pathogens in childhood may be contributing to an increase in the observed rates of allergic diseases. Medical advances against infectious diseases have been hindered by changes in patient populations. Immunocompromised hosts now constitute a significant proportion of the seriously infected population. Physicians immunosuppress their patients to prevent the rejection of transplants and to treat neoplastic and inflammatory diseases. Some infections, most notably that caused by HIV, immunocompromise the host in and of themselves. Lesser degrees of immunosuppression are associated with other infections, such as influenza and syphilis. Infectious agents that coexist peacefully with immunocompetent hosts wreak havoc in those who lack a complete immune system. AIDS has brought to prominence once-obscure organisms such as Pneumocystis, Cryptosporidium parvum, and Mycobacterium avium. . Chapter 113. Introduction to Infectious Diseases: Host–Pathogen Interactions (Part 1) Harrison's Internal Medicine > Chapter 113. Introduction to Infectious Diseases: Host–Pathogen. Infectious Diseases: Host–Pathogen Interactions Host–Pathogen Interactions: Introduction Despite decades of dramatic progress in their treatment and prevention, infectious diseases remain a major. pandemic. Many infectious agents have been discovered only in recent decades (Fig. 113- 1). Ebola virus, human metapneumovirus, Anaplasma phagocytophila (the agent of human granulocytotropic ehrlichiosis),