The new england journal of medicine n engl j med 366;5 nejm.org february 2, 2012 454 anniversary article The Perpetual Challenge of Infectious Diseases Anthony S. Fauci, M.D., and David M. Morens, M.D. From the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Address reprint requests to Dr. Fauci at the National Insti- tute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 31, Rm. 7A-03, Bethesda, MD 20892, or at afauci@niaid.nih.gov. N Engl J Med 2012;366:454-61. Copyright © 2012 Massachusetts Medical Society. A mong the many challenges to health, infectious diseases stand out for their ability to have a profound impact on the human species. Great pandemics and local epidemics alike have influenced the course of wars, determined the fates of nations and empires, and affected the progress of civiliza- tion, making infections compelling actors in the drama of human history. 1-11 For 200 years, the Journal has captured the backdrop to this human drama in thousands of articles about infectious diseases and about biomedical research and public health efforts to understand, treat, control, and prevent them. The Uniqueness of Infectious Diseases Infections have distinct characteristics that, when considered together, set them apart from other diseases (Table 1). Paramount among these characteristics is their un- predictability and their potential for explosive global effect, as exemplified by the bubonic–pneumonic plague pandemic in the 14th century, 1,12 the 1918 influenza pandemic, 13,14 and the current pandemic of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), 15 among others. Infectious diseases are usually acute and unambiguous in their nature. The onset of an infectious illness, unlike the onset of many other types of disease, in an otherwise healthy host can be abrupt and unmistakable. Moreover, in the absence of therapy, acute infectious diseases often pose an all-or-nothing situation, with the host either quickly dying or recovering spontaneously, and usually relatively promptly, often with lifelong immunity to the specific infecting pathogen. Not only are some infectious diseases transmissible to others, a unique charac- teristic among human diseases, but their transmission mechanisms are relatively few (including inoculation and airborne and waterborne transmission), well under- stood, and comparatively easy to study, both experimentally and in the field. In addi- tion, such transmission is generally amenable to medical and public health interven- tions. Unlike many chronic and lifestyle-associated diseases resulting from multiple, interacting risk cofactors, most infectious diseases are caused by a single agent, the identification of which typically points the way not only to general disease-control measures (e.g., sanitation, chemical disinfection, hand washing, or vector control) but also to specific medical measures (e.g., vaccination or antimicrobial treatment). Given their nature, infectious diseases are potentially preventable with personal protection, general public health measures, or immunologic approaches such as vaccination. As preventive measures have become more effective and efficient, history has shown that certain infectious diseases, particularly those with a broad global health impact and for which there is no nonhuman host or major reservoir, can be eliminated. Such diseases include poliomyelitis, which has been eliminated in the Western Hemisphere, 16 and smallpox, which has been eliminated globally. 9 Another unique aspect is that the extraordinary adaptability of infectious pathogens (i.e., their replicative and mutational capacities) provides them with a temporary evolutionary advantage against pressures aimed at their destruction. These pres- The New England Journal of Medicine Downloaded from nejm.org by Julian Cardona on March 27, 2014. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.