Almost a quarter century ago, the Surgeon General of the United States testified to Congress that it was time to "close the book on infectious diseases" [2]. The wide use of effective antibiotics, the potential for universal vaccination for many major childhood illnesses, and success stories, such as the eradication of smallpox in 1977, encouraged the perception that infectious diseases had been conquered.

The stark reality is that infectious diseases are the leading cause of death worldwide [3] and remain a leading cause of illness and death in the United States [4]. Human immunodeficiency virus (HIV) infection, pneumonia, and influenza rank among the 10 leading causes of death in the United States. Lyme disease has become the leading vector-borne disease with more than 50 000 cases reported since 1982, many resulting in chronic disability. "Old" diseases such as tuberculosis and measles—long thought to have been under control—have recently re-emerged in the United States.

Our once seemingly invincible array of antimicrobial drugs is declining in effectiveness for many hospital- and community-acquired infections. For a large proportion of Staphylococcus aureus isolates, for example, only vancomycin remains effective, and vancomycin resistance has now been reported in enterococci [5] and coagulase-negative staphylococci [6]. If the resistance acquired by these organisms spreads to methicillin-resistant S. aureus, no effective treatment will remain for this organism. Similarly, resistance to penicillin is increasing among strains of Streptococcus pneumoniae, the most common cause of community-acquired pneumonia [7-10]. Penicillin resistance is emerging in some geographic areas where resistance to erythromycin, tetracycline, and trimethoprim-sulfamethoxazole already exists; some isolates also have decreased susceptibility to third-generation cephalosporins, including cefotaxime and ceftriaxone [9].

Emerging infections include those diseases whose incidence has increased within the past 20 years or whose incidence threatens to increase in the near future; many factors are contributing to their emergence. Years of complacency have allowed the public health infrastructure for infectious diseases to deteriorate. For example, national surveillance of drug-resistant Mycobacterium tuberculosis was discontinued in 1984 and has only recently been reinstituted. Surveillance of food-borne disease is inadequate in most areas of the United States, and many outbreaks go undetected [11].

Demographic and social changes have contributed to the emergence of infectious diseases. Changes in sexual behavior and use of illicit injection drugs have contributed to the rapid spread of HIV. The dramatic increase in the use of child-care centers as women have re-entered the workplace in increasing numbers has resulted in a greater risk for infectious disease, not only for children but also for parents and child care staff [12] and may be facilitating the transmission of antibiotic-resistant organisms [13]. Widespread use of invasive medical devices has led to an increase in hospital-acquired infections; changes in food production, processing, and distribution can compromise food safety and increase food-borne disease; and use of new products can cause illness or even death, as illustrated by the role of superabsorbent tampons in the toxic shock syndrome.

Changes in land use also affect the emergence of infectious diseases. The emergence of Lyme disease in the eastern United States, for example, coincided with the explosive increase in the deer population as much of the land was reforested and people moved further into suburban areas or explored wilderness areas. Animal rabies increased in the Middle Atlantic states and New England when rabid raccoons were transported from one area of the country to another to replenish hunting stocks [14].

International commerce and travel have become so extensive that the terms "domestic" and "global" are losing their significance in the context of infectious diseases. More than 10 times the number of cases of malaria in U.S. travelers were reported in the United States in 1991 than in 1960 [15]. In 1992, more cases of cholera were reported in the United States than in any other year since cholera surveillance began in 1961 [15]. In addition, the first documented case of cholera, associated with toxigenic Vibrio cholerae 0139, was imported into the United States in 1993, only a few months after the strain was first described in southern Asia [16]. Epidemics caused by new influenza strains in other areas of the world, particularly Asia, are often quickly followed by outbreaks caused by similar strains in the United States [17]. Exotic diseases can also move quickly around the world: After visiting Nigeria, a 43-year-old mechanical engineer was hospitalized in Chicago with a fulminating febrile illness later diagnosed as Lassa fever—a viral hemorrhagic fever with a high mortality rate that can be transmitted to health care workers [18].

In addition to new and re-emerging infections, results of research are proving that conditions previously thought not to be infectious do have infectious causes. Infection with specific genotypes of human papillomavirus may be the most important risk factor for the development of invasive cervical cancer [19]; Helicobacter pylori has a causative role in the development of peptic ulcer disease, and antibiotics reduce the frequency of recurrence of this disease [20]; and hepatitis C is a major cause of chronic liver disease [21].

Finally, and probably most importantly, microbes mutate and adapt to changing environments, often with astonishing rapidity. The microbe itself may change; for example, the high rate of mutation necessitates annual reformulation of influenza vaccines and is an obstacle in developing an effective vaccine for HIV. Many microorganisms develop drug resistance in response to selective pressure from exposure to antimicrobial agents.

All of these issues are highlighted in a report published by the Institute of Medicine in October 1992 [22]. The report, "Emerging Infections: Microbial Threats to Health in the United States," was written by a committee chaired by Joshua Lederberg and Robert E. Shope. It emphasizes the need for strong national and global systems of disease detection to maintain vigilance against emerging infections; recognizes the need to enhance our diagnostic capacity and to apply biotechnologic advances to infectious disease prevention and control; and identifies development of new vaccines, improvement in antibiotic usage, and enhancement of health-promoting behaviors as critically important for responding to the mounting threats of infectious disease.

How will new and re-emerging infections affect the internist's everyday practice? The emergence and re-emergence of infectious diseases have already had a profound effect, radically changing the spectrum of diseases treated by internists and increasing the infection control procedures in use. Drug resistance has and will continue to pose a challenge to clinicians [23, 24]. The need for an accurate diagnosis and for determination of drug susceptibility patterns will require increased dependence on the clinical microbiology laboratory. Physicians need to know drug susceptibility patterns in their geographic area before starting empiric antibiotic therapy. An individual patient may represent a sentinel event indicating a community-wide outbreak, and effective communication is needed between clinicians and public health professionals to determine whether further investigation and public health intervention are needed. A patient with chronic liver disease should be tested for hepatitis C as well as hepatitis B virus infection and, if infected, receive counseling to prevent transmission of the virus to others. Physicians must be aware of the global distribution of infectious diseases to counsel their patients about minimizing the risk for infection while abroad; to provide immunizations and prophylaxis; and to diagnose illnesses in returning travelers.

What new challenges should we expect in the future? The recent history of new and re-emerging infectious diseases teaches us that specific predictions are difficult to make. However, experience suggests that diseases will undergo changes in their clinical manifestations. Diseases will appear in new geographic areas, and microorganisms will continue to evolve. New modes of transmission will be identified and the distribution of disease vectors will change. New disease associations will continue to be established. Such challenges are well illustrated by the recent recognition of hantavirus as a cause of the acute respiratory distress syndrome in the southwestern United States [25]. In addition, the increasing number of persons with compromised immune systems (for example, the elderly, HIV-infected persons, organ transplant recipients, and other persons receiving immunosuppressive therapy) favors the emergence of additional opportunistic infections.

Clinicians, microbiologists, and public health professionals must work together to prevent infectious diseases and to detect emerging diseases quickly. Monitoring trends of resistance of both hospital- and community-acquired microorganisms and using appropriate antimicrobial drugs are essential. In consultation with local and state health departments, other federal agencies, and professional organizations, the Centers for Disease Control and Prevention is currently evaluating what strategies will be most useful to meet these challenges. One possibility is for internists to participate in a sentinel network for surveillance of emerging infections. As the authors of the Institute of Medicine report state, "Pathogenic microbes can be resilient, dangerous foes. Although it is impossible to predict their individual emergence in time and place, we can be confident that new microbial diseases will emerge" [22].