James M. Hughes
Infectious diseases are a leading cause of death worldwide and the third leading cause of death in the United States. According to the World Health Organization (1998), of the 52 million deaths that occurred globally in 1997, one-third, or 17 million, were attributable to infectious disease. The leading killers are acute lower respiratory tract infection (primarily pneumonia), tuberculosis, diarrhea and dysentery, HIV infection and AIDS, malaria, measles, and hepatitis B. Many of these diseases have a propensity for drug resistance, which contributes to some of the mortality. In the United States, infectious disease mortality has been on the rise, largely due to the rapid spread of HIV but also due to pneumonia and bloodstream infection. Despite these data, because of improvements in sanitation and the availability of effective antibiotics and vaccines, considerable complacency has developed over the past 30 years in the United States regarding infectious diseases.
More recently, infectious disease outbreaks have presented major challenges and have reminded us that we live in a global village. These outbreaks have included:
Plague in India.
Ebola hemorrhagic fever in Zaire and Gabon.
Leptospirosis in Nicaragua and the United States.
Cyclospora gastroenteritis in the United States and Canada.
Escherichia coli O157:H7 hemorrhagic colitis in Japan and the United States.
Staphylococcus aureus infections caused by strains with diminished susceptibility to vancomycin in Japan and the United States.
H5:N1 influenza in Hong Kong.
Rift Valley fever in Kenya, Somalia, and Saudi Arabia.
Nipah virus infection in Malaysia and Singapore.
Foodborne salmonellosis, shigellosis, and listeriosis in the United States.
West Nile encephalitis in New York City and nearby areas.
Addressing the major challenges posed by these outbreaks requires timely epidemiologic investigations, use of sophisticated laboratory techniques, and effective communication of results and recommendations for prevention. We cannot afford to ignore infectious disease problems in other parts of the world. From our experience at the Centers for Disease Control and Prevention (CDC) in dealing with a number of these emerging and reemerging infection outbreaks over the past 6 to 7 years, several important and recurrent lessons have emerged. These outbreaks emphasize the importance of surveillance, the need to have the ability to conduct prompt epidemiologic investigations, and the need to have available critically important public health laboratory capacity. In addition, human resource development through training is necessary to strengthen prevention and control programs at all levels.
In 1992 a landmark Institute of Medicine (IOM) report, Emerging Infections: Microbial Threats to Health in the United States, highlighted this complacency, emphasized the threats posed by infectious diseases, identified the factors that contribute to disease emergence and reemergence, and stressed the need to heighten vigilance and strengthen disease detection and response capacity. Notably, the report provided the following definition of emerging infections: “New, re-emerging, or drug-resistant infections are those whose incidence in humans has increased within the past few decades, or whose incidence threatens to increase in the near future.” Notice that this definition is very broad and that it specifically includes drug resistance. The report identified six major factors that contribute to disease emergence and reemergence:
Changes in human demographics and behavior.
Advances in technology and industry.
Economic development and changes in land-use patterns.
Dramatic increases in the volume and speed of international travel and commerce, including foodstuffs and animals.
Microbial adaptation and change in response to selective pressures in the environment.
Breakdown in public health measures.
The IOM report could not have been timelier. Within 6 months of its publication, clinicians, microbiologists, and public health officials in the United States were confronted with three dramatic examples of infectious disease threats. The first was an interstate foodborne disease outbreak of hemorrhagic colitis and hemolytic uremic syndrome caused by E. coli O157:H7 linked to undercooked hamburger served by a fast food restaurant chain. The second event was the largest waterborne disease outbreak in U.S. history, which resulted in more than 400,000 cases of cryptosporidiosis in Milwaukee, Wisconsin. The third event was an outbreak of acute respiratory distress syndrome caused by a previously unrecognized hantavirus in the southwestern United States. Simultaneously, the incidence of nosocomial infections caused by vancomycin-resistant enterococci and that of penicillin resistance in community-acquired pneumococcal infections caused by penicillin-resistant strains have increased.
Because more than half of the recommendations in the 1992 IOM report were directed at the CDC, that agency developed a strategy for addressing emerging infections in consultation with outside experts in the areas of clinical infectious diseases, microbiology, and public health. The strategy contains four goals that focus on strengthening surveillance and response capacity; addressing applied research priorities; strengthening the public health infrastructure at the local, state, and federal levels; and improving prevention and control programs. Incremental implementation of this strategy began in 1994, and an updated version was issued in September 1998 (CDC, 1998).
Two initiatives under way to incrementally implement this plan are worth mentioning. First, the CDC has organized and provided support for nine emerging-infections programs. These are financial awards made competitively to state health departments to develop consortia within their states, reaching beyond the traditional public health system to involve the clinical and academic communities in these projects.
In addition, the CDC has provided support to 43 additional jurisdictions, including 39 state public health departments and four large cities —Los Angeles, New York City, Houston, and Philadelphia—to help them repair some of their deteriorated public health laboratory capacity and to provide resources for strengthening surveillance capacity, particularly via molecular fingerprinting. Without this molecular tool, the ability of public
health departments to recognize, intervene, and control many outbreaks is severely limited.
Because of the importance of molecular fingerprinting, the CDC has begun to develop an integrated foodborne disease surveillance system in the United States. This national network, called PulseNet, involves four regional laboratories as well as the U.S. Department of Agriculture, the Food and Drug Administration, CDC laboratories, and many state public health laboratories that perform molecular fingerprinting. This effort has been critical in recognizing a number of regional and national foodborne disease outbreaks in the past three years.
Antimicrobial resistance is a critically important clinical and public health issue, especially since the drug development pipeline has largely dried up. Dealing with the problem of antimicrobial resistance is complicated and requires a multifaceted strategy that starts with surveillance and requires rational use of antimicrobial agents, which relies on the availability of rapid diagnostic tests. Physicians need office-based tests to help them determine whether a patient has a bacterial or a viral infection and, if bacterial, whether it is drug susceptible or drug resistant. Regarding the crux of the problem of antimicrobial resistance, however, John Burke wrote a few years ago: “Despite the multifactorial nature of antibiotics resistance, the central issue remains quite simple. The more you use it, the faster you lose it” (Burke, 1995).
For many years professional societies have developed a number of recommendations for clinicians in an effort to improve antimicrobial usage. A recent publication developed by the CDC and the American Academy of Pediatrics provided family practitioners and pediatricians with some principles for judicious use of antimicrobial agents for pediatric upper respiratory tract infections. However, the public needs to be brought into this campaign against antimicrobial resistance to begin to understand that antimicrobial agents are important resources that must be conserved and used appropriately.
The bombings of the World Trade Center in New York and the federal building in Oklahoma City have demonstrated that we are vulnerable to terrorist attacks, adding a new dimension to the challenges posed by infectious diseases. Biological attack, which in the past was considered unlikely, now seems entirely possible, given that information on how to prepare such weapons is widely available and that actions have been car-
ried out by groups such as Aum Shinrykyo, which released nerve gas in Tokyo's subway system and experimented with biological weapons.
Four components of the public health response to disease outbreaks are important regarding preparedness in addressing acts of bioterrorism. First, since initial disease detection is likely to take place at the local level, it is essential to work with the medical community, including emergency departments, infection control practitioners, poison control centers, and emergency responders. A 1998 report of the National Research Council on chemical and biological terrorism, recommends expanding the CDC's emerging-infections initiative to improve state and local surveillance infrastructure for detecting naturally occurring outbreaks as well as those potentially resulting from bioterrorism.
The second component is investigation and response, activities that are also likely to take place initially at the local level. Third, rapid diagnosis will be critical so that prevention and treatment measures can be implemented quickly. Because the agents that are most likely to be used as bioweapons are not currently major public health problems in the United States, biocontainment laboratory space and surge capacity to investigate and respond to outbreaks have been limited. In addition, future bio-weapons events could involve organisms that have been genetically engineered to increase their virulence, manifest antibiotic resistance, or evade natural or vaccine-induced immunity. Finally, communication is crucial, as delays will increase the probability that more people will be exposed. Preparedness will require effective partnerships with local, state, and other federal public health agencies; clinicians and clinical microbiologists; research institutions; and industry. Preparedness for bioterrorism requires that these partnerships be extended to include the emergency response and law enforcement communities.
Infectious diseases are important, evolving, and complex public health problems. Their prevention and control require application of sophisticated epidemiologic, laboratory, statistical, behavioral, and informatics approaches and technologies. An integrated approach involving epidemiologic, laboratory, behavioral, and information sciences is critical to the prevention and control of infectious diseases. A strong and flexible public health infrastructure is the best defense against any disease outbreak, whether naturally occurring or intentionally caused.
Burke, J. P. 1995. How to maintain the miracle of antibiotics. Lancet, 345:977.
Centers for Disease Control and Prevention (CDC). 1998. Preventing Emerging Infectious Diseases: A Strategy for the 21st Century. Atlanta: CDC (http://www.cdc.gov/ncidod/emergplan).
Institute of Medicine. J. Lederberg, R. E. Shope, and S. C. Oaks, eds. 1992. Emerging Infections: Microbial Threats to Health in the United States Washington, D.C.: National Academy Press.
National Research Council and Institute of Medicine. 1998. Improving Civilian Medical Response to Chemical or Biological Terrorist Incidents. Washington, D.C.: National Academy Press.
World Health Organization (WHO). 1998. The World Health Report 1998: Life in the 21st Century: A Vision for All. Report of the Director General. Geneva: WHO.