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By David J. Karras, MD, FAAEM, FACEP
Many notable physicians practicing in the mid-20th century confidently predicted that infectious diseases would soon be eliminated as significant factors in the landscape of modern life. New antibiotics enabled people to survive previously fatal illnesses and few bacteria demonstrated any resistance to our arsenal of antimicrobials. The advent of effective public sanitation, organization of public health departments, modern food processing techniques, and development of vaccines led to proclamations of victory in the war against microbes.
By the end of the 20th century, however, it was obvious that the victory dance was premature and highly naïve. Mortality rates related to infectious diseases actually rose 58% between 1980 and 1992, and infectious diseases remained the third leading cause of death in the United States. On a global scale, the 1990s were proclaimed the "new era of plagues" and the World Health Organization stated that "the threat of serious global pandemic with profound world-wide human devastation is more significant than at any time in history."1
Many of the factors implicated in the resurgence of infectious disease as a paramount threat to public health are, in fact, related to technological advances. Global movement of both people and food has become widely available and essentially instantaneous, allowing for rapid transmission of devastating illnesses.
Sexual promiscuity is common, despite the HIV epidemic. Americans still tend to have sex at younger ages and with more partners than in previous generations (as evidenced by the dramatic rise in serologic evidence of exposure to herpes).1
The greatest threat to our complacency regarding infectious disease, however, is the rapid emergence of antibiotic resistance. While bacteria always have had the ability to develop mechanisms allowing evasion of antimicrobial effects, there is overwhelming evidence that abuse of antibiotics by both physicians and patients has greatly accelerated this natural evolutionary process. The crisis of antibiotic resistance that we now face is to a great degree a crisis of our own making.
Of course, new infectious diseases have always cropped up from time to time. Whereas some diseases are predictable, others make dramatic and unforeseeable entrances. To detect and counter these threats, we rely almost entirely on our public health departments, which have been strongly criticized by the Institute of Medicine for lacking comprehensive surveillance systems.2 In the remainder of this article, a sample of some of the emerging infections that have the potential to profoundly affect the practice of medicine will be reviewed.
At least 13 new foodborne illnesses have been identified over the past 20 years.3 A number of factors conspire to make these illnesses extremely difficult to control: Most of the organisms have reservoirs in healthy animals, they often survive traditional food preparation techniques, and contamination often does not alter the appearance or taste of the food. Outbreaks usually can be identified only after hundreds (or thousands) of individuals have ingested an organism. Contamination in a single processing plant can pose a national or global threat, and multiple government agencies (mostly understaffed) have jurisdiction over the food chain. The antibiotics routinely fed to livestock appear to have enhanced the development of resistant bacterial strains that routinely contaminate food products.
While Salmonella has historically been the most common foodborne illness, data from the 1998 FoodNet surveillance program reveal Campylobacter to be the greatest offender, accounting for 40% of identifiable enteropathogens compared to 28% for Salmonella and 15% for Shigella.4 Camplylobacter, which was not even identified as a stool pathogen until 1972, now is believed to be responsible for almost 2.5 million cases of bacterial enteritis per year. The organism has reservoirs in the intestines of poultry and cattle, as well as in fresh water (which often is contaminated by animal waste). Although treatment for campylobacteriosis is primarily supportive, there is good evidence that patients with moderate-to-severe symptoms (high fever, bloody stool, and/or frequent bowel movements) benefit significantly from antibiotic therapy. Quinolones are the drugs of choice for treatment of this and most other causes of bacterial enteritis; azithromycin or trimethoprim/sulfamethoxazole are good alternatives.5
Escherichia coli O157:H7 is a toxin-producing enteropathogen that has been responsible for a number of serious outbreaks of hemorrhagic colitis. The primary reservoir of the organism is in cattle intestines, and from there it can go on to contaminate not only meat, cheese, and unprocessed milk, but also well water and fresh fruit that comes in contact with contaminated soil. In the typical E. coli O157:H7 infection, a patient develops cramps and diarrhea 3-4 days following ingestion of contaminated food or water. Stool becomes frankly bloody within 1-2 days. The duration of illness is typically a week, after which most patients will have a complete recovery. Between 5% and 10% of patients (usually children or older individuals) develop hemolytic- uremic syndrome (HUS), which results in renal insufficiency, chronic renal failure, stroke, or death in about one-half of affected individuals.6 The risk of HUS is markedly greater in patients treated with antibiotics (specifically trimethoprim/sulfamethoxazole).7 Antimicrobial agents, therefore, are not recommended for patients with hemorrhagic enteritis deemed likely to be associated with an E. coli epidemic.
Rodent-Borne Illness: Hantavirus
In 1994, a new disease was reported in New Mexico that caused 17 deaths in mostly healthy young couples within a matter of weeks. The etiologic agent was found to be the hantavirus, which was known to have been the cause of hemorrhagic fever during the Korean War but had not been previously known to cause human illness in this hemisphere. The virus, it was discovered, was ubiquitous in mice in the southwestern United States. Because of a few particularly warm and wet El Niño seasons, the local mouse population had exploded during the year of the initial outbreak.8 The resulting disease, termed hantavirus pulmonary syndrome (HPS), continues to occur sporadically and carries a 43% fatality rate.
HPS presents dramatically with a flu-like prodrome that is abruptly followed by pulmonary edema and often cardiogenic shock. No radiographic or laboratory abnormalities are pathognomonic of the disease, and diagnosis requires serologic testing.9 Antimicrobial therapy is not effective, although extracorporeal membrane oxygenation appears to improve the prognosis of patients with severe disease. The only effective mechanism of controlling hantavirus infections appears to be eradication of mouse infestations, which obviously is quite difficult. As of last year, 234 cases of HPS had been confirmed, and the disease had been reported throughout the United States, with the notable exception of the southeastern states.10 Awareness of this syndrome, therefore, is now essential for physicians throughout the country, particularly those working in rural areas.
Tick-Borne Illness: Ehrlichiosis
Ehrlichia is an obligate intracellular bacterium that was not known to cause disease in humans until 1987. Since that time, more than 2000 cases of human disease have been reported in this country. E. chaffeensis is the cause of human monocytic ehrlichiosis (HME), which is transmitted by the Lone Star tick and American dog tick. Human granulocytic ehrlichiosis (HGE) is associated with E. ewingii and is spread by deer ticks.11 The disease appears to be even more common than previously recognized, as one recent study found that 18% of patients with flu-like symptoms living in a tick-endemic region had serologic evidence of acute ehrlichiosis.12
The typical ehrlichiosis patient is a middle-age male living in the south-central United States who recently has been exposed to ticks. The disease presents with flu-like symptoms—fever, myalgias, and malaise. Later, abdominal pain and vomiting may be seen and a nonspecific, indistinct rash may be detected. About 20% of patients develop mental status changes and/or meningismus; lumbar puncture reveals pleocytosis and elevated protein in the cerebrospinal fluid. Other laboratory abnormalities include leukopenia with a left shift, thrombocytopenia, and hepatic transaminitis. The disease may have a fulminant course with multisystem organ involvement. Although a 2-10% mortality rate has been reported, it is likely that many milder cases go undetected.13
Presently, ehrlichiosis is diagnosed by a compatible history, a peripheral blood smear showing morulae (microcolonies of organisms) within neutrophils or monocytes, and characteristic rises in serum antibodies. At least one-half of patients may be managed as out-patients. Tetracycline is highly effective therapy, as are chloramphenicol (in children), trovafloxacin, and rifampin.
As stated in the report from the Institute of Medicine, when pitted against microbes physicians have mainly their wits to rely upon.2 Pharmaceutical science clearly will not eradicate infections in the near future as microorganisms always seem to find a way to dodge whatever ammunition is fired. New infectious diseases inevitably will emerge and existing diseases will evolve. Our best bets are to support regional and national surveillance programs. As evidenced by the response of the Centers for Disease Control and Prevention and local agencies to the hantavirus outbreak, such programs have the ability to promptly recognize and respond to serious public health threats, if appropriately funded. Individual physicians need to keep abreast of emerging infections. The Annals of Emergency Medicine regularly reviews articles from Morbidity and Mortality Weekly Report (MMWR) that are relevant to emergency physicians; MMWR itself is available on-line free of charge (www.cdc.gov/mmwr). Finally, it is critical that the health care community recognize its contribution to the problem of widespread antibiotic resistance and develop a healthy reluctance to prescribe antibiotics unless they clearly are indicated.
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2. Lederberg J, et al. Emerging Infections: Microbial Threats to Health in the United States. Washington, DC: National Academy Press; 1992.
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4. Incidence of foodborne illness: Preliminary data from the Foodborne Diseases Active Surveillance Network (FoodNet)—United States, 1998. MMWR Morb Mortal Wkly Rep 1999;48:189-194.
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6. Slutsker L, et al. Escherichia coli O157:H7 infection in the United States: Clinical and epidemiologic features. Ann Intern Med 1997;126:505-513.
7. Wong CS, et al. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342: 1930-1936.
8. Duchin JS, et al. Hantavirus pulmonary syndrome: A clinical description of 17 patients with a newly recognized diseases. N Engl J Med 1994;330:949-955.
9. Shope RE, et al. A midcourse assessment of hantavirus pulmonary syndrome. Emerg Infect Dis 1999;5: 172-174.
10. Update: Hantavirus pulmonary syndrome—United States. MMWR Morb Mortal Wkly Rep 2000;49:205.
11. Buller RS, et al. Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N Engl J Med 1999;341: 148-155.
12. Bakken JS, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199-205.
13. Walker D, et al. Emerging bacterial zoonotic and vector-borne diseases. Ecological and epidemiological factors. JAMA 1996;275:463-469.