Residents of deteriorating inner cities are a newly identified population at risk for a bacterial disease carried by rats, according to a Nov. 15 Annals of Internal Medicine study led by Joseph M. Vinetz, M.D., a postdoctoral fellow in the National Institute of Allergy and Infectious Diseases (NIAID). "Our results suggest that leptospirosis may be yet another re-emerging infectious disease in urban United States," he and his co-authors conclude.
"Leptospirosis may be the most common disease that rats carry and transmit to humans in the United States," comments Dr. Vinetz, "but it's simply underrecognized."
Although leptospirosis is not new to the United States, it is difficult to diagnose, hence its prevalence is unknown. The current study is based on findings obtained from using a sensitive experimental diagnostic test.
Dr. Vinetz urges clinicians to consider the diagnosis of leptospirosis in urban patients who complain of flu-like symptoms (especially during the warm months outside the flu season) and could have been exposed to the urine of rats or to pools of infected water, which can be present in alleys and parks in the inner city and possibly in the suburbs.
Human leptospirosis infection usually causes a mild syndrome of aches, pains and fever that resolves spontaneously or after treatment with antibiotics. But up to 10 percent of infected persons develop a serious systemic form of the illness, Weil's disease, which can result in high fever, jaundice, aseptic meningitis, acute kidney failure, internal bleeding and, occasionally, death.
In their report, Dr. Vinetz and his co-authors from NIAID's Laboratory of Parasitic Diseases and Johns Hopkins Schools of Medicine and Hygiene and Public Health describe three sporadic cases of severe leptospirosis infection diagnosed within a year in an urban hospital in Baltimore. The authors could remember no cases diagnosed there in the previous decade, and no cases had been diagnosed by the Maryland State Health Department for at least five years.
The investigators confirmed the link to infected rodents when they identified Leptospira interrogans in 19 of 21 rats trapped in the alleys where the patients had sustained cuts before their illnesses developed. The disease agent--a thin, spiral-shaped bacterium--enters the body through cuts in the skin and through the linings of the eyes, nose and throat.
Although a variety of mammals worldwide harbor the infection, in the United States the most common carriers are rats, dogs and livestock. Humans do not transmit the infection to others. It is common practice for livestock and dogs to be immunized against the disease, but even vaccinated animals can shed the bacteria in their urine for long periods of time and be an occasional source of human infection.
Surveys of rat populations have not been conducted since the 1940s and 50s. City officials today often estimate two rats for every resident, but this is not known to be based on any hard data. An indirect gauge of the problem is the tally of complaints about rats received from residents. Most recent annual figures show New York City with about 40,000 complaints, Philadelphia with 10,000, Baltimore with 5,000 and Washington, D.C., with 4,000.
People traditionally recognized at highest risk for leptospirosis have been those engaged in certain occupations (farmers, veterinarians, sanitation and sewer workers, and meat processors) or recreational activities (campers, freshwater swimmers) as well as individuals exposed to flooding as a result of hurricanes or other natural disasters. Travel to endemic areas (most often in tropical climates) also is a risk factor. The Annals report is the first study to establish the risk to residents of U.S. inner cities.
However, at least two previous surveys provided indirect evidence that unrecognized leptospirosis might be common in city dwellers. A 1992 survey from a Baltimore sexually transmitted diseases clinic found that 16 percent of blood samples taken from 1,150 patients for reasons unrelated to leptospirosis were positive for exposure to leptospiral antigen. An earlier study found that about one-third of children tested in Detroit had antibodies to Leptospira. More inner-city children had antibodies than did children from the suburbs, yet none of the inner-city children had been diagnosed with leptospirosis.
"These serosurveys indicated that the risk to city dwellers was there," says Dr. Vinetz, "but nobody could make use of this data until someone could identify patients with acute disease."
Dr. Vinetz and his colleagues accomplished this by using an experimental polymerase chain reaction (PCR) test, which can detect within 24 hours tiny amounts of the bacterium's genetic material.
Currently available diagnostic tests for leptospirosis detect antibodies to the bacterium. Local laboratories, however, ordinarily do not perform these tests. Blood samples must be sent to the state health department first, and if positive, to the Centers for Disease Control and Prevention laboratory for confirmation. The results typically come back weeks to months later, according to Dr. Vinetz, much too late to impact on clinical care.
"What the PCR test allowed us to do," comments Dr. Vinetz, "is connect the seroepidemiology data to the clinical data and make it real."
All three patients in their study lived in inner-city Baltimore. None had recently traveled outside the city, had pets or had been exposed to farm animals. Although Dr. Vinetz recognized that the first patient had the classic symptoms of leptospirosis, to confirm the diagnosis, he had to establish that she had been exposed to the bacteria.
After a week in the intensive care unit, the patient finally recalled that 10 days before the onset of her illness she had been walking barefoot in an alley behind her house and had stepped on some broken glass. "That's the perfect incubation period," comments Dr. Vinetz. "I checked, and she had a healing gash on the bottom of her right foot. As soon as I got that information, for all intents and purposes, the diagnosis was established. Nobody has ever shown that you can get leptospirosis just by walking around in a city," he notes. "That was novel." Likewise, the second patient told the investigators he cut his hand on glass in a rat-infested alley about 10 days before he developed his illness. The third patient acknowledged walking barefoot in rat-infested alleys near the Baltimore harbor.
More research is needed to validate the PCR assay as the best way to diagnose leptospirosis. If the assay is adopted, the authors say, its widespread use would allow physicians to initiate specific therapy earlier and to avoid unnecessary invasive and expensive tests to rule out other diseases.
To accelerate the validation of the PCR test for leptospirosis, Dr. Vinetz encourages physicians to send sera, urine and cerebrospinal fluid from patients with suspected leptospirosis, along with clinical and epidemiologic information, to the Clinical Microbiology Laboratory at Johns Hopkins. For more information, call Dr. Vinetz at 301-496-3655.
The co-authors on the report were Gregory E. Glass, Ph.D., Charles E. Flexner, M.D., and Paul Mueller, M.D., of Johns Hopkins; and David C. Kaslow, M.D., of NIAID.
NIAID, a component of the National Institutes of Health, conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the Public Health Service, U.S. Department of Health and Human Services.
Vinetz JM, Glass GE, Flexner CE, Mueller P, and Kaslow DC. Sporadic urban leptospirosis. Ann Int Med 1996;125:794-98.
Farr RW. Leptospirosis. Clin Infec Dis 1995;21:1-8.
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