Vol. 17, No. 21
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Tuesday, May 26, 1998
A. Provided by Marguerite-Hawkins, Epidemiology and Disease Control Program, Division of Outbreak Investigation, Maryland Department of Health and Mental Hygiene.
From May 15, 1998 through May 21, 1998, 5 outbreaks have been reported to the Maryland Department of Health and Mental Hygiene. They are as follows: 1 food-related gastroenteritis, 2 presumed viral gastroenteritis, 1 presumed viral meningitis, and 1 ringworm in a food coop.
B. The Johns Hopkins Hospital. Information provided by Dr. Edward Weir, Dept. of Pathology.
Case History: A 25 year old lifeguard was seen in the ER with complaints of a sudden onset of fever, chills, rigors, and intense headache four days prior to presentation. He also reported severe muscle aches in his legs and his back. Physical examination was remarkable for a fever of 39.6oC, focal subconjunctival hemorrhages, mild hepatosplenomegaly, and a diffuse petechial skin rash. Cultures of blood and CSF taken at the time of presentation were positive for Leptospira at 72hrs of growth.
Organism: Although the taxonomy of the genus Leptospira is currently in a state of transition, the organisms have traditionally been subdivided into two species: L. biflexa (63 serovars) and L. interrogans (210 serovars). The species names are derived from the fact that Leptospira are thin coiled bacilli (0.1 x 6 to 12 um) with a hook at one or both ends (biflexa = "twice bent"; interrogans = "shaped like a question mark"). L. biflexa is a free-living saprophyte found in moist environmental sites and is not associated with disease. L. interrogans is pathogenic for many wild and domestic animals, as well as humans. About 22 serotypes of L. interrogans cause human disease in the United States. The pathogenic leptospires are obligatively aerobic and motile by means of two periplasmic flagella, each anchored at opposite ends of the bacterium. They utilize fatty acids and alcohols as sources of carbon and energy.
Clinical Disease: Leptospirosis is a zoonotic disease with a worldwide distribution. Fewer than 100 human infections are documented in the U.S. each year, the majority of which are reported in Hawaii. However, the incidence of the disease is significantly underestimated because most infections are mild and misdiagnosed as a "viral syndrome" or a viral aseptic meningitis. Many wild and domestic animals are colonized with leptospires. The organisms usually cause asymptomatic infections in their reservoir host, in which the spirochetes colonize the renal tubules and are shed in urine in large numbers. Serologic studies have shown a high incidence of human exposure to leptospires which can be attributed to incidental contact with the urine of infected rodents (particularly rats), dogs, and farm animals, commonly in association with urine-contaminated water. Most human infections occur during the warm months when recreational exposure is greatest. Person-to-person spread has not been documented. Symptomatic infections develop after a 1- to 2-week incubation period. The initial presentation is similar to a flu-like illness with fever and myalgias. During this phase the patient is bacteremic with the leptospires, and the organisms can frequently be isolated in the CSF despite an absence of meningeal signs. The fever and myalgias may remit after one week, or the patient may develop an aseptic meningitis or a more advanced systemic disease (Weil's disease) with renal and hepatic failure, extensive vasculitis, hemorrhage and thrombocytopenia, myocarditis, and death. The severity of the disease is influenced by the number of infecting organisms, the host's immunological defenses, and the virulence of the infecting strain. The mortality of the systemic disease approaches 10%. Although hepatic involvement with jaundice is striking in patients with severe leptospirosis, hepatic necrosis is not seen, and surviving patients do not suffer permanent liver damage. Similarly, most patients recover full renal function.
Laboratory Diagnosis: Because leptospires are exceedingly thin, they are not easily visualized with conventional light microscopy. Neither Gram stain nor silver stain is reliable in the detection of leptospires. Darkfield microscopy is also relatively insensitive and can yield nonspecific findings. The spirochetes can be cultured on specially formulated media (Fletcher, EMJH, or Tween 80-albumin). They grow slowly (generation time 6 to 16 hrs), requiring incubation at 28o to 30oC for as long as 4 months; however, most cultures are positive within 2 weeks. L. interrogans can be recovered in blood or CSF during the first ten days of infection and in urine after the first week and for as long as 3 months. The concentrations of the organism may be low so multiple specimens should be collected if leptospirosis is suspected. Because of the need for specialized media and prolonged incubation, most labs rely on serologic techniques for detection of the organisms. Using the microscopic agglutination test (MAT), serial dilutions of the patient's serum are mixed with test antigens and then examined microscopically for agglutination. Agglutinins usually appear in the blood of untreated patients by the second week of illness. Infected patients have a titer of at least 1:100 and it may be as high as 1:25,000. Patients treated with antibiotics may have a diminished antibody response and nondiagnostic titers. Alternative tests such as indirect hemagglutination and ELISA are less sensitive and specific and are not recommended.
Treatment: Leptospirosis is usually not fatal, especially in the absence of icteric liver disease. Patients with severe disease should be treated with IV penicillin or ampicillin, and patients with less severe disease can be treated with oral doxycycline, ampicillin, or amoxicillin. Doxycycline should be used to prevent disease in individuals at high risk of exposure. Also, the vaccination of livestock and pets has been successful in reducing the incidence of disease in these populations and therefore subsequent human exposure. Rodent control is also effective in eliminating leptospirosis in communities.
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