Symposium: LeptospirosisA Re-emerging Disease
Symposium: LeptospirosisA Re-emerging Disease
CONFERENCE COVERAGE
By Frank J. Bia, MD, MPH
Source: Program and Abstracts of the 46th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Suppl. to Am J Trop Med Hyg 1997;57:43.
One real highlight of the 46th annual meet-ing of the American Society of Tropical Medicine and Hygiene was an extensive update the speakers provided in a symposium on a widespread zoonosis, leptospirosis, which, as recently as 1995, had been deleted from the Centers for Disease Control and Prevention (CDC) listings of nationally notifiable diseases. However, a recent large outbreak in Nicaragua during late 1995, the "rediscovery" of urban leptospirosis,1 and the well-recognized potential for leptospiral infections to occur during popular surface water sports activities provided ample material for this excellent symposium, which is summarized below. This session was chaired by Drs. Ansdell and Faine.
The session was opened by Dr. Vernon Ansdell, who reviewed the epidemiology of human leptospirosis, emphasizing several new and important issues related to the diverse circumstances in which this disease may present. He noted that Sir Philip Manson-Bahr had recognized the entity we now refer to as "urban leptospirosis" in London as early as 1922 and that a mortality rate exceeding 30% could be reached in patients over the age of 70. Three urban cases were recently characterized and reported from Baltimore by Vinetz et al, each associated with probable percutaneous exposure to infected rat urine in alleys where rodents were prevalent. Ansdell, who is on the faculty at the University of Hawaii, provided a vignette for a typical case from Hawaii, which continues to provide a majority of reported cases in the United States.
A 51-year-old man lost his eyeglasses in a freshwater pond while hiking. He submerged himself several times in the pond with his eyes open in an attempt to retrieve them, only to present 10 days later with a flu-like systemic illness, associated with an elevation of serum muscle enzyme levels (CPK). Acute respiratory distress syndrome put the patient into an intensive care unit on a ventilator for two weeks. Ansdell emphasized the severity with which this disease can present and the time lost from employment, particularly if a suggestive history is not obtained and early antibiotic treatment is not instituted. In this case, submersion in fresh water with opened eyes was the important exposure clue. Physicians, as well as the general public, in Hawaii are far more aware of leptospirosis and its epidemiology than those of us in the rest of North America due to vigorous public health measures and effective education initiatives, including some very sharp t-shirts.
Dr. David Sasaki of the Hawaii State Department of Health reviewed the surveillance, prevention, and epidemiology of leptospirosis in that state. The incidence rates for Hawaii from 1992 to 1996 were several hundred-fold greater than for the rest of the United States, and the most common risk activities in Hawaii are associated with exposures to freshwater streams. The island of Kauai has the highest incidence rate of all the Hawaiian islands. Peak incidence rates are seen from July throughout the second half of the year. Caucasians are over-represented as cases in the Hawaiian population, with students and office workers leading the list of those infected, but leptospirosis is rarely documented in tourists, at least while they are in Hawaii. The incubation period ranged from two to 23 days, with a median of nine days. Clinical diagnosis did not come easily, even in Hawaii, since the initial presentation suggested leptospirosis to health care providers in only 96 of the 182 (53%) cases studied over that time period.
In Hawaii, surveillance is laboratory-based, and the indirect hemagglutination (IHA) serum test samples are submitted to the CDC. Only 7% of those samples submitted acutely were positive, but the second sample, on day 14 or later, was positive in 62% for the same group of patients, emphasizing the need for careful clinical diagnosis early in the disease when no form of laboratory confirmatory testing is readily available yet.
Dr. Jeffrey Goodman, of the Kauai Medical Clinic, provided the experienced practitioners’ perspective from the most leptospirosis-endemic area in Hawaii. He still considers leptospirosis a truly protean disease in its clinical manifestations. Diagnostic clues in history, physical, and laboratory examinations are paramount in raising his level of suspicion. He looks for a history of cuts and abrasions, particularly in association with surface water sports, as an important risk factor to be elicited in the history. He carefully distinguishes conjunctival suffusion from conjunctivitis. In his experience, suffusion is very common during early leptospirosis. Unlike conjunctivitis, which is painful, suffusion is not, and it may appear more like an allergic reaction, later followed by subconjunctival hemorrhage. Goodman has rarely observed rashes in his patients on Kauai and does not consider absence of a rash sufficient reason to eliminate a diagnosis of leptospirosis. A leukocytosis or shift to the left is not usually present. More often, he observes thrombocytopenia and mild elevations of serum transaminases with serum bilirubin elevations, direct greater than indirect. Since he directly views the urine sediment himself, Goodman notes the urine is often "dirty" with RBC clumps and mucous threads. If muscles are tender, the serum CPK concentrations are often elevated, indicative of rhabdomyolysis. The electrocardiogram may offer clues in the form of arrhythmias and nonspecific repolarization abnormalities.
While textbooks tend to emphasize two distinct forms of the disease, the anicteric vs. the icteric form (Weil’s Disease), they are not really two separate disease entities, and he emphasized the biphasic nature of leptospirosis. The first 4-7 days are characterized by the septicemic phase with few specific clues to the diagnosis, followed by a one- to three-day interval, and then the immune phase, which can be characterized by severe renal and hepatic disease. Aseptic meningitis, with severe headache, is a feature of both phases of leptospirosis. In the 182 cases from Hawaii, summarized by David Sasaki, 59% had been hospitalized and 7% required hemodialysis, with an average of 10 days of work lost per case. Goodman also reminded his audience that leptospirosis during pregnancy may increase both the abortion and stillborn rate. In the pediatric population, leptospirosis can mimic Kawasaki’s syndrome, with its manifestations of apparent conjunctivitis and systemic illness. Because there has been no rapid laboratory method available to make an early definitive diagnosis, the clinical observations offered by this experienced practitioner, from a highly endemic region, were particularly well-received and appreciated.
On a broader epidemiological level, there were several lessons to be learned from recent outbreaks in Nicaragua and Puerto Rico. Dr. Richard Spiegel of the CDC noted that the appearance of leptospirosis associated with pulmonary hemorrhage in Nicaragua was, at first, easily confused with possible dengue hemorrhagic fever, or even yellow fever, as it had been in the past. This similarity between the clinical presentations of dengue and leptospirosis was the subject of another presentation at the meetings originating from Barbados, where leptospirosis is endemic and a large outbreak of dengue type 1 infection occurred in 1995.2 It wasn’t until spirochetal organisms were observed during histopathological examination of autopsy specimens in Nicaragua that the picture became clearer.
The role of rodents in the Nicaraguan outbreak was apparently less than that of seropositive dogs roaming the affected towns following heavy rains in the region. Infected dog urine in contaminated storm waters coursed down muddy streets, where people walked barefoot, which resulted in a high attack rate of 6.1% for a population of 37,000 people. Multiple serovars were identified in the outbreak, as might be expected under such circumstances. Spiegel noted that tropical Mexico has a similar problem with some dog populations in which the rate of seropositivity is as high as 60%. Outbreaks of leptospirosis in Puerto Rico during 1996 were also related to widespread flooding, but, in Costa Rica, white water rafting has emerged as another risk factor for leptospirosis.
Between 1994 and 1996, yet another potential ocular complication of leptospirosis was observed. More than 750 cases of uveitis occurred in Tamil Nadu State, India. In 1994, Rathinam et al reported the clinical features of 73 consecutive cases of uveitis during an outbreak of leptospirosis in Madurai, India. A majority of cases were bilateral, over 95% of affected eyes showing panuveitis.3 Recurrent uveitis is a leading cause of equine blindness, often occurring as a sequel of systemic leptospirosis and strongly associated with leptospiral seroreactivity.4
The laboratory diagnosis of leptospirosis is advancing to the point where "pinning it down" at the time of presentation is now within reach. Dr Robbin Weyant outlined the current state of this art, which is what it truly is. The "Holy Grail" of laboratory culture for body fluids requires both specialized media and up to three months for some serovars to grow. The ability of any lab to isolate these organisms is very much dependent upon the expertise available in any given laboratory outbreak. Darkfield microscopy requires many organisms in order for spirochetes to be visualized and the ability to distinguish them from protein fibers, which are easily mistaken for them. For fluorescence microscopy to be useful in the detection of leptospires, the conjugate must be tailored to detect those serovar(s) one is seeking in a particular case or outbreak. Histopathological techniques that employ silver staining or immunohistochemistry can be useful, as in the Nicaragua epidemic where histopathology provided a first clue to the etiology of the outbreak. Because newer techniques employing the polymerase chain reaction (PCR) can be very sensitive during early disease, when serology is not as useful, they are being looked upon as important advances in diagnosis, with clear applications for the immediate future.5
The diagnosis of leptospirosis has rested upon serological techniques, which are also evolving. The microagglutination test (MAT) can detect both recent and past infection, but it is complex and requires the serovars of the geographic area to detect antibodies. The CDC must maintain stocks of 21 strains for this test, which takes up to three days to complete. The indirect hemagglutination assay (IHA) employs L. biflexa-coated erythrocytes, with a relatively short test time of 4-6 hours, but neither the sensitivity nor the specificity of this test is at the 90% level, where it was originally thought to be. A one-hour Leptospira IgM ELISA has been tested on MAT-positive sera at the CDC with a sensitivity approaching 100%. When used on samples submitted to the CDC that were MAT-negative, specificity for these "non-cases" appeared to be only 83%. However, it is possible that the newer ELISA test is picking up early cases that the MAT did not. The Royal Tropical Institute in the Netherlands has developed a Leptospira-specific IgM dipstick assay.6 The major advantages are ease of use, rapidity, no need for electricity or special equipment, and easy storage of dipsticks and reagents for prolonged periods in warm climates. The system is currently under evaluation by the CDC.6
The organizers and presenters of this symposium were successful at bringing their audience up to speed on the current status of the art of diagnosing leptospirosisboth a clinical and laboratory artwith the latter showing signs of becoming more sensitive in early disease and more readily available than in the past.
References
1. Vinetz JM, et al. Sporadic urban leptospirosis. Ann Intern Med 1996;125:794-798.
2. Levett PN, et al. Detection of dengue infection in patients investigated for leptospirosis in Barbados. Abstract 582. In: Programs and Abstracts of the 46th Annual Meeting of the American Society of Tropical Medicine and Hygiene. Am J Trop Med Hyg 1997; 57:299.
3. Rathinam SR, et al. Uveitis associated with an epidemic outbreak of leptospirosis. Am J Ophthalmol 1997;124:71-79.
4. Dwyer AE, et al. Association of leptospiral seroreactivity and breed with uveitis and blindness in horses: 372 cases (1986-1993). J Am Vet Assoc 1995;207:1327-1331.
5. Merien F, et al. Comparison of polymerase chain reaction with microagglutination test and culture for diagnosis of leptospirosis. J Infect Dis 1995;172:281-285.
6. Gusshoven GC, et al. LEPTO dipstick assay for detection of Leptospira-specific immunoglobulin M antibodies in human sera. J Clin Microbiol 1997;35:92-97.
Which one of the following statements is true?
a. Most reported cases of leptospirosis in the United States are from the Gulf coast states.
b. The most rapid means to diagnose an acute case of leptospirosis is to submit urine for leptospiral cultures on specialized prepared media and examine cultures daily with darkfield microscopy.
c. In the urban transmission of leptospirosis, stray dogs are usually responsible for transmission of disease to humans.
d. Leptospirosis is easily confused with some clinical presentations of dengue fever.
e. Polymerase chain reaction (PCR) technology will not be useful in the acute diagnosis of human leptospirosis.
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