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As of March 22, 1995, an addendum has been appended to this article.

Leptospirosis is a complex disease affecting most species of warm-blooded animals.¹ We describe here 3 actual cases of this disease, all of which involve transmission from domestic or wild animals to human beings.

Transmission to a human being from aborting cows

Eighty yearling Hereford heifers were retained by a rancher as breeding replacements for his herd. After being bred in March and April, they were kept in fenced pastures and given access to water in a pond at the headwaters of a river. The heifers were observed to wade into the pond and alternately drink and urinate. They were inoculated only with a blackleg-malignant edema bacterin/toxoid.

In October, the rancher noticed abortions among these heifers. The number of abortions increased rapidly and continued over 4 to 5 weeks. On 2 consecutive days during this time, the rancher manually removed dead fetuses from affected cows and treated several others with antibiotics for retained placentas. During an 8-week period, 60 of the 80 heifers aborted, and 6 died. Urine and paired serum samples from several of the aborting cows, as well as tissues and thoracic fluid from 2 fetuses, were submitted by the attending veterinarian to a veterinary diagnostic laboratory.

Ten days after pulling the 2 dead fetuses, the rancher experienced sudden onset of severe muscle pain, nausea, and other influenza-like symptoms. When the symptoms worsened during a 24-hour period, he sought emergency treatment. Influenza was diagnosed. Initially, the physician refused to order diagnostic tests but, at the insistence of the rancher, laboratory tests, including complete microbial blood culture, were conducted. The rancher was sent home and was advised to take over-the-counter analgesics for pain as needed.

The clinical picture in the cattle was suggestive of leptospirosis, and results of tests performed by the diagnostic laboratory were confirmatory. An increased titer of agglutinating antibodies against Leptospira interrogans serovar pomona was detected in the second of 2 serum samples obtained 2 weeks apart (one near the time of abortion and a second 2 weeks later). Urine, collected from 2 heifers 3 to 5 days after abortion, yielded isolates of serovar pomona. Discernible microscopic lesions were not observed in badly autolyzed tissues from aborted fetuses, and attempts to isolate leptospires were unsuccessful because of gross contamination by bacteria that invaded the fetuses after death. However, sections of fetal lung, liver, and kidney were silver-stained, and numerous leptospires were detected.

The rancher's symptoms lessened in 4 to 5 days and his recovery was complete and uncomplicated. Results of diagnostic tests of a single serum sample obtained at the time of his hospital visit revealed no antileptospiral agglutinin titer, but 3 months later, leptospires were detected in one of the media used for blood cultures. The isolate was discarded without typing.

Several weeks later, the rancher met with his veterinarian to discuss the episode of abortions and to plan the following year's breeding program. At that time, he asked the following questions:

Q: What was the probable source of the infection and how did it spread through the cattle and then to me?

A: Because these heifers were replacements from your herd, because your heifers did not intermingle with cattle from neighboring ranches, and because your herd had never been vaccinated against leptospirosis, it is a likely (but unconfirmed) possibility that the source of the infection was wildlife. Your heifers and deer were observed using the same pond. The behavior pattern of the cattle while drinking caused further contamination of the water with infected urine, encouraging the development of secondary and tertiary cases of the disease. The likely route of infection for you was uterine and vaginal secretions, urine, and tissues of aborted fetuses.^1-6

Q: Is leptospirosis always a severe disease?

A: Leptospirosis can be a severe, life-threatening disease or a mild, subclinical illness. In domestic animals, this varies with the infecting serovar. Serovars inducing mild infections often are referred to as host-adapted. Examples include serovars hardjo and bratislava, and Australis serogroup organisms, for which cattle, swine, and sheep, respectively, are the maintenance hosts.^7-11 Nonadapted strains, such as serovars pomona and icterohaemorrhagiae in cattle or swine, induce more severe disease, with marked clinical signs and sometimes death.^12,13 Host-adapted strains have not been identified in human beings, but there are variations in virulence among the serovars infecting human beings.^1,4,14

Q: Were the clinical signs and diagnostic test results typical of infection of domestic animals with a non-adapted strain of L interrogans?

A: In cattle infected with a nonadapted strain of leptospire, such as serovar pomona, abortion and a few deaths are not uncommon.¹⁵ The organism is shed in urine and uterine secretions after abortion. The duration of shedding may be long, but generally shedding lasts for only a few weeks. This is in contrast to infections of cattle by serovar hardjo, wherein the number of affected cattle, and therefore abortions, are sporadic, and adult cattle rarely die. This serovar also is shed after infection, but the duration of shedding most often is long, possibly for life.^16,17 The upper genital tract carrier rate can be about equal to the kidney carrier rate in infections by host-adapted strains.¹⁸

Serologic testing often is useful for diagnosis of infections by nonadapted strains of L interrogans. The most widely accepted serologic test is the microscopic agglutination test.¹⁹ An increasing titer usually is detected by comparing the agglutinating antibody titers in samples obtained at the time of first signs of disease with those obtained 2 weeks later.¹⁵ On the other hand, serologic testing often is not useful if infection is by a host-adapted strain such as serovar hardjo in cattle or bratislava in swine.²⁰ Titers in paired samples may be increasing, decreasing, or static, or there may be no titer, even against organisms isolated from the cow or pig being tested.^20,21 Tests more sensitive and specific than microscopic agglutination may eliminate this problem in the future but currently are not widely used.^22-26 It should also be mentioned that the antibody response to vaccination with commercial bacterins may cause false-positive results, confusing the results of serologic tests.²⁷

Detection of leptospires in tissues or fluids has been by darkfield or phase-contrast microscopy, bacteriologic culture, and inoculation of hamsters.^12,13,28,29 None of these detection methods is ideal; darkfield microscopy is insensitive and inoculation of hamsters is cumbersome. Further, some serovars that induce disease in domestic animals do not kill hamsters and therefore are not detected by this method. Nonadapted strains of leptospira tend to be shed in urine for a short period, and attempts at isolation may fail because urine was collected too late in the course of the disease. Veterinary diagnostic laboratories continually are improving their abilities to isolate for leptospira, but still are hampered by lack of culture media that are easily prepared, can readily support the growth of leptospira, and can selectively inhibit overgrowth by contaminants. Similar problems exist for host-adapted strains of leptospira, although these strains often are much more difficult to cultivate, particularly serovar hardjo from cattle and serovar bratislava from swine.^11,29

Examination of fetal tissues and fluids also can be helpful in the diagnosis of leptospirosis. The most common staining method used for microscopic examination of these tissues is silver impregnation. Fluorescent antibody techniques also are helpful and can be applied to fixed smears of pooled tissues for rapid testing. Reagents for fluorescent antibody tests are not commercially available but may be obtained by qualified individuals from the USDA, National Veterinary Services Laboratory, Ames, Iowa. Antileptospiral antibodies can be detected in fetal fluids,^30,31 and this procedure may be useful in the future as an aid to diagnosis of leptospirosis.

Q: Was my illness typical of other human cases?

A: Transmission of leptospirosis from domestic animals to human beings has been widely reported, often with a more minimal exposure than yours.^6,9,32-37 In your case, transmission may have been through infected uterine secretions, which should be considered as important a source of infection for human beings as infected urine. Your signs and symptoms were typical of acute leptospirosis.¹ Had appropriate tests been performed, it is likely that transient changes in renal function would have been detected.^1,14,38 Leptospirosis is rare enough that physicians often fail to consider it during establishment of a diagnosis. In your case, detection of the organism in microbiologic blood culture was fortuitous, as many clinical microbiology laboratories do not attempt to culture leptospires. Human-to-human transmission of leptospirosis is rare; thus human beings usually are dead-end hosts for the disease.

There also are misconceptions that leptospirosis in human beings is manifested by jaundice and that administration of antibiotics is ineffective if not begun during the first few days of the disease. In fact, jaundice is reported in less than 10% of cases of leptospirosis, and administration of antibiotics has been shown to be effective into the late stages of disease.

Transmission from an infected cow at necropsy, with secondary transmission to suckling infant

While conducting a necropsy on a cow, a veterinary diagnostician cut her hand and was exposed to tissue fluids from the animal. Twelve days later, the veterinarian experienced mild fever and malaise of 3 days' duration, followed in 10 days by higher fever, severe headaches and myalgia, and joint pain. During the next 3 weeks, periods of improvement were interspersed with recrudescence of fever, headache, and joint pain. A diagnosis of leptospirosis was established in the cow and, because the clinical picture in the veterinarian was suggestive of leptospirosis, serologic tests and microbiologic culture of urine were performed on specimens from the veterinarian. There was no microscopic agglutination titer in a serum sample obtained before the exposure, but the titer was 1:200 in serum obtained about 14 days after the first clinical signs. Two weeks later, the titer was 1:6,400. Leptospira interrogans serovar hardjo was isolated from urine, and leptospiruria continued for at least 60 days after the clinical phase of the disease.

The veterinarian continued to breast-feed her 4-month-old infant throughout the illness, and for this reason, antibiotic therapy was not instituted. Twenty-one days after the initial appearance of the mother's clinical signs, the infant became acutely ill and experienced fever, anorexia, irritability, and lethargy. A complete blood count revealed leukocytosis with neutrophilia and anemia. After 3 days of treatment with penicillin G IV and 10 days of amoxicillin orally, the infant's clinical condition improved dramatically and recovery was without incident. Leptospira interrogans serovar hardjo was isolated from the infant's urine.

During a final review of this case by the diagnostician, her supervisors, and the attending physicians, several points were discussed.

Q: Would the results of serologic testing alone have been sufficient to diagnose the disease in the mother?

A: In combination with the history and clinical signs, a 5-fold increase in antileptospiral agglutinating antibody titer is highly indicative of a leptospiral infection.^1,4

Q: What was the probable route of transmission of leptospires to the infant?

A: Milk seems to have been the most likely route. Serovar hardjo causes agalactia and mastitis in cattle,¹⁰ and leptospires have been isolated from the milk of a woman with clinical disease.³⁹ In the latter case, breast-feeding was discontinued during the mother's illness and the infant did not become infected. Although it does not apply to this particular case, transplacental infection, with fetal death and abortion, has been reported in human beings.^39-41

Transmission from wild rodents

A 23-year-old healthy male fell into a heavily polluted, inner-city river in early August. The river was known to contain raw sewage, and rats inhabited areas along the banks. The water was only a few inches deep, and he emerged uninjured but covered with mud and soaked with the polluted water. Twelve days after this incident, the man went to the emergency room of a hospital, complaining of fever, chills, stiff neck, and various muscle aches. After examination, he was sent home with a diagnosis of viral influenza and was urged to take analgesics and to drink fluids. Two days later, he returned to the hospital and was admitted, with a preliminary diagnosis of viral hepatitis. Hematuria and decreased kidney and liver function were detected, but a diagnosis of leptospirosis was not seriously considered. Microbiologic culture of blood and serologic testing for leptospirosis were performed later. Antibiotics were not administered until the fourth day after admission. The patient's fever increased, and he died after developing kidney and respiratory failure on the sixth day after admission. Postmortem examination revealed lesions pathognomonic of leptospirosis, including extensive damage to kidney and liver. Results of laboratory testing revealed the patient to have a 1:6,400 titer to serovar icterohaemorrhagiae, and leptospires were isolated from the blood sample. When the case was reviewed, attending physicians and local health officials discussed the following questions:

Q: The source of the infecting organisms probably was the water from the polluted river. How did the organisms get there?

A: The water was most likely contaminated by the urine of infected rats. It has been determined that more than 90% of adult brown Norway rats are infected with leptospires, and large numbers of the organisms, often of serovar icterohaemorrhagiae, are shed in urine.⁴² Human beings serve as accidental hosts for these spirochetes.

Q: Was this a typical case?

A: Yes, in all its signs and symptoms, this was a typical case of human infection with a nonadapted serovar of L interrogans, although not all such cases are fatal. The failure of physicians to diagnose the disease probably was attributable to unfamiliarity with leptospirosis, as it has a low annual incidence in the United States at this time. However, leptospirosis is common enough that physicians, especially those in areas whose populations are at highest risk, would be well advised to familiarize themselves with the disease and to consider including it in the differential diagnosis when patients develop acute febrile illness with other pertinent clinical signs and appropriate history. In this case, the wise course would have been microbiologic culture of blood and serologic testing for leptospirosis, followed by initiation of antibiotic treatment with tetracycline or doxycycline immediately upon admission.^43,44

Discussion

Leptospirosis has largely become a forgotten disease in the United States and has been overlooked by the medical community since the early 1960s. Since the extensive work on pathogenesis, diagnosis, and epidemiology of leptospirosis of the 1940s and 1950s, this and many other zoonotic diseases have been neglected in favor of pursuing more newsworthy conditions. The cases cited above, all of which are based on actual episodes of leptospirosis in human beings or domestic animals, illustrate the fact that this disease still is important as a cause of morbidity and mortality in the United States. Higher prevalence of human leptospirosis recently reported in New Zealand and the United Kingdom are thought to be attributable to renewed interest by diagnosticians and not to increased annual incidence.^45,46 The same is likely to be true in the United States.

Leptospirosis is a classic example of a disease that will require close collaboration of human medical and veterinary medical communities if public health is to be maintained. Veterinarians can best participate in this process by encouraging clients to adopt preventive measures (such as vaccination of cattle, swine, sheep, and companion animals) and by taking every opportunity to increase physicians' awareness of leptospirosis as a zoonosis of great potential importance.

References

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4. Sakula A, Moore W. Benign leptospirosis: first reported outbreak in British Isles due to strain belonging to the Hebdomadis serogroup of Leptospira interrogans. Br Med J 1969; 1:226-228.

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13. Hanson LE, Tripathy DN. Leptospirosis. In: Leman AD, Glock RD, Mengeling WL, et al, eds. Diseases of swine. 5th ed. Ames, Iowa: Iowa State University Press 1981; 386-395.

14. Kennedy ND, Pussey CD, Rainford DJ, et al. Leptospirosis and acute renal failure--clinical experiences and a review of the literature. Postgrad Med J 1979; 55:176-179.

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16. Thiermann AB. Experimental leptospiral infections in pregnant cattle with organisms of the Hebdomadis serogroup. Am J Vet Res 1982; 43:780-784.

17. Ellis WA, O'Brien JJ, Cassells JA. Role of cattle in the maintenance of Leptospira interrogans serovar hardjo infections in Northern Ireland. Vet Rec 1981; 108:555-557.

18. Ellis WA, Songer JG, Montgomery J, et al. Prevalence of Leptospira interrogans serovar hardjo in the genital and urinary tracts of non-pregnant cattle. Vet Rec 1986; 118:11-13.

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Addendum (1995)

Prepared by Carole Bolin, DVM, PhD, USDA-ARS, NADC, Ames, IA 50010.

Leptospirosis in dogs has long been recognized as an important source of exposure for human beings. Dogs tend to have more contact with human beings than do livestock species and, therefore, represent an important risk. Leptospirosis in dogs in the United States has traditionally been associated with infection by Leptospira interrogans serovars canicola and icterohaemorrhagiae. Widespread use of vaccines containing these leptospiral serovars has decreased prevalence of infection in dogs, and has, therefore, decreased risk of exposure of human beings to these agents.

Recently, infection of dogs with leptospiral serovars pomona, grippotyphosa, and bratislava has become common. Protection against infection with these serovars is not provided by currently available vaccines for dogs. Caution should be exercised when handling urine and body fluids from dogs with illness compatible with leptospirosis, regardless of the vaccination history.