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Overview of Leptospirosis

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Leptospirosis is a zoonotic disease with a worldwide distribution caused by infection with any of several pathogenic serovars of Leptospira. The disease affects virtually all mammals and has a broad range of clinical effects from mild, subclinical infection to multiple-organ failure and death.

Leptospira are aerobic, gram-negative spirochetes that are fastidious, slow growing, and have characteristic corkscrew-like motility. The taxonomy of Leptospira is complex and can be confusing. Traditionally, Leptospira were divided into 2 groups; the pathogenic Leptospira were all classified as members of L interrogans and the saprophytic Leptospira were classified as L biflexa. Within each of these species, leptospiral serovars were recognized, with ~220 different serovars of pathogenic Leptospira identified (based on surface antigens) throughout the world. With the increased use of genomic information for the classification of bacteria, the genus Leptospira was reorganized with the pathogenic leptospires now identified in 7 species of Leptospira. Some of the common leptospiral pathogens of domestic animals now have different species names. For example, L interrogans serovar grippotyphosa is now L kirschneri serovar grippotyphosa. The 2 types of serovar hardjo have been formally split into 2 species: serovar hardjo type hardjo-bovis (found in the USA and much of the world) is now L borgpetersenii serovar hardjo and the less common serovar hardjo type hardjo-prajitno (found primarily in the UK) is now L interrogans serovar hardjo. The revised nomenclature is now reflected in the scientific literature but not on labels for vaccines and pharmaceutical products. The serovar names remain and are useful when discussing the epidemiology, clinical features, treatment, and prevention of leptospirosis.

Essentially all mammals are susceptible to infection with pathogenic Leptospira, although some species are more resistant to disease. Among common companion animals and livestock, leptospirosis is most frequently recognized in cattle, swine, dogs, and horses. Cats seem to be relatively resistant to disease. Leptospirosis in wildlife is common, although the disease is most often noticed only when the wildlife serve as a source of infection for domestic animals or humans.

Leptospirosis occurs throughout the world. The infection and disease is more prevalent in warm, moist climates and is endemic in much of the tropics. In temperate climates, the disease is more seasonal with the highest incidence associated with periods of rainfall.

Although >220 serovars of pathogenic Leptospira are recognized, a subset of leptospiral serovars are prevalent within a particular region or ecosystem and are associated with 1 or more maintenance hosts, which serve as reservoirs of infection (see Common Maintenance Hosts of the Pathogenic Leptospires Associated with Disease in Domestic Animals in the USA and CanadaTables). Maintenance hosts are often wildlife species and, sometimes, domestic animals and livestock. Each serovar behaves differently within its maintenance host species than it does in other, incidental host species. In maintenance hosts, leptospirosis is generally characterized by a high prevalence of infection, relatively mild acute clinical signs, and persistent infection in the kidney and sometimes the genital tract.

Table 1

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Diagnosis of maintenance host infections is difficult because of relatively low antibody responses and the presence of few organisms in the tissues of infected animals. Examples of this type of infection are serovar Bratislava infection in swine and serovar Hardjo infection in cattle. In incidental hosts, leptospirosis is characterized by a low prevalence of infection, severe clinical signs, and a short renal phase of infection. Diagnosis of incidental host infections is less problematic because of a marked antibody response to infection and the presence of large numbers of organisms in tissues of infected animals. Examples of this type of infection are serovar Grippotyphosa infection in dogs or serovar Icterohaemorrhagiae infection in cattle and swine.

Characterization of a host/serovar interaction as a maintenance or incidental host infection is not absolute. For example, swine and cattle infected with serovar Pomona behave as a host intermediate between the two forms, with the organism persisting in the kidney but the host showing a marked antibody response to infection.

Transmission among maintenance hosts is often direct and involves contact with infected urine, placental fluids, or milk. In addition, the infection can be transmitted venereally or transplacentally with some host/serovar combinations. Infection of incidental hosts is more commonly indirect, by contact with areas contaminated with urine of asymptomatic maintenance hosts that shed leptospires in their urine. Environmental conditions are critical in determining the frequency of indirect transmission. Survival of leptospires is favored by moisture and moderately warm temperatures; survival is brief in dry soil or at temperatures <10°C or >34°C.

Despite the many serovars of Leptospira and host species, the key steps in the pathogenesis of the disease are similar in all host/serovar combinations. Leptospires invade the body after penetrating exposed mucous membranes or damaged skin. After a variable incubation period (4–20 days), leptospires circulate in the blood and replicate in many tissues including the liver, kidneys, lungs, genital tract, and CNS for 7–10 days. During the period of bacteremia and tissue colonization, the clinical signs of acute leptospirosis, which vary by serovar and host, occur. Agglutinating antibodies can be detected in serum soon after leptospiremia occurs and coincide with clearance of the leptospires from blood and most organs. As the organisms are cleared, the clinical signs of acute leptospirosis begin to resolve, although damaged organs may take some time to return to normal function.

At this point, the disease in incidental and maintenance hosts diverges. Leptospires remain in the tubules of the kidney of incidental hosts for a short period of time and are shed in the urine for a few days to several weeks. In maintenance hosts, however, leptospires often remain in the renal tubules, genital tract, and less commonly, the eyes, despite the presence of high levels of serum antibody. Leptospires are shed in the urine and genital secretions of persistently infected animals for months to years after initial infection, and these animals become an important reservoir of the infection.

The clinical signs of leptospirosis depend on the host species, the pathogenicity of the strain and serovar of Leptospira, and the age and physiologic state of the animal. Subclinical infections are common, particularly in the maintenance host. In incidental hosts, leptospirosis is an acute, systemic, often febrile illness characterized by alterations in renal and/or hepatic function. In addition, there may be effects on other body systems resulting in clinical signs (eg, vomiting, uveitis, pancreatitis, bleeding, hemolytic anemia).

In both incidental and maintenance hosts that are pregnant at the time of infection, localization and persistence of the organism in the uterus may result in fetal infection, with subsequent abortion, stillbirth, birth of weak neonates, or birth of healthy but infected offspring. In general, incidental hosts abort acutely whereas, in maintenance hosts, abortions or other reproductive sequelae may be delayed by several weeks or months.

Diagnosis of leptospirosis depends on a good clinical and vaccination history and laboratory testing. Diagnostic tests for leptospirosis include those designed to detect antibodies against the organism and those designed to detect the organism in tissues or body fluids. Serologic testing is recommended in each case, combined with one or more techniques to identify the organism in tissue or body fluids.

Serologic assays are the most commonly used technique for diagnosing leptospirosis in animals. The microscopic agglutination test is most frequently used. It involves mixing appropriate dilutions of serum with live leptospires of serovars prevalent within the region. The presence of antibodies is indicated by the agglutination of the leptospires. Enzyme immunoassays have been developed using a number of different antigen preparations and assay protocols. An assay that measures anti-leptospiral IgM is useful for detecting recent infection in livestock and dogs. Use of these assays is complicated in areas of the world where vaccination is common, and they are not commercially available in North America.

Interpretation of serologic results is complicated by a number of factors including cross-reactivity of antibodies, antibody titers induced by vaccination, and lack of consensus about what antibody titers indicate infection. Antibodies produced in an animal in response to infection with a given serovar of Leptospira often cross-react with other serovars. In some cases, these patterns of cross-reactivity are predictable based on the antigenic relatedness of the various serovars of Leptospira, but the patterns of cross-reactive antibodies vary between host species. However, in general, the infecting serovar is assumed to be the serovar to which that animal develops the highest titer. Paradoxical reactions may occur with the agglutination test early in the course of an acute infection, with a marked agglutinating antibody response to a serovar other than the infecting serovar.

Widespread vaccination of dogs and livestock with leptospiral vaccines also complicates interpretation of leptospiral serology. In general, vaccinated animals develop relatively low agglutinating antibody titers (1:100 to 1:400) in response to vaccination, and these titers persist for 1–3 mo after vaccination. However, some animals develop high titers after vaccination which persist for ≥6 mo.

Consensus is lacking as to what titer is diagnostic for leptospiral infection. A low antibody titer does not necessarily rule out a diagnosis of leptospirosis because titers are often low in acute disease and in maintenance host infections. In cases of acute leptospirosis, a 4-fold rise in antibody titer is often observed in paired serum samples collected 7–10 days apart. Diagnosis of leptospirosis based on a single serum sample should be made with caution and with full consideration of the clinical picture and vaccination history of the animal. In general, with a compatible clinical history and vaccination >3 mo ago, a titer of 1:800 to 1:1,600 is good presumptive evidence of leptospiral infection. Consultation with the diagnostic laboratory is often useful for titer interpretation. Antibody titers can persist for months following infection and recovery, although there is usually a gradual decline with time.

Immunofluorescence can be used to identify leptospires in tissues, blood, or urine sediment. The test is rapid and has good sensitivity but interpretation requires a skilled laboratory technician. Immunohistochemistry is useful to identify leptospires in formalin-fixed tissue but, because there may be small numbers of organisms present in some tissues, the sensitivity of this technique is variable. A number of PCR procedures are available, and each laboratory may select a slightly different procedure. These techniques allow detection of leptospires but do not determine the infecting serovar. Culture of blood, urine, or tissue specimens is the only method to definitively identify the infecting serovar. Blood may be cultured early in the clinical course; urine is more likely to be positive 7–10 days after clinical signs appear. Culture is rarely positive after antibiotic therapy has begun. Culture of leptospires requires specialized culture medium, and diagnostic laboratories rarely culture specimens for the presence of leptospires.

Avoidance of exposure to free-ranging wildlife and domestic animals that may be maintenance hosts for Leptospira is difficult because rodents, raccoons, opossums, and skunks are frequently found in rural and urban environments. The cornerstone of leptospirosis prevention is vaccination with polyvalent inactivated vaccines. Immunity to leptospirosis is serovar specific and therefore, vaccines are formulated for various species to include the relevant serovars. There are currently no leptospiral vaccines for horses. Leptospiral vaccines are generally designed and evaluated for the ability to prevent clinical signs of disease and should generally not be expected to completely prevent infection and shedding.

People are susceptible to infection with most of the pathogenic serovars of Leptospira but are incidental hosts and, therefore, not important reservoirs of the infection. Occupational exposure is a rick factor, and veterinarians, veterinary staff, livestock producers, and dairy workers are at increased risk. In addition, recreational exposure to waters contaminated with the urine from domestic animals or wildlife presents a risk. Animal owners have contracted leptospirosis via contact with infected companion animals and livestock.

The principal route of infection is contact with infectious body fluids (blood in acute cases or urine) via mucous membranes. In people, the disease varies from subclinical to severe and can be fatal when renal or hepatic failure occurs. The most common signs are fever, headaches, rash, ocular pain, myalgia, and malaise. Transplacental infection, abortion, and infection of infants via breast feeding have been described, making exposure of pregnant women of particular concern. Laboratory techniques are necessary for a definitive diagnosis. Because diagnosis of leptospirosis in animals is difficult based on clinical signs, veterinarians may wish to implement an infection control program whereby animal body fluids are handled only with gloved hands and hand washing is routine.

Last full review/revision March 2012 by Carole Bolin, DVM, PhD

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