Jonathan Fradkin, DVM, MS DACVIM
Leptospirosis is an infectious disease of historic & resurgent clinical significance. Due to the many factors involved in disease incidence & the transient decline in infection rates after development of the first vaccines, Leptospirosis is often under-emphasized in evaluation of disease & in preventive medicine program development.
Clinical infection is caused by a variety of gram negative motile spirochetes in the genus Leptospira. At least 17-18 species & over 200 serovars have been identified but only two species & 6-8 serovars are significant problems in pets. As species & serovar designations are continuously refined/changed & because serovar isolates do not directly correlate to clinical severity or form of disease, memorizing specifics of phylogeny is generally not necessary. Serovars of most concern in canine practice are [V=vaccine available for dogs]:
• L. [kirshneri or interrogans] grippotyphosa –V • L. [interroggans] canicola –V • L. [interroggans] icterohaemoragica –V • L. [interroggans] pomona –V • L. [interroggans] bratislava • L. [interroggans]autumnalis • Others: L. i. bataviae, hardjo, javanica, panama, pyrogenes, hebdomadis, tarassovi
All Leptospires share characteristics which contribute to their persistence. They are stabile in moist or wet environments with near neutral pH & are maintained in nature through a cycle of infection in Reservoir Hosts who have mild to absent clinical disease but chronically shed Leptospires into the environment. Contact with contaminated soil, water, bedding & food leads to infection of incidental hosts including dogs, people & cats. The most common Reservoir Hosts & most susceptible Incidental Hosts vary by Leptospire species & serovar (chart). Direct transmission is considered a less significant route of infection in Incidental Hosts though it is a concern in Veterinary Hospitals & boarding kennels.
After exposure to Leptospires, the severity & course of disease depends somewhat on serovar but more on extent of exposure & host immune status. In all cases the Leptospires enter through exposed mucous membranes or compromised skin. This initiates an Antibody response. Animals with strong Ab response will eliminate the organisms before systemic distribution. Those with inadequate response undergo a period of intravascular leptospire multiplication with leptospiremia, vasculitis, & thrombocytopenia. Distribution through the bloodstream results in infection of other target organs including kidneys, liver, spleen, CNS, & reproductive tract. If a moderate immune response has occurred, minimal or no clinical signs will be noted even after systemic distribution of the infection & urinary shedding (leptospiruria) will be minimal or absent. Inadequate immune response allows more severe inflammation & toxic effects leading to organ function compromise or failure (diagram).
The classic “HepatoRenal” syndrome of jaundice & acute kidney failure occurs as bacterial toxins stimulate acute hepatitis & vasculitis within the kidneys leading to acute renal failure. Historically this was most common in large breed, adult, rural male dogs, & was due to L. icterohemorragica or L. Canicola. In recent years, “transformation” of the disease has been noted. Subsequent to initial use of “2-way” bacterins against L. ictero. & L canicola, more infections with other serovars have been noted nationwide, esp. L. grippotyphosa, L. Pomona, & L. bratslava. Recent epidemiologic evaluation shows both urban & suburban dogs are at high risk & that small & large breed dogs are at similar risk. Concurrently, the zoonotic profile of leptospirosis has shifted from an occupational hazard affecting mainly meat-production workers & veterinary personnel to a disease associated with recreational exposure to contaminated water & soil, e.g. boating, fishing, etc.
Epidemiology can not identify a single specific cause for these transforming changes in the character of Leptospirosis but several factors are thought to be important: (1) Impact of use of Bivalent vaccine in late 1970s & 1980s with subsequent reduced use in the 1990s (2) Expansion of suburbs into formerly rural lands, & (3) Increased interaction/encroachment of people & pets upon wildlife. This combination has contributed to a resurgence of leptospirosis, often in absence of classic “hepatorenal syndrome.”
While acute liver & kidney disease are still common, other common problems include: thrombocytopenia & coagulopathy; fever & nonspecific signs such as anorexia, vomiting, lethargy; muscle pain; (peri)ocular inflammation; & chronic hepatic &/or renal disease. These findings strongly indicate that leptospirosis is a reasonable differential for any dog with nonspecific illness & that reconsideration of preventive medical care is appropriate.
As prevention is most crucial, appropriate vaccine protocols are needed. Concerns regarding leptospira vaccines are numerous including: increased risk of adverse reaction, lack of need due to low incidence of disease, & lack of designation as a “core” vaccine in published protocols. In fact, while leptospira vaccines are commonly blamed for adverse reactions, recent studies have shown that incidence of adverse effects correlates only with: Lyme vaccination &/or use of increased number of separate vaccines concurrently. Numerous studies document increasing incidence of leptospirosis in dogs, & people, & lack of designation as a “core” vaccine emphasizes risk based assessment rather than recommended exclusion from a vaccine plan. When Lepto Vaccine is administered, a “4-way” including coverage for L. grippotyphosa & L. pomona as well as L. ictero. & canicola is appropriate.
Definitive diagnosis of Leptospirosis depends on identification of the organism by culture, darkfield urine microscopy, PCR, or immunohistochemistry; or elevation of serum titer(s). Microagglutination Titer (MAT) is the gold-standard but Immunofluoresence may also be used. Interpretation of titers is specific to individual diagnostic labs but general guidelines are that individual titers of <1:400 are likely vaccine or early infection, while those >1:1600 are likely current or recent infection. Antibody titer peaks 3-4 weeks after infection and may not become elevated for up to 10 days so serial evaluation is important if signs & history suggest infection but initial titer is not conclusive. PCR detection of leptospiruria is becoming more common but there is slight concern that recently vaccinated dogs may test false positive. Presumptive treatment is often appropriate to reduce affects of disease & zoonotic risk pending diagnosis.
“Stage 1” treatment with a Penicillin (Ampicillin or Amoxicillin) inhibits Leptospire multiplication & dissemination to rapidly intervene in the clinical course of disease and reduce shedding of infectious leptospires. Supportive care for systemic vasculitis, thrombocytopenia and organ dysfunction is often needed during Stage 1 treatment. “Stage 2” therapy is aimed at eliminating leptospiruria and chronic carrier conditions due to residual infection of the kidneys. The drug of choice for Stage 2 is a Tetracycline, generally Doxycycline. Aminoglycosides are also effective but generally contraindicated due to route of administration and renal compromise. Fluoroquinolones & Macrolides have also been used but are not generally effective in long-term elimination of carriers. In dogs without severe clinical signs, Doxycyline can be started at diagnosis and Stage 1 treatment with Amoxicillin omitted.