Leptospira spp. Infection
Edited October 14, 2015
Leptospirosis is a bacterial disease affecting a variety of domestic and wild animals and humans worldwide that has been reported in over 150 mammalian species. It is considered an emerging infectious disease in humans and in dogs. Subclinically infected wild and domestic animals serve as reservoir hosts and are a potential source of infection for incidental hosts and humans (Greene et al., 2006; Adler and de la Pena Moctezuma, 2010; Sykes et al., 2011).
Reports of leptospirosis in cats are rare, but cats shedding Leptospira spp. and serving as a source of infection have recently gained attention. Leptospira spp. antibodies are commonly present in the feline population, and Leptospira spp. shedding by cats with outdoor exposure has been demonstrated (Rodriguez et al., 2012; Fenimore et al., 2012). Cats mostly acquire the infection from captured rodents. The role of healthy carrier cats as source of contamination as well as the role of leptospires as a pathogen in cats might have been underestimated.
Leptospires are mobile, thin, filamentous bacteria belonging to Spirochetes that appear as fine spirals with hook-shaped ends (Fig. 1; Adler and de la Pena Moctezuma, 2010). Leptospires can remain infectious for several months under optimal environmental conditions, at temperatures around 25 °C, moisture, and a neutral soil pH (Greene at al., 2006).
There are over 250 pathogenic serovars based on differences in the carbohydrate component of the bacterial lipopolysaccharide. Different serovars are adapted to different wild or domestic animal reservoir hosts. Serovars are further grouped into antigenically related serogroups. Immunity to leptospires is serogroup-specific. Leptospirosis in dogs and humans is caused primarily by serogroup Leptospira interrogans and Leptospira kirschneri. Several serovars of both serogroups also have been reported to cause infections in cats (Greene et al., 2006; Sykes et al., 2011).
In dogs, serovars icterohaemorrhagiae and canicola were responsible for most cases of canine leptospirosis before 1960. Since the widespread use of a bivalent serovar-specific vaccine against canicola and icterohaemorrhagiae, there has been an apparent shift to other serovars that are now more commonly identified in dogs suffering from leptospirosis (Greene et al., 2006). Recently, new vaccines for dogs have reached the market in the USA and several European countries, which contain not only canicola and icterohaemorrhagiae, but also grippotyphosa, and in some vaccines additionally bratislava or pomona.
Leptospires cause infections in many animal species. Subclinically infected wild and domestic animals serve as reservoir hosts and are a potential source of infection for incidental hosts, including humans. In the incidental hosts, severe clinical signs can develop. Incidental hosts also shed the organism, although generally only for a short period (Greene et al., 2006).
Leptospires are transmitted by direct or indirect contact; direct transmission between hosts in close contact occurs through urine, venereal routes, placental transfer, bites, or ingestion of infected tissues as the organism penetrates mucosa or broken skin. Infected animals shed leptospires mainly through urine. Indirect transmission is more frequent in dogs and occurs through exposure to contaminated environment, e. g., soil, food, or bedding (Greene et al., 2006). Water contact is most important in dogs and humans, and habitats with stagnant or slow-moving warm water favour survival of the organism. Leptospires in contaminated water invade the host through skin wounds but also through intact mucous membranes. In cats, this type of transmission is less likely, due to their natural aversion to water. Cats rather get infected by feeding on animals harbouring leptospires. Rodents are the natural reservoir for many serovars, and prey-predator transmission between cats and rodents is likely (Shophet, 1979). Cats may also be exposed to urine of cohabitating dogs. Spirochetes have been shown to survive in insects and other invertebrates, but their role as vectors is unknown (Greene et al., 2006).
Antibody prevalence in cats ranges from 0 to 35%. Infections with several serovars have been identified in cats, including icterohaemorrhagiae, canicola, grippotyphosa, pomona, hardjo, autumnalis, and ballum (Rodriguez et al., 2012; Agunloye and Nash, 1996; Dickeson and Love, 1993; Mylonakis et al., 2005; Larsson et al., 1984; Batza and Weiss, 1987; Markovich et al., 2012). Prevalence of different serovars and preference of reservoir hosts differ significantly between geographical regions. Most studies based on antibody detection have used micro-agglutination tests (MAT). Cross-reactions between serovars occur, and therefore serovar prevalence studies are sometimes difficult to interpret. No correlation was found between antibodies, sex and breed. However, an association with age has been reported, with old cats being more likely to possess antibodies (Rodriguez et al., 2012; Mylonakis et al., 2005; Larsson et al., 1984). Antibodies are more common in outdoor cats, those living in urban areas, and known hunters (Rodriguez et al., 2012).
Recent studies have looked into shedding of Leptospira spp. in the urine of cats (Rodriguez et al., 2012; Fenimore et al., 2012). Using a quantitative real-time PCR, leptospiruria was studied in shelter cats in Colorado, and 10 out of 85 stray or feral shelter cats with previous outdoor exposure were found shedding pathogenic leptospires in the urine. This is comparable to that occurring in healthy dogs, and outdoor cats might be a reservoir or incidental hosts in the transmission of leptospires (Fenimore et al., 2012). Urinary shedding and the role of cats as a source of infection have been underestimated in the past. Some serovars may be shed by cats without detectable antibodies (Shophet, 1979).
Wild felids can be infected with Leptospira spp. as well; in captive healthy felids in Brazil antibodies were found in 2/57 healthy felids (Ullman et al., 2012)
The pathogenesis of feline leptospirosis is not well known but likely similar to that in dogs and humans. In them it occurs via direct contact with a host or its urine, or indirectly via contaminated soil or water (e. g., recreational activities, drinking, or bathing). After penetration through mucous membranes, abraded or scratched skin, leptospires multiply rapidly upon entering the blood vascular space as early as one day after infection. They invade the kidneys, liver, spleen, CNS, eyes, and genital tract amongst others, and damage these organs by replicating and causing inflammation. Initial replication mainly causes damage to the kidneys and liver. The extent of damage is variable and depends on virulence of the organism and host susceptibility. The immune response clears the leptospires from most organs except from the kidneys, where the agent can persist. In dogs, shedding may continue for weeks to months (Green et al., 2006; Sykes et al., 2011).
In dogs, infection with leptospires results in illness of varying severity, depending on infecting strain, geographical location, and host immune response. Some dogs display no or only mild signs of disease, whereas others develop severe illness or even death, often as a result of renal injury. In general, signs of hepatic and renal dysfunction and of coagulation defects are predominant in dogs with leptospirosis. In addition, dogs with leptospirosis can show signs of uveitis, pulmonary haemorrhage, abortion, or acute febrile illness (Green et al., 2006; Sykes et al., 2011).
Presence of antibodies as well as experimental infections have shown that cats can be infected with leptospires, but the infection is usually mild or even clinically inapparent (Agunloye and Nash, 1990; Dickeson and Love, 1993; André-Fontaine, 2006). Also, there was no significant difference in antibody prevalence between sick and healthy cats (Bryson and Ellis, 1976).
Experimental infections resulted in leptospiraemia, leptospiruria and mild clinical signs with histologic evidence of renal and hepatic inflammation. In a cat with ascites, enlarged liver, and impaired hepatic function, but without icterus, antibodies against L. hardjo could be detected (Agunloye and Nash, 1990). Leptospires have been isolated from thoracic fluid, aqueous humour, and kidneys of a cat, which at necropsy had widespread haemorrhages and straw-coloured fluid in the thoracic and peritoneal cavities (Bryson and Ellis, 1976). The most common clinical manifestation seems to be an interstitial nephritis, as reported in experimentally and naturally infected cats (Fessler and Morter, 1964; Hemsley, 1956; Rees, 1964; Arbour et al., 2012). A relationship between polyuria/polydipsia and the presence of antibodies against Leptospira spp was reported (André-Fontaine, 2006; Luciani 2004). A case series of three cats with leptospirosis had renal failure without liver involvement (Arbour et al., 2012).
In persons and animals, immunity to leptospires is serogroup-specific, with no cross-protection between different serogroups. Recovery from infection depends upon the production of specific antibodies. As these increase, the organism is cleared from most tissues, except from the kidneys. Renal colonization occurs in most infected animals, and the organism usually persists in tubular epithelial cells causing shedding for months to years after clinical recovery. Prognosis is highly dependent on the conservation of renal function (Greene et al., 2006).
Direct detection of the organism is difficult, and antibody testing using MAT is mostly used for the diagnosis.
Direct detection of the leptospires
Direct identification of the organisms can be achieved by several techniques including visualization in fresh urine by dark-field microscopy or in tissue sections or on air-dried smears by light microscopy, culturing of the organism, or detection of DNA by PCR. All direct methods, however, are only reliable in case of a positive result, and a negative result never excludes presence of the infectious agent due to the fact that leptospires are only shed intermittently and sometimes in low numbers (Greene et al., 2006).
Direct identification of viable leptospires by dark field microscopy is not recommended. A more reliable method is antibody staining (by immunofluorescence or immunoperoxidase), which can be used to identify leptospiral agents in body fluids and imprints of liver or kidneys (Fig. 2), if appropriate samples are available (Greene et al., 2006).
Leptospires can be cultured from blood, urine, and CSF, but they grow very slowly. Cultures may take weeks to months before becoming positive, and reliable results can only be expected when the animal had not been pretreated with antibiotics. Thus, in most cases culturing is no useful option in practice.
PCR methods have been developed to detect leptospiral DNA in body fluids, like blood, CSF, aqueous humour, and urine (Merien et al., 1995; Bal et al., 1994; Harkin et al., 2003a, b). In humans, PCR was shown to be more reliable in early diagnosis than antibody testing or culture (Brown et al., 1995). PCR to identify the organisms in urine, where it reaches high concentrations, has been experimentally shown to be sensitive and specific, and allows a diagnosis at an early stage of infection. But also PCR is only useful in untreated animals. Non-viable Leptospira spp. will also be detected, as well as subclinical carriers and non-pathogenic serovars. Sensitivity and specificity of available PCR tests for the diagnosis in dogs have not been fully assessed (Greene et al., 2006).
PCR was used in a few studies to detect Leptospira spp. shedding in cats (Rodriguez et al., 2012; Fenimore et al., 2012).
Antibodies can be detected using the MAT or an ELISA, the former being the most common diagnostic method in dogs and humans, and also in cats (Rodriguez et al., 2012; Agunloye and Nash, 1990; Dickeson and Love, 1993; Mylonakis et al., 2005; Larsson et al., 1984; Batza and Weiss, 1987; Markovich et al., 2012). However, MAT is not serovar-specific (Greene et al., 2006; Sykes et al., 2011), and cross-reactions make identification of the infecting serovar difficult. Variations of results between laboratories and differences in humoral immune responses may make correct interpretation of antibody tests even more difficult. Different serogroup antigens are included in the assay, and false-negative results will occur when the infecting serogroup is not included. In dogs, antibody titres of 800 against non-vaccine serovars, or a fourfold increase of the titre are considered presumptive of leptospirosis with compatible clinical signs (Greene et al., 2006). Diagnosis of the infection by antibody detection in cats might be easier because there is no vaccine in cats.
Treatment of dogs consists of supportive therapy and antibiotics, and the same should be done in cats. Supportive treatment depends on the severity of clinical signs and the presence of renal or hepatic dysfunction and other complicating factors. Treatment of acute renal failure is the most crucial aspect in dogs and the same is likely true for cats. Acute renal failure with anuria commonly requires renal replacement therapy with haemodialysis that is life saving for many animals with severe anuric leptospirosis. Thus, animals should be referred early to facilities with haemodialysis. Haemodialysis is indicated in animals with inadequate urine output that are developing volume overload, hyperkalaemia, or signs of uraemia that are not responsive to medical management (Sykes et al., 2011). The extent of renal damage after treatment determines the overall prognosis.
Antimicrobial therapy usually consists of two stages. The first stage is aimed to immediately inhibit multiplication of the organism and rapidly reduce fatal complications of infection such as hepatic and renal failure. Penicillin and its derivatives are the antibiotics of choice for terminating Leptospira spp. replication. Initially, ampicillin (20 mg/kg q 8 h IV) or amoxicillin, if available for IV use (20 mg/kg q 12 h IV), should be given parenterally to the vomiting, uremic, or hepatically compromised animal. These drugs prevent shedding and transmission of the organism within 24 hours of initiation of therapy. They are neither able to clear the infection from the kidneys nor to prevent a carrier state with chronic shedding.
In the second stage other drugs should be administered to address the carrier state. Doxycycline (5 mg/kg q 12 h PO for 3 weeks) is the drug of choice, and treatment should start as soon as the clinical condition allows oral application. Intravenous application can cause shock and vomiting, and subcutaneous injection leads to development of abscesses in cats. Doxycycline can also cause liver toxicity. Thus, it should only be started after the animal stops vomiting and liver enzymes are in the reference range. In cats, use of doxycycline suspension is preferred over tablets or capsules due to the risk of oesophageal strictures. In animals without or only mild clinical signs, doxycycline can be used for both initial and elimination therapy (Greene et al., 2006). In healthy cats shedding leptospires, treatment with doxycycline should be initiated to control the carrier state.
No vaccine is available for cats. To prevent cats from getting infected, they should be prevented from feeding on (potentially infected) rodents and stay away from stagnant water. Cats that are kept indoors have a very low risk to get infected.
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