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Leptospirosis is a disease caused by infection with pathogenic Gram-negative obligate aerobic spirochaete bacteria of the Leptospira genus. Leptospires are distinctively shaped helically coiled motile bacteria with a complex taxonomy. These bacteria are found worldwide and can cause clinical disease in most mammals, including cattle, horses, sheet and rodents (Levett, 2001). Dogs, and less commonly cats, can become infected with Leptospira, which can cause a variety of clinical signs, ranging from mild and non-specific to severe, multi-systemic, fulminant disease that can lead to death (van de Maele et al., 2008; Schuller et al., 2015b). Both species can also be asymptomatic shedders of this potential zoonosis in the urine, so awareness and control of the disease is important from a public health perspective (Riss and Brown, 2014).

Taxonomy
Prior to 1989, two species were recognized: the pathogenic Leptospira interrogans sensu lato and the saprophytic Leptospira biflexa sensu lato (Levett, 2001). Further subclassification into serovars was based mostly on the use of serological methods, based on agglutination after cross-adsorption of rabbit antisera with heterologous antigen (Dikken and Kmety, 1978). Specific antisera recognize over 250 different serovars (Ko et al., 2009). In addition, 24 serogroups are currently recognized; these are groups of antigenically related serovars that agglutinate when incubated with serum containing antibodies to an individual serovar from the same serogroup (Ko et al., 2009). They have no taxonomic standing, but are useful from an epidemiological perspective (Levett, 2001). More recently, genetic classification based on DNA hybridization has identified at least 9 pathogenic species, 6 saprophytic species and 5 intermediate species (Schuller et al., 2015b). The molecular classification, whilst technically correct, does not correspond with the serological classification, but the system of serogroups is still in widespread use by clinicians and epidemiologists (Levett, 2001; Ellis, 2010).

  • Serovar – a term commonly used to describe the specific strain of Leptospira that has been diagnosed in a specific case using serology; reacts with a specific monoclonal antiserum (Goldstein et al., 2006; Schuller et al., 2015b).
  • Serogroup – group of antigenically closely related leptospiral serovars (Schuller et al., 2015b).
  • Strain – a specific isolate of a defined leptospiral serovar (Schuller et al., 2015b).

Serovars present in the UK and Europe
There is a paucity of evidence regarding current circulating serovars, partly due to different testing methodologies being used by different laboratories, but also because comprehensive relevant studies are lacking. Different serovars are considered to be adapted to specific reservoir or maintenance hosts and vary in different geographical regions (Levett, 2001; Ellis, 2010), so the local situation will differ.

Dogs in Europe are potentially exposed to the serogroups Icterohaemorrhagiae (maintenance host = rat), Australis (maintenance host = wildlife), Canicola (maintenance host = dog), Grippotyphosa and Sejroe (maintenance host for both serogroups = rodents). The importance of the latter two groups varies with the presence of the maintenance host (Ellis, 2010).

Dogs in Europe are mostly exposed to infection with serovars Icterohaemorrhagiae and Copenhageni from the serogroup Icterohaemorrhagiae and these are the most commonly recognized cause of clinical leptospirosis in dogs. Cases have been reported in the UK, with farm and sporting dogs over-represented (Ellis, 2010).

Clinical infection of dogs with the serovar Canicola is now considered rare in the UK, although a serological prevalence of 18.4% was reported in unvaccinated dogs in 1991 (van de Broek et al., 1991). Serovar Bratislava from the serogroup Australis is most commonly isolated from domestic animals and dogs. Maintenance hosts include pigs, horses, hedgehogs and probably dogs. There is evidence of widespread exposure to serovar Bratislava infection, and strains from the serogroup Australis have been detected in dogs with acute clinical disease and nephritis/reproductive problems in Italy and the UK, respectively (Ellis, 2010).

Exposure to serovar Grippotyphosa in mainland Europe, particularly Germany, has been shown in seroprevalence studies, with higher seroprevalences identified in dogs from rural environments considered to reflect the distribution of wildlife hosts. A study in 1973 reported antibodies to the serovar Grippotyphosa in wild mammals, including goats and wood mice (Twigg et al., 1973), but had not been reported subsequently until the time of the review by Ellis in 2010.

Until recently, low levels of exposure to serovar Pomona have been reported in dogs in Europe. Serovars Mozdok and Pomona have been reported in the UK, with serovar Mozdok infection having been identified in cattle and pigs in the southwest of England. Serovar Pomona has been identified in a horse and a monkey in Northern Ireland, probably as a result of exposure outside the UK (Ellis, 2010). More recent studies in Germany (Mayer-Scholl et al., 2013) and Greece (Arent et al., 2013) have identified antibodies to serogroup Pomona in dogs with disease and in Ireland from five blood samples from 464 dogs not suspected to have leptospirosis (Schuller et al., 2015a).

Table 1 shows the leptospiral serovars and serogroups of potential relevance in Europe for inclusion on the microscopic agglutination test (MAT) panel. The major serogroups to which dogs in Europe are seroconvert are highlighted in bold.

Serogroup Serovars Maintenance host  Potential relevance in Europe 
Australis Bratislava, Lora, Jalna, Muenchen Pig, horse, dog, hedgehog Evidence of exposure across Europe a, including Ireland b; disease reported in Italy c, France d and Switzerland e
Autumnalis Autumnalis, Bim Mouse Included on MAT panel ef
Ballum Ballum Rodents Insufficient evidence of infection/clinical disease in Europe a; detected in dogs in Ireland, rarely reported in infected dogs b
Canicola Canicola Dog Still serological evidence of exposure, although cases rare likely due to vaccination a
Grippotyphosa Grippotyphosa Rodents One of the most common causes of leptospirosis in Germany g and France d. Seroconversion rare in UK a and Ireland b
Icterohaemorrhagiae Copenhageni, Icterohaemorrhagiae  Rat One of the most prevalent serogroups and most common recognized cause of clinical leptospirosis in European dogs a
Pomona Mozdok, Pomona Small rodents, cattle, sheep, pig Low levels of exposure in Europe (c.f. USA). Evidence of seroconversion thought to have been identified in the UK only, in Northern Ireland a, until recently identified in Ireland b
Pyrogenes Pyrogenes Rodents Should be included in the MAT panel f
Sejroe Hardjo, Saxkoebing, Sejroe Cattle, sheep, rodents Insufficient evidence of infection/clinical disease in Europe a

References: a Ellis, 2010; b Schuller et al., 2015a; c Mastorilli et al., 2007; d Ayral et al., 2014; e Major et al., 2014; f Schuller et al., 2015b; g Mayer-Scholl et al., 2013.

Clinical signs

Clinical manifestations of disease may vary geographically, depending on the serovars circulating (Levett, 2001; Goldstein et al., 2006; Ellis, 2010; Moore, 2013), and are determined by the virulence and load of the infecting serovar, environmental facts and the age and immune status of the host (Levett, 2001; van de Maele et al., 2008; Schuller et al., 2015b). Risk factors for clinical leptospirosis can vary with country, time of year and studies, although dogs that swim in or drink from outdoor water sources and/or hunt wildlife may be at increased risk (van de Maele et al., 2008; Lee et al., 2014; Schuller et al., 2015b), and clinical disease has been associated with heavy rainfall and flooding (Ward, 2002; van de Maele et al., 2008; Damborg et al., 2016).

The disease presentation may be subacute, acute or peracute. Clinical signs can be non-specific and multi-systemic and include vomiting, weakness, lethargy, fever, polyuria/polydipsia (PU/PD) and jaundice (van de Maele et al., 2008; Schuller et al., 2015b). Dyspnoea may be present and, in such patients, leptospiral pulmonary haemorrhagic syndrome (LPHS) should be considered. This is an emerging severe form of leptospirosis identified in humans and has been described in dogs in Germany (Klopfleisch et al., 2010; Kohn et al., 2010) and Switzerland (Major et al., 2014), although it has been reported to occur in the absence of obvious respiratory distress (Kohn et al., 2010). An acute fatal presentation has been described in 10 dogs in Georgia, USA, nine of which were younger than 6 months old. The authors reported similarities to the clinical presentation of Weil’s disease in humans with subtle hepatic and renal changes on histopathology, suggesting it represents a septicaemic or endotoxaemic disease (Riss and Brown, 2014).

Supportive findings on biochemical tests include increases in urea and creatinine, elevation of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin, and electrolyte abnormalities. Common haematological abnormalities include leucocytosis and thrombocytopenia, and both hypocoagulable and hypercoagulable states have been reported. Isosthenuria and hyposthenuria have been described, as have proteinuria, glucosuria and granular casts (Mastorilli et al., 2007; van de Maele et al., 2008; Schuller et al., 2015b).

The many clinical signs and preliminary diagnostic findings compatible with leptospirosis, and the variation between Europe and North America, are discussed in more detail by various authors (van de Maele et al., 2008; Sykes et al., 2010; Schuller et al., 2015b), but dogs at potential risk of exposure with icterus and/or signs of acute kidney injury may be considered as suspected leptospirosis until a definitive diagnosis is made (Mastorilli et al., 2007; van de Maele et al., 2008).

Indications for testing
Table 2 details the indications for testing for leptospirosis.

Clinical syndromes or conditions that should prompt a search for leptospirosis 

Acute kidney injury
Isosthenuria associated with glucosuria without hyperglycaemia
Acute hepatopathy ± jaundice
Acute respiratory distress ± haemoptysis of unclear aetiology with focal or generalized pulmonary reticulonodular interstitial pattern ± patchy alveolar consolidationscute kidney injury

Clinical syndromes or conditions for which leptospirosis should be included as differential diagnosis
Acute haemorrhagic gastroenteritis not due to parvoviral infection
Acute febrile illness
Uveitis, retinal bleeding
Additional features/laboratory abnormalities reinforcing a clinical suspicion of leptospirosis
Complete blood count (CBC) abnormalities (thrombocytopenia, anaemia)
Abnormal urine sediment (pyuria, haematuria, proteinuria, casts)
Surface bleeding/coagulation abnormalities (rare)
Ultrasonographic abnormalities (renomegaly, perirenal fluid accumulation, medullary band of increased echogenicity, mild pyelectasia)
Epidemiological clues (bathing or drinking in marshy areas or standing water, contact with wild rats)

Reproduced from Schuller et al., 2015b with permission from the Journal of Small Animal Practice.

Diagnosis

A definitive diagnosis of leptospirosis is difficult because of a number of factors. The gold standard is to culture the fastidious leptospires from blood, urine or tissue samples; and once isolated, the organisms can be serotyped and genotyped. However, this process is time-consuming (it can take up to 26 weeks and so is more helpful for epidemiological studies than clinical cases), technically demanding (requiring a specialist laboratory and trained staff), involves a potential health risk and is not routinely available. Dark field microscopy of cultures or urine samples can identify entire leptospires, but is of low sensitivity and specificity. Silver staining and Warthin-Starry staining can be used for histological examination. Immunohistochemical and immunofluorescent methods are also available (Levett, 2001; Wild et al., 2002).

Microscopic Agglutination Test (MAT)
This is the most widely used diagnostic test for acute leptospirosis and can be used to demonstrate prior exposure in asymptomatic dogs. It is relatively inexpensive, widely available and there is a substantial body of evidence regarding its use (Sykes et al., 2010). Although it has its limitations, it is still the preferred confirmatory test. Serial dilutions of the patient’s serum are incubated with live antigen suspensions of leptospiral serovars in vitro and assessed for agglutination under dark field microscopy. The antibody titre is defined as the reciprocal of the highest serum dilution causing 50% of the leptospires to agglutinate (Levett, 2001; van de Maele, 2008; Schuller et al., 2015b).

This test is difficult to perform, control and interpret, and presents a health risk to the technician (Levett, 2001). There are marked limitations to this test with respect to sensitivity, specificity and repeatability, and there is inevitable variability between laboratories. Ideally, laboratories should subscribe to a quality control scheme such as The International Leptospirosis Proficiency Scheme (Miller et al., 2011; Schuller et al., 2015b).

Reactivity to a serovar on the MAT indicates exposure to a serovar from the same serogroup, but does not confirm that the serovar reacted to is the one causing disease. The serovars included on the panel tested should reflect the antibody prevalence data for the local area, although this is not always available (Sykes et al., 2010; Miller et al., 2011; Schuller et al., 2015b). In Europe, it is suggested that at least the serogroups Australia, Autumnalis, Canicola, Grippotyphosa, Icterohaemorrhagiae, Pomona, Pyrogenes and Sejroe are included (Schuller et al., 2015b).

Antileptospiral antibodies in the patient’s serum may react with multiple serogroups due to the presence of several common antigens, and this cross-reactivity is especially apparent in acute-phase samples as the MAT detects both immunoglobulin (Ig) M and IgG antibodies (Levett, 2001). ‘Paradoxical reactions’, where the greatest titres detected relate to a non-infecting serogroup, are common, particularly where the patient has previously been infected by a different serogroup and the anamnestic response complicates interpretation. The serogroup with the highest titre can also vary over time. Thus, the MAT does not reliably predict the infecting serogroup in acutely infected animals (Levett, 2001; van de Maele et al., 2008; Miller et al., 2010; Schuller et al., 2015b).

Antibodies can be low in chronically infected animals, so the MAT cannot be used to detect carriers. A wide range of serovars should be included on the panel to ensure that a negative test is not the result of missing an infection with a new or previously undetected serovar in the locality. Samples submitted for testing before seroconversion will return a misleading negative result. Prior vaccination can complicate interpretation of MAT results (van de Maele et al., 2008; Andre-Fontaine, 2013; Schuller et al., 2015b).

A single MAT cannot reliably differentiate between vaccinated dogs and infected dogs. Vaccination produces an antibody response, which is generally at a lower titre and shorter-lived (antibody negative by 15 weeks post-vaccination, although Martin et al. (2014) demonstrated that some titres can persist for 12 months) compared with natural infection, but different authors quote different titres at which infection might be suspected in a dog with clinically compatible signs (Andre-Fontaine, 2013; Fraune et al., 2013). Post-vaccinal titres of at least 1:6400 to both vaccinal and non-vaccinal serovars have been reported in non-infected dogs (Martin et al., 2014).

The sensitivity of the MAT is increased when paired titres are interpreted 1-2 weeks apart (Fraune et al., 2013; Schuller et al., 2015b). If the patient’s titre was initially negative but the convalescent titre to one or more serovars is at least 800, or there is at least a four-fold rise between the initial and second titre, this is suggestive of clinical leptospirosis (van de Maele et al., 2008; Schuller et al., 2015b). Treatment with antibiotics can depress antibody titres or supress an increase in the convalescent titre (van de Maele et al., 2008).

Molecular testing
Leptospiral DNA can be detected by conventional polymerase chain reaction (PCR) or (more commonly) quantitiative/real-time qPCR of blood, urine and/or tissue samples. Several assays have been described, which aim to detect genetic sequences from conserved regions of the genome of pathogenic Leptospira spp. With time and increasing sophistication of the databases informing such techniques, some of these assays have been shown to detect the DNA of certain commensal or environmental sources, including those present on the skin or in the soil; such an assay which aimed to amplify only a region of the 16SrRNA gene but that shares a high level of nucleotide sequence identity with these unintended targets is no longer recommended for diagnostic use (Fink et al., 2015).

Other assays target a sequence such as one on the lipL32 gene, which encodes the LipL32 lipoprotein present only in the outer membrane of pathogenic leptospires (Fink et al., 2015), or the lig genes encoding the Lig (leptospiral immunoglobulin-like) proteins that are virulence determinants of pathogenic leptospiral species (Xu et al., 2014). The assay used and thus the sensitivity and specificity varies with laboratory, as may the quality control.

A qPCR with appropriate positive and negative controls can be used to identify the presence of pathogenic leptospiral DNA. A positive blood sample result from a patient with compatible clinical signs is supportive of clinical leptospirosis, and can be used instead of MAT in the acute phase of infection prior to seroconversion occurring. As the technique can detect viable and non-viable organisms, it can still be used to attempt diagnosis during the early stages of antibiotic therapy. A positive urine sample result indicates renal shedding and can be used to detect renal carriers. qPCR results are unaffected by previous leptospirosis vaccination. qPCR can also be used to test tissue sample when these are available (Sykes et al., 2010; Fink et al., 2015; Schuller et al., 2015b).

Whilst PCR and qPCR do not identify infecting serovars, sequencing or other advanced molecular methods may offer epidemiological data, although these are not routinely commercially available at this time (Levett, 2001; Sykes et al., 2010; Schuller et al., 2015b).

Negative results may indicate that pathogenic leptospires are not present, or that they are not present at the time of sampling (leptospiraemia is transient and renal shedding is intermittent), or that they are present at levels below the detectable limit of the assay. Negative results may be seen with dogs on antibiotic treatment (Fraune et al., 2013) or if inhibitors are present in the reaction.

Fluorescent in situ hybridisation (FISH) can be used to identify leptospires in tissue samples and is currently only commercially available at Langford Veterinary Diagnostics. This technique uses fluorescent probes designed to bind specifically to the DNA of target bacteria where present in a biopsy or post-mortem tissue sample submitted freshly fixed in formalin as a tissue block or on a slide.

Other methods
A modified semi-quantitative enzyme-linked immunosorbent assay (ELISA) that detects canine IgG to serovars Icterohaemorrhagiae, Canicola, Pomona and Grippotyphosa for use in practice has recently been licensed in Europe, and an in-house test to detect canine IgM to pathogenic leptospires has been evaluated (Abdoel et al., 2011; Schuller et al., 2015b). As these tests are subject to similar limitations as the MAT, the European Consensus Statement on Leptospirosis in Dogs and Cats panel recommends that these tests are used alongside MAT titres. A recent study has also identified potential candidates of immunodominant leptospiral proteins for use in a novel diagnostic serological assay (Thomé et al., 2014).

The in-house ELISA (Idexx SNAP® Lepto) is a qualitative patient-side test that uses three drops of serum to detect antibodies to the Lip32 antigen, the most abundant outer membrane protein of pathogenic Leptospira spp. The test can detect antibodies to the serovars Grippotyphosa, Canicola, Pomona and Icterohaemorrhagiae. It cannot differentiate between serovars or between antibodies produced as a result of natural exposure or those resulting from vaccination. It can be used to provide a rapid assessment of leptospiral antibody status and interpreted in light of clinical findings, vaccination history and other diagnostic test results.

Agreement between the positive results of this test (205 positive results) and the MAT (259 positive results) has been described as 79.2% from 460 canine serum samples, with agreement increasing with increasing peak MAT titre. However, agreement between the positive results of the SNAP® Lepto test and peak MAT titres from 100-1600 ranged from 55.0-73.5%. The overall negative test result was reported as 82.1% (Curtis et al.,2015). The SNAP® Lepto test has also been evaluated in a clinical setting (Winzelberg et al., 2015). Idexx provide a diagnostic algorithm which should be used when interpreting the results of their test.

What samples to take and when to take them
Knowledge about the pathogenesis of the clinical disease and the availability and limitations of various test methodologies can help clinicians take the most appropriate sample(s) at the correct time. Not only is this more clinically relevant, but such laboratory data may contribute to epidemiological studies that can help inform local knowledge about circulating serovars and, therefore, make informed vaccine choices.

For the first 10 days post-infection, leptospires are generally found in the blood; after this time they are intermittently shed in the urine. However, this is dependent on the properties of the infecting strain and the immune response of the host, and in naturally infected dogs, the exact timing of exposure to the infectious agent is often unknown. In addition, leptospires have been identified in blood samples by culture and PCR on day 4 post-infection but not on day 5. Seroconversion can occur as early as 3-5 days post-infection , but it is known for samples to be negative on antibody testing at day 7 post-infection (Levett, 2001; Sykes et al., 2010; Schuller et al., 2015b).

The European Consensus Statement of Leptospirosis in Dogs and Cats panel recommends PCR testing of both blood and urine collected before antibiotic administration in each dog with a clinical suspicion of leptospirosis, regardless of the duration of the clinical signs, and that PCR results should always be interpreted cautiously and in conjunction with MAT results, taking into account the clinical context (Schuller et al., 2015b).

Whole blood in ethylenediaminetetraacetic acid (EDTA) is general preferred for qPCR testing, and is stable in the fridge or freezer for this test for 5-7 days. Fresh urine can be sent in plain tubes and tissue samples can be transported in saline in plain tubes, but check with the individual laboratory for their specific requirements and preferences before submission. As for any infectious zoonotic disease, samples should be packed and identified appropriately.

Summary of a suggested testing protocol for a vaccinated or unvaccinated dog presenting with suspected leptospirosis
The sampling protocol depends on the time at which the dog was likely exposed to infection and when it is presented. The schedule below illustrates the potential time course to consider when trying to diagnose leptospirosis. The time of infection is usually unknown, so deciding on what samples to take when is largely a matter of clinical judgement. The diagnostic yield may be increased by taking paired samples of both blood and urine at initial presentation and again 7-14 days later.

  • 0-3 days post-infection – leptospiraemic but not likely seroconverted yet; not had antibiotics; send whole blood sample for qPCR.
  • 3-5 days post-infection – likely leptospiraemic, may be seroconverting; send serum sample for MAT and whole blood sample for qPCR; aim to send a paired sample in 7-14 days.
  • 7-10 days post-infection – likely still leptospiraemic, likely to have seroconverted; send serum sample for MAT and whole blood sample for qPCR; send fresh urine for qPCR.
  • 7-14 days after sending the initial sample, and after 10 days post-infection – not likely leptospiraemic, should have seroconverted; send second/convalescent samples – serum sample for MAT and fresh urine for qPCR.
  • Consider repeating qPCR on urine sample 7 days post-treatment to check that the dog is no longer shedding.

NB If the dog is on antibiotics, be aware that both the MAT and qPCR may give falsely negative results, even in cases of clinical leptospirosis.

Check with the individual laboratory for their specific sample requirements and preferences, but generally:

  • MAT – at least 1 ml of serum/2 ml clotted blood (Animal and Plant Health Agency, APHA); at least 0.5 ml serum (Agri-Food and Biosciences Institute, AFBI)
  • qPCR – whole blood in EDTA (≥0.5 ml) is generally preferred; the DNA is stable in the fridge or freezer for this test for 5-7 days
  • Fresh urine (≥0.5 ml, but larger volumes are preferred) in plain tubes
  • Tissue samples (usually kidney or liver if biopsy is performed or post-mortem samples are available) can be transported in saline in plain tubes; some laboratories may be able to process formalin-fixed, wax-embedded samples.

In Northern Ireland, the leptospirosis laboratory at AFBI, Stormont is an OIE leptospirosis reference laboratory. The laboratory uses an antigen end-point test for four serovars (Bratislava, Canicola, Hardjo and Icterohaemmorrhagiae) for canine samples and can offer an extended panel on request. The laboratory requires ≥0.5 ml of serum, and a fast turnaround time is possible on request. A detailed history, particularly vaccination details, is helpful. Submission information, including forms, can be found on their website.

In England, the MAT can be performed at the APHA, Weybridge. Information of scientific tests and submission forms can be found on their website.

Export to Australia from the UK
With regard to leptospirosis, for export to Australia dogs must either be:

  • 'Fully vaccinated against Leptospira interrogans serovar Canicola according to the manufacturer’s recommendations at least 14 days prior to export and the vaccination must be valid at the time of export, and all vaccines must be administered in an approved country’

Or:

  • ‘If the dog has not been vaccinated, a blood sample must be taken by a government approved veterinarian Leptospira interrogans serovar Canicola using a microscopic agglutination test (MAT) within 45 days before export. The test must produce a negative result (less than 50% agglutination) at a serum dilution of 1:100.’

Further details are available on the Australian government website.

Treatment and prognosis

Effective treatment is centred on appropriate supportive care in light of potential multi-systemic manifestations of the disease and, in dogs currently, antibiosis. In human medicine, the use of antibiotics is controversial. Two Cochrane systematic reviews did not show a statistically significant improvement in survival or a shorter duration of clinical signs during hospitalization (Guidugli et al. 2000; Brett-Major and Coldren, 2014), but the World Health Organization (WHO) recommends antibiotic therapy, especially in the early stages, of people with suspected leptospirosis.

Given the potential risk of zoonotic transmission and fulminant disease, the European Consensus Statement on Leptospirosis in Dogs and Cats panel recommends early use of appropriate antibiotics in dogs with suspected leptospirosis; typically intravenous penicillin G, ampicillin or amoxicillin until the dog can tolerate oral doxycycline (Schuller et al., 2015b), which is used to reduce renal shedding. Fluoroquinolones are not recommended for dogs with leptospirosis; third-generation cephalosporins are increasingly used to treat human leptospirosis (Schuller et al., 2015b).

More detailed information on drug dosages, duration of treatment and supportive care strategies can be found in the European Consensus Statement on Leptospirosis in Dogs and Cats (Schuller et al., 2015b), although successful treatment options for LPHS have yet to be defined (Kohn et al., 2010). An earlier and briefer review is provided by van de Maele et al. (2008). The North American perspective on treatment and management is given in the American College of Veterinary Internal Medicine (ACVIM) Small Animal Consensus Statement on Leptospirosis (Sykes et al., 2010).

Prevention

The 2015 World Small Animal Veterinary Association (WSAVA) Guidelines for Vaccination of Dogs and Cats have defined core vaccines as those which all dogs and cats, regardless of circumstances or geographical location, should receive. Core vaccines protect animals from severe, life-threatening diseases that have a global distribution. Non-core vaccines are those used to protect against diseases where the animal’s geographical location, lifestyle or environment puts them at risk. The WSAVA Guidelines class leptospirosis as a non-core vaccination worldwide, but remind the reader that they are intended to be used by national associations and individual veterinary practices to develop vaccination schedules relevant to the local situation. As such, the BSAVA Scientific Committee has recommended that leptospirosis should be considered to be a core vaccine for dogs in the UK as they are at risk of contact with rodents or potentially contaminated water. Cases of leptospirosis have been identified in urban dogs with no known access to wildlife or water sources (Schuller et al., 2015b).

Leptospira bacterin vaccines containing L. interrogans serogroups Canicola and Icterohaemorrhagiae (bivalent vaccine) have been available for administration to dogs since the 1980s (Yao et al., 2015). After a primary course consisting of two injections 2-4 weeks apart, these vaccines induce serogroup-specific immunity, with only partial immunity to heterologous serogroups (Sykes et al., 2010; Schuller et al., 2015b). The epidemiological picture varies across Europe, but in the UK clinical infection with Canicola is now very rare (Ellis, 2010). Acute infections are now commonly caused by other serogroups and clinical infections have been reported in dogs in Europe vaccinated against Canicola and Icterohaemorrhagiae (Kohn et al., 2010; Schuller et al., 2015b). The altered epidemiological situation in Europe has led to calls for an expansion of the number of Leptospira serovars included in vaccines, to reflect the most prevalent serovars found in dogs (Ellis, 2010; Klassen et al., 2014; Schuller et al., 2015b). Consideration should also be given to the ability of the vaccine to not only reduce clinical disease and mortality, but to induce protection from renal infection, renal carrier state and urinary shedding of leptospires (Klassen et al., 2014).

At the time of writing, a number of leptospirosis vaccines are available for dogs in the UK, including bivalent vaccines (eight brands) and tetravalent vaccines (three brands), which provide protection against the serogroups Canicola, Icterohaemorrhagiae, Australis and Grippotyphosa. More detailed information, including the serovars/strains used in the currently available leptospirosis vaccines in the UK, can be found in Table 3.

Vaccine name    Company     Leptospiral serogroup    
Canicola Icterohaemorrhagiae Grippotyphosa Australis 
Serovar/Strain where stated 

Canigen Lepto 2

(NOAH datasheet)

Virbac

Canicola       Ca-12-000

Icterohaemorrhagiae 820K   X  X

Canigen L4

(NOAH datasheet)

Virbac Portlandvere Ca-12-000  Copenhageni                Ic-02-001 Dadas              Gr-01-005 Bratislava As-05-073

Canixin L

(NOAH datasheet)

 Virbac Canicola Icterohaemorrhagiae 

Duramune DAPPi & LC (lyophilisate and solvent)

(NOAH datasheet)

Zoetis Canicola Icterohaemorrhagiae X X

Duramune Pi & LC (lyophilisate and solvent)

(NOAH datasheet)

Zoetis  Canicola  Icterohaemorrhagiae 

Eurican L

(NOAH database)

Merial  Canicola Icterohaemorrhagiae 

Nobivac Lepto2

(NOAH datasheet)

MSD Canicola       CA-12-000  Icterohaemorrhagiae 820K X

Nobivac L4

(NOAH datasheet)

MSD Portlandvere Ca-12-000  Copenhageni                Ic-02-001 Dadas              Gr-01-005 Bratislava As-05-073

Vanguard 7/ Vanguard CPV-L

(NOAH datasheet)

Zoetis  Canicola  Icterohaemorrhagiae  X X

Vanguard Lepto ci

(NOAH datasheet)

Zoetis Canicola  Icterohaemorrhagiae 

Versican Plus L4

(NOAH datasheet)

Zoetis  Canicola   MSLB 1090  Icterohaemorrhagiae MSLB 1089 Grippotyphosa MSLB 1091 Bratislava MSLB 1088

The duration of immunity (DOI) for leptospirosis vaccines has been shown to be at least 12 months, but evidence to show a duration far beyond that is lacking (Sykes et al., 2010; Klassen et al., 2014; Schuller et al., 2015b). DOI against naturally occurring leptospirosis is considered difficult to predict (Martin et al. 2014), and it is unknown if natural infection results in lifelong immunity (Sykes et al., 2010). Serological/antibody titre testing is not an appropriate way of testing for protection as the correlation between antibody levels and protection is poor, and because the antibodies do not persist for a long time.

Adverse reactions to leptospiral vaccination, particularly in some small breeds, have reportedly been a concern. It is recognized that such reactions can occur in any vaccinated animal and, although such reactions may be reported more in small breeds with any vaccine, antileptospiral vaccines were not found to be more reactive than other vaccines for dogs (Sykes et al., 2010; Moore, 2013; Schuller et al., 2015b). A recent study reported a slightly increased risk of owner-reported adverse effects, but no significant difference in hypersensitivity reactions between leptospiral and non-leptospiral vaccines (Yao et al., 2015).

The European Consensus Statement on Leptospirosis in Dogs and Cats panel recommends the use of quadrivalent vaccines, given the widespread recognition of leptospirosis in European dogs which have received the bivalent vaccine, with annual revaccination for all at-risk dogs. They also state that a need to revaccinate more frequently than every 12 months has not been substantiated, and that revaccination might be best performed in the Spring, at least where environmental leptospires have been inactivated by cold winter temperatures (Schuller et al., 2015b).

The ACVIM Small Animal Consensus Statement on Leptospirosis also recommends the use of a quadrivalent vaccine for at-risk dogs (Sykes et al., 2010). Both groups consider that evidence shows the leptospirosis bacterins to be effective at preventing disease from experimental challenge specific to that vaccine serogroup and that this protection lasts for at least 12 months (Sykes et al., 2010; Schuller et al., 2015b) and may reduce shedding (Sykes et al., 2010; Klassen et al., 2014; Martin et al., 2014). Partial immunity to heterologous serogroups has been reported, but Schuller et al. (2015b) recommends that dogs recovering from natural infection be vaccinated against other serovars, if available, as soon as possible after recovery.

When deciding on which type of leptospiral vaccine to use, vets should consider:

  • The availability of evidence of serovars in circulation in the locality
  • Knowledge of the local area with regards to weather, flooding and environmental risks
  • The dog’s lifestyle and travel plans with respect to the risk of exposure to leptospirosis
  • The public health aspect, particularly with respect to the owner/family situation
  • The ability of the vaccine used to provide effective coverage against the relevant serogroups and to provide protection from clinical disease, renal carriage and urinary shedding.

Further methods of reducing access to potential sources of exposure include ensuring dogs avoid drinking from or wading/swimming in fresh or stagnant water sources and marshland, controlling rodent sources and avoiding hunting or access to wildlife. The prophylactic use of antibiotics in dogs is not recommended (Sykes et al., 2010; Schuller et al., 2015b).

Public health implications

Brown and Prescott (2008) state that direct transmission of leptospirosis from dogs to their owners in North America is low but likely underreported. The reported incidence rate of human infection in Germany is 0.06/100,000 people and likely underestimated (Jansen et al., 2005), but zoonotic transmission from dogs is poorly documented despite the same serovars often affecting both dogs and humans (Damborg et al., 2016). Owners, vets and laboratory personnel may be at greatest risk of zoonotic transmission from dogs, and it is thought that pet rat owners may be most at risk of pet-associated leptospirosis as rats are the main reservoir for L. icterohaemorrhagiae, the serovar most pathogenic to humans (Damborg et al., 2016).

Contact with livestock, wildlife and animal urine deposits may post an occupational hazard, particularly for farmers. Bats have also been associated with the development of Weil’s disease (renal and hepatic failure) in humans (Vashi et al., 2009; Sykes et al., 2010; Damborg et al., 2016). The disease has also been reported to occur in people who walk barefoot or garden with bare hands, presumably through contact with animal urine (Levett, 2001). It is important to reduce the risks of exposure (particularly in the young, elderly and immunocompromised) through the development and use of vaccines against regionally significant serovars in dogs, addressing hygiene standards and by educating people at high risk of exposure (Brown and Prescott, 2008; Damborg et al., 2016). Brown and Prescott (2008) state that the ‘best protection for the family is to ensure that their dogs are vaccinated annually’ and that pregnant women are ‘at risk of abortion following exposure to leptospires and are prime candidates for prophylactic antibiotic therapy.’ More details on reducing the risk of occupations exposure to leptospires in the veterinary environment can be found in the ACVIM Small Animal Consensus Statement of Leptospirosis (Sykes et al., 2010).

References and further reading

Abdoel TH, Houwers DJ, van Dongen AM et al. (2011) Rapid test for the serodiagnosis of acute canine leptospirosis. Veterinary Microbiology 150, 211-213
Andre-Fontaine G (2013) Diagnostic algorithm for leptospirosis in dogs: disease and vaccination effects on the serological results. Veterinary Record 172, 502-506
Arent ZJ, Andrews S, Adamama-Moraitou K et al. (2013) Emergence of novel Leptospira serovars: a need for adjusting vaccination policies in dogs? Epidemiology and Infection 141, 1148-1153
Ayral FC, Bicout DJ, Pereira H et al. (2014) Distribution of Leptospira serogroups in cattle herds and dogs in France. American Journal of Tropical Medicine and Hygiene 91, 756 759
Brett-Major DM and Coldren R (2012) Antibiotics for leptospirosis. Cochrane Database of Systematic Reviews 2, CD008264
Brown K and Prescott J (2008) Leptospirosis in the family dog: a public health perspective. Canadian Medical Association Journal 178, 399-401
Curtis KM, Foster PC, Smith PS et al. (2015) Performance of a recombinant LipL32 based rapid in-clinic ELISA (Snap® Lepto) for the detection of antibodies against Leptospira in dogs. International Journal of Applied Research In Veterinary Medicine 13, 182 189
Damborg P, Broens EM, Chomel BB et al. (2016) Bacterial zoonoses transmitted by household pets: state-of-the-art and future perspectives for targeted research and policy actions. Journal of Comparative Pathology 155 (Suppl 1), S27-S40
Dikken H and Kmety E (1978) Serological typing methods of leptospires. Methods in Microbiology 11, 259-307
Ellis WA (2010) Control of canine leptospirosis in Europe: time for a change? Veterinary Record 167, 602-605
Fink JM, Moore GE, Landau R et al. (2015) Evaluation of three 5' exonuclease-based real-time polymerase chain reaction assays for detection of pathogenic Leptospira species in canine urine. Journal of Veterinary Diagnostic Investigation 27, 159-166
Fraune CK, Schweighauser A and Francey T (2013) Evaluation of the diagnostic value of serological microagglutination testing and a polymerase chain reaction assay for diagnosis of acute leptospirosis in dogs in a referral centre. Journal of the American Veterinary Medical Association 242, 1373-1380
Goldstein RE, Lin RC, Langston CE et al. (2006) Influence of infecting serogroup on clinical features of leptospirosis in dogs. Journal of Veterinary Internal Medicine 20, 489-494
Guidugli F, Castro AA, Atallah AN et al. (2000) Antibiotics for treating leptospirosis. Cochrane Database of Systematic Reviews 2, CD001306 (intervention review 2010; withdrawn as not maintained by authors)
Jansen A, Schöneberg I, Frank C et al. (2005) Leptospirosis in Germany, 1962-2003. Emerging Infectious Diseases 11, 1048-1054
Klassen HLBM, van der Veen M, Sutton D et al. (2014) A new tetravalent leptospirosis vaccine provides at least 12 months immunity against infection. Veterinary Immunology and Immunopathology 158, 26-29
Klopfleisch R, Kohn B, Plog S et al. (2010) An emerging pulmonary haemorrhagic syndrome in dogs: similar to the human leptospiral pulmonary haemorrhagic syndrome? Veterinary Medicine International 2010, Article ID 928541 (doi:10.4061/2010/928541)
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Kohn B, Steinicke K, Arndt G et al. (2010) Pulmonary abnormalities in dogs with leptospirosis. Journal of Veterinary Internal Medicine 24, 1277-1282
Lee HS, Guptill L, Johnson AJ et al. (2014) Signalment changes in canine leptospirosis between 1970 and 2009. Journal of Veterinary Internal Medicine 28, 294-299
Levett PN (2001) Leptospirosis. Clinical Microbiology Reviews 14, 296-326
Major A, Schweighauser A and Francey T (2014) Increasing incidence of canine leptospirosis in Switzerland. International Journal of Environmental Research and Public Health 11, 7242 7260
Martin LER, Wiggans KT, Wennogle SA et al. (2014) Vaccine-associated Leptospira antibodies in client-owned dogs. Journal of Veterinary Internal Medicine 28, 789-792
Mayer-Scholl A, Luge E, Draeger A et al. (2013) Distribution of Leptospira serogroups in dogs from Berlin, Germany. Vector Borne Zoonotic Disease 13, 200-202
Mastorilli C, Dondi F, Agnoli C et al. (2007) Clinicopathologic features and outcome predictors of Leptospira interrogans Australis serogroup infection in dogs: a retrospective study of 20 cases (2001-2004). Journal of Veterinary Internal Medicine 21, 3-10
Miller MD, Annis KM, Lappin MR et al. (2011) Variability in results of the microscopic agglutination test in dogs with clinical leptospirosis and dogs vaccinated against leptospirosis. Journal of Veterinary Internal Medicine 25, 426-432
Moore GE (2013) Leptospirosis: preventing a complex and elusive disease Veterinary Record 172, 179-180
Riss DR and Brown CA (2014) Diagnostic features in 10 naturally occurring cases of acute fatal canine leptospirosis. Journal of Veterinary Diagnostic Investigation 26, 799-804
Schuller S, Arent ZJ, Gilmore C et al. (2015a) Prevalence of antileptospiral serum antibodies in dogs in Ireland Veterinary Record 177, 126-128
Schuller S, Francey T, Hartmann K et al. (2015b) European Consensus Statement on Leptospirosis in Dogs and Cats. Journal of Small Animal Practice 56, 159-179
Sykes JE, Hartmann K, Lunn KF et al. (2010) 2010 ACVIM Small Animal Consensus Statement on Leptospirosis: diagnosis, epidemiology, treatment, and prevention. Journal of Veterinary Internal Medicine 25, 1-13
Thomé S, Lessa-Aquino C, Ko AI et al. (2014) Identification of immunodominant antigens in canine leptospirosis by Multi-Antigen Print Immunoassay (MAPIA). Veterinary Research 10, 288-296
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van den Broek AHM, Thrusfield MV, Dobbie GR et al. (1991) A serological and bacteriological survey of leptospiral infection in dogs in Edinburgh and Glasgow. Journal of Small Animal Practice 32, 118-124
Vashi NA, Reddy P, Wayne DB et al. (2009) Bat-associated leptospirosis. Journal of General Internal Medicine 25, 162-164
Ward MP (2002) Seasonality of canine leptospirosis in the United States and Canada and its association with rainfall. Preventative Veterinary Medicine 56, 203-213
Wild CJ, Greenlee JJ, Bolin CA et al. (2002) An improved immunohistochemical diagnostic technique for canine leptospirosis using antileptospiral antibodies on renal tissue. Journal of Veterinary Diagnostic Investigation 14, 20-24
Winzelberg S, Tasse SM, Goldstein RE et al. (2015) Evaluation of Snap® Lepto in the diagnosis of leptospirosis infections in dogs: twenty two clinical cases. International Journal of Applied Research In Veterinary Medicine 13, 182 189
Xu C, Loftis A, Ahluwalia SK et al. (2014) Diagnosis of canine leptospirosis by a highly sensitive FRET-PCR targeting the lig genes. PLoS One 9, e89507
Yao PJ, Stephenson N, Foley JE et al. (2015) Incidence rates and risk factors for owner-reported adverse events following vaccination of dogs that did or did not receive a Leptospira vaccine. Journal of the American Veterinary Medical Association 247, 1139 1145

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