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Leptospirosis in Cats: Current Literature Review To Guide Diagnosis and Management

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Journal­of­Feline­Medicine­and­Surgery (2020) 22, 216–228

CLINICAL REVIEW

LEPTOSPIROSIS IN CATS
Current literature review to guide
diagnosis and management
Global importance: Leptospirosis is the most widespread zoonosis worldwide. Mammals
(eg, rats, horses, cows, pigs, dogs, cats and aquatic species, such as sea lions and northern
elephant seals) can all be infected by leptospires. Infection in animals occurs through contact
with urine or water contaminated with the bacteria. In people, the disease is acquired mainly
from animal sources or through recreational activities in contaminated water.
Andrea Murillo1 Practical relevance: Literature on the clinical presentation of leptospirosis in cats is scarce,
MV, MSc
although it has been demonstrated that cats are susceptible to infection and are capable of
Marga Goris2
MSc, PhD developing antibodies. The prevalence of antileptospiral antibodies in cats varies from 4% to 33.3%
Ahmed Ahmed2
depending on the geographical location. Urinary shedding of leptospires in naturally infected cats has
MV, MSc, PhD been reported, with a prevalence of up to 68%. Infection in cats has been associated with the consumption
Rafaela Cuenca1* of infected prey, especially rodents. Thus, outdoor cats have a higher risk of becoming infected.
MV, MSc, PhD Clinical challenges: Clinical presentation of this disease in cats is rare and it is not known what role cats
Josep Pastor1 have in the transmission of leptospirosis. Ongoing work is needed to characterise feline leptospirosis.
MV, MSc, PhD, Dip ECVCP Audience: This review is aimed at all veterinarians, both general practitioners who deal with cats on a daily
1
Departament de Medicina basis in private practice, as well as feline practitioners, since both groups face the challenge of diagnosing
i Cirurgia Animals, and treating infectious and zoonotic diseases.
Facultat de Veterinària,
Universitat Autònoma
Evidence base: The current literature on leptospirosis in cats is reviewed. To date, few case reports have
de Barcelona, been published in the field, and information has mostly been extrapolated from infections in people and
08193 Bellaterra, dogs. This review is expected to serve as a guide for the diagnosis and management of the disease in cats.
Cerdanyola del Vallès,
Barcelona, Spain
Keywords: Leptospirosis; microscopic agglutination test; real-time PCR; zoonosis
2
OIE and National
Collaborating Centre for
Reference and Research
on Leptospirosis (NRL), Aetiology each with distinct antigenic compositions; to
Amsterdam UMC, date, over 260 pathogenic serovars, arranged
University of Amsterdam,
Medical Microbiology, Leptospirosis is caused by spirochetal bacteria into 26 serogroups, have been identified. This
Meibergdreef 39, of the genus Leptospira. These are highly serological classification, based on determin-
1105 AZ, Amsterdam, motile, elongated and helically coiled bac- ing antigenic characteristics, is more useful
Netherlands
teria that differ morphologically from other diagnostically and also better serves epidemi-
*Corresponding author: spirochetes by having a ‘question mark’ or ological purposes.
rafaela.cuenca@uab.cat
hook-shaped end.1–3 The genus Leptospira All mammals may be susceptible to Lepto­-
was originally divided into two species: spira­infection.3 There are primary (definitive)
Leptospira­ interrogans, containing the patho- or carrier hosts for some serovars (eg, dogs
genic serovars, and Lepto­spira­biflexa, contain- are hosts for Canicola; cows and sheep for
ing the non-pathogenic saprophytic serovars.4 Hardjo; pigs for Pomona and Bratislava;
However, this phenotypic classification has and rats for Icterohaemorrhagiae and Copen-
been largely superseded by genetic classi- hageni). These contribute to a greater extent to
fication, based on genotypic identification the spread of bacteria in the environment
techniques, that includes all serovars of compared with incidental or dead-end hosts
L­interrogans­sensu lato and L­biflexa­sensu lato (ie, that suffer acute disease and are unlikely
(sensu lato is a Latin phrase meaning ‘in the to serve as a source of transmission; eg,
broad sense’ and is often used taxonomically humans). The definitive host is typically infect-
to indicate a species complex).3 ed at a young age and commonly exhibits
Currently, 22 species of Leptospira have minimal clinical disease, whereas animals
been identified;4 at least 10 of these are infected with non-host-adapted serovars are
pathogenic. There are also seven saprophytic expected to exhibit more severe clinical signs.3
species and five species of indeterminate
pathogenicity.5 It is likely that more species
will be described in the future. Pathogenic
Leptospira species are divided into serovars,

216 JFMS CLINICAL PRACTICE


DOI: 10.1177/1098612X20903601
© The Author(s) 2020
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R E V I E W / Leptospirosis in cats

Outdoor
cats have
an increased
risk of
leptospirosis,
through
contact with
reservoir
hosts.

Figure 1 Map indicating (in red) the countries where the prevalence of leptospirosis in cats has been reported, based on
microscopic agglutination test (MAT) and/or urinary and blood PCR

Epidemiology lence of leptospirosis in cats has been report-


At present, it is ed, based on MAT and/or urinary and
Leptospirosis is endemic in almost all regions blood PCR. Table 1 summarises previous
of the world.2 Its incidence usually increases not completely research on feline leptospirosis prevalence
at the end of the summer months, while understood by MAT diagnosis. Overall seropositivity
in the tropics most infections occur during reported in these studies ranged from 4%
and after periods of rainfall.1,2 Pathogenic which serovars to 33.3%, with no clear association with clini-
Leptospira­ species experience optimal growth cal disease.
at temperatures of 28–30ºC. Although they do
cause Leptospiral infection in cats has been associ-
not replicate outside of the host, they can sur- incidental ated with the consumption of infected prey,29
vive for months in moist soil saturated with involving serovars of the Autumnalis and
urine,1,3 and this can lead to significant envi- infections in Ballum serogroups.3 Outdoor cats have an
ronmental contamination. In people, there cats and which increased risk of becoming infected with lep-
are three main factors associated with the risk tospires since they are in close contact with
of disease transmission: (1) water exposure; have developed reservoir hosts. In rural areas, cats can also
(2) exposure to carrier rodents; and (3) trans- become infected via urine from pigs and
mission from livestock or pets.6 adaptation to cows.12,15,28–30 The presence of another cat in
Feline leptospirosis was first described in feline species. the household significantly increases the risk
1972,7 and prevalence studies show the main of seropositivity for leptospirosis.14
serovars belong to serogroups Australis, At present, it is not completely understood
Autumnalis, Canicola and Sejroe,8–18 although which serovars cause incidental infections
there are geographical variations. The most in cats. Based on previously published
frequent serovars involved in feline lepto- reports of acute leptospirosis in cats, serovars
spirosis in Europe – according to the European belonging to Autumnalis, Australis, Ictero-
consensus statement on leptospirosis, and haemorrhagiae, Grippotyphosa, Pomona
based on the prevalence of antibodies mea- and Sejroe serogroups are involved.14,18,30–32
sured by the microscopic agglutination test Several studies have confirmed renal carriage
(MAT) – belong to serogroups Australis, of Leptospira species by PCR, and these
Autumnalis, Ballum, Canicola, Grippotyphosa, cats had antibodies mainly against serovars
Icterohaemorrhagiae, Pomona and Sejroe.19 belonging to Australis, Canicola, Ictero-
The most commonly reported serovars in cats haemorrhagiae and Pomona serogroups.
in the USA belong to serogroups Australis, Given this fact, cats could be a chronic reser-
Autumnalis, Grippotyphosa and Pomona.8,20 voir host for the bacteria and a possible risk
Figure 1 shows the countries where the preva- factor for human infection.10,11,13,14,16,26,30,33,34

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R E V I E W / Leptospirosis in cats

Table 1 Prevalence data for leptospirosis in cats diagnosed by microscopic agglutination test

Location n Positive serovar(s) Negative serovar(s) Prevalence (%) Reference


Malaysia – Johor and 110 Ballum, Bataviae*, Australis, Autumnalis, Canicola, Celledoni, Cynopteri, 18.1 9
Selangor Copenhageni and Javanica Djasiman, Grippotyphosa, Hardjo, Hardjo-bovis,
Hebdomadis, Icterohaemorrhagiae, Lai, Malaysia,
Pomona, Pyrogenes and Tarassovi
Thailand – 13 locations 260 Anhoa, Autumnalis, Celledoni, Australis, Ballum, Bataviae, Bratislava, Broomi, 5.4 10
Copenhageni, Djasiman, Canicola, Coxi, Cynopteri, Grippotyphosa,
Icterohaemorrhagiae Haemolytica, Khorat, Paidjan, Pomona, Pyrogenes,
and Patoc* Rachmati, Saxkoebing and Sejroe
USA – Iowa 139 Bratislava*, Grippotyphosa, Canicola 8.6 8
Hardjo, Icterohaemorrhagiae
and Pomona
Germany – Munich 215 Australis*, Autumnalis, Canicola, Pomona and Saxkoebing 17.9 11
Bratislava, Copenhageni
and Grippotyphosa
Caribbean island 50 Cynopteri and Pomona Alexi, Australis, Autumnalis, Bataviae, Ballum, 4 21
of St Kitts Borincana, Bratislava, Canicola, Celledoni, Cynopteri,
Djasiman, Georgia, Grippotyphosa, Hardjo,
Icterhemorrhagiae, Javanica, Mankarso, Pomona,
Pyrogenes, Tarassovi and Wolffi
Brazil – Lago Grande 43 Andamana and Patoc Autumnalis, Australis, Bataviae, Bratislava, Butembo, 4.7 22
Canicola, Castellonis, Copenhageni, Cynopteri,
Grippotyphosa, Guaricura, Hardjo-prajitno,
Hebdomadis, Icterohaemorrhagiae, Javanica,
Panama, Pomona, Pyrogenes, Shermani, Tarassovi,
Whitcombi and Wolffi
Mexico – Mérida 13 Australis and Canicola* Autumnalis, Bratislava, Grippotyphosa, Hardjo, 23.2 23
Icterohaemorrhagiae, Pyrogenes, Panama, Pomona,
Tarassovi and Wolffi
Iran – Mashhad 147 Hardjo*, Icterohaemorrhagiae Autumnalis, Ballum, Canicola and Grippotyphosa 12.9 12
and Pomona
Taiwan – Southern 225 Australis, Autumnalis, Bataviae, Canicola, Panama, Pomona 9.3 13
Taiwan Icterohaemorrhagiae, and Tarassovi
Javanica, Pyrogenes
and Shermani*
Canada – Quebec 240 Bratislava, Grippotyphosa, Canicola and Hardjo 10.8 14
Icterohaemorrhagiae and
Pomona*
Chile – Valdivia, 124 Autumnalis*, Bataviae Ballum, Hardjo, Icterohaemorrhagiae and Pomona 25.2 15
Osorno, Paillaco and Canicola
and San Pablo
Serbia – Belgrade 161 Australis*, Bratislava, Autumnalis, Bataviae, Icterohaemorrhagiae 26.7 24
Canicola, Grippotyphosa and Sejroe
Pomona* and Pyrogenes
Canada – Quebec 40 Autumnalis and Bratislava* Canicola, Grippotyphosa, Icterohaemorrhagiae 25 25
and Pomona
Reunion Island 30 Panama Australis, Autumnalis, Bataviae, Canicola, 26.6 26
Castellonis, Cynopteri, Grippotyphosa, Hardjo-bovis,
Hebdomadis, Icterohaemorrhagiae, Copenhageni,
Pomona, Pyrogenes, Sejroe and Tarassovi
Iran – Ahvaz 102 Australis and Ballum* Canicola, Grippotyphosa, Hardjo, 4.9 27
Icterohaemorrhagiae and Pomona
USA – Massachusetts 63 Autumnalis*, Bratislava, Canicola, Grippotyphosa and Hardjo 4.8 20
Icterohaemorrhagiae
and Pomona
Spain – Andalucia 53 Ballum and Australis, Autumnalis, Bataviae, Bratislava, Canicola, 14 16
Icterohaemorrhagiae* Grippotyphosa, Hardjo, Hebdomadis, Pomona,
Saxkoebing, Sejroe and Tarassovi
Greece – Thessaloniki 99 Ballum, Bataviae, Bratislava, Hebdomadis, Panama and Pomona 33.3 17
Canicola, Panama, Pyrogenes
and Rachmati*
Scotland – Glasgow 87 Autumnalis, Hardjo-bovis* Autumnalis, Bratislava, Ballum, Canicola, Cynopteri, 9.2 18
and Icterohaemorrhagiae Grippotyphosa, Javanica, Pomona and Tarassovi
New Zealand – North 225 Balcanica, Ballum, Canicola, Australis, Bataviae, Javanica, Pyrogenes and 8.8 28
Island Copenhageni*, Hardjo* and Tarassovi
Pomona
*Most prevalent serovar reported in the study

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R E V I E W / Leptospirosis in cats

Table 2 summarises the scant research that has Summary of current research on prevalence of urinary
Table 2
been carried out in cats in different countries
shedding of Leptospira DNA in cats
to determine the prevalence of Leptospira
DNA shedding in urine. In these studies, Location n Gene target/primer set Prevalence (%) Reference
the prevalence ranged from 0% to 67.8%, Reunion Island 172 rrs2, lipL32 and lipL41 0.6 35
with no clear association with clinical disease.
The prevalence may differ depending on the Thailand – 13 260 lipL32 0.8 10
locations
geographical location and the PCR-selected
primers, among other factors. Algeria – Algiers 107 rrs (16S) and hsp 0 36

Germany – 215 lipL32 3.30 11


Pathogenesis Munich
Australia – 59 23S 42.4 33
Depending on the host and infecting serovar, Christmas Island
leptospiral infection may cause a spectrum of
Canada – 240 G1 and G2 and 3.33 14
syndromes from asymptomatic carriage to Quebec B64-I/B64-II
fulminant, acute disease.3 Reports of clinical
disease due to Leptospira species in pet cats are Réunion Island 30 lipL32 26.6 26
scarce. Taiwan – 225 G1/G2 and Leptospira rrs 67.8 13
Leptospires can enter the body through cuts Southern Taiwan (16S)
and abrasions, mucous membranes, such as
the conjunctiva, or through moist, weakened
skin. The bacteraemia lasts around 7 days.
The pathogenesis of the disease in cats Cats can act as carrier hosts,
remains unknown, although it is assumed not developing clinical disease, but shedding
to be similar to that in humans and dogs37
(Figure 2). Acute clinical disease occurs with bacteria into the environment in their urine.
the bacteraemic phase of the disease.1,2,38
It is seen mainly in young incidental hosts
and is usually associated with haemolysin- The duration of elimination via the urine
producing bacteria, such as the Ictero- and its intensity varies from species to species
haemorrhagiae or Pomona serogroups, which and animal to animal, and depends on the
cause haemolytic disease, haemoglobinuria, infecting serovar;3 precise information on
jaundice and, in severe cases, death.3 After these aspects is currently unavailable in cats.
leptospires have reached a critical level in the As mentioned earlier, cats can act as
blood, clinical signs appear due to the action carrier hosts, not developing clinical disease,
of leptospiral toxins or toxic cellular compo- but shedding bacteria into the environment
nents.1,2,38 Organ damage occurs as a result of in their urine. An epidemiological study
leptospires replicating and inducing cytokine has confirmed the presence of leptospiral
production and by direct invasion of inflam- DNA in the urine of cats for more than
matory cells.3 8 months after infection, with little or no
The primary lesions develop in the endo- association with disease.11 However, this does
thelium of the small blood vessels, leading not rule out the possibility that infected
to localised ischaemia, and resulting in animals could develop kidney disease at a
renal tubular necrosis, among other target later stage. The development of the carrier
organ damage (Figure 2). Renal colonisation state and the specific mechanisms required for
occurs in most infected animals because leptospires to enter the lumen of the proximal
the bacteria replicate and persist in the cells renal tubules, adhere to renal epithelial cells,
of the renal tubule epithelium. This multi- evade antibodies in the filtrate and acquire
plication process causes the release of the nutrients they need to replicate are not
cytokines and the recruitment of inflam- well understood.3
matory cells, which trigger nephritis.1,2,38 Leptospiral pulmonary haemorrhage syn-
Chronic interstitial nephritis, which may drome (LPHS) has been recognised in people
result in chronic renal damage, has been and dogs. This syndrome may be present
described in cats infected with leptospires.16 in 70% of dogs infected with leptospires.39
After 10 days of infection, leptospires enter The clinical signs associated with canine
the tubular lumen and are eliminated in LPHS are mainly acute and findings corre-
the urine over a period of days to months.1,2,38 spond to severe alveolar and subpleural

Although the pathogenesis of feline leptospirosis is not yet well understood,


it is assumed to be very similar to that in humans and dogs.

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R E V I E W / Leptospirosis in cats

The
presence of
another cat
in the
household
significantly
increases
the risk of
seropositivity
for
leptospirosis.

Figure 2 Proposed pathogenesis of leptospirosis in cats. The figure depicts the transmission mechanisms through which a cat can
become infected by Leptospira species: preying on rodents, sharing the environment with farm animals that shed the bacteria in
urine, or through standing water containing bacteria. Once the animal has become infected it suffers a period of bacteraemia of
approximately 7 days and leptospires can be identified in blood. The main target organs in cats are the kidney and the liver;
lungs, brain and eyes may also be affected, especially in dogs. Replication of leptospires occurs in the kidney leading to urinary
bacterial shedding. Image ©Biorender

haemorrhages, which cause an associated necrosis have been reported.14,16,31 Damage to


dyspnoea. While, to date, LPHS has not been organs including the spleen, eyes, meninges,
described in cats, chronic liver inflammatory muscle and placenta has also been reported in
infiltration, fibrosis and multifocal hepatic species other than cats.2,3,40

Virulence mechanisms and host factors


The virulence mechanisms of leptospires and the cytokines and chemokines is more prolific in
intrinsic factors of the host that determine the animal species susceptible to severe leptospirosis
result of infection remain poorly understood. compared with resistant animal species.49
Recent mutagenesis studies in animal models of Pathogenic leptospires are resistant to the bacte-
acute infection and of renal colonisation have ricidal activity of complement, while saprophytic
demonstrated that specific genes and proteins, leptospires are highly susceptible.41,50,51 The abili-
among them lipoproteins LipL32 and LipL41 and ty to acquire iron in vivo is a key virulence property
LigB adhesin, are present in pathogenic Leptospira for most bacterial species. Pathogenic leptospires
species, but are not necessary for virulence.3,41,42 possess haemoxygenase (HemO), which facili-
Loa22, an outer membrane protein containing a tates the acquisition of iron from heme, the
C-terminal OmpA domain, plays an indirect role major source of iron in the mammalian host.52,53
in the virulence of Leptospira species.43 Changes However, no conclusive results were obtained in
in motility through modifications in or mutations relation to attenuation of virulence of leptospires
of genes involved in flagellar structure also play a in a study using a HemO mutant.54
role in the specific virulence of leptospires.44,45 Mutagenesis studies have also demonstrated
Adhesion to host tissues appears to be a pre- that several stress response genes, which are
requisite for successful infection; however, genet- upregulated with bacterial transition from the
ic studies have not confirmed a definitive role for environment to the host, increase their suscepti-
many adhesins in the pathogenesis of Leptospira bility to oxidative stress and therefore render
species.3 With regard to the survival of leptospires the bacteria less virulent.55–57 In the same way,
in vivo, it has been suggested that pathogenic the inactivation of Mce, a homologue of the
leptospires undergo receptor-mediated endo- mycobacterial mammalian cell entry protein in
cytosis46,47 and are able to survive inside leptospires, has been found to result in a signifi-
macrophages.48 Production of pro-inflammatory cant reduction in virulence.58

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R E V I E W / Leptospirosis in cats

Table 3 Clinical signs of leptospirosis in cats based on published studies of acute disease

Reference Serovar(s) Clinical signs Diagnosis MAT PCR


11 Australis Seizures Not reported + +
Prospective

11 Australis, Bratislava and Copenhageni Acute diarrhoea Not reported + +


study

14 Bratislava, Grippotyphosa, Icterohaemorrhagiae Not reported AKI 4+ NP


and Pomona
18 Autumnalis, Hardjo, and Icterohaemorrhagiae Not reported AKI 8+ NP

32 Saxkoebing Vomiting and diarrhoea, hyperaesthesia AKI – + +


and painful on handling leptospirosis
Case report

31 Grippotyphosa, Hardjo, Icterohaemorrhagiae Polyuria and polydipsia AKI – + NP


and Pomona leptospirosis
31 Bratislava, Grippotyphosa and Pomona Polyuria, polydipsia, haematuria and lameness AKI – + NP
leptospirosis
31 Autumnalis, Bratislava, Grippotyphosa Comatose AKI – + +
and Pomona leptospirosis
30 Autumnalis and Pomona Haematuria Leptospirosis + +

MAT = microscopic agglutination test; + = positive; – = negative; AKI = acute kidney injury; NP = not performed; 4+, 8+ = number of positive cats
in the study

Clinical signs in Diagnosis with antibodies against Leptospira species have


been found to have signs associated with renal
cats are mild or Clinical signs disease and/or histopathological evidence
absent despite In cats, clinical signs are, at most, mild, of renal inflammation.14,16,30,35,59 As in dogs,
despite the presence of leptospires in the leptospirosis in cats can cause acute kidney
the presence blood and urine. injury that leads to chronic kidney disease.19,60
of leptospires Clinical signs reported in infected cats Lesions in the liver of affected cats have been
(based on confirmation by MAT and/or PCR) reported less commonly than in dogs.11,18,29,31,32
in the blood include polyuria, polydipsia, haematuria, Tables 3–5 collate information from several
uveitis, lameness, lethargy, anorexia, weight papers that detail the clinical signs in cats
and urine. loss, ascites, vomiting, diarrhoea, pain on han- at the time of presentation, the laboratory
dling, and inflammatory lesions on the skin test used for diagnosis and the Lepto­­spira­
and digits.11,14,17,18,25,30–32,59 Pathological find- serovars­involved. The cases have been divid-
ings reported in these animals include the ed into cats with acute disease (Table 3), those
presence of haemorrhagic or straw-coloured identified as chronic carriers (Table 4) and
thoracic and peritoneal fluids.31,18 Some cats those with a history of exposure (Table 5).

Table 4 Clinical signs of leptospirosis in cats according to published studies of chronic carrier cases

Reference Serovar(s) Clinical signs Diagnosis MAT PCR


11 Australis and Bratislava Asymptomatic Incidental infection (routine + +
health check)
11 Grippotyphosa Not reported Mast cell tumour in spleen and liver + +

11 Not determined Not reported Foreign body in pharynx (grass) – +


Prospective study

11 Grippotyphosa Not reported CKD and abdominal mass + +

11 Australis, Autumnalis, Bratislava Chronic diarrhoea Not reported + +


and Copenhageni
14 Bratislava, Copenhageni, Not reported CKD 13+ 6+
Grippotyphosa and Pomona
14 Bratislava, Grippotyphosa, Not reported Incidental infection (routine 9+ 2+
Icterohaemorrhagiae and health check)
Pomona
16 Icterohaemorrhagiae Kidney: Chronic interstitial nephritis. Not reported + NP
Chronic inflammatory infiltrate
(macrophages and lymphocytes)
Liver: Chronic inflammatory infiltration
16 Canicola Asymptomatic Not reported + NP

MAT = microscopic agglutination test; + = positive; – = negative; CKD = chronic kidney disease; NP = not performed; 13+, 6+, etc = number
of positive cats in the study

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R E V I E W / Leptospirosis in cats

Table 5 Clinical signs of leptospirosis in cats based on published studies of animals with a history of exposure

Reference Serovar(s) Clinical signs Diagnosis MAT PCR


9 Ballum, Bataviae and Javanica Not reported Feline upper + NP
respiratory disease
15 Autumnalis, Bataviae, Canicola Asymptomatic Incidental infection 10+ NP
and Grippotyphosa (routine health check)
24 Australis, Bataviae, Bratislava, Asymptomatic Incidental infection 43+ NP
Canicola, Grippotyphosa, (neutering)
Icterohaemorrhagiae,
Pyrogenes, Pomona and Sejroe
25 Autumnalis and Bratislava Not reported CKD + NP
25 Autumnalis and Bratislava Polyuria and polydipsia Not reported + NP
Prospective study

25 Autumnalis and Bratislava Not reported Hepatic lipidosis 2+ NP


25 Autumnalis and Bratislava Asymptomatic Not reported 3+ NP
27 Australis and Ballum Asymptomatic Not reported 5+ NP
16 Icterohaemorrhagiae Kidney: Chronic interstitial nephritis. Chronic Not reported + NP
inflammatory infiltrate (macrophages, lymphocytes
and plasma cells). Proliferative glomerulonephritis
Liver: Multifocal hepatic necrosis. Chronic inflammatory
infiltrate (lymphocytes and plasma cells)
16 Ballum Kidney: Chronic interstitial nephritis. Chronic Not reported + NP
inflammatory infiltrate (macrophages and plasma cells)
16 Ballum Asymptomatic Not reported + NP
16 Icterohaemorrhagiae Kidney: Chronic interstitial nephritis. Chronic Not reported + NP
inflammatory infiltrate (macrophages and lymphocytes)
17 Rachmati Asymptomatic Not reported 15+ NP

17 Rachmati Not reported Various chronic 18+ NP


diseases
Retrospective

59 Bratislava and Not reported CKD – azotaemia 4+ NP


Icterohaemorrhagiae
study

59 Bratislava and Not reported CKD – non-azotaemia 8+ NP


Icterohaemorrhagiae

MAT = microscopic agglutination test; + = positive; – = negative; CKD = chronic kidney disease; NP = not performed; 10+, 43+, etc = number of
positive cats in the study

Polyuria, polydipsia, haematuria, uveitis, laminitis, lethargy, anorexia, weight loss,


vomiting and diarrhoea, painful handling, and inflammatory lesions on skin and foot
digits are some of the clinical signs reported in affected cats.

Clinicopathological data with azotaemia at the time of diagnosis.


Table 6 summarises some of the most common The increase is usually moderate to sev-
clinicopathological abnormalities associated ere.11,14,25,31,32,59 In affected dogs, serum liver
with leptospirosis in cats. enzyme (alkaline phosphatase [ALP] more
commonly than alanine aminotransferase
Complete blood count [ALT]) and total bilirubin increases are associ-
Leukocytes can fluctuate according to the ated with liver dysfunction.38,40,60 Conversely,
stage and severity of infection. Leukopenia is in feline leptospirosis these increments are
a possibility during leptospiraemia, evolving not as characteristic, and only slight increases
to leukocytosis owing to neutrophilia with a have been reported.11,18,25,31,32 Leptospire tox-
left shift. In advanced states, leukocyte counts ins inhibit Na+K+-ATPase activity in the
may be in the range of 16.5–45 x 109/l (refer- epithelial cells of the renal tubules in cats and
ence interval 2.75–11.75 x 109/l).18,19,60,61 dogs, which can lead to significant renal
losses of electrolytes, resulting in severe hypo-
Serum biochemistry kalaemia.60 In cats, increases in serum phos-
Urea and creatinine concentrations are phorus concentration have been reported,
increased in 80–90% of cases of canine probably associated with a decrease in the
leptospirosis.60 Most infected cats present glomerular filtration rate.31

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R E V I E W / Leptospirosis in cats

Urine analysis
Table 6 Clinicopathological findings in 19 cats diagnosed
Findings in dogs include isosthenuria or occa-
with leptospirosis11,18,30–32
sionally hyposthenuria, glycosuria, protein-
uria, bilirubinuria, haematuria, pyuria and the Affected/sampled
Finding Clinical course cats
presence of casts in fresh urine sediment.38,60
In cats, hyposthenuria, haematuria and pro- Haematology Non-regenerative Chronic carrier 2/19 (10.5%)
anaemia
teinuria have been reported.30,31 Leptospires
are not visible on routine fresh urinary sedi- Haemoconcentration Acute disease 2/19 (10.5%)
ment examination, as the size of the bacteria is Neutropenia Acute disease 1/19 (5.2%)
below the resolution of light microscopy.19 Neutrophilia Acute disease 2/19 (10.5%)
Leukocytosis with Acute disease 2/19 (10.5%)
Ultrasonographic findings left shift
The few published reports of feline lepto- Thrombocytopenia Acute disease 1/19 (5.2%)
spirosis describe renal ultrasonographic Biochemistry Hypoalbuminaemia Acute disease 2/2 (100%)
findings that are similar to those in canine Azotaemia Acute disease and 9/19 (47.4%)
leptospirosis, including a granular appear- chronic carrier
ance of the kidney, enlarged kidneys with Liver enzymes increased Acute disease 6/8 (75%)
a cortex that is thinner than the medulla, Hyperglycaemia Acute disease 1/2 (50%)
a slightly hyperechogenic renal cortex and
Hyperphosphataemia Acute disease 1/1 (100%)
a decrease in the definition of the corti-
Bicarbonate decreased Acute disease 1/1 (100%)
comedullary junction.31,32 Heterogeneity in the
pancreatic and liver parenchyma has also Urine analysis Low USG Acute disease and 3/5 (60%)
chronic carrier
been reported in one case.32
Proteinuria Acute disease 3/6 (50%)
Specific testing Haematuria Acute disease 2/6 (33.3%)
Laboratory diagnosis of leptospirosis in veteri- Renal and red cell casts Acute disease 1/5 (20%)
nary medicine is usually based on the demon- Serological FeLV/FIV negative Acute disease 5/5 (100%)
stration of serum antibodies by MAT and test
ELISA, and/or isolation of Leptospira­ DNA USG = urine specific gravity; FeLV = feline leukaemia virus; FIV = feline
from blood and urine by PCR. Bacterial cul- immunodeficiency virus
ture of blood and/or urine is not widely used
because it is time consuming. Specific diag- Several studies have confirmed renal
nostic tests that are available for cats are MAT
and PCR. carriage of Leptospira species in cat
Microscopic agglutination test
populations, which means cats could be a
Determination of antibody titre by MAT is chronic reservoir host for the bacteria and a
the recommended technique for leptospirosis
diagnosis, as MAT reactivity to a serovar sug- possible risk factor for human infection.
gests exposure to a serovar belonging to the
corresponding serogroup (though not neces- MAT results are strongly dependent on labo-
sarily to the specific serovar tested).62 The selec- ratory quality control, and there is considerable
tion of the serogroups and the serovars to be inter-laboratory variability.63 Practitioners are
evaluated depends on the geographical loca- encouraged to submit diagnostic samples to
tion of the patient’s likely exposure. Antibodies laboratories that adhere to a proficiency
(IgM and IgG) are detected at around 15 days scheme.64 Test interpretation may be more reli-
post-infection by MAT.3 Little information is able in cats than in dogs because no interfer-
available on the duration of these antibodies ence with vaccine antibodies exists as cats
in the blood of cats. Clinical interpretation are not vaccinated.37 Furthermore, laboratory-
should always be based on the results of paired reared young adult specific pathogen-free cats
serum titres, and it is worth noting that some infected with Borrelia­ burgdorferi did not form
infected animals may produce a result that is antibodies against Leptospira­species as a cross-
lower than the widely accepted minimum sig- reaction.59 The authors of that study suggest
nificant titre result of 1:100.3 It is even possible that positive Leptospira­ species MAT results
that seroconversion in cats is expressed at a from cats in the field are likely to reflect anti-
lower titre compared with dogs.59 bodies against leptospires and not B­burgdorferi.

MAT results are strongly dependent on quality control procedures


in the laboratory. Practitioners are encouraged to submit diagnostic
samples to laboratories that adhere to a proficiency scheme.

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R E V I E W / Leptospirosis in cats

ELISA and rapid immunodiagnostic PCR


screening tests PCR directly identifies leptospiral DNA. It
ELISAs used for leptospirosis identify the pres- ELISA does not determine the infecting serogroup
ence of leptospiral antibodies (specific IgM class or serovar, but it can indicate the Leptospira
antibodies) earlier than MAT, at between 4–6 days and rapid species. The test can be performed on blood,
post-infection.3 The main advantages of ELISA patient-side urine, cerebrospinal fluid and body tissues.
compared with MAT are, in the authors’ opin- In cases of acute leptospirosis, this would be
ion, the stability of antigenic preparations and tests for the test of choice to perform on blood and
the genus specificity, meaning all types of lep- urine in cats. Compared with culture, PCR
tospires can be diagnosed with a single antigenic Leptospira gives fast results, contributing to an early
preparation, irrespective of the causal serovar.65 species diagnosis.65 Real-time PCR techniques are rec-
In dogs, a combination of ELISA plus MAT is ommended, due to their greater sensitivity
recommended for leptospirosis diagnosis.19 diagnosis in and specificity. Genes that have more than
Rapid patient-side tests for leptospirosis diag- one copy in the genome, such as lig or rrs,­
nosis were developed almost a decade ago.66
cats have not should be selected with the aim of increasing
Curtis et al performed a recombinant LipL32- yet been the sensitivity of the technique. Genes present
based rapid in-clinic ELISA (SNAP Lepto) for only in the pathogenic species can also be
the detection of antibodies against Leptospira­ developed. added as they will increase the specificity of
species­ in dogs in 2015.67 Neither of the tests the test.68
distinguish between serovars, nor do they pro- A positive PCR result means that leptospiral
vide a titre magnitude. The first test66 is based DNA is present in the sample. In acute
on the detection of Leptospira-specific IgM and infections or in chronic carriers, the test
has demonstrated a sensitivity and specificity would be positive in urine, indicating that
of 100% and 95.3%, respectively. It can there- bacterial DNA is being shed. However,
fore detect dogs with clinically suspected acute negative results in blood and urine do not
leptospirosis. Dogs previously vaccinated or suf- rule out leptospirosis, as leptospiraemia is
fering from an acute but subclinical infection can transient (only occuring in the initial phases
also produce positive results. A LipL32-based in- of the disease); also results are usually
clinic ELISA for the rapid detection of Leptospira- negative if the cat has received antibiotic
specific antibodies in dogs is not IgM specific, therapy,19,60 and shedding in urine can be
but the study authors considered it a convenient intermittent.3 In one report, leptospires were
tool to assess Leptospira antibody status in dogs.67 cultured from cat urine and the results were
Neither rapid test techniques, nor ELISA, to confirmed by PCR,34 suggesting that cats
diagnose leptospirosis in cats have yet been can shed living Leptospira­ bacteria, not just
developed. their DNA.

Diagnostic approach for a cat with suspected leptospirosis


Supportive therapy with
intravenous ampicillin while the
LEPTOSPIROSIS patient is stabilised. Doxycyline LEPTOSPIROSIS
oral suspenion for 6 weeks.
POSITIVE Then perform real-time PCR on
History of exposure,
urine to rule out carrier status YES
and clinical findings
and clinicopathological Real-time PCR on
abnormalities YES Perform MAT Antibodies, paired
blood and urine
consistent with samples (2 weeks apart),
leptospirosis seroconversion
Blood
1. Antimicrobial therapy prior to sampling
and/or NO
2. Sampling after leptospiraemia (>7 days)
NEGATIVE
Urine
Rule out
1. Antimicrobial therapy prior to sampling NO
leptospirosis
and/or
2. Sampling before leptospiruria (<10 days)
and/or
3. Intermittent Leptospira DNA shedding (>10 days)

MAT = microscopic agglutination test

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R E V I E W / Leptospirosis in cats

Treatment
Prognosis
The prognosis depends principally on the severity of any organ damage. Supportive therapy
In dogs that develop LPHS, the prognosis is usually poor since the animal is Intravenous fluids should be given to
in acute respiratory failure with associated dyspnoea resulting from damage affected animals to correct the electrolyte
to the small pulmonary vessels, as described earlier; LPHS is one of the most fluid imbalance. The use of centrally acting
common leptospiral-associated causes of death in dogs. The prognosis antiemetics and the parenteral administration
is also poor for affected animals that develop acute renal injury unless of gastric protectors is recommended in cats
haemodialysis is available.60 that develop associated renal failure. Pain
In cats with mild clinical signs and no severe organ damage, response to management is particularly important in the
specific antimicrobial therapy and outcome are good.30–32 Cats that survive early stages of the disease to treat painful
acute renal failure, and especially those treated in the chronic phase of swollen kidneys, muscle, joints and gastro-
leptospirosis, may develop renal damage as a consequence of the initial intestinal tissue.19
condition, and this may be permanent.

Case notes
A 2-year-old intact male domestic shorthair cat,
showing lethargy and anorexia for 5 days, was Clinical pathology results
presented for investigation.
Complete blood count

Case work-up The cat Result RI


was an indoor–outdoor RBCs (x 1012/l) 6.2 6–10.2
animal with a history of Hb (g/dl) 10.5 9–15
hunting small rodents. HCT (l/l) 0.3 0.3–0.5
Vaccinations were current. MCV (fl) 47.2 41–53
On admission, the cat was MCHC (g/dl) 36 30–34
quiet and depressed. On 9
Leukocytes (x 10 /l) 18.2 5.0–15.0
physical examination, body
Lymphocytes (x 109l) 5.8 1.4–6.1
temperature was 39.7ºC Courtesy of Fundaciò Hospital Clínic
and the cat’s mucous Veterinari, Universitat Autònoma de Monocytes (x 109/l) 1.8 0.1–0.6
Barcelona, Spain Band neutrophils (x 109/l) 0 0–300
membranes were pale and
dry. Heart rate was 180 beats per minute and pulse strength Segmented neutrophils (x 109/l) 12.0 2.5–11.3
was normal; no murmurs or gallop rhythms were detected. Platelets (x 109/l)* 115 200–600
Clinical dehydration was estimated to be 7%. There were no Serum biochemistry (selected data)
other remarkable findings upon physical examination. Owing Result RI
to the non-specific clinical signs, blood samples were
Albumin (g/l) 24.8 23–34
collected for haematology, biochemistry and feline leukaemia
Globulins (g/l) 44.0 26–38
virus (FeLV)/feline immunodeficiency virus (FIV) testing. A urine
Total proteins (g/l) 96.9 54–78
sample was obtained by cystocentesis for complete urine
analysis. Clinical pathology results are shown in the table. Creatinine (µmol/l) 91 44.2–132.6
Mild leukocytosis with mature neutrophilia and Urea (mmol/l) 8.6 3.32–8.3
thrombocytopenia were observed. Serum biochemistry profile ALT (UI/l) 51.4 <50
showed a mild uraemia, increase in ALT and hyperproteinaemia Urine analysis (cystocentesis)
(mainly due to an increase in the globulin fraction). FeLV Result
antigen and FIV antibody testing were negative (IDEXX Specific gravity >1.050
SNAP Combo Test). Most of the clinical pathological
pH 6
changes were suspected to be due to dehydration. However,
Nitrite Negative
thrombocytopenia and leukocytosis suggested a possible
infectious origin. Ancilliary tests, including an abdominal Protein Negative
ultrasound examination and thoracic radiography, were Glucose Negative
performed. The results were unremarkable. Ketones Negative
Given the patient’s predation habits, leptospirosis was Bilirubin Negative
considered and PCR (blood and urine) was performed. In Blood No abnormalities identified
addition, serum was serologically examined by MAT against Sediment Moderate fat droplets
eight Leptospira serovars: Australis, Autumnalis, Canicola, UPC 0.23
Grippotyphosa, Icterohaemorrhagiae, Javanica, Pomona
*Only mild platelet aggregates were observed on blood smear
and Sejroe. MAT serology for leptospirosis was negative. RBCs = red blood cells; Hb = haemoglobin; HCT = haematocrit;
MCV = mean cell volume; MCHC = mean cell haemoglobin
Diagnosis Blood PCR for leptospirosis was positive and urine concentration; ALT = alanine aminotransferase; UPC = urine
protein:creatinine concentration; RI = reference interval
PCR was negative.
Continued on page 226

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Enteral feeding tubes are highly recommend- study suggest further work is needed before a
ed in cats with anorexia, until they can feed vaccine against Leptospira­species for cats can
themselves in a self-sufficient manner, min- Doxycycline be considered.
imising the risk of secondary complications.38 Given the current lack of a vaccine, the best
is advised to way to avoid infection in cats is via prevention
Antimicrobial therapy of exposure. Cats that are kept indoors have a
The antimicrobial therapy suggested in cats is eliminate the lower risk of being infected.37 Prevention of
based on the treatment recommended for carrier state. predation opportunities and avoidance of
dogs. Intravenous ampicillin may be the contact with stagnant water, urine from infect-
antibiotic of choice while the patient is sta- It should be ed animals and dogs at risk of clinical lep-
bilised. Once the animal is stable, 6 weeks of tospirosis is recommended.6,30,31,37 For cats
doxycycline oral suspension has been sug-
administered that share an environment with a positively
gested in order to eliminate the carrier state.37 as a diagnosed animal, doxycycline can be given
Monohydrate salt of doxycycline, which is less at 5 mg/kg PO q12h or at 10 mg/kg PO q24h
irritating to the cat’s oesophagus than hyclate monohydrate for 2 weeks.19,60
or hydrochloride doxycycline salt, is market-
salt to avoid
ed as tablets or suspension. Doxycycline
monohydrate tablets should be administered oesophagitis.
immediately before a meal or with a treat in KEY POINTS
order to avoid secondary oesophagitis.69,70
✜ Cats may act as chronic reservoir
hosts of Leptospira bacteria and
Prevention
are a possible risk factor in the
transmission and maintenance
There is no commercial vaccine available for
of leptospirosis, the most widespread
cats. However, one study has shown that cats
zoonosis worldwide.
can produce antibodies (of lower titre magni-
tude than vaccinated dogs) when experimen- ✜ Research on leptospirosis
tally inoculated with a commercial dog should highlight the
vaccine (containing four different serovars).59 importance that cats
The follow-up time for the animals was 42 have in the disease
days, at which point only one animal main- maintenance cycle.
tained antibody levels. The authors of that

Continued from page 225


Treatment and outcome The cat was maintained cleaning the litter box during this period, to use routine
on fluid therapy and antimicrobial therapy with ampicillin household disinfectants to clean the litter box and to wash
(20 mg/kg IV q12h) for 4 days. On day 4 of hospitalisation, their hands after handling their cat.
ALT, creatinine and urea were re-checked; values were within Six weeks later, the cat had recovered completely and
reference intervals. On discharge, after receiving PCR blood no abnormalities were observed upon physical examination.
results, doxycycline at 5 mg/kg PO q12h for 6 weeks was A further urine PCR was recommended in order to rule out
prescribed. Instructions were given to keep the animal a chronic carrier state, as well as a further MAT to assess
confined during the next 6 weeks and isolated from other seroconversion, but for economic reasons this was not
cats and dogs. The owners were advised to wear gloves while approved by the owners.

What this case demonstrates:


✜ While leptospirosis is an uncommon infectious disease in cats, practitioners should consider leptospirosis as a differential
diagnosis in cats that hunt small rodents.
✜ At the time of admission, clinical pathological data in sick cats are not always characteristic of the disease, as in this case.
✜ For acute infections, PCR on blood and urine is the first-choice test to perform; MAT antibody titres are likely to be
negative or low at that point, and seroconversion is not expected until 15 days post-infection.
✜ Leptospirosis is a zoonosis and special handling methods are needed in these cases: (1) avoiding contact with the cat’s
urine and wearing gloves when cleaning the litter box; (2) using disinfectants to clean the cat’s litter box as well as any
other areas where the cat urinates; (3) preventing the cat from going outside to urinate in the environment; and (4) always
washing hands after handling the cat.
✜ Owing to the zoonotic potential of leptospires, prophylactic treatment of other pets in the same household that may
have been exposed to leptospires in the environment is recommended.
✜ When a diagnosis of leptospirosis is made, veterinarians should inform pet owners of the zoonotic risk of
Leptospira bacteria, and recommend medical attention if any family member develops signs of illness consistent
with leptospirosis.

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Conflict of interest detection of feline Leptospira in southern Taiwan. Vector-


Borne­Zoonotic­Dis­2014; 14: 118–123.
The authors declared no potential conflicts of interest with respect 14 Rodriguez J, Lapointe C, Arsenault J, et al. Serologic and
to the research, authorship, and/or publication of this article. urinary PCR survey of leptospirosis in healthy cats and in
cats with kidney disease. J­Vet­Intern­Med 2014; 28: 284–293.
Funding 15 Azócar-Aedo L, Monti G and Jara R. Leptospira spp. in
domestic cats from different environments: prevalence of
The authors received no specific financial support for the antibodies and risk factors associated with the seropositivity.
research, authorship, and/or publication of this article. Animals­2014; 4: 612–626.
16 Millán J, Candela MG, López-Bao JV, et al. Leptospirosis in
Ethical approval wild and domestic carnivores in natural areas in Andalusia,
Spain. Vector-Borne­Zoonotic­Dis 2009; 9: 549–554.
This work did not involve the use of animals and therefore ethical 17 Mylonakis ME, Bourtzi-Hatzopoulou E, Koutinas AF, et al.
approval was not required. Leptospiral seroepidemiology in a feline hospital popula-
tion in Greece. Vet­Rec­2005; 156: 615–616.
Informed consent 18 Agunloye CA and Nash AS. Investigation of possible
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This work did not involve the use of animals and therefore 1996; 37: 126–129.
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