Canine Leptospirosis A Retrospective Study of 17 Cases

Virginia T. Rentko, VMD, Nancy Clark, DVM, Linda A. Ross, DVM, MS, and Scott H. Schelling, DVM

Seventeen dogs were diagnosed with leptospirosis on the basis of clinical findings, laboratory abnormali- ties, and serology. This article summarizes and characterizes the historical and physical findings, labora- tory data, serology, treatment, and outcome of these dogs. All of the dogs had serologic evidence of infection with interrogans serovars pomona and grippotyphosa. These findings are compared with pre- vious reports of canine infection with Leptospira interrogans serovars icterohaemorrhagiae and canicola. The clinical presentation of these dogs did not correspond to the classic description of the disease in dogs in which concurrent renal and hepatic diseases are present. This may be due to infection with different serovars than those previously reported. In addition, this article suggests that canine leptospirosis should be considered in the differential diagnosis of dogs with acute or subacute renal failure. (Journal of Veterinary Internal Medicine 1992; 6:235-244)

LEPTOSPIROSIS is a zoonotic disease that affects many species of animals worldwide. Humans often are ex- posed to the same sources of infection as dogs. Patho- genic leptospires are serovars of Leptospira interrogans. The dog is the maintenance host for serovar canicola. Serovars icterohaemorrhagiae, canicola, and grippoty- phosa are reported to be the most common leptospires isolated from dogs with clinical signs oftleptospirosis. ' In contrast to these infections, infection by other serovars is characterized by decreased susceptibility, a short renal phase, a severe pathogenic effect, and a marked antibody response. The dog is considered an incidental host for reported infections with serovars icterohaemorrhagiae, grippotyphosa, autumnalis, australis, tarassovi, ballum, pomona, bataviae, and bratislava.'-'

The classic clinical picture of canine leptospirosis in- volves acute renal failure and hepatic disease with ic- terus; correlation exists between the infecting serovar and the clinical signs. Both acute and chronic forms of

From the Departments of Medicine (Rentko, Clark, Ross) and Pathol- ogy (Schelling), School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts.

Theauthors thank Dr. RobertDenk(Commonwealth Animal Hospi- tal, Newton, MA) for his assessment and management of three of the cases in this study.

Accepted for publication February 5, 199 1. Reprint requests: Linda A. Ross, DVM, MS, Department of Medi-

cine, Tufts University School of Veterinary Medicine, 200 Westboro Road, North Frafton, MA 0 1536.

the disease have been reported. Serovar icterohaemor- rhagiae has been associated with three clinical syn- dromes in the dog: 1) acute hemorrhagic disease charac- terized by high fever, prostration, and death; 2) a less acute hepatic syndrome with severe icterus, depression, fever, and hemorrhages; and 3 ) uremia, hemorrhagic en- teritis, and death.' Serovar canicola causes an acute in- terstitial nephritis without significant hepatic damage. Both acute and subclinical infections with serovar cani- cola may result in chronic interstitial nephritis. Chronic active hepatitis has been reported in dogs with serologic evidence of infection with serovar grippotypho~a.~?~

The epidemiology of canine leptospirosis may be changing. Serovars icterohaemorrhagiae and canicola have been considered primary pathogens in canine lepto- spirosis." However, serovar grippotyphosa was noted as an important pathogen in dogs in 1990.' The proportion of infections caused by serovar canicola in dogs has de- clined in the past 30 years, probably due to widespread vaccination against serovars canicola and icterohaemor- rhagiae of dogs.'

Canine leptospirosis was a rare diagnosis at Tufts Uni- versity School of Veterinary Medicine from 198 1-1985, during which time the small animal hospital was located in an urban environment. The disease has been diag- nosed more frequently since 1985, after the move ofthe hospital to a location in central Massachusetts. The clini- cal presentation of many of these dogs does not fit the

235

236 RENTKO ET AL. Journal of Veterinary

Internal Medicine

classical description of the disease. In addition, the in- fecting serovars in this study have not been commonly reported in dogs. This study characterizes the clinical findings in dogs with serologic evidence of infection with Leptospira interrogans serovars pomona and grippoty- phosa.

ling in Maine for 2 days when it became ill, and dog 7 had been to New York within 1 month of becoming ill. Eighty-two percent of all cases occurred September, Oc- tober, and November. Two dogs (dogs 6,7) had an acute illness of less than 2 weeks in December and January. Twelve dogs had been previously vaccinated for Lepto- spira interrogans serovars canicola and icterohaemorr- hagiae. Sixty-six percent of these dogs had been vacci- Materials and Methods

Records of dogs that were serologically tested for leptospi- rosis at Tufts University Foster Hospital for Small Ani- mals from September 1986 through October 1989 and at a private practice in suburban Boston* during 1989, were reviewed. In each dog, the first serologic titer was measured when clinical signs were present. Titers were determined by the microscopic agglutination test (MAT)? for serovars pomona, hardjo, icterohaemorrha- giae, grippotyphosa, and canicola. A positive titer due to previous infection or vaccination is usually less than 1:30O,l2 and the convalescent titer of a previously in- fected dog should remain unchanged. Because titers as high as 1: 1250 have been reported in vaccinated dogs,13 only dogs with single titers of more than 1 :3200 or paired titers that showed a fourfold change and compatible clin- ical signs were included in the study.

Parameters that were evaluated included age, breed, sex, home geographic location, clinical signs including depression, abdominal pain, vomiting, diarrhea, icterus, pyrexia, and muscle tenderness, physical examination findings, laboratory data, radiographic findings, serovars identified, vaccination ’ history, histopathology, treat- ment, and outcome.

Results

No age or breed predilection was found (Table 1). Thir- teen dogs (76%) weighed more than 20 kg, and males exceeded females twelve to five. Most dogs (76%) came from a suburban environment. Twenty-four percent were from a rural area, and none of the dogs were from an urban environment. Only one dog was described as having access to a livestock area. More than 50% of the dogs had been confined to their home or yard. Fourteen dogs came from Massachusetts, and 86% of these were from central Massachusetts. The three other dogs were from Connecticut, New Hampshire, and Maine. In one suburban Boston community geographically close to the original location of Tufts Small Animal Hospital, a sin- gle veterinary practice* diagnosed leptospirosis in three dogs in 1989 (dogs 9, 15, 16).

All dogs were at least 2 years old. Only two dogs had a history of travel in recent months. Dog 2 had been travel-

* Commonwealth Animal Hospital, Newton, MA. t Diagnostic Laboratory, New York State College of Veterinary Med-

icine, Ithaca, NY.

nated within 6 months of presentation. The time be- tween the onset of clinical signs and the last vaccination ranged from 1 week to more than 3 years (Table 1).

Seventy-six percent of the dogs had clinical signs for less than 14 days before diagnosis. Five dogs (dogs 1, 9, 1 1, 14, 16) were presented to veterinarians on two differ- ent occasions. All five of these dogs initially had an- orexia, vomiting, lethargy, fever, and polyuria or poly- dypsia. The clinical signs resolved within days, usually without specific treatment. These dogs represented 3 to 6 weeks later with recurrence of similar clinical signs, at which time the diagnosis was made. Most of the dogs had subacute courses.

History

The most common historical signs were anorexia, de- pression, and vomiting (88%). Nine dogs (53%) had an increased rectal temperature before presentation (range 103-104°F). These nine animals were considered to be quiet and depressed at presentation and all had clinical courses of less than 3 days. Forty-one percent of the dogs were stiff, had pain, and/or were reluctant to move (Ta- ble 2).

Other signs reported by owners, in decreasing fre- quency, included polydypsia/polyuria (PU/PD) (35%), weight loss (29%), and posterior paresis (24%) (Table 2). All the dogs with PU/PD had increased serum creatinine concentrations. In some dogs, the weight loss was pro- found; dog 12 lost 25% of its body weight in 1 week.

Four dogs (dogs 3, 4, 9, 14) had diarrhea during their clinical courses. Two dogs had fecal flotations done; dog 14 had hookworms. Three dogs (dogs 8,12,17) had histo- ries of labored breathing (Table 2).

Physical Examination

Twenty-nine percent of the dogs had painful abdomens on palpation and one quarter of the dogs had signs of depression (Table 3). Three dogs ( 18%) had palpably en- larged kidneys (dogs 1,9, 1 1). Two dogs had an oculona- sal discharge (dogs 12, 17), and one dog had only an ocular discharge (dog 13). Other findings included an increased body temperature (dog 9), bradycardia (dog 1 l), reluctance to move (dogs 1 1, 13), and posterior pare- sis (dog 12) (Table 3). Two dogs had decreased rectal temperatures (dogs 6, 12). Dog 17, which was severely azotemic, had a cough, labored respiration, and radio- graphic evidence of pneumonitis.

Vol. 6 . NO. 4, 1992 CANINE LEPTOSPIROSIS 237

TABLE I . Demographic and Epidemiologic Data for Dogs with Leptospirosis

Interval Duration of Since Last Signs Before

w t / Confined?/ State of Lepto Presentation Outcome Dog Breed Sex Age* Kg Domestile Roams Origin Vaccine$ (Days)

I 2 3

4 5

6 7 8

9

10 I 1 12 13

14

15

16 17

Golden Retriever Sheperd Cross Miniature

Schnauzer Boxer Doberman

Pinscher Lhasa Apso Golden Retriever German

Shepherd Labrador

Retriever Cocker Spaniel Temer Cross Golden Retriever Doberman

Pinscher Welsh Springer

Spaniel Miniature

Schnauzer Golden Retriever Newfoundland

M SF CM

M M

SF SF M

M

M CM F SF

M

CM

M M

4 9 7

6 3

6 7 9

7

4 14 3

I 1

2

9

10 2

31 Suburban 30 Suburban 6.8 Suburban

21.5 Rural 33.4 Suburban

9 Rural 29.5 Suburban 36 Suburban

45 Suburban

14 Suburban 20 Suburban 22 Rural 30.9 Suburban

16.3 Suburban

7.6 Suburban

35.9 Suburban 69 Rural

Roams Confined Roams

Confined Confined

Roams Roams Confined

Roams

Confined Confined Confined Unknown

Confined

Unknown

Unknown Confined

MA MA MA

MA MA

CT MA MA

MA

MA MA NH MA

MA

MA

MA ME

None 3 mo > I yr

5 mo 1 wk

>3 yr None Unknown

3 mo

None 4 mo >2 yr Unknown

5 mo

6 mo

4 mo 6 mo

17 3 3

7 7

7 14 4

29

5 7 5 I

30

10

45 5

Recovery Recovery Died day 1 I

Recovery CRFQ

Recovery Died at 12 mo CRF Died at 22 mo CRF

CRF

Recovery Recovery Died day 8 Recovery

Died at 10 mo CRF

CRF (mild)

Recovery Recoverv

* Age at presentation, in years. t Confined to house or yard. $ Leptospiru interroguns cunicolu & huemorrhugiue. Q CRF = chronic renal failure.

Blood pressure was. measured in eight dogs. Three dogs were mildly hypertensive ( 170/90- 185/ 120) (dogs 2, 4, 17). All three dogs had acute renal failure, with abnormal renal function within 7 days of the onset of clinical signs. Their blood pressures returned to normal within 2 days after improvement of renal function. A fourth dog (dog 9) with chronic renal fajlure was persis- tently hypertensive (1 89/140) 4 months after diagnosis. Two dogs that were presented with serum creatinine concentrations greater than 10 mg/dL (dogs 3, 12) were normotensive.

TABLE 2. Historical Signs of Dogs with Leptospirosis

Complaint Number of Cases %

Depression, lethargy Anorexia Vomiting Increased body temperature Reluctance to move, stiffness Pol y uria/polydypsia Weight loss Posterior paresis Diarrhea Labored respiration Cough Nasal discharge Low body temperature Hematuria

15 15 15 10 7 6 5 4 4 3 3 I I 1

88 88 88 59 41 35 29 24 24 18 18 6 6 6

Laboratory Data

The mean packed cell volume (PCV) was 41% with a range of 30-50%. Dog 17, whose PCV was 30%, had a normal mean corpuscular volume (MCV) and mean cor- puscular hemoglobin concentration (MCHC). The aver- age white blood cell count on admission was 18,300 cells/pL (range 6500-29,000 cells/pL) for dogs that had been ill between 1 day and 6 weeks (Table 4). White blood cell counts greater than 17,000 cells/pL were seen in eight animals. Eleven dogs had mature neutrophilia. No dog had a leukogram with a left shift. Eosinopenia,

TABLE 3. Abnormal Physical Findings in Dogs with Leptospirosis

Abnormal Number Physical Findings of Cases %

Painful abdomen Depression, lethargy Renomegal y Ocular discharge Nasal discharge Decreased body temperature Stiff, reluctant to move Increased body temperature Cough Labored respiration Bradycardia Posterior Daresis

5 4 3 3 2 2 2 1 I I I 1

29 24 18 18 12 12 12 6 6 6 6 6

238 RENTKO ET AL. Journal of Veterinary

Internal Medicine

O W 8 o m O b 0- W r - woo 2 3 - M W d

n N N O - N O N

0 0

O N zoo m Z % m W b b N - O - W b -

O W 0 0 b W N W M Q I N

g'D",=N'D<

;Er;03,30< 8

0 0 OP- 0 - z s

O b 0 0 0 - b - m

Q P - O W - W W m w w r i - N O -

0 0

0 0

P - w * * - - o - O w - - N N m m N - b b W W m

o m

8 s W b N W W b

- m ~ - m m T f - - w - - 0 Q

0 0

- N - O N m O * - - o m w h ( m

0. O m s0 o m 0 0

lymphopenia, and monocytosis were seen in eight, five, and six dogs, respectively (Table 4).

Platelet counts were estimated in eight dogs by relative comparison under high-power microscopy of stained blood smears; they were within reference range in seven animals and increased in one dog. Nine dogs had abso- lute platelet counts completed, of which five were de- creased (dogs 2,5,9, 12, 13) (Table 4). The lowest counts (25,000 and 35,000/mm3) occurred on day 7 of clinical signs in dogs 5 and 12, respectively. Decreased platelet counts of 70,000/mm3 (dog 2) and 169,000/mm3 (dog 13) were noted on day 1 in two dogs, and 147,000/mm3 on day 28 in another dog (dog 9). The platelet numbers were within reference range by day 4 in two dogs that had sequential platelet counts (dogs 5, 13).

Blood coagulation profiles were evaluated in six dogs by measuring platelet counts, prothrombin times, partial thromboplastin times, fibrinogen, and fibrin degrada- tion products (FLIP). Three dogs (dogs 2, 4, 10) were evaluated early in their clinical courses, before day 10, and the counts were within the reference range. Dog 5 had marked thrombocytopenia, and dog 9 had increased FDP. Dog 12 had increased FDP and fibrinogen, mild prolongation of partial thromboplastin time, and marked thrombocytopenia.

All of the dogs had increased serum creatinine concen- trations at some point during their clinical courses. Five dogs (dogs 1, 2, 5, 9, 16) had normal serum creatinine concentrations at the time of the initial presentation (Ta- ble 5, 6). One of these dogs (dog 2) had an increase in serum creatinine concentration from 1.7 mg/dL to 4.2 mg/dL within 36 hours, despite therapy with intrave- nous fluids and penicillin (Table 5). Three of these dogs (dogs 1,9, 16) had increased serum creatinine concentra- tions when presented a second time, 3 to 6 weeks after onset of clinical signs (Table 5). The serum creatinine concentration of dog 5 increased over a 5-day period. Three of these five dogs (dogs 1, 5, 9) had compensated renal failure as an outcome.

Eighty-two percent of dogs had increases in liver en- zymes (Table 6). Serum alkaline phosphatase (SAP) ac- tivity was commonly increased (10 dogs). The range of increase was 1.1 to 23 times the maximum reference range activity. Increases greater than fivefold were seen in only two dogs. Seven dogs had SAP activity that was within reference range. The increase in SAP activity was less than 3.5 times the reference range in 82% ofthe dogs with abnormal activity. Alanine aminotransferase (ALT) activity was mildly increased in six dogs (35%). All dogs had ALT activity of less than 300 U/L (normal, 10-70 U/L) (Table 6). Increases in the aspartate amino transferase (AST) activity and total bilirubin concentra- tion were less than 4.5 times the reference ranges except in one dog (dog 2) that had a serum total bilirubin con- centration of 7.92 mg/dL (Table 6). This dog had extrahe- patic biliary obstruction, diagnosed by ultrasonography.

Vol. 6 * NO. 4, 1992 CANINE LEPTOSPIROSIS 239

TABLE 5. Changes in Serum Chemistry During Clinical Course of Leptospirosis in Dogs

I Day I 23 Day 17 5 1

2 Day I 23 Day 2 74

5 Day I 22 Day 5 48

9 Day I 14 Day 29 I22

16 Day I 15 Day 45 47

1 .o 4.0 1.7 4.2 1.3 3.7 I .o 8.9 I .2 4.0

Phosphorus SAP ALT (mg/dL) (U/L) (U/L)

3.1 248 58 4.8 107 27 4.2 2545 I97 5.8 4565 I74 4.6 249 30 7.4 334 25 4.0 I984 139

12.3 448 31 2.6 555 34 4.7 143 24

Total Bilirubin (mg/dL)

0.36 0.29 3.27 7.92 0.20 0.2 I 0.55 0.26 0.33 0.30

Day I = first day of referral.

Five dogs (dogs 1, 2, 5 , 9, 16) that had serum creatinine concentrations within reference range at the onset of dis- ease had concurrent increases in ALT and SAP activi- ties. In three of these dogs, the liver enzyme activities had decreased to within reference ranges by the time renal failure was diagnosed 5 to 17 days after onset.

Liver function tests were completed on four dogs (dogs 1,4, 8, 9). Dog 1 had 12 bromosulfaphthalein retention (BSP) (reference range, less than 5%) and a resting blood ammonia concentration within reference range. Dog 8 had 22 BSP retention when admitted 5 days after the onset of clinical disease. The dog was mildly hyperbiliru- binemic at the time. When reevaluated 6 weeks later, BSP retention was 6%. Dog 4 had mild increases in serum bile acid concentrations; the fasting concentration was 5 umol/L and the 2-hour postprandial concentra- tion was 23 umol/L (reference range, less than 5 umol/l fasting; less than 10 umol/L postprandial). The resting blood ammonia concentration in dog 9 was within refer- ence range.

Thirteen dogs had serum amylase and/or lipase activi- ties measured. Three dogs had normal serum amylase

activities despite serum creatinine concentrations rang- ing from 4.0- 16.1 mg/dL. The serum amylase activities of all other dogs were less than twice the reference range (range 2129-3565 U; reference range, 625-1950 U). Serum lipase activities were increased in three dogs (dogs 2,3,4). All three of these dogs had histories of vomiting.

Urinalysis A urinalysis was completed on every dog. Urine specific gravity was isosthenuric ( 1 .O 12- 1 .O 16) at the time of diagnosis in 12 dogs, all of which were azotemic, thereby, suggesting abnormal concentrating ability. In four dogs (dogs 2, 8, 12, 16), the specific gravity ranged from 1.02 1 to 1.035. Dog 14 had a specific gravity of 1.003 (Table 7). Dogs 4, 6, 14, and 17 had been treated with subcutane- ous or intravenous fluids before measurement of the urine specific gravity. In two of the dogs with two presen- tations, loss of urine concentrating ability and concur- rent azotemia were noted during the 4 weeks between presentations (dogs 1, 9).

Fifty-three percent of dogs had glucosuria, as mea- sured by dip stick. Two of these urine samples tested

TABLE 6. Serum Chemistries of Dogs with Leptospirosis

Dogs 90 of Reference Abnormal

Range I 2 3 4 5 6 7 8 9 10 I I 12 13 14 15 16 17 Cases

BUN 6-24 mgJdL 23 23 85 116 22 82 82 96 14 149 40 155 45 44 118 15 175 100 Creatinine 0.4-1.4 mg/dL 1.0 1.7 12.2 4.3 1.3 5.4 4.9 3.5 1.0 6.2 2.4 10.2 3.0 3.3 7.2 1.2 16.1 100 Albumin 2.5-4.3 g/dL 2.8 2.4 3.9 3.4 3.2 3.8 3.6 3.1 3.1 2.7 3.2 1.8 3.3 2.6 3.4 3.1 2.4 6 Calcium 9.5-12.0 mg/dL 11.0 9.9* 7.9* 11.4 10.3 10.9 1 1 . 1 10.5 10.9 9.4 11.2 9.3* 9.0 9.4 1 1 . 1 10.7 11.3* 12 Phosphorus 3.3-6.8 mg/dL 3.1 4.2 31.5 7.5 4.6 14.7 5.9 7.0 4.0 15.3 3.6 26.6 4.0 4.0 12.4 2.6 12.3 59 ALP 20-200u/L 248 2545 278 686 249 156 76 1143 1948 321 174 160 289 22.4 179 555 662 59 ALT 10-70 u/L 58 197 102 296 30 22 39 101 139 53 115 61 63 50 27 44 120 35

GGT 1.2-10.0 lU/l 5.3 13.2 12.4 8.8 23 5.3 18 13.2 4.4 7.1 4.4 2.6 0.0 4.4 11.5 26.5 2.6 35 LDH 30-190u/L 127 120 143 308 106 54 43 64 87 123 75 234 114 207 96 107 99 18

Sodium 140-151 mEq/L 145 147 134 143 137 165 147 142 148 149 147 148 139 150 148 148 150 18

Chloride 105-120mEq/L 116 130 67 107 103 124 114 113 118 102 113 102 104 119 105 113 I l l 35

AST 10-40 u/L 18 173 32 110 30 15 28 22 27 39 26 173 24 58 28 29 77 29

T. bilirubin .04-.40 mg/dL 0.36 3.27 .47 .34 .20 .38 .29 1.12 0.55 .29 .I7 .27 .41 .I6 .30 0.33 .75 24

Potassium 3.4-5.4mEq/L 4.7 3.2 5.1 4.2 4.0 5.5 3.5 3.3 4.7 3.2 4.3 7.8 3.6 3.7 4.2 4.5 5.6 24

* Calcium corrected for albumin; corrected calcium = (measured calcium - Serum albumin) + 3.5. All chemistry profiles performed at time of presentation; except dog 2, performed 36 hours later, dog 15,4 days later.

240 RENTKO ET AL. Journal of Veterinary

Internal Medicine

TABLE 7. Urinalyses of Dogs with Leptospirosis

Specific Bacterial Sediment* P/C Timet Previous Rx Dog Gravity Protein Blood Bilirubin Glucose Cast Culture

I

2 3 4

5

6

7 8

9 10 I I 12

13 14

15

16

17

1.037

I .02 I 1.013 1.013

I .008

1.010

1.013 I .025

I .02 1 1.008 1.013 1.017

1.013 1.033

1.012

1.035

1.015

-

- - -

++++ -

Tr ++++ - - -

+++ Tr Tr

-

++++ +++

Tr

Tr Tr -

++++ ++++

++ +++ - -

+++ + Tr ++ ++ -

+

2-4 WBC 1-4 Epithelial

- -

3-6 WBC 10-15 RBC >I5 WBCS TNTC RBC

6-7 RBC

2-4 WBC 10-12 RBC

2-3 WBC

-

- - -

6-8 WBC 8-1 I RBC

- 10-13 WBCS 10-20 RBC 10-15 WBCS 8-12 RBC 2-5 WBC 2-3 RBC 0-WBC 0-2 RBC

1.1

N D N D 3.4

N D

ND

N D N D

1 . 1 4.5 N D N D

N D ND

N D

N D

N D

3

I 4 5

3

6

1 4

1 5

30 14

3 2

14

I

5

- Amoxicillin, fluids

Trimethoprim/sulfa

Fluids

Amoxicillin, fluids -

Prednisone Trimethoprim/sulfa Trimethoprim/sulfa Tetracycline

Amoxicillin, fluids

* Cells per high power field t Time in clinical course (days) 4 Free catch sample, all others cystocentesis. Tr = trace, Occ. = occasional, GR = granular, N D = not done. P/C = protein/creatinine ratio.

negative for glucose by chemical assay$ when simulta- neous samples were checked. The glucosuria was mild, ranging from trace to 250 mg/dL. Subsequent urinalyses of three dogs tested negative for glucose 2-3 weeks later. Eighty-nine percent of dogs that had glucosuria had been ill for less than 6 days.

Twenty-nine percent of the dogs (dogs 4,8, 14, 15, 16) had casts in the urine sediment (Table 7). Three of these five dogs had granular casts in urine samples obtained within 5 days of onset of clinical signs.

Four dogs had urine pr0tein:creatinine ratios deter- mined. Two dogs (dog 1, 9) had a ratio within reference range (less than one) when tested after 4 weeks of clinical disease. Five days after presentation, one dog (dog 10) had a urine pr0tein:creatinine ratio of 4.5:l. This dog had an inactive urine sediment and a negative bacterial urine culture. Three weeks later, the ratio had returned to 1 : 1. Another dog (dog 4) had a urine protein:creati- nine ratio of 3.4: 1 5 days after the onset of clinical signs; this dog had an active urine sediment. A bacterial culture of the urine obtained while the dog was receiving antibi- otic therapy was negative.

Bacterial culture of the urine was done at the time of diagnosis in 14 dogs. Thirteen urine cultures were nega-

$ Clinitest, Miles, Inc., Elkhart, IN

tive; eight ofthese dogs had been given antibiotics during the week before presentation. One dog (dog 17) had a positive culture of Corynebacteria spp. and Micrococcus spp. Darkfield microscopy was done on the urine of three dogs (dogs 1,2,4). Each of these dogs had received antibiotic and fluid therapy before samples were ob- tained. All samples tested negative for leptospires. Isola- tion of spirochetes from the urine was not attempted in any of the dogs.

Serology The serologic and vaccination data are summarized in Table 8. Paired titers were measured in 47% of the dogs for serovars pomona, hardjo, icterohaemorrhagiae, grip- potyphosa, and canicola, with the second sample drawn 14 to 2 1 days after the first sample. Late convalescent titers were done in three additional cases (dogs 10, 1 1 , 17) at 2,5, and 3 months, respectively. The convalescent titer on dog 17 was performed at a different laboratory and was not paired with the original serum sample. Thir- teen dogs (76%) had titers > 1:3200 for serovar pornona, whereas 1 1 dogs (65%) had titers > 1:3200 for serovar grippotyphosa. None of the 17 dogs had titers of > 1 : 1600 for serovar canicola, and only one dog had a titer of 1 :3200 for serovar hardjo (dog 17) or icterohaemorrha- giae (dog 8). Of the nine dogs vaccinated within 6

VOI. 6 . NO. 4, 1992 CANINE LEPTOSPIROSIS 24 1

TABLE 8. Serologic Data of Dogs with Leptospirosis

Time Since Last

Vaccination

I None 2 3 mo 3 > I yr 4 5 mo 5 1 wk 6 >3 yr 7 None 8 ? 9 3 mo

10 None I 1 4 mo 12 >2 yr 13 ? 14 5 mo 15 6 mo

Pomona Hardjo Icterohaemorrhagiae Grippotyphosa

1 :3200/ 1 : 1600 O/O 1 :200/ 1 :200 1 : 12800/> 1: 12800

1:3200/ND l:IOO/ND I:200/ND

1 :6400/ND I:800/ND I : I OO/ND I:6400/ND I : 12800/> I : 12800 o/o 1 :200/ I :200 I: I2800/1: I2800 1:3200/1:800 o/o 1:100/0 > I : 12800/> 1: 12800 1: 1OO/1:6400 O/ I : 1600 I : 100/ 1 :3200 1 : 1600/ 1 :SO0 1 :200/0 0/1:100 1: 12800/1: I2800 1 :6400/ 1 :6400 1:3200/1:400 o/o 1 :6400/ND 1 : 1 OO/ND 1:100/ND > 1: 12800/1:3200 o/o 1: loo/ I : 100 1 : 1 oo/ I : 100 I : 12800/ND I:400/ND 1 :400/ND >I:12800/ND I:100/ND O/ND O/ND 1 : 12800/ND

1 : 100/1:3200 1 :200/ND

I : 100/1:200 1 :loo/ 1 :so0 o/o 1 : 12800: I : 12800 o/o I : 1600/ 1 :SO0 o/o

1 :800/ I : I2800

1 :200/0

1 :6400/ND

1 :800/ 1 :400 I : I oo/ 1 : 100 1 :200/0 1:12800/1:3200

Canicola ~

1 : 1 oo/ 1 : I 0 0 1 : 100/1:200 O/ND 1 :400/ 1 :200 1:800/ND o/o 1 :800/0 O/ I : 1600 o/o 1 : I oo/o 1 :200/0 O/ND 1 : 1 oo/o I :800/ND O/ND

16 4 mo > I : I ~SOOIND O/ND I 4 0 0 1 ~ ~ > I : 12800/ND O/ND 17 6 mo > 1: 12800/1: 1200 I:3200/ND 1:100/1:1100 O/ND O/ND

Initial/convalescent titer; all convalescent titers were measured 14-2 1 days after first titer, except for dogs 10, I I , 17 which had titers done at 2,5,

Convalescent titer for dog 17 performed at a different laboratory. ND = not done. ? = Unknown vaccination history.

and 3 months after first titer, respectively.

months of the onset of clinical signs, five dogs had titers > 1:3200 for serovar pomona, five had titers > 1:3200 for serovar grippotyphosa, three dogs had titers > 1:3200 for both serovars pomona and grippotyphosa, and one dog had a titer > 1 :3200 for serovar hardjo. The highest titer for serovar icterohaemorrhagiae or canicola in the re- cently vaccinated dogs was 1 : 1600 in dog 4, which had been vaccinated 5 months previously. Seven of nine dogs vaccinated with Leptospira bacterin within 6 months of presentation had titers < 1 :400 for serovar icterohaemor- rhagiae and six of these dogs had titers of <1:400 for serovar canicola.

Miscellaneous titers for Lyme disease, Rocky Moun- tain spotted fever and Ehrlichiosis wwe determined in five dogs (dogs 1, 4, 10, 12, 16). None had significant antibody titers.

Radiographic Findings

Abdominal radiographic reports were available for 13 animals. Two dogs had results of radiographs that were considered within normal limits. Four dogs had reno- megaly (dogs 1, 6, 9, 1 I), three had splenomegaly (dogs 2,8, lo), and two had hepatomegaly (dogs 8, 12). Other findings included mineralization of the kidney in dog 5, mineralization in the caudal abdomen in dog 9, and di- minished abdominal detail in dog 13.

Thoracic radiographs were taken in seven dogs. Find- ings were within normal limits in four dogs (dogs 1, 8, 10, 13). In the other three dogs (dogs 9, 12, 17), mild cardiomegaly, microcardia, and pneumonitis were re- ported, respectively.

Ultrasonographic evaluation of the kidneys were done in 1 1 dogs, and abnormalities were found in 73% of these

dogs. Two dogs had renomegaly (dogs 1, 1 l), and one had reduced kidney size (dog 7). Mineralization was noted in the renal cortices of two dogs (dogs 7, 10). Three dogs had dilated renal pelvices (dogs 5, 13, 14) and two had uneven renal cortical texture (dogs 11, 14). Dog 17 had prominent renal vasculature.

Excretory urography was done in four dogs (dogs 4, 11, 13, 14). All had received intravenous fluids for sev- eral days before the radiographic study, and their serum creatinine concentrations varied from 2.0 to 3.7 mg/dL. All of the dogs had abnormal findings; three had de- creased concentrating abilities (dogs 4, 13, 14), and two had dilated renal pelvices (dogs 1 1, 13).

Histopathology

Five of the dogs (dogs 1, 4, 9, 10, 14) underwent renal biopsies 2-5 weeks after the onset of clinical disease. Specimens from the renal biopsy of dog 4, composed only of pelvis and medulla, were considered nondiagnos- tic for this study. Numerous spirochetes were seen in the renal tubules of dog 1 in a section stained by the Warthin-Starry method for the demonstration of spiro- chetes.I4 Warthin-Starry stains were done retrospectively on the biopsy specimens from the remaining dogs. Spiro- chetes were identified in the renal interstitium in dog 10; they were not found in any other dog. Four of the five biopsies showed severe lymphoplasmacytic and neutro- philic interstitial nephritis. Two dogs (dogs 1, 14) had positive bacterial cultures of renal tissue. The microor- ganisms isolated were Staphylococcus epidermidis and Proteus spp., respectively.

Only one dog (dog 12) had a complete postmortem examination. This dog had an acute clinical course and

242 RENTKO ET AL. Journal of Veterinary

Internal Medicine

died during hospitalization. Membrano proliferative glo- merulonephritis, diffuse interstititial fibrosis, and mild lymphoplasmacytic nephritis were found. Extrarenal manifestations of uremia (alveolar septa1 mineraliza- tion, multifocal fibrinoid necrosis, erythroid hypoplasia) were apparent. No hepatic pathology was seen.

Treatment

soil pH, which commonly occur in summer and fall.' The occurrence of disease in the winter months in this report may reflect mild environmental temperatures, hu- midity, and rainfall or an increased exposure to reservoir hosts.

The clinical signs in dogs in this report were nonspe- cific; lethargy, depression, anorexia, and vomiting were noted in 88% of dogs. These findings are similar to other

Eight dogs received no medical therapy before presenta- tion at the time of diagnosis. Four dogs (dog 5, 10, 11, 14) had received trimethoprim/sulfa from 4 days to 3 weeks before presentation. Dogs 4 and 7 received amoxi- cillin for 4 and 7 days before presentation, respectively, and dog 12 received tetracycline for 3 days before presen- tation. Sixteen dogs were given specific antibiotic ther- apy for leptospirosis. Twelve dogs (dogs 1,2,3,4, 5,6,7, 9, 10, 13, 14, 16) were given penicillin or procaine peni- cillin; two dogs (dogs 8, 11) were given ampicillin, and two dogs (dogs 12, 15) received tetracycline. Treatment was initiated between 3 days and 7 weeks after the onset of clinical signs. Six dogs (dogs 4, 7, 10, 11, 16) were given streptomycin or dihydrostreptomycin after peni- cillin or ampicillin to eliminate leptospires from the kid- ney~. ' , '~ Another dog (dog 1) received doxycycline for this purpose.16 All dogs were given intravenous fluids during the clinical course of disease.

Outcome Fifty three percent of the dogs in the study recovered completely with respect to 'clinical status and renal and hepatic laboratory parameters. These dogs have re- mained healthy to date (6 to 22 months after treatment).

Five dogs died due to leptospirosis. Two dogs (dogs 3, 12) died acutely during hospitalization and three dogs (dogs 7, 8, 14) died 12 months, 22 months, and 10 months later, respectively, due to chronic renal failure. No dogs showed evidence of chronic hepatic disease at follow-up examination (6 to 22 months).

Discussion No age or breed predilection for canine leptospirosis was present in this study, and more males than females were affected, which is in agreement with previous reports. The lack of cases in dogs less than 2 years of age is un- usual in that young dogs have been reported to be more severely affected clinically than older dogs." All of the dogs in the study resided in New England; 7 1% of the dogs were from central Massachusetts. The latter may reflect the referral population of our hospital. The sea- sonal incidence of leptospirosis in late summer and early fall (August through October) in 59% of the dogs corre- sponded to previous reports. However, 4 1 % of the dogs were diagnosed from November through January. Opti- mal environmental conditions for the survival of lepto- spires include warmth (25"C), moisture, and a neutral

reports and reflect the systemic nature of the disease." Most physical examination abnormalities were also non- specific and similar to previous reports. The abdominal pain present in almost one-third of the dogs may have resulted from the inflammatory reaction associated with leptospiremia. Pain of abdominal musculature is a prom- inent clinical sign of the disease in people." The dog with severe respiratory signs (dog 17) had evidence of pneu- monitis, a finding compatible with the severe uremia in the dog. Hypertension occurred only in association with renal disease.

The hematologic abnormalities seen in dogs in this study were similar to those in previous The lack of anemia in all dogs despite the presence of renal failure can be attributed to the acute course of the dis- ease. The leukocytosis, lymphopenia, and monocytosis seen in many of the dogs are nonspecific, and probably reflect response to the acute systemic infection. Throm- bocytopenia was present in 55% of the dogs in which a platelet count was done, is also reported to be a common finding in canine and human l e p t o s p i r ~ s i s . ~ ~ ~ ~ ~ ~ * ~ ~ ~ ~ ~ Al- though thrombocytopenia was severe in two dogs, no bleeding occurred. The thrombocytopenia may be re- lated to vasculitis, associated with leptospiremia, or in response to the acute systemic infection. Because the thrombocytopenia occurred early in the course of the disease and was transient, the leptospiremic phase of in- fection would seem to be the most likely cause.6,18

Urinalyses of dogs in this study were similar to those of cases previously reported, with a low specific gravity, proteinuria, red blood cells, white blood cells, and casts in the sediment. However, glucosuria occurred early in the disease in more than one-half of the dogs. This find- ing has not been previously associated with canine lepto- spirosis. The glucosuria may have been due to renal tu- bular damage associated with leptospiremia or leptospira colonization of the renal tubules.

The diagnosis of leptospirosis in this study was based on correlation of clinical signs with serologic testing. Al- though a fourfold increase in antibody titer is the most accurate serologic method for diagnosis, single high titers coupled with clinical signs are considered Animals in the incubation stage of the disease or chronic carriers with localized infections may show negative or low agglutination titer^.^ Dogs tend to be chronic carriers for serovar cani~ola .~ Therefore, the presence of a low titer associated with chronic infection is serovar specific. Similarly, vaccinated dogs develop either a low titer or

VOl. 6 . NO. 4, 1992 CANINE LEPTOSPIROSIS 243

no titer at all.” Postvaccinal titers are transient when they do occur, lasting approximately 1 to 3 months5

The MAT is a standard, specific, and frequently used serologic test. One limitation of the test is that crossreac- tivity can occur; therefore, it may not distinguish sero- vars within a serogroup.22 Crossreactivity may occur also between serogr~ups.~ Serovars such as bratislava that may crossreact with serovars pomona and grippotyphosa were not tested. However, the high titers to serovars po- mona and grippotyphosa make it likely that these or closely related serovars are the infecting serovars. The negative or low titers for canicola, icterohaemorrhagiae, and hardjo make the possibility of infection with these serovars unlikely. Even those dogs with high titers to serovars hardjo or icterohaemorrhagiae had higher titers to serovars pomona or grippotyphosa. Therefore, sero- vars pomona or grippotyphosa are likely to be the sero- vars causing disease. The usual reservoir hosts for sero- vars grippotyphosa and pomona are wild carnivores such as skunks, raccoons, and opossum^.^,^ The presence of these species in suburban and sometimes urban habitats provides a source of infection for pets. The fact that lepto- spirosis in the dogs of this study was probably due to contact with these infected species lends support to the observation that leptospirosis is not only a disease of farm dogs.

Recent vaccination did not protect against infection. The reason for this is that immunity to leptospires is serovar specific. The commercial canine bacterin con- tains serovars icterohaemorrhagiae and canicola and protects against pyrexia, urinary shedding, and renal co- lonization by these serovars only.23

Some correlation between clinical signs and specific serovars have been reported. Signs referable to hepatic disease in the dog have been most commonly associated with serovars icterohaemorrhagiae3.” and grippoty- p h o ~ a , ~ and icterus has been reported to be a common clinical sign in dogs with subacute leptospirosis.’,21 None of the dogs in this report were icteric on presentation. The lack of icterus in 16 of 17 dogs throughout the ill- ness, as well as mild increases in SAP and ALT activities, suggests that liver disease is not a prominent clinical fea- ture in dogs infected with serovarspomona and grippoty- phosa. However, dogs that are less than 1 year of age and have leptospirosis are usually severely affected clinically, and they are most likely to show both hepatic and renal disease. Because dogs in this study did not belong to this age group, hepatorenal signs could occur with infection due to serovars grippotyphosa and pomona but may not be represented in this retrospective study. The liver may have been transiently affected because SAP and ALT activities were increased in 53% of the dogs. However, the clinical signs of all dogs in this study related to renal disease and renal failure.

Penicillin remains the antibiotic of choice for its lepto- spirocidal activity in the dog. Ampicillin, amoxicillin,

oxytetracycline, doxycyline, and cefotaxime are also ef- f e ~ t i v e . ~ ~ , ’ ~ Two dogs (dogs 4,7) had worsening azotemia despite treatment with fluids and amoxicillin before diagnosis. No correlation could be made between treat- ment regimen and outcome.

Complete recovery from leptospirosis can occur;’* however, renal colonization by leptospires can cause irre- versible damage to the kidney despite clinical recovery. Ten dogs (59%) in this study had severe renal failure, of which five (50%) died from acute complications or chronic failure. Prognostic factors for survival or devel- opment of chronic renal failure could not be determined from this study.

Although leptospirosis is an uncommon problem in dogs, this article suggests that some cases of canine lepto- spirosis do not fit the classic clinical description of con- current hepatic and renal disease, and that leptospirosis should be considered in the differential diagnosis of acute or subacute renal failure. This difference in clinical presentation may be attributed to infection with differ- ent serovars than have been reported in the past. This apparent change in serovars may be due to several fac- tors. A new reservoir host, or newly infected reservoir host, may have been introduced into the reported area. All of the dogs in this study were from a suburban or rural environment. The migration of wildlife mainte- nance hosts such as raccoons, skunks, and opossums into suburban areas may account in part for this in- creased incidence. The widespread vaccination of dogs has decreased the incidence of leptospirosis due to sero- vars icterohaemorrhagiae and ~anicola .~

The zoonotic potential of leptospirosis should be noted. Dogs with acute or subacute renal failure in which leptospirosis is a differential diagnosis should be isolated. Gloves should be worn when handling and treating the animal, and wastes, particularly urine, should be dis- carded appropriately.

Further studies are needed to define canine leptospiro- sis. Isolation and culture of Leptospira serovars pomona and grippotyphosa would provide definitive evidence of infection by these serovars in the dog. In addition, an epidemiologic and serologic survey of the common wild- life carriers of leptospirosis in New England would be beneficial in determining the source and defining the in- cidence of Leptospira serovars in the area.

References

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1987; 9:499-507.

Books Received But Not Reviewed UROLOGIC SURGERY OF THE DOG AND CAT. Elizabeth A. Stone, Jeanne A. Barsanti. Lea & Febiger, Philadelphia, PA, 1992.

VETERINARY UPDATE-CLINICAL ABSTRACT SERVICE-SMALL ANIMALS. Vol. 33, No. 1, January, February, March. American Veterinary Publications, Inc., Goleta, CA, 1992.

A GUIDED TOUR OF VETERINARY ANATOMY. James E. Smallwood. W. B. Saunders, Philadelphia, PA, 1992. Price $32.95.

VETERINARY DENTAL TECHNIQUES. Steven E. Holmstrom, Patricia Frost, Ronald L. Gammon. W. B. Saunders, Philadelphia, PA, 1992. Price $49.95.

EQUINE SURGERY. Jorg A. Auer. W. B. Saunders, Philadelphia, PA, 1992. Price $195.00.