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Coccidiomycosis in a Dog in Calgary

by Dr. Mark Rubensohn, DVM, B.V.Sc.

Abstract:

A diagnosis of Coccidiomycosis has been made in a Greyhound in Calgary. This dog was introduced from Arizona. She was presented with a mild fever, unilateral hind leg lameness, and later with a suppurating peri-anal fistula. Swabs revealed fungal spherules, and fungal titres were positive for Coccidioides immitis. Treatment was started with ketoconazole at 5mg/kg bid and an immediate improvement was achieved. It is expected that this dog will receive medication for a minimum of one year, and possibly for life.

Case History:

A 2-year-old spayed female Greyhound “Cabby” was presented for a post adoption examination on March 9, 2002. She was adopted via the Greyhound Rescue Society and had originated in Arizona.

On presentation “Cabby” was bright, alert, and responsive. The right submandibular lymph node was enlarged (¾” diameter), she had a right otitis externa and a nail bed infection (L/F D2). She was placed on antibiotics (Cephalexin 250 mg bid) for 2 weeks. She was then re-examined and the lymph node had reduced in size (½ “ diameter) and the nail bed infection and ear were healed.

On July 13, 2002, “Cabby” was presented with a fever (39.5 C) and limping on the left hind leg. Clinical examination was unremarkable and she was placed on Metacam (Meloxicam 0.1 mg/kg sid). On July 23, 2002, the limp had not improved (painful upon extension of the left hind and sensitive in the groin area), “Cabby” had developed a draining fistula at the site of the left anal gland. She was placed on antibiotics (Amoxicillin 500 mg bid for 1 week) for a suspected anal gland abscess, and appeared to improve after 3 days with decreased discharge and discomfort. On August 6, 2002, “Cabby” was checked again. The left hind lameness was worse, she was again febrile (40.5 C), with persistent peri-anal fistula drainage.

The fistula was probed to a depth of 3.5 cm. A swab from the fistula showed a pyo-granulomatous discharge containing spherules of Coccidiodes immitis. Hematology revealed a monocytosis of 1.730 10e9/L (0.000-0.980) as well as a basophilia of 0.111 10e9/L (0-0.100). Blood chemistry revealed severe hyperproteinemia of 86 g/l (54-71) due to an exaggerated hyperglobulinemia of 62 g/l (20-40). Radiographs showed granulomatous pelvic osteomyelitis. The systemic fungal panel was positive for antibodies to Coccidiodes (+1:16). As low grade infections with Ehrlichia canis is not uncommon in dogs of the southern USA, an E. canis titre was run and found to be negative.

After discussion with the owner, “Cabby” was started on ketoconozole at a dosage of 100mg every 12 hours (5mg/kg bd). She was also placed on a diet of canned puppy food (Medi-Cal Development) to augment her diet as ketoconozole can act as an appetite suppressant. “Cabby” responded well to treatment. Her fever reduced (39.2C); she is bright and eats well. The treatment will continue for a minimum of one year, after which her condition will be reassessed.

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DISCUSSION: (Courtesy of Suzanne Stack, D.V.M.)

The desert southwest (Arizona, N. Mexico, S. California) is the hotbed for Coccidiomycosis (Coccidiodes immitis) in the U.S. “Cocci” or "Valley Fever" is a fungus that lives in the desert soil and forms spores when released into the air. Events such as the digging of building foundations and pools help to release the spores more quickly. Periods of rain, which cause fungal growth, are usually followed by more cases of Valley Fever being diagnosed. The spores are inhaled by man, dogs, and horses (cats seem to be resistant), causing the disease, VF. Any dog that breathes air in an endemic region can become infected. There is no vaccine or prevention in existence short of moving away from the area.

Greyhounds seem particularly susceptible to VF, perhaps due to their normally low white blood cell numbers. Natural immunity plays a part in which dogs contract VF (a new arrival to the area is more susceptible than a dog that grew up there). We see as many cases of VF in indoor dogs that are out only briefly to do their duty as in outdoor dogs that run around all day with their noses to the ground. Additionally, if one dog in a household gets VF, there is no increased risk to other dogs in that home.

Symptoms:

Valley Fever is a disease that can be obscure and may progress before the owner sees sufficient reason to visit a veterinarian. Some dogs display no specific signs, especially early on; they may not feel as well, eat inconsistently, or lose weight. Despite the name, half of Valley Fever dogs have normal temperatures at presentation. They may, however, run fluctuating fevers at home and have times of feeling well interspersed with times of lethargy.

These ADR ("Ain't Doin' Right") dogs inevitably go on to develop more specific signs if undiagnosed and untreated. The most common signs are poor appetite, weight loss, lameness, bone pain, spinal pain, and coughing. This is because in the early ("primary") form, the fungus infects the lungs, then moves on to infect the bones ("secondary" form). Lungs and bones account for most cases; other systems VF can affect are the central nervous system, eyes, and less commonly, the heart or skin.

With Greyhounds, we seldom see the coughing stage. In most cases, the Greyhound presents with bone involvement or nonspecific illness/weight loss. While other dogs tend to present with equal proportions of lung vs. bone form, Greyhounds run approximately 10% lung, 30% ADR, 60% bone, and the odd neurological case.

Of particular concern with Greyhounds is how much the VF bone lesions resemble bone cancer (osteosarcoma) on radiographs. Lesions can be either osteoproliferative or osteolytic. If your Greyhound is ever diagnosed by radiography with "bone cancer," be sure a Coccidiosis antibody titre is done. I strongly recommend a titre be done early on any Arizona Greyhound, sick for any reason. Catching the disease a few weeks early may save months or years of treatment down the road. Additionally, be sure to also check the Greyhound for Ehrlichia, as some Greyhounds have both diseases together.

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Treatment:

Ketoconazole is the first line of treatment. It is used at a dose of 5 mg/kg every 12 hours with food. MINIMUM treatment time is one year, unless there is only lung involvement, in which case a minimum of 6 months. In reality, most Greyhounds are on anti-fungal medications for years. Treatment is continued until titers are negative and radiographs are clear (if bone involvement).

In the first 2-3 weeks of treatment, the Greyhound is usually anorexic, due both to the disease and to the ketoconazole. Ketoconazole is an appetite killer – it depresses steroids in the body which is why it can be used as a treatment for Cushing’s Disease (fun fact). We usually force-feed the dogs through the first few weeks. That way a full dose of medication can be administered, thereby keeping them from losing any more weight until they begin to improve. From there on it's usually smooth sailing. Relapses are rare in a dog that is on full dose medication; they are more common when medications are being discontinued. So, while the Greyhound may be on ketoconazole for years, he is not necessarily sick for years.

Ketoconazole is absorbed better with a fatty meal, so it helps to feed substantial amounts of canned dog food at least in the beginning of treatment. Once they are stable, I usually just feed mostly dry food and a few spoons of canned. If you don't get food into the dog, don't give the ketoconazole because he will likely vomit. That's why the force-feeding is so important.

Though ketoconazole is labeled as hepato-toxic, I cannot think of having to take a dog off it for that reason. If we have to try medications other than ketoconazole, it is usually because of appetite suppression. With the adoption dogs we muscle our way through the first few weeks with force-feeding until things start to improve.

If a dog vomits even when ketoconazole is given with food, you can try using itraconazole (Sporonox) at a dose of 2.5 mg/kg every 12 hours. Itraconazole does not generally have any advantages over ketoconazole except to reduce side-effects. The premium VF medication (if you can afford it) is fluconazole (Diflucan) at a dose of 2.5 mg/kg BID. With really sick dogs sometimes it is helpful to use it for the first month or two, then revert back to ketoconazole for the long haul. The main advantage is that most dogs tolerate fluconazole much better than the other two (however even fluconazole can be an appetite suppressant). Although it is the drug of choice for CNS involvement, we have treated cases successfully with ketoconazole and amphotericin B before fluconazole was available. Whether or not fluconazole actually shortens the treatment period is uncertain. Regardless of which medication you use, I think it's critical to keep calories in the dog. He can't win this battle if he is not eating and is losing weight.

Some veterinarians recommend MSM to help with VF, some add Program (kills VF skeletons as well as flea skeletons), but this makes treatment relatively expensive. The dosage is one white (409.8 mg) Program tablet daily. Others give a Vitamin C (500 mg) with the medication as antifungals work better in an acidic stomach.

Lastly, with really sick dogs, amphotericin B is an option. It is a potent drug with the possibility of serious side effects. (It is known for kidney damage but I had one Greyhound become icteric after just one treatment.) Interestingly enough, this Greyhound had to discontinue amphotericin B and go right onto ketoconazole while still icteric. He stayed on ketoconazole for 4 years with no liver problems. Therefore amphotericin B (“amphoterrible") is usually reserved for seriously sick dogs. The drug itself is very inexpensive, but it has to be given over a period of 12 hours, first with a liter of 0.9% saline to flush, followed by a liter of 5% dextrose. Before each treatment, a urinalysis and blood urea nitrogen should be run. Full treatment course is twice weekly for 2 months. I've used it on perhaps 20 dogs that failed to improve with ketoconazole treatment, and many of them survived because of it, including two Greyhounds. Some dogs will still need to be maintained on oral medication after finishing the amphotericin B. Veterinarians who have actually used it get a sense of risk vs. benefit. It certainly is a stronger and faster working drug for seriously ill patients.

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Prognosis:

VF can relapse even if the titres are negative. Some veterinarians consider VF to only be in remission and not cured, until the dog has gone several years without a relapse. One of my first Greyhounds had a vertebral lesion and was on ketoconazole for 4 years. His titres finally became negative, but every time I tried to take him off ketoconazole, his neck would start hurting again in a month or two, so we continued medicating. He eventually died at the fair age of 7 from right-sided heart failure - somewhat unusual, but I didn't autopsy to find out if it was from VF (titres were negative at the time). I do know of another Greyhound that started out terribly sick who also died of right-sided heart failure 2 years into ketoconazole treatment. (He was doing well on his medication until his heart gave out).

The Greyhounds do seem to have a worse time with VF than other dogs. Weaning dogs off the medication seems preferable to stopping medication entirely and risking a relapse, which can sometimes get the better of them.

Approximately 1/3 of VF dogs will die, 1/3 are cured, and 1/3 are OK as long as medication is continued.

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References:

1. Suzanne Stack, DVM, Ironwood Veterinary Clinic, Yuma, Arizona

2. Central Laboratory for Veterinarians, Calgary, AB

3. R.V. Morgan: Coccidiomycosis. pp. 1119-1121. Handbook of Small Animal Practice, 3rd Edition, W.B. Saunders, Philadelphia, 1997

4. Ettinger SJ, Feldman EC: Coccidiomycosis. pp. 444-448. Textbook of Veterinary Internal Medicine, 4th Edition, Volume 1, W.B. Saunders, Philadelphia, 1995
Chapter 71, Wolf, Troy: Deep Mycotic Diseases

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Laboratory Results:

Calgary-Central Lab for Vets
Unit 19, 5080 12A Street SE
Calgary, Alberta T2G 5K9
(403) 214-1506
BRIDLEWOOD VET CLINIC PATIENT: CABBY
1-403-201-6427 AGE: 2 Y SEX: F
26-17107 JAMES MCKEVITT RD SW SPECIES: CANINE DRWN: 08/06/02 17:50
CALGARY, ALBERTA RCVD: 08/06/02 17:50
T2Y 3Y4 PRNT: 08/07/02 10:43

* * COMPLETE REPORT * * ATTENDING VET: RUBENSOHN

TEST NAME NORMAL OUT OF RANGE UNITS REFERENCE RANGE

General Panel . . . . .
cbc with differential . . . . .
White cell cnt 11.7 10.9/l 4.0 - 15.0
CD-NEUTR 8.91 10e9/L 2.80 - 10.56
CD-LYMPHS 0.937 L 10e9/L .960 - 4.800
CD-MONOCYTES 1.730 H 10e9/L 0.000 - 0.980
CD-EOSINOPHILS 0.012 10e9/L 0 - 1.231
CD-BASOPHILS 0.111 H 10e9/L 0 - 0.100
MORPHOLOGY T

This is an automated differential, all absolute number are in SI units.
Platelet numbers are adequate. Platelets clumped. Variability
in platelet size apparent. Rbc morphology normal.

Red cell cnt 8.12 H 10.12/l 5.50 - 8.00
Hemoglobin 188 g/l 138 - 199
Hematocrit 0.545 l/l 0.390 - 0.560
Mean Corp Vol. 67 fl 63 - 77
Mean Corp Hemoglobin 23.1 pg 22.0 - 27.4
Mean Corp Hemoglobin Conc 345 g/l 326 - 374
RDW 16.6 10.0 - 19.0
Platelet cnt INV 10.9/l 170 - 400
Mean Platelet Volume INV fl 7. - 14
Chemistry Screen . . . . .
Glucose 4.2 mmol/l 3.0 - 6.6
Grey Glucose 4.0 mmol/l 3.0 - 6.1
Blood Urea Nitrogen 4.9 mmol/l 2.5 - 9.20
Creatinine 110 umol/l 68 - 141
Bun/Cr Ratio 11
Sodium 150 mmol/l 140 - 151
Potassium 4.7 mmol/l 4.0 - 5.4
Na/K Ratio 32
Calcium 2.37 mmol/l 2.24 - 2.83
Phosphorus 1.56 mmol/l 0.72 - 2.08
Total protein 86 H g/l 54 - 71
Albumin 24 L g/l 31 - 42
Globulin 62 VH g/l 20 - 40
Albumin/Globulin Ratio 0.4 L 0.8 - 2.3
Bilirubin total 5 umol/l 0 - 7
Alkaline phosphatase 82 iu/l 04 - 113
Sgpt (alt) 35 iu/l 0 - 113
Gamma gt 9 iu/l 2.- 20
Chloride 118 mmol/l 108 - 118
Carbon Dioxide 20 mmol/l 15 - 26
Calculated Osmolality 296.8 mmol/kg 278 - 306
Anion Gap 17 10.- 22
Creatinine Phosphokinase 59 iu/l 00 - 314

Cytology T
THE ONE SMEAR FROM THE PERIANAL REGION REVEALED
A HIGH NUCLEATED CELLULARITY WITH A PREDOMINANCE
OF NEUTROPHILS AND MACROPHAGES A LOW NUMBER OF
VARIABLE SIZED SPHERULES WITH THE RARE CLUMP AND
INDIVIDUAL ENDOSPORES WERE NOTED. THESE STRUCTURES
MOST CLOSELY RESEMBLE COCCIDIOMYCOSIS ORGANISMS
SUGGEST SYSTEMIC FUNGAL PANEL SEROLOGY AND BIOPSY
TO HELP CONFIRM THESE INITIAL FINDINGS RADIOLOGY
IS RECOMMENDED ANY LAMENESS OR RESPIRATORY SIGNS?
Dr. Norman Lowes

COMMENT TO15
STRESS LEUKON WITH MONOCYTOSIS INCREASED TISSUE
DEMAND FOR PHAGOCYTOSIS SHIFT IN AG RATIO CHECK
ELECTROPHORESIS IF NOT RESOLVING WITH SURGICAL
INTERVENTION?
Dr. Norman Lowes

SYSTEMIC FUNGAL PANEL, SUSPECT COCCIDIOMYCOSIS

Systemic Fungal Panel T A TITER
BLASTOMYCES AB: NEGATIVE
COCCIDIOIDES AB: POS 1 : 16
HISTOPLASMA AB: NEGATIVE
APERGILLUS AB: NEGATIVE
CRYPTOCOCCUS AG: NEGATIVE
COMMENT TO15
Dr. Lily Edwards

Ehrlichia canis NEG
COMMENT TO15
Dr. Sally Lester

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Article courtesy of:

Dr. Mark Rubensohn

Bridlewood Veterinary Clinic

26-17107 James McKevitt Rd. S.W.

Calgary, AB T2Y 3Y4

Telephone: 403 201-6427

Fax: 403 201-6429

Email: bridler@telus.net

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