CASE REPORTS
Disseminated Protothecosis Associated With Diskospondylitis in a Dog Paul M. Manino, DVM, Fabiano Oliveira, DVM, DACVP, Martin Ficken, PhD, DVM, DACVP, Amy Swinford, MS, DVM, DACVM, Derek Burney, PhD, DVM, DACVIM
ABSTRACT A 6 yr old female Labrador retriever was evaluated for an acute onset of difficulty walking and a head tilt. Initial physical examination revealed bilateral retinal detachment, a left-sided head tilt, positional rotary nystagmus, and lumbar hyperpathia. Pertinent preliminary diagnostic findings included systemic hypertension, bony lysis and adjacent sclerosis of the vertebral endplates of the first and second lumbar vertebrae, and positive urine and blood cultures for a yeast identified as Candida spp. Concerned about disseminated candidiasis after subsequent subretinal aspirates confirmed the presence of a yeast-like organism, therapy with voriconazole was initiated. Because of progressive clinical deterioration and the poor prognosis for recovery, the dog was eventually euthanized. Postmortem histological examination of tissues, including the affected vertebral endplates, revealed numerous intralesional algae compatible with Prototheca spp. To the authors’ knowledge, this report is the first to document a case of protothecal diskospondylitis with possible concurrent candidiasis in a dog. Although typically associated with signs referable to the gastrointestinal tract, this report underscores the importance of not excluding protothecosis as a differential diagnosis when such signs are absent. Lastly, the use of voriconazole appears ineffective for reversing the clinical course of late-stage disseminated protothecosis. (J Am Anim Hosp Assoc 2014; 50:429–435. DOI 10.5326/JAAHA-MS-6083)
Introduction
reported.1,3,4 In the present case report, the authors describe a case
Protothecosis is an uncommon disease caused by several species of
of disseminated protothecosis associated with diskospondylitis
saprophytic, achlorphyllous algae belonging to the genus Proto-
and possible concurrent candidiasis in a dog presenting with pri-
theca.1,2 The causative organisms exist ubiquitously within envi-
mary ocular and neurologic symptoms. To the authors’ knowledge,
ronmental niches of most major continents and have been
this report represents the first documented case of protothecal
implicated in localized and systemic disease in both animals and
diskospondylitis and possible coinfection with Candida in the vet-
people worldwide.
1–6
Dermatologic manifestations of infection
erinary literature.
predominate in most species and are often associated with a more favorable prognosis.2–6 In contrast, more severe, life-threatening
Case Report
cases of disseminated protothecosis appear to occur with much
A 6 yr old female Labrador retriever weighing 34 kg was referred to
greater frequency in dogs and are believed to be associated with
the Internal Medicine service at Texas Gulf Coast Veterinary
immune compromisation.2–8 Signs of dissemination are generally
Specialists for sudden-onset blindness that had rapidly progressed
referable to the gastrointestinal, ocular, and neurologic systems;
to include difficulty walking and a head tilt. Three days prior to the
however, lesions involving other organ systems have also been
dog’s presentation to the veterinary specialists, therapy with oral
From the Texas Gulf Coast Veterinary Specialists, Houston, TX (P.M.); Texas Veterinary Medical Diagnostic Laboratory, College Station, TX (F.O., M.F., A.S.); and Veterinary Specialist of North Texas, Dallas, TX (D.B.).
CSF, cerebrospinal fluid; OS, oculus sinister
Correspondence:
[email protected] (P.M.)
ª 2014 by American Animal Hospital Association
JAAHA.ORG
429
doxycycline (5.88 mg/kg q 12 hr) and prednisone (1.17 mg/kg q
mild, equivocal, small intestinal ileus, sonographic evaluation of
12 hr) had been initiated after an evaluation with a veterinary
the abdomen was unremarkable.
ophthalmologist revealed chronic panophthalmitis oculus dexter
With those new findings, a disseminated infectious etiology
and retinal detachment associated with hemorrhage oculus sin-
causing diskospondylitis was suspected, prompting the dog’s hos-
ister (OS). Allowed to roam freely outdoors with access to two
pitalization for parenteral antibiotic administration, blood pressure
nearby ponds, the dog was not on a heartworm preventative and
measurement, pain management, and further diagnostics. Prior to
had historically been treated with repeated courses of cortico-
initiating any further therapy, additional laboratory diagnostics
steroids and antibiotics for recurrent bouts of pyoderma and otitis
included blood and urine cultures, serum protein electrophoresis,
externa. Having previously whelped a litter of 11 puppies several
serology for Brucella canis and Aspergillus spp., urine antigen testing
years earlier, the dog was last reported to experience a heat cycle
for Blastomyces dermatitidis and Histoplasma capsulatum, and an
approximately 3 mo prior to her presentation.
extended vector-borne polymerase chain reaction panelb. Serologic
At the time of referral, the dog was nervous, blind, but
testing for Brucella and Aspergillus was performed by immunofluo-
otherwise mentally appropriate and responsive to stimuli. She was
rescent antibody and agar gel immunodiffusion, respectively,
mildly overweight with a body condition score of 6 out of 9 and
whereas a quantitative sandwich enzyme immunoassayc was used
normal vital parameters. Preliminary systolic blood pressure,
for detection of Blastomyces and Histoplasma. An echocardiogram
determined via Doppler, was markedly elevated (mean, 220 mm
to evaluate the integrity of the heart valves was also performed but
Hg). Ocular examination revealed bilateral mydriasis with absent
failed to identify any significant pathology. Needle aspiration of
menace, dazzle, and direct and indirect pupillary light reflexes.
the dog’s spinal lesion for culture and cytology as well as a cere-
Intraocular pressures measured 3 mm Hg oculus dexter and 5 mm
brospinal fluid (CSF) tap and MRI were recommended but de-
Hg OS and cursory fundoscopic examination noted bilateral retinal
clined by the owner.
detachment. Neurologically, the dog exhibited signs referable to
Over the next 3 days, the dog was maintained on IV fluidsd,
a central vestibular lesion as determined by a general tendency to
parenteral clindamycine (11 mg/kg IV q 12 hr) and enrofloxacinf
veer to the left while walking, a mild left-sided head tilt, positional
(10 mg/kg IV q 24 hr), and the oral doxycycline that was previ-
rotary nystagmus, and left-sided hemiparesis. Mild to moderate
ously prescribed. Oral tramadolg (2.2 mg/kg q 8 hr) and enalaprilh
hyperpathia was also encountered on spinal palpation at the level of
(0.44 mg/kg q 24 hr) were also used to help manage the dog’s
the first and second lumbar vertebrae. Otoscopic examination,
spinal discomfort and hypertension, respectively. Within 24 hr of
thoracic auscultation, abdominal palpation, and digital rectal
starting those medications, the dog’s hypertension was noted to
examination were all unremarkable. Based on those findings and
significantly improve, measuring on average 213 mm Hg on day 1,
the dog’s clinical history, a systemic vasculopathy was initially
161 mm Hg on day 2, 133 mm Hg on day 3, and 142 mm Hg on
suspected, and differential diagnoses commonly associated with
day 4. Because of the concurrent improvement in the dog’s dis-
systemic hypertension were considered most likely.
comfort, it was concluded that the high blood pressure readings
Initial diagnostics included a hemogram, serum biochemical
initially recorded were most likely pain-induced. Brucellosis was
profile, urinalysis, cage-side serology for Anaplasma spp., Borrelia
ruled out on day 2 after the immunofluorescent antibody assay
burgdorferi, Ehrlichia spp., and Dirofilaria immitisa, abdominal and
was reported as negative. Early on day 4, topical 1% prednisolone
thoracic radiographs, and an abdominal ultrasound. Hematology
acetatei (1 drop oculus uterque q 6 hr) was started after observing
subsequently revealed leukocytosis (24,300/mL; reference range,
increased scleral injection bilaterally. Despite that new observa-
4000–15,500/mL), neutrophilia (21,384/mL; reference range, 2060–
tion, a persistent lack of vision, and ongoing neurologic deficits,
10,600/mL), and monocytosis (972/mL; reference range, 0–840/mL).
the dog was discharged later that same day at the owner’s request
Serum biochemical analysis showed elevations in both total protein
with oral clindamycin, doxycycline, enrofloxacin, tramadol, and
(7.5 g/dL; reference range, 5–7.4 g/dL) and globulins (4.4 g/dL;
topical prednisolone acetate.
reference range, 1.6–3.6g/dL) as well as a low amylase (240 IU/L;
With the exception of the blood cultures, final reports on all
reference range, 290–1125 IU/L). Cage-side serology was negative
outstanding diagnostics were provided within 2 days of the dog’s
for the four organisms assayed, and no significant abnormalities
discharge. Results of the remaining fungal immunoassays and the
were reported on routine urinalysis. Thoracic and abdominal
extended vector-borne polymerase chain reaction panel were
radiographs revealed a mild, diffuse, interstitial lung pattern
negative for all organisms assayed. Serum protein electrophoresis
and bony lysis with adjacent sclerosis of the vertebral endplates
revealed a polyclonal elevation in the b fraction (1.55 g/dL; ref-
of the first and second lumbar vertebrae (Figure 1). Aside from
erence range, 0.7–1.3g/dL) and a low normal g fraction (0.64
430
JAAHA |
50:6 Nov/Dec 2014
Protothecosis and Diskospondylitis in a Dog
FIGURE 1
Cropped image of a right lateral abdomi-
nal radiograph of the dog cited in this report. Note the illdefined lysis and adjacent sclerosis of the vertebral endplates (arrow) of the first and second lumbar vertebrae consistent with diskospondylitis.
g/dL; reference range, 0.5–1.3 g/dL). Urine culture yielded growth
vertebral bodies. Multiple, white, variably-sized, discolored foci were
of a yeast (10,000–50,000 colony-forming units/mL) that was later
encountered in the myocardium of both ventricles, along the
identified as Candida zeylanoides based on results obtained from
capsular and cut surfaces of both kidneys, and in the muscles and
j
a single yeast identification system . On day 3 postdischarge, the
subcutaneous fat overlying the right side of the lumbosacral area
possibility of disseminated candidiasis was more strongly sus-
(Figure 2). Histologically, stained sections of heart, kidney, eye,
pected after a second veterinary ophthalmologist reported a yel-
subcutaneous fat, skeletal muscle, colon, thyroid, and parathyroid
low/tan subretinal exudate on fundoscopic examination of both
gland revealed multifocal areas of necrosis and minimal granulo-
eyes. That suspicion was bolstered when blood culture results
matous inflammation associated with numerous intralesional algae
were returned the following day indicating the isolation of yeast
compatible with Prototheca spp. Those organisms were round to
from broth media that was also identified as Candida spp. by the
oval, measured 8–22 mm in diameter, had a clear 2–4 mm thick
above-mentioned identification system. To confirm the diagnosis
wall, and contained either central granular amphophilic material or
of candidiasis, a recommendation to obtain either a subretinal or
multiple (2–5) wedge-shaped endospores. Focal osteomalacia with
spinal aspirate for culture and cytology was made. The following
fibrosis and intralesional algae was identified within the spinal
day, the dog was prescribed voriconazole (4 mg/mg per os q 12
column at the first and second lumbar vertebrae (Figures 3, 4) with
hr) after obtaining three aspirates from the subretinal and vitreal
outward extension of exudate into the dura mater surrounding the
k
spaces OS. Cytologic analyses of those aspirates using standard Wright’s stain revealed marked suppurative inflammation and multiple degenerated fungal-like organisms that proved unidentifiable. Fungal cultures were performed but yielded no growth of identifiable pathogens. Five days after starting the voriconazole, the dog’s clinical status began deteriorating rapidly. Concerned about quality of life and the grave prognosis for recovery, the owner elected humane euthanasia. Approximately 6 hr after euthanasia, a sample of CSF was aseptically collected via a cisternal tap, and the body submitted for postmortem examination at the Texas Veterinary Medical Diagnostic Laboratory. Fluid and cytology of the CSF revealed marked elevations in both protein (327 mg/dL; reference range, #30 mg/dL) and WBCs (7325/mL; reference range, 0–5/mL) and was characterized by a mixed pleocytosis consisting predominantly of lymphoid and mononuclear cells. No infectious organisms were identifiable within
FIGURE 2 Photomicrograph of the subcapsular surface of the
the sample and no cultures were submitted.
right and left kidneys from the dog in this report. Note the multifocal
At necropsy, pertinent gross observations included thickening
distribution of variably sized white foci (granulomas) along the
of the subcutaneous fat overlying the dorsal aspect of the right hip
capsular surface of the cortex of both kidneys. Histological evaluation
and softening of the intervertebral disc between the first and second
revealed numerous protothecal organisms associated with minimal
vertebral vertebrae with outward extension into the adjacent
granulomatous inflammation.
JAAHA.ORG
431
Discussion The clinical features of protothecosis in dogs are unique in many respects compared with those observed in other species. Although usually restricted to the skin of cats, the mammary glands and corresponding lymph nodes of cows, and the skin and bursae of people, infections in dogs tend to be insidious and relentlessly progressive with widespread dissemination common.2–6,9 At the time this article was written, 52 cases of canine protothecosis were documented in the veterinary literature. Of those, 28 (53.8%), 14 (26.9%), and 6 (11.5%) presented with a clinical history of diarrhea, ocular abnormalities, or neurologic deficits, respectively.8–13 Within that same population of dogs, another 9 (17.3%), 17 (32.7%), and 17 (32.7%) had each of the aforementioned problems, respectively, by the time of either diagnosis or death.8–14 FIGURE 3
Photomicrograph of the intervertebral space between
the first and second lumbar vertebrae from the dog described in this report. There is loss and remodeling of bone (*) adjacent to the intervertebral space. Hematoxylin and eosin staining, bar ¼ 5 mm.
Adhering somewhat to that general trend, the dog in this report presented with an acute onset of vision loss that quickly progressed to include neurologic deficits. Interestingly, despite histological evidence of colonic involvement, signs referable to the lower gastrointestinal tract were neither reported nor observed until just days before the dog’s euthanasia. That was surprising
adjacent segment of spinal cord. Examined sections of cerebrum,
given the extensive involvement of other organ systems docu-
cerebellum, and medulla were histologically unremarkable. Cul-
mented and the general consensus that most canine protothecal
tures of samples taken from heart, kidney, muscle, and subcuta-
infections arise and disseminate from the colon.1,3,4 A detailed
neous fat all yielded heavy growth of yeast-like organisms later
review of the dog’s history failed to identify any significant epi-
identified as Prototheca spp. based on their morphologic charac-
sodes of diarrhea or other pertinent gastrointestinal signs within 3
teristics and the results of two separate yeast identification systemsl.
yr of the dog’s presentation to the authors’ hospital. However, as
Unfortunately, neither of those tests was reliably able to determine
the dog was allowed to roam freely outdoors, it is possible that
the species of the organism.
episodes of diarrhea went unnoticed by the owners. In addition to its ocular and neurologic abnormalities, the dog described in this report was also found to exhibit signs of spinal hyperpathia and was subsequently diagnosed with vertebral spondylitis at the first and second lumbar vertebrae. Although initially thought to represent a lesion associated with a rare case of disseminated candidiasis, postmortem histological analysis of the site confirmed infection with Prototheca spp. Apart from the more common sites of the colon, eyes, and brain, protothecal dissemination has also been documented to affect the kidneys, heart, skeletal muscle, skin, spinal cord, stomach, liver, spleen, pancreas, ileum, cecum, lungs, diaphragm, lymph nodes, omentum, ears, tongue, thyroid gland, aorta, and bone of dogs.3,4,7,9,11,15–21 Until this current publication, disseminated protothecosis involving skeletal lesions in dogs was only reported in two cases.9 In both of those cases proliferative periosteal lesions confined to the long bones of
FIGURE 4
Photomicrograph of a section of the vertebral body of
the appendicular skeleton were documented in two young boxers
the first lumbar vertebra from the dog described in this report. Notice
from Australia with chronic histories of diarrhea. The present case
that numerous protothecal organisms are present in areas of bone
is the third case to document protothecal dissemination to bone,
loss. Hematoxylin and eosin staining, bar ¼ 20 mm.
and it is the first to report involvement of a vertebral endplate.
432
JAAHA |
50:6 Nov/Dec 2014
Protothecosis and Diskospondylitis in a Dog
Although there exists a paucity of cases documenting bone in-
with what would seem more plausible in a case of disseminated
volvement, it is possible that skeletal lesions actually occur with
protothecosis and could be supported by the absence of Candida
greater frequency and are merely overshadowed by more prom-
within any of the affected tissues examined. Although that failure
inent clinical signs of neurologic dysfunction. Such a contingency
could have been caused by the effects of voriconazole, a medica-
could very easily have been the case in this dog if abdominal
tion shown to possess excellent activity against the various species
radiographs were not performed. Indeed, in reviewing the cases of
of Candida, the time span between the initial administration of
canine protothecosis in which signs of lameness or paresis were
the medication and the collection of histologic samples would
described, radiographic studies were either omitted, not performed,
seem inadequate to completely eradicate all evidence of the or-
7,9,10,17,20,22–25
ganism in tissue.29
or incomplete in almost all situations.
The pathogenesis of canine protothecosis remains poorly
The limitations inherent within yeast identification systems
understood, but despite the causative organism’s ubiquity within
could also potentially account for the possibility of misidentifi-
the environment, the sporadic occurrence of the infection sug-
cation of Prototheca as Candida. One such limitation involves the
1,4,7,8,26
gests some form of immune dysfunction is likely involved.
possibility of discordant results with differing incubation periods.
Among the mechanisms postulated to play a role, defects in cell-
The laboratory that reportedly isolated Candida zeylanoides from
2,4–8
Yet,
blood and urine used an identification kit that can provide results
whether such defects are the cause or effect of infection remains to
in as little as 4 hr (incubation time). Although such kits work well
be clearly elucidated. Within the veterinary literature, evidence
for many species of Candida, one study determined that mis-
supporting a mechanism by which an inherited or acquired defect
identifications were more likely for less commonly isolated yeasts
in cell-mediated immunity contributes to the development of
and yeast-like organisms compared with systems employing 24 hr
disease is furnished by an apparent predisposition to infection
incubation periods.30 Moreover, in another study, the manufac-
among collies and boxers, observations of suppressed T lymphocyte
turer of an automated identification system reported that Proto-
and neutrophil function in a collie with disseminated proto-
theca zopfii could not be accurately identified before a 48 hr
thecosis, and an inverse relationship between the number of
incubation was completed, thus providing further evidence that
protothecal organisms and the surrounding cellular infiltrate in
longer incubation periods may be necessary to correctly identify
mediated immunity have garnered the most attention.
Although specific im-
Prototheca from samples assayed.31 Unlike the first laboratory, the
munologic studies were not conducted in this case report, further
laboratory that isolated Prototheca from the necropsy-derived
support for such defects can be inferred from several observations.
samples did so utilizing both a 4 and 24 hr kit but opted to use
First, as has been reported in other cases, a significant cellular re-
an optional longer incubation period (24–72 hr) thereby ensuring
sponse to the infecting organisms was not recognized within any of
adequate growth and accuracy of identification.
a dog with cutaneous protothecosis.
7,9,26
the histological samples examined.7,8,18,24,26 Second, the inflamma-
Additional limitations often associated with the use of various
tory responses that were recognized were universally characterized
yeast identification systems include a need for both relatively high
by minimal numbers of plasma cells, lymphocytes, and macro-
inoculum densities and strict adherence to kit instructions. Yeasts
phages, and a general lack of neutrophils. Lastly, although firm
and yeast-like organisms tend to be much slower growing than
conclusions regarding any association between the dog’s heat cycles,
bacteria; therefore, if any single inoculum is too light, inadequate
chronic pyoderma, or recurrent antibiotic and corticosteroid use
growth will likely ensue, thereby resulting in discordant substrate
and immune dysfunction could not be made, the role those po-
reactions. If the laboratory that identified Candida in this case used
tential predisposing factors may have played in contributing to an
a light inoculum and inadequate growth resulted, one could ex-
immunocompromised state cannot be ignored.
pect false-negative reactions to occur. In turn, those factors could
Additional support for underlying dysfunctional immunity
increase the odds of inaccurate identification. Additionally, if
can also be garnered from the possibility of a concurrent infection
a laboratory technician in that same laboratory underestimated
with the opportunistic fungus Candida. Implicated primarily in
the importance of following kit manufacturer instructions, inac-
disease states of immunocompromised animals and people, that
curate results may have been provided. Indeed, in one of the
possible infection was one of the most intriguing aspects of this
aforementioned studies only 48 of 97 yeast isolates were correctly
case and yet could conceivably have been the result of misiden-
identified when the inoculum was prepared directly from the
tification.27,28 Instead of representing a species of Candida as re-
primary isolation media rather than from the media specified by
ported, the positive blood and urine cultures obtained may have
the kit manufacturer.30 Because the organism isolated from blood
represented Prototheca. Such a contingency would certainly follow
and urine was not available to be compared with the organism
JAAHA.ORG
433
isolated from tissues and identified as Prototheca, it is impossible
reported an inflammatory response characterized by an eosinophilic
to know the exact reasons for the discrepant identification results.
pleocytosis.9,24,25 In contrast to those findings, a mixed pleocytosis
Nonetheless, it is probable that Prototheca was simply mis-
composed predominantly of lymphocytes and mononuclear cells
identified as Candida zeylanoides from the initial blood and urine
was recognized in this case. Although commonly associated with
samples obtained in this case report.
mycotic or protozoal encephalitides, the current study’s findings
Despite a rather comprehensive diagnostic evaluation, successful
may have differed from those of previous reports because of the
antemortem diagnosis proved elusive in this case. This, undoubtedly,
early corticosteroid use used by the dog’s referring veterinarian.33
was due in large part to the isolation of an organism identified as
That theory could be supported by one of the aforementioned
Candida from blood and urine cultures that lead to a preliminary
reports in which a follow-up CSF analysis revealed resolution of an
diagnosis of disseminated candidiasis. The general lack of signs re-
eosinophilic pleocytosis after treatment with systemic steroids had
ferable to the gastrointestinal tract also proved misleading, de-
been implemented.24 As the CSF sample was collected after eutha-
creasing the authors’ index of suspicion for protothecosis. In most
nasia, postmortem changes could not be excluded as contributing
cases, an accurate diagnosis of protothecosis can usually be made
factors to the discrepancy between the study authors’ findings and
by identifying the organism within either cytological or histo-
those of previous cases.
3
logical samples of affected tissues. Although fungal-like organ-
The treatment of disseminated protothecosis in dogs remains
isms were recognized within the subretinal and vitreal aspirates
challenging and although various regimes have been attempted,
the authors obtained, unfortunately those organisms proved dif-
optimal therapeutic guidelines remain poorly established.1,4,9 To
ficult to definitively identify and were ultimately presumed to
date, treatment with amphotericin B, fluconazole, itraconazole,
represent Candida. This difficulty was likely due to the high de-
ketoconazole, clotrimazole, aminoglycosides, and tetracycline have
gree of degenerative changes present within each of the aspirates
all proven unsuccessful in the dog.1,4 Among those medications,
examined, complicating the ability to distinguish between path-
however, both amphotericin B and itraconazole have exhibited
ologic organisms and surrounding inflammatory cells.
some ability to slow the progression of the disease.9,15,34 Driven out
Apart from the spinal lesion identified radiographically, the
of concern for disseminated candidiasis, voriconazole was selected
purported isolation of Candida from blood and urine cultures,
in this case. A synthetic derivative of fluconazole, this newer triazole
and the results of our CSF analysis, few of the diagnostic find-
was specifically chosen because of its widespread distribution, su-
ings in this case deviated from what has been reported in other
perior ability to penetrate nervous tissues, and efficacy against in-
cases of canine protothecosis. Indeed, in accordance with pre-
creasingly prevalent nonalbicans Candida infections with resistance
viously published cases, the results of most of the laboratory
to traditional antifungal medications.29 Although unintentional, this
diagnostics were either normal or nonspecific.7–10,14–25,32 More-
is the first report to document the use of voriconazole in a dog with
over, on histologic samples of infected tissues, Prototheca were
disseminated protothecosis. Unfortunately, like so many other
usually readily identifiable and often associated with only
antimicrobials used in the treatment of this devastating disease,
minimal cellular responses. Of notable exception to that general
voriconazole failed to elicit any significant positive clinical outcome.
trend was the lack of either identifiable organisms or lesions
That failure aside, the delay with which that medication was started,
within any sections of brain tissue evaluated despite obvious
coupled with the extent of systemic involvement manifested in this
signs of central neurologic dysfunction. Considering the multi-
dog, make drawing definitive conclusions regarding the efficacy of
focal distribution of organisms and lesions manifested in other
voriconazole in the treatment of canine protothecosis difficult.
affected tissues, that absence was likely the result of the chance sampling of unaffected brain tissue.
Conclusion
Another somewhat deviant result among all the diagnostics
Protothecosis remains an uncommon but devastating disease in
performed in this case was the cytological findings of the CSF
dogs. Although most often associated with signs referable to the
obtained. Despite the frequency with which neurologic signs have
gastrointestinal tract, this report underscores the importance of not
been reported in cases of canine protothecosis, few dogs exhibiting
excluding protothecosis as a differential diagnosis when such
such abnormalities have actually undergone a comprehensive
symptoms are absent. Moreover, this report also validates the need
neurodiagnostic evaluation. As such, information regarding expected
to consider protothecosis in any dog presenting with signs of
findings of advanced imaging or CSF analysis remains somewhat
diskospondylitis. Given the immunocompromised state believed to
lacking. Of the three cases of canine protothecosis in which abnormal
be inherent in many protothecal infections, the possibility of
CSF findings have been described within the veterinary literature, all
a concurrent infection with another infectious disease cannot be
434
JAAHA |
50:6 Nov/Dec 2014
Protothecosis and Diskospondylitis in a Dog
ignored. Lastly, although firm conclusions regarding the therapeutic efficacy of voriconazole in all cases of protothecosis cannot be made from a single case, it appears this newer triazole is of little utility in treating late-stage disseminated infections. FOOTNOTES a SNAP 4Dx; IDEXX Laboratories, Westbrook, ME b Extended vector-borne PCR panel; Antech Diagnostics, Irvine, CA. Species assayed included Anaplasma phagocytophilum, A. platys, Bartonella henselae, B. vinsonii, Babesia canis, Babesia spp., Ehrlichia canis, Ehrlichia spp., Mycoplasma hemocanis/hematoparvum, Neorickettsia risticii, and Rickettsia rickettsii c Urine Histoplasma and Blastomyces antigen tests; MiraVista Diagnostics, Indianapolis, IN d Plasmalyte-A; Baxter, Deerfield, IL e Clindamycin; Hospira, Lake Forest, IL f Baytril; Bayer, Shawnee Mission, KS g Tramadol; Amreal Pharmaceuticals, Hauppauge, NY h Enalapril; Wockhardt, Mumbai, India i 1% prednisolone acetate; Falcon Pharmaceuticals, Fort Worth, TX j RapID Yeast Plus System; Remel, Lenexa, KS k Voriconazole; Pfizer, New York, NY l API 20C AUX Yeast Identification System; Biomerieux, Durham, NC REFERENCES 1. Greene CE, Rakich PM, Latimer KS. Protothecosis. In: Greene CE, ed. Infectious diseases of the dog and cat. 3rd ed. Philadelphia (PA): WB Saunders Co.; 2006:659–65. 2. Leimann BC, Monteiro PC, Lazéra M, et al. Protothecosis. Med Mycol 2004;42(2):95–106. 3. Strunck E, Billups L, Avgeris S. Canine protothecosis. Compend Contin Educ Pract Vet 2004;26:96–102. 4. Hollingsworth SR. Canine protothecosis. Vet Clin North Am Small Anim Pract 2000;30(5):1091–101. 5. Lass-Flörl C, Mayr A. Human protothecosis. Clin Microbiol Rev 2007;20(2):230–42. 6. Thiele D, Bergmann A. Protothecosis in human medicine. Int J Hyg Environ Health 2002;204(5–6):297–302. 7. Rakich PM, Latimer KS. Altered immune function in a dog with disseminated protothecosis. J Am Vet Med Assoc 1984;185(6):681–3. 8. Thomas JB, Preston N. Generalised protothecosis in a collie dog. Aust Vet J 1990;67(1):25–7. 9. Stenner VJ, Mackay B, King T, et al. Protothecosis in 17 Australian dogs and a review of the canine literature. Med Mycol 2007;45(3): 249–66. 10. Tsuji H, Kano R, Hirai A, et al. An isolate of Prototheca wickerhamii from systemic canine protothecosis. Vet Microbiol 2006;118(3–4): 305–11. 11. Souza LN, Estrela-Lima A, Moreira ELT, et al. Systemic canine protothecosis. Braz J Vet Pathol 2009;2:102–6. 12. Salvadori C, Gandini G, Ballarini A, et al. Protothecal granulomatous meningoencephalitis in a dog. J Small Anim Pract 2008;49(10):531–5. 13. Ribeiro MG, Rodrigues de Farias M, Roesler U, et al. Phenotypic and genotypic characterization of Prototheca zopfii in a dog with enteric signs. Res Vet Sci 2009;87(3):479–81.
14. Rizzi TE, Cowell RL, Meinkoth JH, et al. More than meets the eye: subretinal aspirate from an acutely blind dog. Vet Clin Pathol 2006; 35(1):111–3. 15. Schultze AE, Ring RD, Morgan RV, et al. Clinical, cytologic and histopathologic manifestations of protothecosis in two dogs. Vet Ophthalmol 1998;1(4):239–43. 16. Buyukmihci N, Rubin LF, DePaoli A. Protothecosis with ocular involvement in a dog. J Am Vet Med Assoc 1975;167(2):158–61. 17. Imes GD, Lloyd JC, Brightman MP. Disseminated prothothecosis in a dog. Onderstepoort J Vet Res 1977;44(1):1–6. 18. Migaki G, Font RL, Sauer RM, et al. Canine protothecosis: review of the literature and report of an additional case. J Am Vet Med Assoc 1982;181(8):794–7. 19. Cook JR Jr, Tyler DE, Coulter DB, et al. Disseminated protothecosis causing acute blindness and deafness in a dog. J Am Vet Med Assoc 1984;184(10):1266–72. 20. Gaunt SD, McGrath RK, Cox HU. Disseminated protothecosis in a dog. J Am Vet Med Assoc 1984;185(8):906–7. 21. Meredith RE, Gwin RM, Samuelson DA, et al. Systemic protothecosis with ocular manifestations in a dog. J Am Anim Hosp Assoc 1984;20:153–6. 22. Povey RC, Austwick PK, Pearson H, et al. A case of protothecosis in a dog. Pathol Vet 1969;6(5):396–402. 23. Holscher MA, Shasteen WJ, Powell HS, et al. Disseminated canine protothecosis: a case report. J Am Anim Hosp Assoc 1976;12:49–52. 24. Tyler DE, Lorenz MD, Blue JL, et al. Disseminated protothecosis with central nervous system involvement in a dog. J Am Vet Med Assoc 1980;176(10 pt 1):987–93. 25. Gupta A, Gumber S, Bauer RW, et al. What is your diagnosis? Cerebrospinal fluid from a dog. Eosinophilic pleocytosis due to protothecosis. Vet Clin Pathol 2011;40(1):105–6. 26. Pérez J, Ginel PJ, Lucena R, et al. Canine cutaneous protothecosis: an immunohistochemical analysis of the inflammatory cellular infiltrate. J Comp Pathol 1997;117(1):83–9. 27. Heseltine JC, Panciera DL, Saunders GK. Systemic candidiasis in a dog. J Am Vet Med Assoc 2003;223(6):821–4, 810. 28. Chakravarthi S, Nagaraja HS. A comprehensive review of the occurrence and management of systemic candidiasis as an opportunistic infection. Microbiology Journal 2010;1:1–5. 29. Kofla G, Ruhnke M. Voriconazole: review of a broad spectrum triazole antifungal agent. Expert Opin Pharmacother 2005;6(7): 1215–29. 30. Espinel-Ingroff A, Stockman L, Roberts G, et al. Comparison of RapID yeast plus system with API 20C system for identification of common, new, and emerging yeast pathogens. J Clin Microbiol 1998; 36(4):883–6. 31. el-Zaatari M, Pasarell L, McGinnis MR, et al. Evaluation of the updated Vitek yeast identification data base. J Clin Microbiol 1990;28 (9):1938–41. 32. Pressler BM, Gookin JL, Sykes JE, et al. Urinary tract manifestations of protothecosis in dogs. J Vet Intern Med 2005;19(1):115–9. 33. Dewey CW. Inflammatory, infectious, and other multifocal brain diseases. In: Ettinger JS, Feldman CE, eds. Textbook of veterinary internal medicine. 7th ed. Philadelphia (PA): WB Saunders Co.; 2010:1453–61. 34. Moore FM, Schmidt GM, Desai D, et al. Unsuccessful treatment of disseminated protothecosis in a dog. J Am Vet Med Assoc 1985;186 (7):705–8.
JAAHA.ORG
435