Is Corynebacterium pseudotuberculosis infection (pigeon fever) in horses an emerging disease in western Canada?

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Is Corynebacterium pseudotuberculosis infection (pigeon fever) in horses an emerging disease in western Canada?
Case Report Rapport de cas

Is Corynebacterium pseudotuberculosis infection (pigeon fever) in horses
an emerging disease in western Canada?
Louise E. Corbeil, Jennifer K. Morrissey, Renaud Léguillette

         Abstract — This report describes 5 horses in the southern Alberta region with typical and atypical external
         abscessation due to Corynebacterium pseudotuberculosis (pigeon fever). “Pigeon fever” has recently been diagnosed
         in new geographic regions in North America and should be kept as a differential diagnosis by practitioners when
         an external or internal abscess is identified in a horse.

         Résumé — L’infection par Corynebacterium pseudotuberculosis (fièvre du pigeon) chez les chevaux est-elle
         une maladie émergente dans l’Ouest canadien? Ce rapport décrit cinq chevaux dans la région sud de l’Alberta
         atteints d’abcès externes typiques et atypiques causés par Corynebacterium pseudotuberculosis (fièvre du pigeon). La
         «fièvre du pigeon» a récemment été diagnostiquée dans de nouvelles régions géographiques de l’Amérique du Nord
         et devrait être conservée comme diagnostic différentiel par les praticiens lorsqu’un abcès externe ou interne est identifié.
                                                                                                         (Traduit par Isabelle Vallières)
         Can Vet J 2016;57:1062–1066

C      orynebacterium pseudotuberculosis is a Gram-positive,
       intracellular rod-shaped facultative anaerobic bacterium.
It is the causative agent of caseous lymphadenitis in sheep and
                                                                         of external abscesses is aimed at maturation of the abscess and
                                                                         establishing adequate drainage. Antibiotic treatment is indicated
                                                                         in cases of internal infection and ulcerative lymphangitis but it
goats and also infects other species including horses. Equine            is usually avoided with external abscesses unless drainage cannot
C. pseudotuberculosis isolates are nitrate positive while sheep and      be established (2). Corynebacterium pseudotuberculosis infections
goat isolates are nitrate negative. Infection is thought to occur        in the United States have been reported in states not previously
through contact with contaminated soil via skin abrasions or             recognized as having endemic disease (4). This case series from
mucous membranes and recent studies support the role of insect           southern Alberta describes cases of typical and atypical external
vectors (1). The 3 main clinical manifestations of the disease           abscessation with various treatment approaches. All 5 affected
are external abscessation, internal abscessation, and ulcerative         horses had no travel history to endemic areas within the United
lymphangitis. External abscesses are the most prevalent and              States, suggesting infection occurred from local sources and
commonly develop in the pectoral muscle region, hence the                that practitioners should be aware of this potentially emerging
name “pigeon fever.” However, external abscesses may occur               disease in Canada.
in a variety of locations including deep intramuscular, axillary,
inguinal, and mammary. Differential diagnosis includes other                                 Case descriptions
bacterial causes of suppurative myositis or internal abscessa-           The blood parameters, clinical form, epidemiological and
tion such as Streptococcus equi subspecies equi (2). Definitive          laboratory data and treatment of the horses are summarized
diagnosis of infection is made via culture of abscess content.           in Table 1.
Serology can be used in conjunction with bacterial culture and
is most useful in cases of internal abscessation (3). Treatment          Farm A — 2 cases
                                                                         Two horses from a herd of 16 on a farm southeast of Calgary
                                                                         were presented with pectoral swelling in October 2013. The
Moore Equine, Balzac, Alberta (Corbeil, Morissey, Léguillette);          first, a 6-year-old Quarter Horse gelding, had pectoral edema
Department of Veterinary Clinical and Diagnostic Sciences,               (Figure 1), and after 3 d of applying hot packs to the chest,
Faculty of Veterinary Medicine, University of Calgary, Calgary,          a 5 cm 3 3 cm abscess located 10 cm deep to the skin was
Alberta (Léguillette).                                                   lanced under ultrasound guidance. A penrose drain was placed
Address all correspondence to Dr. Renaud Léguillette; e-mail:            and left in place for 2 wk and the abscess was lavaged with
rleguill@ucalgary.ca                                                     betadine solution. The exudate cultured positive for C. pseudo-
Use of this article is limited to a single copy for personal study.      tuberculosis and anti-C-pseudotuberculosis toxin antibody titers
Anyone interested in obtaining reprints should contact the               measured via synergistic hemolysin inhibition (SHI) (California
CVMA office (hbroughton@cvma-acmv.org) for additional                    Animal Health and Food Safety Laboratory, UC Davis, Davis,
copies or permission to use this material elsewhere.                     California, USA) was 1:2048 2 wk after initial presentation. At

1062                                                                                                                CVJ / VOL 57 / OCTOBER 2016
Table 1. Clinical data for 5 equine cases of Corynebacterium pseudotuberculosis infection in Alberta
						Total			                                                                           Initial
 Geographical Travel history  Clinical Hematocrit Leukocytes protein Fibrinogen Positive SHI                                                                Antibiotic
 area         outside Alberta form     (L/L)      (3 109/L)  (g/L)   (g/L)      culture  titer                                                              therapy
Farm A
  East of                    Travelled within       External            0.28            13.8             67          2               Yes         1:2048     None
  High River                 AB 6 mo                abscess:
		                           earlier. Closed        Pectoral

                                                                                                                                                                                CA S E R E P O R T
		                           herd for previous
		                           1.5 mo
Farm A
  East of                    No travel.             External            0.30            12.8             69          2               Yes         1:2048     None
  High River                 Closed herd for        abscess:
		                           previous 1.5 mo        Pectoral
Farm B
 Northeast of No history                            External 0.29 7.5 75 5 Yes 1:512                                                                        Trimethoprim/
 High River   of travel                             abscess:							                                                                                         sulfonamide
			                                                 Parotid
Farm C
  Northwest                  Brought from           External 0.28 9.9 N/A N/A Yes 1:1024                                                                    Ceftiofur,
  of Calgary                 lower mainland         abscess:							                                                                                         Enrofloxacin
		                           of BC 15 mo            Mammary
		                           earlier
Farm D      South of         No history             Lymphangitis:       N/A             N/A              N/A         N/A             Yes         N/A        Doxycycline
            Calgary          of travel              Distal limb
AB — Alberta; BC — British Columbia; N/A — No results available.
Reference ranges: Hematocrit: 0.32 to 0.52 L/L; Leukocytes: 4.6 to 11.4 3 109/L; Neutrophils: 2.3 to 8.6 3 109/L; Total Protein: 57 to 70 g/L; Fibrinogen: 0.5 to 4.0 g/L.
Trimethoprim sulfonamide (Apotex), Ceftiofur (Excenel), Enrofloxacin (Trutina pharmacy), Doxycycline (Trutina pharmacy).

a 5-week recheck, a small draining tract remained which was                               flunixin meglumine (Trutina compounding pharmacy, Ancaster,
excised under ultrasound guidance. Repeat serology revealed                               Ontario), 1.1 mg/kg BW, PO, q24h, for 5 d but clinical signs
a C. pseudotuberculosis titer of 1:4096. The tract was flushed                            progressed. On recheck physical examination, radiographs, and
on-farm until closure occurred and at an 8-week recheck had                               endoscopy, a space-occupying soft tissue mass was diagnosed in
healed completely. Recheck antibody titer at 10 wk after pre-                             the left guttural pouch region. Ultrasound identified an 8-cm
sentation was 1:1024.                                                                     heterogeneous encapsulated mass axial to the parotid salivary
   The second affected horse on Farm A was a 1.5-year-old                                 gland. An ultrasound-guided aspirate of the mass was nega-
Arabian gelding that had a spontaneously draining pectoral                                tive for S. equi by PCR and its culture revealed light growth of
abscess which healed uneventfully in 2 wk with daily lavage                               C. pseudotuberculosis. The abscess was lanced using ultrasound
with betadine solution. Culture of the abscess contents yielded                           guidance and a Foley catheter was placed. The abscess was
a heavy growth of C. pseudotuberculosis and SHI titer (California                         flushed with 0.1% betadine solution and 10 million IU of
Animal Health and Food Safety Lab) taken at presentation was                              sodium penicillin was instilled after lavage. The mare was treated
1:2048. At 5-week recheck the tract had healed completely and                             again with trimethoprim-sulfamethoxazole (Apo Sulfatrim;
antibody titer was 1:512.                                                                 Apotex) and flunixin meglumine (Trutina compounding phar-
   Screening antibody titers were measured for the remain-                                macy), PO. An SHI titer measured on the day of discharge from
ing horses in the herd on Farm A 5 wk after the index cases                               hospital was1:512. The mare was treated with trimethoprim-
presented. The titers obtained were # 1:8 for 8 horses, 1:16                              sulfamethoxazole for an additional 10 d on-farm and complete
for 3 horses, 1:32 for 1 horse, 1:64 for 1 horse, and 1:128 for                           resolution of the abscess was noted at a 4-week recheck, at which
1 horse. Four horses from Farm A, including the 6-year-old                                the time antibody titer was 1:128. This horse had no history
gelding (first case), had a history of travel to southern Alberta                         of travel to the United States. The other 2 horses in contact
earlier that summer but did not travel to the United States.                              on-farm remained asymptomatic and titers were negative for
                                                                                          both at 1:8.
Farm B — 1 case
A 13-year-old Quarter Horse mare was presented for evalua-                                Farm C — 1 case
tion of a left-sided retropharyngeal swelling, mild inappetence,                          A 4-year-old Quarter Horse reining mare living in the Calgary
and a left-sided head tilt. The owner noticed difficulty eating                           area was evaluated for right-sided mammary gland abscessa-
and lethargy 2 wk after a routine dental examination was                                  tion. In late fall of 2013 while the horse was living in the lower
performed on-farm. An initial examination on-farm revealed                                mainland area of British Columbia, the owner had noted a
soft tissue swelling in the left parotid area and bilateral sub-                          small superficial lesion on the ventral midline just cranial to the
mandibular lymph node enlargement. Oral examination was                                   udder that burst and drained spontaneously. Right-sided mam-
unremarkable and blood analysis revealed a mild anemia and                                mary swelling was noted in May 2014 while living in Calgary
elevated total protein (Table 1). The mare was treated on-farm                            and the mare was treated with ceftiofur sodium (Excenel;
with trimethoprim-sulfamethoxazole (Apo-Sulfatrim; Apotex,                                Zoetis, Kirkland, Quebec), 2.2 mg/kg BW, IM, q24h, for 8 d.
Calgary, Alberta), 5 mg/kg body weight (BW), PO, q12h, and                                The swelling failed to resolve and an ultrasound examination

CVJ / VOL 57 / OCTOBER 2016                                                                                                                                             1063
R A P P O R T D E CA S

                         Figure 1. Swollen pectoral area in a horse diagnosed with Corynebacterium pseudotuberculosis infection (pigeon fever) in Alberta.

                         revealed diffuse subcutaneous edema and a mixed echogenic           doxycycline (Trutina pharmacy), 10 mg/kg BW, PO, q12h,
                         appearance of the mammary gland without any discrete fluid          for 3 wk and thereafter the leg swelling improved significantly.
                         pockets. Culture of a spontaneously ruptured superficial abscess    This horse had no travel history to the United States. The other
                         revealed C. pseudotuberculosis. A serum sample taken 3 d later      horses at the farm had not developed any infection by the time
                         had a positive SHI titer of 1:1024. The mare was treated with       of the writing of this report.
                         enrofloxacin (Trutina pharmacy), 7.5 mg/kg BW, PO, q24h,
                         for 12 d and phenylbutazone (Vétoquinol, Lavaltrie Quebec),                                 Discussion
                         1.1 mg/kg BW, PO, q12h, for 4 d and clinical signs resolved.        The disease presentation observed on Farm A is comparable
                            This horse had no history of travel to the United States. The    to that of external C. pseudotuberculosis infection reported in
                         other horses at the farm have not developed any abscesses to        endemic areas in the southwestern United States. The most com-
                         date.                                                               mon areas for external abscesses to develop are in the pectoral
                                                                                             region and ventral abdomen (2). Slightly less commonly affected
                         Farm D — 1 case                                                     sites include the prepuce, mammary gland, triceps, limbs, and
                         A 14-year-old Quarter Horse gelding used for ranch work was         head (2,5). A 25% occurrence of abscesses in secondary loca-
                         presented with chronic diffuse swelling and superficial absces-     tions has been reported (6). Diagnosis of deep intramuscular
                         sation of the left hind limb. Six months earlier, the horse had     abscesses in the limbs and abscesses in the axillary region can
                         been cast in the stall and sustained a laceration to the dorsal     present a diagnostic challenge in horses with a history of chronic
                         aspect of the left hind metatarsal region. Since then, intermit-    severe lameness and no external swelling (5). Less common
                         tent swelling of the left hind limb had occurred with periodic      sites for abscess formation include parotid gland (as was seen
                         breaking and draining of small abscesses. On presentation for       on Farm B), the neck, thorax, guttural pouches, larynx, flanks,
                         evaluation of chronic limb swelling, the horse was sound and        umbilicus, tail, and rectum (2,6).
                         radiographs of the distal limb did not show significant findings.      Hematologic findings in the horses in this study were com-
                         The horse was treated daily with nitrofurazone (WeCan Sales,        parable to those reported previously. In a retrospective study,
                         Beamsville, Ontario) sweat bandages, and weekly with sodium         40% to 50% of horses with external abscesses showed either
                         iodide (Vétoquinol, Cambridge, Ontario), 30 mg/kg BW, IV,           anemia of chronic disease, neutrophilia, hyperfibrinogenemia,
                         q24h, for 3 wk. Several days later another abscess spontaneously    or hyperproteinemia (6). Similar changes were found in horses
                         ruptured and culture of a sample from the lesion resulted in        with internal disease and are observed more commonly than
                         isolation of C. pseudotuberculosis. The horse was treated with      in horses with external disease (2,6). Interestingly, we only

                         1064                                                                                                       CVJ / VOL 57 / OCTOBER 2016
observed hyperfibrinogenemia in the horse from Farm B, in              the MICs for 50% of the time, which may explain the failure
which abscessation occurred in the parotid gland region. This          of the first ceftiofur treatment of the horse on Farm C (7). A
horse also had increased total protein at 79 g/L, possibly due         single dose of 6.6 mg/kg BW of ceftiofur crystalline free acid
to hyperglobulinemia from prolonged antigenic stimulation.             (Excede; Zoetis) does not reach appropriate MIC concentrations
In the 6-year-old gelding from Farm A with the deep pectoral           of 2 mg/mL (9). A recent study found no changes in MIC sus-
abscessation, changes in hematologic parameters such as leuko-         ceptibility trends in samples submitted to UC Davis from 1996

                                                                                                                                             CA S E R E P O R T
cytosis were more marked compared to those in the 1.5-year-old         to 2012 (7); however, further studies are needed to specifically
Arabian cross on Farm A with a more superficial, spontaneously         test the MIC susceptibilities of those strains being isolated from
draining abscess.                                                      horses in Canada.
   Antibody titers were measured using the synergistic hemolysis          The incidence of disease on Farms A and B in this study as
inhibition (SHI) test, which measures IgG specific for C. pseu-        determined by positive cultures was 13% for Farm A and 33%
dotuberculosis exotoxin (2,3). While culture remains the gold          for Farm B. Other documented outbreaks in non-endemic areas
standard for diagnosis, titers can be used in conjunction with         within the US have reported a 26% mean prevalence and a range
clinical signs in cases in which a sample for culture cannot be        of 3% to 100% (4,10). The present study raises the question of
obtained from an abscess or to support a diagnosis of internal         the overall prevalence of C. pseudotuberculosis infection in horses
infection in the absence of external abscesses (2,3). High titers      in Alberta, as several practitioners in the southern Alberta area
alone are only indicative of exposure to C. pseudotuberculosis.        reported to us treating confirmed positive and suspect positive
A small proportion of horses with external abscessation can be         cases throughout the summer and fall of 2013.
seronegative at the time of diagnosis; therefore, titers must be          Risk factors for infection from studies in endemic areas in
interpreted in conjunction with clinical signs and hematologic         the United States include increased contact with other horses,
changes (3,6). Titers of 1:256 or greater have been suggested as       increased outdoor activity, summer pasture, and age, with
strongly indicative of active infection, either external or internal   horses 1 to 5 y old being at increased risk of infection (11).
(2), which is consistent with the findings in this case series in      Travel history did not appear to be a contributing factor on
which all horses with positive C. pseudotuberculosis cultures from     Farms A, B, and D but was likely significant for the horse on
external abscesses had titers of 1:512 or greater at the time of       Farm C as clinical signs were first noted by the owner before the
sampling. Screening titers of unaffected, asymptomatic horses          horse was moved to Alberta. For Farm C, clinical signs were first
from farms A and B with either direct or fence line contact with       noted while the horse was living in the lower mainland area of
positive cases and draining abscesses (Farm A Case 2) ranged           British Columbia, and the authors are not aware of any other
from , 1:8 to 1:128, which is consistent with the suggestion           confirmed positive cases originating in the lower mainland.
that titers of 1:16 to 1:128 are indicative of exposure (3). The       Incubation period is variable and reported as 3 to 4 wk (12), and
use of antimicrobials has been shown to potentially prolong            survival of bacteria can be up to 8 mo in manure contaminated
the course of disease in cases of external abscessation (2,6).         soil at 37°C (13). Under experimental conditions, increased sur-
Therefore, antibiotic therapy is usually reserved for cases of         vival of the bacteria in soil at lower temperatures (4°C compared
internal abscesses and ulcerative lymphangitis. However, horses        to 37°C) has been observed (14); however, the effect of below
with external abscesses showing signs of systemic illness such as      freezing winter temperatures on the potential for disease in
fever and anorexia or horses with deep intramuscular abscesses         future years in Alberta is unknown. Most horses are reported to
draining through healthy tissue may benefit from antimicrobial         have a single lifetime episode; however, recurrence or persistence
therapy once drainage has been established (2).                        of infection for greater than 1 year can occur in some individuals
   Antimicrobial susceptibility testing presents a challenge for       (6). Recurrent abcessation at the same site is reported in the lit-
laboratories and practitioners as there are no established Clinical    erature, often with less than a few wk between apparent abscess
Laboratory Standard Institute (CLSI) guidelines for C. pseu-           resolution (6). Horses with recurrent or persistent infections may
dotuberculosis that allow classification of isolates as susceptible    act as a source of environmental contamination or infection of
or resistant (7). Since there are no CLSI minimum inhibitory           naïve horses in southern Alberta and other Canadian provinces
concentration (MIC) breakpoints for C. pseudotuberculosis, the         in the years ahead. Movement of affected horses between western
MICs recently reported for isolates tested at UC Davis can be          provinces, across Canada to eastern provinces, and to and from
used as a guide for therapeutic choices (7). For those cases in        endemic areas in the United States may contribute to emergence
this study in which a sensitivity was reported by the laboratory,      of disease in new areas. In addition, changes in environmental
CLSI guidelines for Staphylococcus were used. Sensitivity results      conditions and their effect on insect vectors may play a role in
were therefore not included in this report because extrapola-          disease emergence. Insect vectors such as Haematobia irritans
tion of sensitivity patterns across bacterial species has not been     (horn fly), Stomoxys calcitrans (stable fly), and Musca domestica
validated (7). Historically, recommended antibiotics have been         (house fly) have been implicated as potential mechanical vectors
trimethoprim sulfamethoxazole at 30 mg/kg BW, PO, q12h or              for disease (1). Insect vectors may have played a role in disease
procaine penicillin at 20 000 U/kg BW, IM, q12h for external           transmission in the cases discussed, especially in Farm B where
abscesses, and rifampin at 2.5 to 5 mg/kg BW, q12h, PO in              no horses had travelled to or from the property for 1.5 y. In
combination with ceftiofur (2.5 to 5 mg/kg BW, q12h IV or              the United States, the geographic distribution of disease has
IM) for internal abscesses (8). It should be noted that ceftiofur      changed significantly in the past 10 y. Sporadic epidemic out-
given only q24h will result in plasma concentrations less than         breaks from 2002 to 2007 have been documented in areas with

CVJ / VOL 57 / OCTOBER 2016                                                                                                         1065
a historically low prevalence of disease such as Colorado, New                              Acknowledgments
                         Mexico, Wyoming, Utah, Oregon and Idaho (10,15). Endemic
                                                                                               The authors thank Drs. Dirk deGraff, Taylor Smith, Kelsey
                         areas such as California and Texas, which usually have a disease
                                                                                               Brandon, Erin Shields, and Gordon Davis, for sharing their case
                         prevalence of 5% to 10%, have seen clusters of disease outbreaks
                                                                                               material. We acknowledge funding from the Clinical Practice
                         and an increase in prevalence of disease (15,16). A recent study
                                                                                               Office, UCVM, for laboratory testing.                        CVJ
                         documenting frequency of C. pseudotuberculosis infection in
R A P P O R T D E CA S

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