Comparison of three treatment regimens
for sheep and goats with caseous lymphadenitis
Kevin E. Washburn, dvm, dacvim, dabvp; Wesley T. Bissett, dvm, phd; Virginia R. Fajt, dvm, phd, dacvcp;
Melissa C. Libal, dvm, ma, dacvm; Geoffrey T. Fosgate, dvm, phd, dacvpm; Joseph A. Miga; Kristine M. Rockey
Objective—To compare the effectiveness of 3 treatment regimens for small ruminants with
Design—Randomized clinical trial.
Animals—44 client-owned sheep and goats.
Procedures—Aspirates were obtained from 48 lesions of 44 enrolled animals and submitted
for bacterial culture. Animals were randomly assigned to 1 of 3 treatment groups.Treatment
for group A (n = 15 lesions) consisted of opening, draining, and flushing the lesions
and SC administration of procaine penicillin G. Treatment for group B (n = 15 lesions) consisted
of closed-system lavage and intralesional administration of tulathromycin. Treatment
for group C (n = 18 lesions) consisted of closed-system lavage and SC administration of
tulathromycin. All animals were reexamined approximately 1 month after treatment, unless
treatment failure was detected prior to that time.
Results—43 animals with lesions had positive results (Corynebacterium pseudotuberculosis)
for bacterial culture. Proportions of lesions that had resolution of infection by 1 month
after treatment did not differ significantly among the treatment groups (group A, 13/14
[92.9%]; 95% confidence interval [CI], 69.5% to 99.6%; group B, 10/12 [83.3%]; 95% CI,
54.9% to 97.1%; and group C, 14/17 [82.4%]; 95% CI, 59.1% to 95.3%).
Conclusions and Clinical Relevance—Acceptable alternatives to opening, draining, and
flushing of lesions may exist for treatment of sheep and goats with caseous lymphadenitis.
Use of tulathromycin and penicillin in this study constituted extralabel drug use, which
would require extended withholding times before milk or meat of treated sheep and goats
can be sold for human consumption. (J Am Vet Med Assoc 2009;234:1162–1166)
Caseous lymphadenitis is a chronic, suppurative disease
caused by Corynebacterium pseudotuberculosis.
Sheep, goats, horses, cattle, and humans can be affected
by this disease. Caseous lymphadenitis is currently of
most interest in small ruminants and is implicated as the
third leading cause of economic loss to the sheep industry
in the western United States.1 In 1 report2 in which
investigators examined samples from culled sheep from
regions representing 9 western states, the prevalence was
estimated as 42.41%. Although prevalence studies for
goats in the United States are lacking, there is an ever-
increasing number of goats3 and caseous lymphadenitis
should be an important health consideration.
The characteristic lesions of caseous lymphadenitis
are single or multiple abscesses of the lymph nodes,
skin, and viscera.4 The causative organism enters the
body through broken or intact skin, via inhalation, or
across mucous membranes. Inside the host, the organism
spreads via the lymphatics to lymph nodes and internal
organs, where abscesses develop during a period
of 2 to 6 months. Bacteria are released into the environment
through discharge from draining superficial
From the Departments of Large Animal Clinical Sciences (Washburn,
Bissett), Veterinary Physiology and Pharmacology (Fajt), Veterinary
Pathobiology (Libal), and Veterinary Integrative Biosciences
(Fosgate), College of Veterinary Medicine and Biomedical Sciences
(Miga, Rockey), Texas A&M University, College Station, TX 77843.
Supported by the American Boer Goat Association.
Address correspondence to Dr. Washburn.
CI Confidence interval
abscesses or are aerosolized from ruptured abscesses in
Treatment and control modalities for caseouslymphadenitis include lancing of abscesses and flushing
with potentiated iodine solutions, treatment with
antimicrobials, culling of affected animals, surgical removal
of abscesses, intralesional injection of formalin,
and isolation from other animals to prevent disease
spread.6 Lancing and flushing abscesses create a potential
hazard for spread of purulent material to fomites
and into the environment during the convalescent period.
Although antibacterial protocols have been used
for pharmacologic treatment of animals with caseous
lymphadenitis,5,7 acceptable efficacy has not been determined
because the abscesses typically are thickly encapsulated,
which hinders penetration of antimicrobials.8Additionally, because of the organism’s intracellular location,
some antimicrobials may not reach efficacious
intracellular concentrations. At best, clinicians canhope for a reduction in size of the abscess and nonrecurrence
of the condition. At worst, the abscesses can
rupture and drain, which spreads organisms into the
environment and could potentially infect others in the
herd. Culling of genetically superior animals is often
not a desirable or economically feasible option; howev
1162 Scientific Reports JAVMA, Vol 234, No. 9, May 1, 2009
er, retaining these animals in the herd greatly increases
the risk of transmission. Although curative in the short
term, surgical resection of abscesses does not address
recurrence, requires local or general anesthesia, and is
a more expensive option than the other reported treatment
alternatives. Injection of formalin into the lesions
reportedly is beneficial9; however, a carcass containing
formalin would be considered adulterated and would
be unfit for human consumption. The potential for negative
public perception related to this practice is also a
Tulathromycin, a newly introduced triamilide
antimicrobial, is a member of a subclass of the macrolide
family labeled for treatment of cattle and swine
with undifferentiated respiratory tract disease. It is
highly lipid soluble and, in cattle, maintains concentrations
in lung tissue greater than the minimum inhibitory
concentration (2.0 µg/mL) for the primary
respiratory pathogens for at least 7 days.10 The long-
lasting properties and high degree of lipid solubility
may allow this drug to enter encapsulated abscesses
and achieve adequate intracellular concentrations.
The safety of tulathromycin used in an extralabel
manner was investigated in another study11 conductedby our laboratory group. In that study,11 tulathromycin
was administered at 25 mg/kg (11.4 mg/lb; 10 times the
label dosage) to goats to investigate deleterious effects.
No short-term adverse effects were detected in that
study. To our knowledge, there have been no reported
pharmacokinetic studies conducted in sheep or goats.
The objective of the study reported here was to
compare the effectiveness of treatments for small ruminants
with caseous lymphadenitis. Specifically, we
evaluated the use of opening, flushing, and draining of
lesions followed by penicillin administration, closed-
system lavage and intralesional administration of tulathromycin,
and closed-system lavage and parenteral
administration of tulathromycin.
Materials and Methods
Sample population—Client-owned sheep and goats
were used in the study. The criterion for enrollment in
the study was that an animal had a solitary subcutaneous
mass consistent with an abscess. The same animal could
be enrolled more than once during the study period when
a lesion resolved within 1 month after initial treatment
and a new lesion developed in another location. A case
was defined as an enrolled study subject whose lesion
yielded positive results when cultured for C pseudotuberculosis.
A study subject could also contribute > 1 case
during the study period when a new lesion developed
in another location and when that lesion also had positive
results for culture of C pseudotuberculosis. Owners
were required to sign a consent form prior to enrollment
of their animals. The consent form and study were approved
by the Texas A&M University Clinical Research
Data obtained for all enrolled animals included
age, sex, breed, number of days the lesion was evident
(ie, detected by the owners) prior to initial examination
by the authors, caseous lymphadenitis vaccination status,
history of caseous lymphadenitis on the farm, and
recent antimicrobial treatments. Physical examinations
were performed, and the lesions were described as firm
or fluctuant, hair or no hair, and draining or not draining.
All lesions were photographed, and the location of
each lesion was recorded.
Isolation and identification of C pseudotuberculosis—
For all sheep and goats enrolled in the study, each lesion
was aseptically prepared by clipping the hair from around
the lesion, scrubbing the area with betadine solution, and
rinsing with isopropyl alcohol. Each lesion was then aspirated
with a 16-gauge, 3-cm needle to obtain material for
bacterial culture. Samples were inoculated onto 5% sheep
blood agara and MacConkey agara and into tryptose broth.
The blood agar and tryptose broth were incubated at 37°C
in 5% carbon dioxide for up to 72 hours. After incubation
for 24 to 48 hours, tryptose broth was subcultured to 5%
sheep blood agar and incubated at 37°C in 5% carbon dioxide
for an additional 24 to 48 hours (total incubation of 72
hours). Plates containing MacConkey agar were incubated
at 37°C in air for up to 72 hours. Suspect colonies were subcultured
for purity and confirmed to be C pseudotuberculosis
by useofa Corynebacterium identification system.b
Serum hemolysin–inhibition test—Blood samples
were obtained from all sheep and goats prior to
treatment. Blood samples were collected via jugular
venipuncture and used for serologic testing to determine
serum hemolysin–inhibition titers. Briefly,
the hemolysin inhibition titer was determined by the
synergistic action of Rhodococcus equi and C pseudotuberculosis
toxins. Establishing the point at which hemolysis
was inhibited was performed on a blood agar
plate. Serum samples were placed in 8 wells cut into
the plate, which contained 8 different serial dilutions
of hemolytic units.c
Treatment groups—Sheep and goats were randomly
assigned to 1 of 3 treatment groups by use of
a block design. For treatment group A, lesions were
opened at their most ventral aspect by use of a No. 21
scalpel blade. An elliptic incision was made to remove
skin and provide a sufficient opening for drainage. The
cavity was drained and flushed thoroughly with diluted
betadine solution. A single dose of procaine penicillin
G (20,000 U/kg [9,091 U/lb], SC) was administered in
the neck region. For treatment group B, lesions were
pierced with a 16-gauge, 3-cm needle and filled with
saline (0.9% NaCl) solution to break up purulent material.
The abscess cavity was then treated with distention
lavage, with saline solution used to remove purulent
material. A single dose of tulathromycin (2.5 mg/kg
[1.14 mg/lb]) was injected into the empty abscess cavity
(ie, intralesional administration). For treatment group
C, lesions were lavaged with saline solution (similar
to the procedure for group B) and a single dose of tulathromycin
(2.5 mg/kg, SC) was administered in the
neck region. All sheep and goats were scheduled for a
reexamination at 1 month after treatment.
Discharge instructions—Sheep and goats were discharged
to their owners. Discharge instructions included
information on the withholding period for animals
because of the extralabel use of tulathromycin (45 days
for milk and 36 days for meat) and penicillin (5 days
for milk and 10 days for meat), as recommended by
JAVMA, Vol 234, No. 9, May 1, 2009 Scientific Reports 1163
the Food Animal Residue Avoidance Databank.12 Owners
were also informed that they would be contacted by
telephone approximately 1 month after the initial treatment
to obtain additional information. Finally, owners
were provided with information regarding biosecurity
and criteria that constituted treatment failure and
would necessitate reexamination prior to the scheduled
Treatment failure was defined as any sheep or goat
whose lesion enlarged to pretreatment size or larger
within 10 days after treatment. For case animals in
groups B and C, treatment failure also included rupture
and draining of the lesion. Owners were instructed
that if there was such a treatment failure prior to the
scheduled 1-month reexamination, they were to return
the animal to the veterinarian that enrolled it into the
Follow-up telephone call—Approximately 1month after initial treatment, owners were contacted by
telephone by an interviewer who was not aware of treatment
group assignment. Information gathered included
whether the lesion had resolved and, if not, whether the
lesion was larger, smaller, or had ruptured and drained.
The interviewer also recorded when a new lesion had
appeared in another location and whether the animal
had any adverse effects, such as anorexia or lethargy.
During the telephone conversation, the appointment
was scheduled for the 1-month reexamination.
Follow-up examination—Approximately 1-month
after initial treatment, all sheep and goats enrolled in
the study were reexamined. At that time, a lesion was
considered unresolved when it was still evident in the
same location as that of the initial examination and was
the same size, larger, or only slightly reduced in size
75% of the original size). Unresolved lesions were
aseptically prepared, and material was aspirated for
bacterial culture. Unresolved lesions were opened,
drained, and flushed in accordance with the protocol
established for group A animals. Although these lesions
were considered unresolved for their originally
assigned treatment groups, another follow-up examination
performed approximately 1 month after the second
treatment was used to ensure resolution of lesions.
Statistical analysis—Data were summarized for
the 3 treatment groups by use of descriptive statistics.
The Kruskal-Wallis 1-way ANOVA was used to compare
medians of quantitative data. Categoric variables
were compared among the 3 treatment groups and on
the basis of lesion characteristics by use of .
2 tests and
Fisher exact tests for pairwise comparisons. Treatment
effects were evaluated by estimating risk ratios (comparing
the proportion of treatment successes withineach group) and their corresponding 95% CIs. Sensitivity
and specificity of the serum hemolysin–inhibition
test were estimated as the proportion of culture-positive
and culture-negative animals, respectively, correctly
identified by the serologic test. Confidence intervals
were calculated for all proportions, and categoric analyses
were performed with available software.d Analysesof quantitative variables were performed with another
program.e All analyses were considered significant at
values of P < 0.05.
Sample population—During approximately 12months, 44 animals (41 goats and 3 sheep) with 48 lesions
were enrolled in the study. Two goats each represented
2 cases and 1 goat represented 3 cases because
they developed lesions in other locations > 1 month
apart. Eighteen farms from 2 states were represented;
12 farms each provided > 1 enrolled animal. Fifteen enrolled
cases were assigned to group A, 15 were assigned
to group B, and 18 were assigned to group C.
Animals ranged from 6 to 96 months of age. Ten
were male and 34 were female. Goat breeds represented
included Boer (n = 33 goats), La Mancha (3), Nubian
(2), and mixed-breed goats (3). The 3 sheep were of
the Suffolk breed. The number of days that the lesion
was evident (detected by the owners) prior to initial examination
by the authors ranged from 1 to 100. Seven
goats had been vaccinatedf against caseous lymphadenitis;
vaccinations were administered from 6 months to
1 year before initial examination by the authors. Thirty-
five sheep and goats originated from farms with a history
of caseous lymphadenitis. None of the animals had
received antimicrobial treatment prior to enrollment in
the study. Signalment and history of caseous lymphadenitis
did not differ significantly among treatment
groups (Table 1).
Initial physical examination of lesions revealed that
26 were firm and 21 were fluctuant. Thirty-eight lesions
were covered with hair, and 9 were considered to have
no hair. Six lesions were draining, and 41 lesions were
not draining. Physical examination information wasnot available for 1 lesion in a goat. Lavage of the firm
(ie, nonfluctuant) lesions was not as rewarding for the
removal of purulent material, compared with removal
of purulent material in fluctuant lesions, and the typical
volume of material aspirated and removed from the
lesions varied widely on the basis of size and maturity
of the lesions.
Culture results—Corynebacterium pseudotuberculosis
was isolated from 43 lesions. Bacteria isolated
from the remaining 5 lesions included Arcanobacterium
pyogenes, coagulase-negative Staphylococcus spp, a-hemolytic
Streptococcus spp, Pseudomonas spp, and Enterococcus
Results for treatment groups—Of the 43 lesions
that yielded C pseudotuberculosis on bacterial culture,
14 were assigned to group A, 12 were assigned to group
B, and 17 were assigned to group C. Examination findings
of lesions for the 43 culture-positive cases prior to
treatment did not differ significantly among treatment
groups (Table 2). No adverse effects were recorded for
any sheep or goat during the study period. Additionally,
there were no treatment failures recorded by the owners.
All 5 lesions that had negative results when cultured
for C pseudotuberculosis were considered resolved
at the 1-month reexamination, whereas 37 of 43 (86%)
culture-positive lesions were considered resolved. Of
the 6 unresolved cases at the 1-month reexamination,
1 had been assigned to group A, 2 to group B, and 3 to
group C. The proportions of resolution at the 1-month
reexamination for the 43 C pseudotuberculosis–positivelesions were 92.9% (95% CI, 69.5% to 99.6%), 83.3%
1164 Scientific Reports JAVMA, Vol 234, No. 9, May 1, 2009
Table 1—Comparisons of quantitative and proportions for categoric variables of sheep and goats with
Variable A(n=15) B(n=15) C(n=1
Overall A vs B and C
SexFemale (No.) 13 11 12 0.411 0.292
Male (No.) 2 4 6
BreedBoer goat (No.) 12 10 15 0.499 1.000
Other goat (No.) 3 3 2 0.726 1.000
Sheep (No.) 0 2 1 0.317 0.542
Vaccinated againstcaseouslymphadenitis (No.)
Yes 2 3 2 0.761 1.000
History of caseouslymphadenitis onfarm (No.)
Yes 12 11 12 0.691 0.727
Age (mo)‡ 16 (8–60) 24 (8–4
24 (6–96) 0.689 0.398
No. of days lesion 7 (1–100) 7 (1–30) 10 (4–60) 0.294 0.473
noticed prior to
*Treatments were as follows: group A, opening, flushing, and draining of lesion followed by SC administration
of penicillin; group B, closed-system lavage and intralesional administration of tulathromycin; and group
C, closed-system lavage and parenteral administration of tulathromycin. †P values for categoric variables
based on comparison of proportions for the variable (eg, female vs male and Boer vs all others) across treatment
groups. Values were considered significant at P . 0.05. ‡Value reported is median (range).
n = Number of lesions; there were 48 lesions for 44 sheep and goats enrolled in the study.
Table 2—Number of findings in sheep and goats with caseous
lymphadenitis whose lesions yielded Corynebacterium
pseudotuberculosis during bacterial culture performed prior to
Treatment group* P value†
Variable A(n=14) B(n=11)‡ C(n=17) Overall AvsBandC
Fluctuant 4 5 9 0.386 0.186
Firm 10 5 8
No hair 3 4 2 0.301 1.000
Hair 11 6 15
Draining 2 2 2 0.894 1.000
Not draining 12 8 15
‡Missing information from 1 animal.
See Table 1 for remainder of key.
(95% CI, 54.9% to 97.1%), and 82.4% (59.1% to 95.3%)
for groups A, B, and C, respectively; these values did
not differ significantly (P = 0.66
groups. Resolution of lesions did not differ significantly
on the basis of lesion characteristics for firm (83%) versus
fluctuant (89%; P = 0.673), hair (85%) versus no
hair (89%; P = 1.00), or draining (100%) versus not
draining (83%; P = 0.569).
Each of the 2 farms that enrolled the most animals
had at least 1 animal that provided multiple cases. One
buck from the farm with the highest number of animals
enrolled was treated 3 times during a 10-month period
(defined as 3 cases for that goat). Initially, this goat was
assigned to group C, and the lesion was considered unresolved
at the 1-month reexamination. At that time, the
lesion was treated in accordance with the protocol for
group A, and it subsequently resolved 1 month later. Five
and 10 months after initial enrollment, the buck devel
oped lesions in new locations. It was assigned to groups A
and C, respectively, and for both of those treatments, lesions
were considered resolved by the 1-month reexamination.
The farm with the second highest number of enrolled
animals had 2 does with lesions that were considered resolved
at 1 month and that subsequently developed new
lesions 8 months after initial treatment. Both of these
does were assigned to group A for the original lesions,
but both were assigned to group C for the lesions that
subsequently developed in new locations.
Serum hemolysin–inhibition test—Antibody titers
against C pseudotuberculosis (as determined by use of the
serum hemolysin–inhibition test) at initial examination
ranged from 0 to 1:64. Of the 43 culture-positive lesions,
35 were in seropositive animals, with titers that ranged
from 1:4 to 1:64, whereas 8 were in seronegative animals.
Sensitivity for the serum hemolysin–inhibition test
was 81% (95% CI, 68% to 91%). For the 5 culture-negative
lesions, 3 were in seropositive animals and 2 were in
seronegative animals. Specificity for the serum hemolysin–
inhibition test was 40% (95% CI, 7% to 82%). Of the
7 animals vaccinated against caseous lymphadenitis, 6
were seropositive (titers ranged from 1:4 to 1:64); 2 of the
6 were culture-negative animals. The remaining vaccinate
was a culture-positive animal that was seronegative.
Animals enrolled in the study reported here were
predominately Boer goats. This breed represents most
of the goats examined at our hospital. Additionally, this
study investigated only 1 form of caseous lymphadenitis.
Diagnostics were not performed to determine whether
JAVMA, Vol 234, No. 9, May 1, 2009 Scientific Reports 1165
any enrolled animals had visceral or internal lymph node
involvement. However, those manifestations of caseous
lymphadenitis are most often accompanied by a history
of chronic weight loss, and none of the animals in this
study had that history. Despite these limitations, it appears
from our data that intralesional or parenteral treatment
with tulathromycin after removal of purulent material via
needle distention lavage may be an acceptable alternative
to opening, draining, and flushing caseous lymphadenitis
abscesses coupled with penicillin administration.
However, the small number of cases in each treatment
group in this study did not provide the power necessary
to make conclusive statements of efficacy. Additional
studies are needed to accurately determine the benefit of
various protocols for resolution of caseous lymphadenitis.
Although not significantly different, lesions treated in accordance
with the protocol for group A had a higher proportion
of resolution than for groups B and C combined.
Because of its spectrum of activity against gram-positive
organisms, administration of penicillin to goats of group
A could have contributed to the higher proportion of lesions
that resolved. However, we believe that the benefits
of not opening these lesions and avoiding spread of bacteria
into the environment during the convalescent period
outweighed the small differences in outcome among these
groups. Thus, we believe that the higher proportion for
resolution in group A is not clinically important.
Interestingly, the sensitivity of the serum hemolysin–
inhibition test at initial examination was lower than that
reported for animals with naturally developing infections,
whereas the specificity was higher.13 False-negative results
could have been attributable to the enrollment of animals
with chronic, well-encapsulated abscesses that may have
had low circulating antibody titers. False-positive results
in this study could have been attributable to internal abscesses
or exposure of animals to the organism, especially
on farms that contributed multiple cases and that had limited
biosecurity prior to participation in our study. Also, 2
animals were vaccinated and were seropositive, but their
lesions did not yield C pseudotuberculosis isolates.
Although no treatment failures were reported by the
owners, it is possible that lesions opened and drained in
such a manner that they were not noticed by the owners.
Nevertheless, there was only 1 new animal that developed a
lesion among all 18 farms represented during the approximately
12-month study period, which indicated that once
affected animals within a herd were identified, enrolled, and
treated, there was no widespread increase in disease incidence.
This suggested that biosecurity measures on those
farms were excellent or lesions that resolved did so in an innocuous
manner. Similarities in outcome among treatment
groups could have been attributable to many factors, most
notably the number of days the lesion was evident before
initial examination. Additionally, the stage of the lesion at
initial treatment may have affected outcome. Lesions that
were draining at the time of initial examination would have
been more representative of animals in group A (without
the betadine flush); therefore, draining lesions assigned to
groups B (n = 2 cases) and C (2) may have resolved because
they were open and not because of intralesional or parenteral
administration of tulathromycin.
It is possible that the physical removal of purulent material
via lesion distention lavage with saline solution, as
performed in groups B and C, may have positively influenced
outcome in these groups. A control group in which
lesions were emptied by intralesional lavage but were not
treated by administration of tulathromycin may have been
an informative addition to the study; however, the willingness
of clients to participate may have been compromised.
To our knowledge, minimum inhibitory concentrations
of tulathromycin against C pseudotuberculosis isolates
in small ruminants are lacking, as are pharmacokinetic data
for tulathromycin in goats. Such studies are warranted to
determine more precisely the pharmacodynamics of tulathromycin
when used to treat animals with caseous lymphadenitis.
Other antimicrobials injected intralesionally may also
be efficacious and should be examined in future studies.
Overall, it appears that intralesional or parenteral
administration of tulathromycin may be an acceptable
alternative to opening, draining, and flushing of caseous
lymphadenitis lesions. More affected animals from diverse
geographic areas and longer follow-up periods are needed
in future studies to investigate the effects of tulathromycin
treatment for animals with caseous lymphadenitis on the
management of this disease in goat herds. Additionally, efficacy
of this treatment for other manifestations of caseous
lymphadenitis remains to be investigated.
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