Curative effect of topical treatment of digital dermatitis with a gel containing activated copper and zinc chelate
M. Holzhauer, C. J. Bartels, M. van Barneveld, C. Vulders, T. Lam
The efficacy of two topical treatments for painful ulcerative stage (M2) of bovine digital dermatitis (BDD) lesions was compared in a clinical trial conducted on five dairy farms in 2009 to 2010. The first treatment was a water-based gel with active components copper and zinc (Intra Hoof-fit gel [IHF]) and the second treatment was a topical chlortetracycline spray (CTC spray). The experimental unit for this study was the hindleg with the presence of a BDD lesion. Cure was defined as the transition of an M2 lesion into a healed (M0) or a non-painful chronic stage (M4) of BDD at D28. On day 0, cows with M2 BDD lesions were photographed and were treated with either IHF or CTC. Subsequently, feet were photographed and scored on D28. The cure rate of M2 BDD lesions treated with IHF at D28 was 0.92 (CI 0.84 to 0.96) and was significantly better than for M2 BDD lesions treated with CTC, which was 0.58 (CI 0.47 to 0.68).
BOVINE digital dermatitis (BDD) was first described as a clinical con-
Table 1: Information of the participating dairy herds in the clinical
dition in 1974 (Cheli and Mortellaro 1974). It appears to have been
a ‘true’ emerging disease as no reference had been made to the clini-cal condition before. The disease is found in housed Holstein-Friesian
dairy cows worldwide and is considered an important cause of infec-
tious lameness (Manske and others 2002b, Holzhauer and others 2006,
Cramer and others 2008). BDD lesions typically develop on the plantar
epidermis of the hindfeet. The ulcerative stage (M2), especially, tends to
be very painful. Hence, BDD has been identified as a major welfare con-
cern (Cornelisse and others 1981, Blowey and Sharp 1988). In addition
to the improvement of hygienic measurements, optimization of cubi-
cal sizes, prevention of overcrowding and regular preventive claw trim-ming (Wells and others 1999) and rapid and effective treatment of infec-tious stages, it is necessary to prevent transmission of BDD within a herd. The main causal factor of BDD is infection with Treponema species
(IHF; Intracare b.v.) on M2 BDD lesions, in comparison with chlortet-
(Evans and others 2011). The most effective therapeutical treatments
racycline spray (CTC; Eurovet), based on the antibiotic CTC.
use antibiotics (Manske and others 2002a, Nishikawa and Taguchi 2008, Berry and others 2010). Worldwide, there is a call for reduction
Material and methods
of use of antibiotics in veterinary medicine (Phillips and others 2004).
Participating herds and dairy cows
Although the quantities of antibiotics used in topical treatments of
The trial was conducted on five commercial dairy farms in the north-
BDD are limited, an alternative would be welcome. The objective of
ern part of the Netherlands (see Table 1). All herds participated in
this study was to evaluate the therapeutic effect of Intra Hoof-fit gel
biannual routine claw trimming programmes and started their par-ticipation in the trial over time. Cows were selected based on regular visits by the claw trimmer. A next planned regular claw trimming
was the starting day per herd. Selection criteria for participation of dairy farms were as follows: BDD prevalence >20 to 25 per cent, as
M. Holzhauer, DVM, PhD, EVS,
assessed during regular previous claw trimming; herd size over 90 lac-
C. J. Bartels, DVM, PhD, MsC,
tating dairy cows; free stall with slatted floors and dairy cows of the
T. Lam, DVM, PhD, EVS,
All lactating cows with M2 BDD lesions (M2) in their hindfeet at
one of these regular claw trimming visits were included in the trial. M. van Barneveld, DVM, University of Applied Sciences, HAS Study design and treatments
The trial was designed as a case-control study in which treatment
with IHF was compared with treatment with CTC, which is an offi-
C. Vulders, BsC,
cially registered product, and this was treated as a positive control. A
positive control was chosen for animal welfare reasons as not to deny
animals treatment of the painful M2 stage of BDD. All BDD lesions
were dry cleaned, macroscopically classified and recorded at D0 and
10.1136/vr.d5513 | Veterinary Record | 1 of 4
300 hindlegs calculated to be necessary for each group. The
FIG 1: Time frame for scorings and treatments of the different products according to protocol
were treated. The comparison of the IHF and CTC group made
D28. Classification of BDD was performed according to a standard-
ised scoring system comprising five stages (M0 to M4) as developed
yield were not statistically different (p values were, respectively, 0.48,
by Döpfer and others (1997). According to this scoring system, M0 is
recorded for feet with normal digital skin where BDD is absent during
In 18 dairy cows (23 hindfeet, nine IHF and 14 CTC), the pro-
macroscopic inspection; M1 is the early-stage lesion (0 to 2 cm) that
tocol could not be fully executed, for different reasons. The most
is not painful; M2 is the classical ulcerative stage with a diameter >2
dominant reason was an extra treatment with CTC, due to a painful
cm that is often painful upon touch; M3 is the healing stage when
lesion (eight hindfeet, all belonging to the CTC group). This repre-
the lesion is covered by a scab and M4 is the chronic stage character-
sented 8 per cent of the cows treated with CTC. For medical reasons,
ised by dyskeratosis or proliferation of the surface that is generally not
five cows (3x mastitis, 1x fractured leg and 1x serious sole ulcer) were
painful. M2 is the most infectious stage (Mumba and others 1999). If
culled by the farmers. Results of six hindfeet had to be excluded, due
different stages of BDD were present, the leg was typed according to
to scoring and/or administrative mistakes. The M2 BDD cure rates
the most prominent stage of the lesion. Besides scoring of the lesions,
of IHF and CTC are presented in Tables 2 and 3. The cure rate of M2
attention was paid to the presence of adverse or side effects with spe-
BDD lesions treated with IHF was 0.92 (86/94, CI 0.84 to 0.96) and
cific attention for redness and swelling of the treated skin. On D0, the
with CTC 0.58 (51/88, CI 0.47 to 0.68), indicating a risk ratio (RR)
first M2 lesion found in a herd was assigned as treatment group A or
of 1.58 (95 per cent CI 1.31 to 1.91). The RR per herd was more
B by flipping a coin. Subsequent lesions were alternately assigned to
than unity for IHF over CTC (four out of five herds) and differed
statistically significant in three out of five herds (see Tables 2 and 3).
In group A, 5 g of IHF was applied with a brush. The lesion was
In herd 4, the cure rate for IHF was 0.90 and for CTC 1.00. On D7,
then covered with cotton wool and held in place by an elastic band-
all M2 (from Day 0) had become non-M2 for IHF compared with
age (CoRip Flexible Cohesive Bandage GB 11). On D3 and D7, again
32 remained M2 for CTC (p <0.01). On day 21, 21 per cent were
approximately 5 g of IHF was applied by use of a brush, but with-
M0 for IHF compared with 2 per cent for CTC and on D28, 51 per
out a bandage (see time frame, Fig 1). In group B, CTC was applied
cent have become M0 for IHF compared with 10 per cent for CTC
by spraying twice for three seconds from 15 to 20 cm distance with
30 seconds in-between treatments. This treatment was, accordingly the prescription of the producers,repeated at days 1 and 2. All scores,
Discussion
recordings and treatments were performed in a trimming chute by
Individual topical treatment with antibiotics is the most common-
the same veterinarian (MvB). All hindlegs with M2 lesions were
ly reported method to treat BDD (Laven and Logue 2007). This is
photographed at D0 and D28 for objective evaluation afterwards. No
widely accepted as the treatment of choice because it is generally
walk-through footbaths or other treatments were applied in the last
accepted as effective and there is a lack of scientific information on
three weeks before the start of and during the trial period. For reasons
the efficacy of non-antibiotic preparations. Topical treatment has the
of practical feasibility, performance in regular herds and for financial
advantage of limited antibiotic usage and it also fulfils the require-
reasons, no further histopathological investigation of the lesions was
ments of legislation. However, alternatives for all antibiotic treat-
performed. Daily evaluations were performed by the dairy farmer for
ments are desirable, because of reasons of possible development of
the presence of painful lesions. In case of necessary extra treatments,
antibiotic resistance and environmental pollution (Tacconelli 2010).
these were always executed with CTC (the registered product). These
In the UK, Pastell and others (2010) found no relationship between
lesions were not followed up any further and were considered not to
lameness and the presence of BDD. In that study, however, BDD
be cured. Cows that were treated for other reasons during the trial (eg,
was not classified based on the stage of infection. Laven and Hunt
(2002) evaluated the effect of two topical antibiotic sprays (with valnemulin and lincomycin) in the treatment of BDD. At D14, a
Statistical analysis
significant reduction in lesion score for both treatment groups was
The experimental unit was a hindleg with an M2 BDD lesion. Cure
found with cure rates of 28 and 40 per cent. Laven (2006) studied
was defined as the transition of M2 BDD into a healed (M0) or non-
the efficacy of two antibiotics, cefquinome applied parenterally for
painful chronic stage (M4) at D28. The sample size was calculated
three days and for five days and erythromycin applied parenterally
to detect a 10 per cent difference between the cure rate of CTC (80
by injection once. He also compared the results with erythromycin
per cent, Holzhauer and others 2008) and IHF (70 per cent; Moore
in a walk-through footbath. Only M2 BDD lesions were included
and others 2001) with 95 per cent confidence and 80 per cent power.
in that study. The results of all treatments were comparable with
Based on these assumptions, a sample size of 300 hindlegs with M2
the erythromycin footbath application; only the five-day applica-
lesions in each group was needed. A Kruskal-Wallis test was used for
tion of cefquinome had a significantly better result. Unfortunately,
comparison of the different treatment groups for parity, days in milk
the best strategy (five days application) is not only expensive, but
and milk yield, where the results might be influenced by these criteria
also has a higher risk of development of resistance against modern
antibiotics, by the increased use of a third-generation cephalosporine.
A two-sample, two-sided proportion test was used to compare the
Therefore, this strategy is less desirable. Recently, Potter and Burnell
cure rate of IHF with CTC. Data were analysed in STATA/SE 10.0
(2010) compared the curative effect of a copper/zinc and aloe vera
comparing the proportions of cured M2 lesions, 28 days after the ini-
gel as treatment of M2 BDD lesions, with an antibiotic powder
tial treatment, in cows treated with IHF or CTC. Finally, a Fisher exact
(tylosin tatrate) on 41 foots. At D7, a lesion surface area reduction
test was used to evaluate the transitions from M2 to M0 at D7 for the
of 74 per cent was found after treatment with the gel while the
different treatment groups and a proportion test was used to evaluate
antibiotic treatment gave a 48 per cent reduction. The copper/zinc
the transitions from M2 to M0 at D21 and D28 for the different treat-
gel used in that study is comparable with the gel used in our study
and the results are in line with this study. In the USA, Britt and others (1996) studied the efficacy of three topical sprays (oxytetracy-
cline, acidified ionised copper solution and acidified sodium chlorite
In total, 205 hindfeet (divided over 172 cows) were treated, 103 with
solution) on lameness three weeks after treatment. Mean lameness
IHF and 102 with CTC. Because the outcomes of the comparison
score decreased (that is, cows were less lame) for all three treatment
differed considerably from the assumptions, these were less than the
groups but increased for the control group. Berry and others (1999)
2 of 4 | Veterinary Record | 10.1136/vr.d5513
TABLE 2: Estimation of the overall cure at D28 of M2 BDD lesions treated for the different
In conclusion, the use of topical IHF gel
under a bandage at D0 and additional appli-cation at D4 and D7 (without bandage)
were effective for the treatment of the M2
stage of BDD and were significantly better
than three consecutive days of topical treat-
Acknowledgements
We acknowledge the participation and assistance of the dairy farmers and the claw
*All transitions from painful M2 lesions to M0, 1, 3 and 4
trimmers of ‘Veepedicure Centrum Noord
CTC Chlortetracycline spray, IHF Intra Hoof-fit gel
Nederland’ for their patience and accurate trimming of the dairy cows. This study
TABLE 3: Scoring of DD lesions on D7, D21 and D28 after treatment
was funded by Intracare b.v., Veghel, The Netherlands. References
BERRY, S. L., READ, D. H., WALKER, R. L. & FAMULA, T. R. (2010) Clinical, his-
tologic, and bacteriologic findings in dairy cows with digital dermatitis (footwarts)
one month after topical treatment with lincomycin hydrochloride or oxytetracycline
hydrochloride. Journal of the American Veterinary Medical Association237, 555-560
BERRY, S. L., GRAHAM, T. W., MANGINI, A. & ARANA, M. (1999) The efficacy
of Serpens spp. bacterin combined with topical administration of lincomycin HCl for
treatment of (papillomatous) digital dermatitis in cows on a dairy in California. Bovine Practitioner33, 6-11
BLOWEY, R. W. & SHARP, M. W. (1988) Digital dermatitis in dairy cattle. Veterinary
CTC Chlortetracycline spray, IHF Intra Hoof-fit gel, M0 Healed stage, M1 Early-stage
Record122, 505-508
BRITT, J. S., GASKA, J., GARRETT, E. F., KONKLE, D. & MEALY, M. (1996)
M2 Ulcerative stage, M3 Healing stage, M4 Chronic stage
Comparison of topical application of three products for treatment of papillomatous digital dermatitis in dairy cattle. Journal of Veterinary Medical Association 209, 1134-1136
CHELI, R. & MORTELLARO, C. M. (1974) La Dermatite Digitale del Bovino.
Proceedings of the Eighth International Conference on Diseases of Cattle. Milan, Italy.
evaluated the efficacy of a Serpens species bacterin vaccine combined
with topical administration of lincomycin HCl for the treatment
CRAMER, G., LISSEMORE, K. D., GUARD, C. L., LESLIE, K. E. & KELTON, D. F.
of the M2 BDD in 30 cows. All cows in that study were examined
(2008) Herd- and cow-level prevalence of foot lesions in Ontario dairy cattle. Journal of Dairy Science91, 3888-3895
on D30 and D110 and a cure rate of approximately 60 per cent was
CORNELISSE, J. L., PETERSE, D. J. & TOUSSAINT RAVEN, E. (1981) [A digital dis-
found in both groups. Shearer and Hernandez (2000) compared the
order in dairy cattle. Dermatitis digitalis? (author’s transl)]. Tijdschrift Voor Diergeneeskunde
efficacy of a topical treatment with oxytetracycline solution with
106, 452-455
the efficacy of a product containing reduced soluble copper and a
DÖPFER, D., KOOPMANS, A., MEIJER, F. A., SZAKÁLL, I., SCHUKKEN, Y.
H., KLEE, W., BOSMA, R. B., CORNELISSE, J. L., ASTEN, A. J. VAN. & TER
peroxide compound with increased levels of cationic agent, among
HUURNE, A. A. H. M. (1997) Histopathological and bacteriological evaluation of dig-
78 dairy cows with M2 BDD. Based on the lesion scores at D28, the
ital dermatitis in cattle, with special reference to Spirochaetes and Campylobacter faecalis.
copper product appeared most effective for the treatment of BDD.
Veterinary Record140, 620-623
The too low efficacy of the oxytetracycline solution (only 20 per
EVANS, N. J., BROWN, J. M., MURRAY, R. D., GETTY, B., BIRTLES, R. J., HART,
C. A. & CARTER, S. D. (2011) Characterization of novel bovine gastrointestinal tract
cent cure at D28) was hypothesised by them to be an indication of
Treponema isolates and comparison with bovine digital dermatitis treponemes. Applied
possible antibiotic resistance. Moore and others (2001) studied the
and Environmental Microbiology77, 138-147
efficacy of treating M2 BBD with a non-antimicrobial cream (solu-
HOLZHAUER, M., BARTELS, C., DÖPFER, D. & SCHAIK, G. V. (2008) Clinical
ble copper with peroxide and a cationic agent) in comparison with
course of digital dermatitis lesions in an endemically infected herd without preventive
a lincomycin HCl paste and a negative control group in 98 cows. At
herd strategies. Veterinary Journal 177, 222-230
HOLZHAUER, M., HARDENBERG, C., BARTELS, C. J. & FRANKENA, K. (2006)
D28, the percentage of healed lesions for the different therapies was
Herd- and cow-level prevalence of digital dermatitis in the Netherlands and associated
45.5, 64.5 and 21.9 per cent and the RR of cure compared with no
risk factors. Journal of Dairy Science89, 580-588
treatment was 2.08 and 2.95. In a recent study in the USA (Berry
LAVEN, R. A. & HUNT, H. (2002) Evaluation of copper sulphate, formalin and peracetic
and others 2010), the efficacy of lincomycin and oxytetracycline
acid in footbaths for the treatment of digital dermatitis in cattle. Veterinary Record151, 144-146
for topical treatment of BDD was examined via gross visual exami-
LAVEN, R. A. (2006) Efficacy of systemic cefquinome and erythromycin against digital
nation, histological evaluation and bacteriologic evaluation in 25
dermatitis in cattle. Veterinary Record159:19-20.
dairy cows with ulcerative BDD. No difference between responses
LAVEN, R. A. & LOGUE, D. N. (2007) Treatment strategies for digital dermatitis for
to lincomycin and oxytetracycline were found (73 and 68 per cent,
the UK. Veterinary Journal 171, 79-88
MANSKE, T., HULTGREN, J. & BERGSTEN, C. (2002a) Topical treatment of digital
dermatitis associated with severe heel-horn erosion in a Swedish dairy herd. Preventive
In most studies on topical antibiotic treatments, cure rates at D30
Veterinary Medicine53, 215-231
around 60 to 70 per cent are found, except in the study of Shearer
MANSKE, T., HULTGREN, J. & BERGSTEN, C. (2002b) Prevalence and interrelation-
and Hernandez (2000). Data in the present study indicated that the
ships of hoof lesions and lameness in Swedish dairy cows. Preventive Veterinary Medicine 54, 247-263
curative effect of IHF at D28 after the start of treatment was 92 per
MOORE, D. A., BERRY, S. L., TRUSCOTT, M. L. & KOZIY, V. (2001) Efficacy of a
cent, which is better than antibiotic treatment in other studies (Table 2).
nonantimicrobial cream administered topically for treatment of digital dermatitis in
Table 3 gives a more detailed insight and it shows that (for IHF) at D7
dairy cattle. Journal of the American Veterinary Medical Association219, 1435-1438
all lesions were cured (≠M2), but at a later stage some M2 lesions
MUMBA, T., Döpfer, D., Dreher M., Gaastra, W. & van der Zeijst, B.A. (1999) Detection
re-occur, where it is not clear if it is reinfection or reoccurrence of a
of spirochetes by polymerase chain reaction and its relation to the course of digital dermatitis after local antibiotic treatment in dairy cattle. Zentralblatt Veterinarmedicin B.
non-healed lesion. The curative effect of topical application of CTC
46,117-126.
in the present study was in line with cure rates of antibiotics applied
NISHIKAWA, A. & TAGUCHI, K. (2008) Healing of digital dermatitis after a single treat-
topically on BDD lesions in other studies. Thus, the application of
ment with topical oxytetracycline in 89 dairy cows. Veterinary Record163, 574-576
IHF seems to be a good alternative for antibiotic treatment of M2
PASTELL, M., HÄNNINEN, L., DE PASSILLÉ, A. M. & RUSHEN, J. (2010) Measures
of weight distribution of dairy cows to detect lameness and the presence of hoof lesions.
BDD lesions. Although copper and zinc are considered to be toxic
Journal of Dairy Science93, 954-960
for the environment, copper/zinc pollution seems to be limited due to
PHILLIPS, I., CASEWELL, M., COX, T., DE GROOT, B., FRIIS, C., JONES, R.,
a limited number of individual cows per herd and the amount of gel
NIGHTINGALE, C., PRESTON, R. & WADDELL, J. (2004) Does the use of antibiot-
applied (<5 g) and is expected to have a very limited influence on the
ics in food animals pose a risk to human health? A critical review of published data. Journal of Antimicrobial Chemotherapy53, 28-52
10.1136/vr.d5513 | Veterinary Record | 3 of 4
POTTER, S. & BURNELL, M. (2010) Comparison of a non-antibiotic gel with antibi-
TACCONELLI, E. (2009) Antimicrobial use: risk driver of multidrug resistant microor-
otic powder for the treatment of digital dermatitis. Proceedings of the Cattle Lameness
ganisms in healthcare settings. Current Opinion in Infectious Diseases22, 352-358
Conference. Sutton Bonington, April 14, 2010. pp 47-48
WELLS, S. J., GARBER, L. P. & WAGNER, B. A. (1999) Papillomatous digital
SHEARER, J. K. & HERNANDEZ, J. (2000) Efficacy of two modified non-antibiotic
dermatitis and associated risk factors in US dairy herds. Preventive Veterinary Medicine
formulations (Victory) for treatment of papillomatous digital dermatitis in dairy cows.
38, 11-24 Journal of Dairy Science83, 741-745 4 of 4 | Veterinary Record | 10.1136/vr.d5513 Curative effect of topical treatment of digital dermatitis with a gel containing activated copper and zinc chelate
M. Holzhauer, C. J. Bartels, M. van Barneveld, et al. Veterinary Recorddoi: 10.1136/vr.d5513
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