Contagious ecthyma is an infectious dermatitis of sheep and goats that primarily affects the lips of young animals. The lesions are characteristic, and diagnosis is confirmed by PCR assay. The disease is typically more severe in goats than in sheep. Treatment usually focuses on secondary infections. Humans are occasionally affected through direct contact.
Contagious ecthyma is a viral, pustular dermatitis of young sheep and goats. Lesions usually involve the lips but can involve other cutaneous junctions such as the coronet, and can extend onto the face and ears as well. Diagnosis is confirmed by PCR assay. Affected animals go off feed, fail to gain weight, and may develop serious secondary infections at the lesion sites, all of which result in production losses.
Etiology and Epidemiology of Contagious Ecthyma in Sheep and Goats
The parapoxvirus that causes contagious ecthyma is related to the viruses that cause pseudocowpox and bovine papular stomatitis. The virus is transmitted by contact. It is highly resistant to desiccation in the environment and has been recovered from dried crusts after 12 years. In the laboratory, it is also resistant to glycerol and to ether.
Contagious ecthyma is found worldwide and is common in young lambs reared artificially and in older lambs during late summer, fall, and winter on pasture, and during winter in feedlots.
Clinical Findings and Diagnosis of Contagious Ecthyma in Sheep and Goats
Clinical evaluation
Laboratory confirmation
Courtesy of Dr. Robert Dunstan.
Courtesy of Dr. Philip Scott.
Courtesy of Dr. Philip Scott.
Courtesy of Dr. Philip Scott.
Courtesy of Dr. Philip Scott.
Courtesy of Dr. Philip Scott.
The primary lesion of contagious ecthyma develops at the mucocutaneous junction of the lips and around erupting incisor teeth, and it may extend to the mucosa of the buccal cavity. Occasionally, lesions are found on the feet and around the coronet, where secondary bacterial infection with Dermatophilus congolensis commonly leads to strawberry footrot. Ewes nursing infected lambs may develop lesions on the teats that extend onto the udder skin. The lesions develop as papules and progress through vesicular and pustular stages before encrusting. Coalescence of numerous discrete lesions often leads to the formation of large scabs, and the proliferation of dermal tissue produces a verrucose mass under them. When the lesion extends to the oral mucosa, secondary necrobacillosis frequently develops.
During the course of the disease (1–4 weeks), the scabs drop off and the tissues heal without scarring. During active stages of infection, more severely affected lambs do not eat normally, and they lose condition. Extensive lesions on the feet result in lameness. Mastitis, sometimes gangrenous, may occur in ewes with lesions on the teats.
The ecthyma lesion is characteristic. The disease must be differentiated from ulcerative dermatosis, which produces tissue destruction and crateriform ulcers. Compared to ulcerative dermatosis, ecthyma usually affects younger animals; however, this criterion can be used only presumptively. Foot-and-mouth disease and bluetongue infection should also be considered as differential diagnoses if morbidity is high and the clinical signs include salivation, lameness, and fever. Staphyloccocal folliculitis affects the skin of the muzzle and surrounding the eyes. Electron microscopic direct demonstration of virus in scab material has now been replaced by PCR assay as the diagnostic method of choice for ecthyma. Historically, inoculation of susceptible and ecthyma-immunized sheep confirmed the diagnosis.
Treatment and Control of Contagious Ecthyma in Sheep and Goats
Secondary infection
Live vaccines
Both parenteral and topical antimicrobials may help combat secondary bacterial infection of the skin lesions of contagious ecthyma. In endemic areas, appropriate repellents and larvicides should be applied to the lesions to prevent myiasis. The virus is transmissible to humans; lesions in humans are usually confined to the hands and face, are more proliferative, and can be very distressing. Veterinarians and sheep handlers should exercise reasonable protective precautions and wear disposable gloves. Most cases in humans are misdiagnosed and mistaken for other diseases (eg, anthrax) which often leads to unnecessary treatment with antibiotics or cryosurgery. Typically, physicians suspect ecthyma only when the patient reports a history of contact with sheep or goats. At this time biopsy of the lesion is performed for diagnostic confirmation by means of PCR testing.
Sheep that have recovered from natural infection are highly resistant to reinfection. Despite there being many immunogenic virus strains, the current commercial single-strain live vaccines have produced fair immunity in all parts of the US (with an occasional exception usually occurring in goats). Vaccine breaks appear to be due to the virulence of the infecting strain rather than to differences in antigenicity of the vaccine. Sheep immunized against contagious ecthyma remain susceptible to ulcerative dermatosis.
Live vaccines should be administered cautiously to avoid contaminating uninfected premises, and vaccinated animals should be segregated from unprotected stock until the scabs have fallen off. A small amount of the live vaccine is brushed over light scarifications of the skin, usually on the inside of the thigh or behind the elbow or caudal fold. Lambs should be vaccinated when ~1 month old. For best results, a second vaccination ~2–3 months later is suggested. Nonimmunized lambs should be vaccinated ~1–2 months before entering infected feedlots.
Although ecthyma is a vesicular disease that could be mistaken for foot-and-mouth disease, its notification is not mandatory by World Organization for Animal Health (formerly OIE) rules. Currently, there is no eradication program or procedure to investigate outbreaks.
Viral Molecular Characterization of Contagious Ecthyma in Sheep and Goats
Orf virus (ORFV) is the prototype of the genus Parapoxvirus (PPV). All PPVs possess a linear double-stranded DNA genome of 130–150 kilobase pairs with unusually high guanine-cytosine (GC) content (~64%). The ORFV genome has 132 genes. The central region of the genome (orf009–orf111) contains core genes of the Chordopoxvirinae family.(1,2) The terminal regions of the genome are variable and contain genes associated with virulence, pathogenesis, tropism, and immune response modulators (1,3)—eg, orf020 for viral interferon resistance; orf112 for chemokine-binding protein;(4) orf127 for viral interleukin-10;(5,6) orf117 for granulocyte-macrophage-colony-stimulating-factor inhibition factor;(7) and orf132 for vascular endothelial growth factor.(8,9)
PCR analysis of the DNA extracted from orf lesion scabs provides molecular confirmation of the clinical diagnosis. The first widely used PCR test was developed in 2000;(10) it is based on conserved regions of gene orf011 (or B2L) of PPVs. This PCR assay has been used to detect ORFV and to conduct phylogenetic analysis of ORFV in different outbreaks. As more orf011 sequences are deposited in gene banks and used for phylogenetic analysis, it is becoming clear that the high nucleotide identity (99%) exhibited by this gene can make the resolution of phylogenetic trees difficult. However, it is very efficient in separating the branches of the different members of the genus PPV (ORFV, PCPV [pseudocowpox virus], and BPSV [bovine papular stomatitis virus]). In some cases, this pan-parapoxvirus PCR assay (based on primers PPP1 and PPP4) fails, making it necessary to perform a heminested PCR assay with primers PPP3 and PPP4 to confirm the diagnosis.
Another pan-parapoxvirus diagnostic PCR assay (11) is based on the amplification of an internal region of the orf045 gene (coding for very late transcription factor 1 [VLTF-1]). This PCR test has high specificity and sensitivity.
The origin of ORFV is not known; however, the relationship among different PPVs on the orf011 gene suggests that it could be closely related to PCPV.(12) In any case, currently ORFV has a worldwide distribution. Only since 2017 have ecthyma outbreaks been reported in the scientific community from countries of different continents—eg, Turkey,(12) France,(13) China,(14) Uruguay,(15,16) Zambia,(17) Malaysia,(18) India,(19) and Argentina.(20) Few phylogenetic studies have been performed to correlate strains with geographic origin. However, molecular methods could be useful as an epidemiological tool during outbreak investigations to detect the origin of exposure.
Phylogenetic analysis based on the orf011 gene (B2L protein) indicates that PCPV and ORFV are closely related. This same result is obtained when analyzing the orf032 gene or with the complete genome.(21) At present, most phylogeny studies are based on the orf011 gene.
Key Points
Contagious ecthyma is an infectious zoonotic disease, affecting mainly sheep and goats.
Lesions are characteristic and usually affect the lips and face, creating vesicles, ulcers and hyperkeratosis.
Although it is considered a mild disease, new strategies for diagnosis and vaccination are needed.
References
Upton C, Slack S, Hunter AL, Ehlers A, Roper RL. Poxvirus orthologous clusters: toward defining the minimum essential poxvirus genome. J Virol. 2003;77(13):7590-7600.
Delhon G, Tulman ER, Alfonso CL, et al. Genomes of the parapoxviruses Orf virus and bovine papular stomatitis virus. J Virol. 2004;78(1):168-177.
Mercer AA, Ueda N, Friederichs S-M, et al. Comparative analysis of genome sequences of three isolates of Orf virus reveals unexpected sequence variation. Virus Res. (2006). 116: 146-158 (2006).
Fleming SB, McCaughan C, Lateef Z, et al. Deletion of the chemokine binding protein gene from the parapoxvirus Orf virus reduces virulence and pathogenesis in sheep. Front Microbiol. 2017;8:46.
Haig DM. Orf virus infection and host immunity. Curr Opin Infect Dis. 2006;19:127-131.
Fleming SB, Anderson IE, Thomson J, Deane DL. Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor. J Gen Virol. 2007;88(7):1922-1927.
Deane D, McInnes CJ, Percival A, et al. Orf virus encodes a novel secreted protein inhibitor of granulocyte-macrophage colony-stimulating factor and interleukin-2. J Virol. 2000;74(3):1313-1320.
Wise LM, Veikkola T, Mercer AA, Stacker SA. Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1. Proc Natl Acad Sci USA. 1999;96(6):3071-3076.
Martins M, Cargnelutti JF, Weiblen R, Eduardo FF. Pathogenesis in lambs and sequence analysis of putative virulence genes of Brazilian orf virus isolates. Vet Microbiol. 2014;174(1-2):69-77.
Inoshima Y, Morooka A, Sentsui H. Detection and diagnosis of parapoxvirus by the polymerase chain reaction. J Virol Methods. 2000;84(2):201-208.
Kottaridi C, Nomikou K, Lelli R, Markoulatos P, Mangana O. Laboratory diagnosis of contagious ecthyma: comparison of different PCR protocols with virus isolation in cell culture. J Virol Methods. 2006;134:119-124.
Şevik M. Orf virus circulation in cattle in Turkey. Comp Immunol Microbiol Infect Dis. 2019;65:1-6.
Andreani J, Fongue J, Bou Khalil JY, et al. Human infection with Orf virus and description of its whole genome, France, 2017. Emerg Infect Dis. 2019;25(12):2197-2204.
Wang Y, Yang K, Wang YA, et al. Identification and phylogenetic analysis of an orf virus strain isolated in Anhui Province, East-central China, in 2018. Acta Virol. 2019;63(3):270-277.
Da Costa RA, Cargnelutti JF, Schild CO, Flores EF, Riet-Correa F, Giannitti F. Outbreak of contagious ecthyma caused by Orf virus () in a vaccinated sheep flock in Uruguay. Braz J Microbiol. 2019;50(2):565-569.
Olivero N, Reolon E, Arbiza J, Berois M. Genetic diversity of Orf virus isolated from sheep in Uruguay. Arch Virol. 2018;163(5):1285-1291.
Simulundu E, Mtine N, Kapalamula TF, et al. Genetic characterization of orf virus associated with an outbreak of severe orf in goats at a farm in Lusaka, Zambia (2015). Arch Virol. 2017;162(8):2363-2367.
Bala JA, Balakrishnan KN, Abdullah AA, et al. An association of Orf virus infection among sheep and goats with herd health programme in Terengganu state, eastern region of the peninsular Malaysia.BMC Vet Res. 2019;15:art.250.
Nagarajan G, Pourouchottamane R, Reddy GBM, et al. Molecular characterization of Orf virus isolates from Kodai hills, TamilNadu, India. Vet World. 2019;12(7):1022-1027.
Peralta A, Robles CA, Micheluod JF, et al. Phylogenetic analysis of ORF viruses from five contagious ecthyma outbreaks in Argentinian goats. Front Vet Sci. 2018;5:134.
Cicculli V, Ayhan N, Luciani L, et al. Molecular detection of parapoxvirus in Ixodidae ticks collected from cattle in Corsica, France. Vet Med Sci. 2022;8:907–916.
