Background
Poxviridae are a family of oval or brick-shaped, quite large, double-stranded DNA viruses that can infect both humans and animals. The genus Parapoxvirus is included among these viruses; these viruses measure 260 X 160-nm and possess a unique spiral coat that distinguishes them from the other poxviruses. Parapoxvirus species are enzootic to hoofed animals (ungulates) throughout the world. Three similar parapoxviruses (orf virus, pseudocowpox virus, and bovine papular stomatitis virus) commonly cause infection in humans; transmission is through direct or indirect contact with infected animals. The zoonotic hosts of these parapoxviruses are sheep and goats (orf, ie, ecthyma contagiosum virus) and cattle (pseudocowpox virus [ie, milker's nodule virus or paravaccinia virus] and bovine papular stomatitis virus).
Other parapoxviruses have been recognized in New Zealand red deer,[1] Finnish reindeer,[2] Japanese serows,[3] European musk oxen,[4] red squirrels in the United Kingdom,[5] harbor seals in the North Sea,[6] and California sea lions.[7] A novel parapoxvirus from white-tailed deer in the United States has caused cases of human infection.[8]
Parapoxvirus infections manifest as pathologic lesions on the animal's oral mucosa (eg, lips, nostrils, eyes) or the moist hairless areas of the skin (eg, udders, groin). The virus may be contacted even in the absence of obvious lesions on the animal.[9]
Incidence of deer-associated parapoxvirus infections may rise as the deer population in the United States continues to increase.[8]
Clinical cutaneous manifestations of infection with the parapoxviruses are identical; therefore, some authors propose the term "farmyard pox" for any of the 3 common parapoxvirus infections.[10]
Go to Poxviruses, Orf, and Milker's Nodules for complete information on these topics.
Pathophysiology
Parapoxvirus infection results in solitary or multiple, relatively painless, cutaneous lesions that heal slowly, usually without complications. Occasionally, the lymphatic system is involved. Even in immunocompromised hosts, little evidence suggests spread of infection outside external surfaces.
Lasting immunity to parapoxviruses does not seem to occur, and reinfection has been reported.[11]
Epidemiology
Frequency
United States
Orf, milker's nodule, and bovine papular stomatitis are viral illnesses enzootic to sheep, goats, and cattle throughout the world. No reports contain data specific to the United States.
International
Data from England and Wales for 1990-1995 indicate an annual mean of 15 human cases of parapoxvirus infections, significantly less than the reported annual mean of 46 cases between 1978 and 1986. Sheep were a more frequent source of infection than other ungulates.[12]
Among high-risk populations, such as animal caretakers or meat handlers,[13] the typical clinical appearance and the benign nature of the infection may be well known. As a result, infected individuals may not seek medical attention and many authors believe that the infection is much more common than actually reported.
Mortality/Morbidity
Parapoxvirus lesions generally heal without treatment, albeit slowly. Scarring is typically absent. Immunocompromised patients and those with atopic dermatitis are at risk for progressive or disseminated disease. One case reported described blindness resulting from ocular involvement; no cases resulting in death have been reported.[14]
Race
Race is often not specified in the existing literature, but the infection occurs throughout the world.
Sex
Most cases occur in males, reflecting the male predominance in the occupations or activities of the infected patients, which include veterinarians, veterinary students, farmers, shepherds, and other animal caretakers. Women are susceptible to infection if they have close contact with animals.
Age
Most cases occur in young to middle-aged adults, although school-aged children also are infected. Parapoxviruses do not appear to have a predilection for any particular age group. Children may be at higher risk due to behavioral reasons that cause them to sustain more animal bites, to have poorer adherence to good hand hygiene and personal protective measures, and to engage in high-risk behaviors such as nuzzling a sick animal.[15] A recent analysis of an orf outbreak found that age less than 20 years was an independent risk factor for infection.[16]
Horner GW, Robinson AJ, Hunter R, Cox BT, Smith R. Parapoxvirus infections in New Zealand farmed red deer (Cervus elaphus). N Z Vet J. Apr 1987;35(4):41-5. [Medline].
Tikkanen MK, McInnes CJ, Mercer AA, Büttner M, Tuimala J, Hirvelä-Koski V. Recent isolates of parapoxvirus of Finnish reindeer (Rangifer tarandus tarandus) are closely related to bovine pseudocowpox virus. J Gen Virol. Jun 2004;85(Pt 6):1413-8. [Medline].
Inoshima Y, Yamamoto Y, Takahashi T, Shino M, Katsumi A, Shimizu S. Serological survey of parapoxvirus infection in wild ruminants in Japan in 1996-9. Epidemiol Infect. Feb 2001;126(1):153-6. [Medline].
Falk ES. Parapoxvirus infections of reindeer and musk ox associated with unusual human infections. Br J Dermatol. Dec 1978;99(6):647-54. [Medline].
Tompkins DM, Sainsbury AW, Nettleton P. Parapoxvirus causes a deleterious disease in red squirrels associated with UK population declines. Proc Biol Sci. 2002;269:529-33.
Hicks BD, Worthy GA. Sealpox in captive grey seals (Halichoerus grypus) and their handlers. J Wildl Dis. Jan 1987;23(1):1-6. [Medline].
Nollens HH, Jacobson ER, Gulland FM, Beusse DO, Bossart GD, Hernandez JA. Pathology and preliminary characterization of a parapoxvirus isolated from a California sea lion (Zalophus californianus). J Wildl Dis. Jan 2006;42(1):23-32. [Medline].
Roess AA, Galan A, Kitces E, Li Y, Zhao H, Paddock CD. Novel deer-associated parapoxvirus infection in deer hunters. N Engl J Med. Dec 30 2010;363(27):2621-7. [Medline].
Bowman KF, Barbery RT, Swango LJ, Schnurrenberger PR. Cutaneous form of bovine papular stomatitis in man. JAMA. Dec 18 1981;246(24):2813-8. [Medline].
Shelley WB, Shelley ED. Farmyard pox: parapox virus infection in man. Br J Dermatol. Jun 1983;108(6):725-7. [Medline].
Groves RW, Wilson-Jones E, MacDonald DM. Human orf and milkers' nodule: a clinicopathologic study. J Am Acad Dermatol. Oct 1991;25(4):706-11. [Medline].
Baxby D, Bennett M. Poxvirus zoonoses. J Med Microbiol. Jan 1997;46(1):17-20, 28-33. [Medline].
Robinson AJ, Petersen GV. Orf virus infection of workers in the meat industry. N Z Med J. Feb 9 1983;96(725):81-5. [Medline].
Lewis-Jones S. Zoonotic poxvirus infections in humans. Curr Opin Infect Dis. Apr 2004;17(2):81-9. [Medline].
Lederman ER, Austin C, Trevino I, Reynolds MG, Swanson H, Cherry B. ORF virus infection in children: clinical characteristics, transmission, diagnostic methods, and future therapeutics. Pediatr Infect Dis J. Aug 2007;26(8):740-4. [Medline].
Bayindir Y, Bayraktar M, Karadag N, Ozcan H, Kayabas U, Otlu B, et al. Investigation and analysis of a human orf outbreak among people living on the same farm. New Microbiol. Jan 2011;34(1):37-43. [Medline].
Mendez B, Burnett JW. Orf. Cutis. Oct 1989;44(4):286-7. [Medline].
Villadsen LS, Zachariae CO. Unusual presentation of ORF in an otherwise healthy individual. Acta Derm Venereol. 2008;88(3):277-8. [Medline].
Leavell UW Jr, McNamara MJ, Muelling R, et al. Orf. Report of 19 human cases with clinical and pathological observations. JAMA. May 20 1968;203(8):657-64. [Medline].
Centers for Disease Control and Prevention. Orf virus infection in humans--New York, Illinois, California, and Tennessee, 2004-2005. MMWR Morb Mortal Wkly Rep. Jan 27 2006;55(3):65-8. [Medline].
Mast J, Demeestere L. Electron tomography of negatively stained complex viruses: application in their diagnosis. Diagn Pathol. Feb 10 2009;4:5. [Medline].
Töndury B, Kühne A, Kutzner H, Palmedo G, Lautenschlager S, Borelli S. Molecular diagnostics of parapox virus infections. J Dtsch Dermatol Ges. Sep 2010;8(9):681-4. [Medline].
Zabawski EJ Jr. A review of topical and intralesional cidofovir. Dermatol Online J. Sep 2000;6(1):3. [Medline].
McCabe D, Weston B, Storch G. Treatment of orf poxvirus lesion with cidofovir cream. Pediatr Infect Dis J. Nov 2003;22(11):1027-8. [Medline].
Ara M, Zaballos P, Sánchez M, Querol I, Zubiri ML, Simal E. Giant and recurrent orf virus infection in a renal transplant recipient treated with imiquimod. J Am Acad Dermatol. Feb 2008;58(2 Suppl):S39-40. [Medline].
Gallina L, Scagliarini A. Virucidal efficacy of common disinfectants against orf virus. Vet Rec. Jun 5 2010;166(23):725-6. [Medline].
Schmidt E, Weissbrich B, Brocker EB. Orf followed by erythema multiforme. Eur Acad Dermatol Venereol. 2006;20:612-3.
Slattery WR, Juckett M, Agger WA. Milkers' nodules complicated by erythema multiforme and graft-versus-host after allogenic hematopoietic stem cell transplantation for multiple myeloma. Clin Infect Dis. 2005;40:e63-6.
Murphy JK, Ralfs IG. Bullous pemphigoid complicating human orf. Br J Dermatol. May 1996;134(5):929-30. [Medline].
White KP, Zedek DC, White WL, Simpson EL, Hester E, Morrison L. Orf-induced immunobullous disease: A distinct autoimmune blistering disorder. J Am Acad Dermatol. Jan 2008;58(1):49-55. [Medline].
de la Torre C. Gianotti-Crosti syndrome following milkers' nodules. Cutis. Nov 2004;74(5):316-8. [Medline].

