Parapoxviruses 

Updated: Oct 07, 2015
Author: Luke Bloomquist, MD; Chief Editor: Mark R Wallace, MD, FACP, FIDSA 

Overview

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]

 

Presentation

History

Most patients report direct contact when feeding or treating animals or when visiting or working on farms, although indirect contact with contaminated fomites also causes infection. Parapoxvirus species are quite resistant to heat, cold, and drying and may persist on fences, feeding troughs, and barn beams for days to months. Patients often have a history of trauma, frequently minor; lesions occur at the site of trauma. Human-to-human transmission is exceedingly rare.

According to some sources, human infections occur with higher frequency in the spring and autumn, corresponding with the lambing and calving seasons. Young animals are more susceptible to infection and infected animals are more likely to require assistance with feeding, which necessitates close contact with the infected animal by the human caretaker.

Other reports suggest a higher incidence during the winter, presumably from the use of gorse, a prickly animal feed that may cause trauma and facilitate infection in an animal.[11]

Physical

Parapoxvirus lesions progress through 6 stages, each lasting approximately 6 days, as follows:

  1. The maculopapular stage, characterized by a discrete erythematous macule(s) or papule(s), follows an incubation period of 3-7 days. These lesions are usually located on the fingers, hands, or forearms; however, several reports show involvement of the face, neck, ear, and periocular area.

  2. The target stage is next; lesions have a red center, a white middle ring, and a red halo.

  3. The acute stage occurs by weeks 2-3. The lesion appears nodular and weeping.

  4. The regenerative stage occurs by weeks 3-4. The lesion becomes ulcerated and thin-crusted.

  5. The papillomatous stage develops by weeks 4-5.

  6. The regressive stage with thick dry crusting and reduction in elevation occurs by week 6, and then the lesion resolves without scarring.[17]

Unusual presentations include giant orf, widespread papulovesicular or bullous lesions, or hemorrhagic pustular nodules. These can occur in immunosuppressed or, rarely, otherwise healthy individuals.[18]

Causes

Direct contact with infected animals, either alive or dead, is most typical but is not required for infection; transmission also occurs from contaminated fomites such as shears, feeding troughs, barn doors, and fences.[19] Skin trauma, even trivial, is a risk factor for infection.

 

DDx

 

Workup

Laboratory Studies

Real-time polymerase chain reaction (PCR) of frozen tissue, vesicle material, or scab debris has a higher sensitivity than standard PCR and enables identification of not only the genus Parapoxvirus but also the specific species.[20] This is not true of the other diagnostic tests available. This is of mostly academic importance in cases in which the affected individual may have had exposure to cattle as well as goats or sheep. Multiplex PCR and specific qPCR assays are also used for the detection and differentiation of parapoxviruses.[21]

Negative-stain electron microscopy (EM) of skin tissue allows direct visualization of the parapoxvirus; identification is based on the characteristic ovoid cross-hatched appearance of the virions.[22]

Serologic testing using serum antibody (IgM and IgG) levels can confirm parapoxvirus infection, but this test unable to distinguish the specific species.

Light microscopy and traditional histopathologic techniques may afford accurate identification of the characteristic cutaneous changes observed in a parapoxvirus infection, although histopathologic features are frequently nonspecific, particularly in later lesions.

Gram stain and bacterial culture are useful in cases in which Bacillus anthracis infection or bacterial superinfection is a concern.

If performed, complete blood cell count and C-reactive protein level are usually normal in uncomplicated parapoxvirus infection.[16]

Histologic Findings

Histologically, parapoxvirus infections are indistinguishable from one another.

Epidermal hyperplasia, mild acanthosis, parakeratosis, spongiform keratinocytic degeneration, and viral cytopathic changes occur, including cytoplasmic inclusion bodies and nuclear and cytoplasmic vacuolization. In the dermis, a dense mixed inflammatory infiltrate develops, consisting of mast cells, lymphocytes, polymorphonuclear leukocytes, eosinophils, and prominent upper-dermal edema. Prominent capillary dilatation and proliferation give the impression of an angiomatous dermal lesion.[11]

Later, histology shows a nonspecific ulcerative process.[23]

 

Treatment

Medical Care

Parapoxvirus infections typically have a benign and self-limited course and no specific treatment is necessary.

Immunocompromised patients or those with large, progressive, or disseminated lesions may benefit from the following interventions:

  • Topical cidofovir[24, 25]

  • Topical imiquimod[26]

  • Antimicrobials for bacterial superinfection

Idoxuridine application may have utility with eye involvement.

Surgical Care

Surgical debridement or excision may be necessary in rare cases that are progressive or destructive.

Consultations

A veterinarian may be helpful in diagnosing parapoxvirus infection in the animal host and in controlling outbreaks.

 

Medication

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Antiviral agents

Class Summary

Therapy of viral infections begins with mechanical debridement of the involved rim and a rim of normal epithelium. This is followed by the topical instillation of antiviral medications.

Cidofovir (Vistide)

Currently approved for treatment of CMV retinitis in AIDS. Cidofovir is the first member of a group of antivirals known as acyclic phosphonate nucleotide analogs. Cidofovir diphosphate, the active intracellular metabolite of cidofovir inhibits herpes virus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

Several small studies and case reports have demonstrated eradication of parapoxvirus or other virally induced cutaneous diseases resistant to usual treatment modalities. Although a topical formulation is not currently commercially available from the manufacturer, it is possible to obtain topical cidofovir cream prepared by a pharmacist.

Idoxuridine (Herplex, Dendrid)

One of the first halogenated pyrimidine derivatives used for their antiviral effect. Used primarily in herpetic keratitis but was replaced by newer better-tolerated agents and for epithelial infections (especially initial attacks). Infections characterized by the presence of a dendritic shape respond better to this medication than stromal infections. Blocks reproduction of herpes simplex virus by producing incorrect DNA copies, preventing the virus from infecting or destroying tissue.

Immunomodulators

Class Summary

These agents modulate immune reactions resulting from diverse stimuli.

Imiquimod (Aldara, Zyclara)

Induces secretion of IFN-alfa and other cytokines. Mechanisms of action are unknown. May be more effective in women than in men.

 

Follow-up

Deterrence/Prevention

Instruct patients with close direct contact with sheep, goats, or cattle to use proper hand hygiene and personal protective equipment (ie, protective gloves) to decrease the risk of infection. This is especially crucial when in contact with herds during an infection outbreak of any of these parapoxviruses or following vaccination with the live attenuated orf virus vaccine.[20]

Several common disinfectants effectively reduce the numbers of orf virus particles present on surfaces, and their use may help to prevent spread of the disease during outbreaks.[27] In addition, infected animals should be isolated from the rest of the herd.

Immunocompromised individuals should avoid contact with infected animals.

Parental education may be useful in the prevention of zoonotic infections among pediatric patients.[15]

Complications

The following complications of parapoxvirus infection in humans may occur:

  • Pain

  • Fever

  • Lymphangitis

  • Lymphadenopathy

  • Secondary bacterial infection

  • Progressive enlargement or dissemination of lesions (primarily in immunosuppressed patients)

  • Hyperglycemia in diabetic patients[15]

  • Erythema multiforme (a number of case reports)[28, 29]

  • Stevens-Johnson syndrome, toxic epidermal necrolysis, immunobullous disorders,[30, 31] and Gianotti-Crosti syndrome[32] (only rare case reports)

  • Blindness following ocular infection (one case report)[14]

No reports exist of human death caused by parapoxvirus infections.

Prognosis

Healing over time and without scarring is the rule in almost every case.