A relevant history, especially targeting occupational hazards and recent travel with an emphasis on animal contact, is paramount. Associated orf virus skin lesions are distinctive, polymorphous, asymptomatic, and diagnosed clinically. Hand and digital involvement comprise the majority of affected sites (90%+). However, involvement of the face, scalp, and even genital regions have been described. In immunocompromised hosts, the lesion may attain a large size, colloquially known as giant orf; and can lead to some level of morbidity.[6]

A positive exposure history and a suggestive physical exam are often enough to diagnose or virus infection in the large majority of affected individuals. However, a punch/shave biopsy is diagnostic and the gold standard.

Although not always readily available, a PCR assay for orf disease is highly sensitive in humans. It can be the non-invasive investigation of choice if the diagnosis is in doubt.[7]

Orf disease being a zoonotic host-switch illness does not carry a particularly grim prognosis. The lesions are self-limiting, and in immunocompetent patients - symptoms would spontaneously resolve in a 4- to 6-week window.

Most cases rarely require anything more than reassurance and expectant care. However, in immunocompromised hosts, this isn’t always the case. Giant orf can grow to several centimeters, and the resultant morphology may mimic those of tumors and pyogenic granulomata.

Because Orfviridae utilizes a novel viral form of DNA dependent RNA polymerase, topical cidofovir (a potent blocker of the enzyme mentioned above) has found almost ubiquitous use as first-line antiviral therapy, along with mechanical eradication (i.e., cryotherapy, surgical excision, imiquimod, etc.) if needed.

Complications with superinfection and lymphangitis are common; therefore, clinicians often start topical antibiotics prophylactically.

Because of the highly conserved and complex antigenicity of the orf virus, vaccination is particularly effective. Many domesticated sheep and goat populations are routinely vaccinated, with varying levels of success. In humans, recurrence is rare but with diminished severity per incident (as anticipated adaptive immunity).[8][9][10]

The two most important differential diagnoses to rule out include those that share zoonotic-exposure history to farm animals and exhibit cutaneous lesions.

Paravaccinia (Milker’s nodules) is a very similar parapoxvirus infection – just arising from cows rather than goats/sheep as in orf disease. Clinically they are indistinguishable and resolve spontaneously within six weeks or so.

Cutaneous anthrax is a bacterial infection from Bacillus anthracis. An eventual “black eschar” evolution is pathognomonic for this lesion. The more infamous pulmonary symptoms can develop in the systemic spread and can be life-threatening. Spores are transmittable from infected animals, wool, and even meat. Gram stain, culture, and even PCR are all available to aid in diagnosis.[11]

Orf disease, being a zoonotic infection, follows a relatively benign course. It usually resolves spontaneously in 6 to 12 weeks and carries a very low rate of human to human spread. A more aggressive course with increased size (giant orf) may appear in immunocompromised hosts, and especially those with cell-mediated immune deficiency. Recurrence is possible but produces a progressively blunted infection.

Secondary bacterial infection and regional adenitis may require antibiotics.

Sporadic immunologic reactions can occur fortuitously with zoonotic infections and especially so with an immunomodulatory virus such as orf. Cases of erythema multiforme, Stevens-Johnson syndrome, and Pemphigoid bullae have all been described. These should be expected and handled carefully.[12][13][14]

There is little doubt that educating farmers, herders, and any other at-risk occupation on proper glove-wearing and hand-washing techniques are essential. Seminars for recognizing/diagnosing infected livestock and proper vaccination protocol / inducting herd immunity is also a great starting point.

However, many skeptical populaces would bring fair resistance to any money and or effort at all allocated to preventing a self-limited infection that holds minimal morbidity for the large majority of affected individuals, and few would be so inclined to disagree.

Genuine deterrence is in funding and development towards research and understanding the zoonotic viral host-switch phenomenon, their virulence, and transmissibility. The sheer danger posed, of which our current comprehension of is so grossly inadequate, is simply terrifying.

The recent COVID-19 pandemic has no doubt served as a rude awakening to this fact. Orfviridae shares extensive genetic similarity to the now extinct smallpox, a virus claimed to have taken more lives than every infectious etiology put together; what little genetic drift or shift it would take fill that haunting niche left by variola is a true uncertainty.

It would be very cost-effective if the healthcare providers in rural areas are well versed in the recognition and treatment of orf disease.

Also, surveillance and infection control measures play a pivotal role in the prevention of infection.