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Orf Infections and Molluscum Contagiosum
Pox Family of Viruses
The poxvirus family Poxviridae consists of a group of large, enveloped, double-stranded DNA viruses capable of infecting vertebrates and invertebrates. Poxviruses are the largest known animal viruses, and the characteristic viral inclusions caused by infection with a poxvirus are identifiable on light microscopy. The subfamily Chordopoxvirinae infects vertebrate animals and humans ( Table 9-1 ), whereas the subfamily Entomopoxvirinae infects invertebrate animals. Poxviruses are epitheliotropic, facilitating their transmission by skin-to-skin contact and making diagnosis possible through skin biopsy or sampling.
Table 9-1
Poxviruses that infect humans
| Subfamily | Genera | Species |
|---|---|---|
| Chordopoxvirinae | Orthopoxvirus | Variola (smallpox) |
| Vaccinia | ||
| Cowpox | ||
| Monkeypox | ||
| Parapoxvirus | Orf virus | |
| Pseudocowpox virus | ||
| Bovine papulosa stomatitis virus | ||
| Seal pox virus | ||
| Yatapoxvirus | Yaba monkey tumor virus | |
| Yaba-like disease virus | ||
| Tanapox virus | ||
| Molluscipoxvirus | Molluscum contagiosum |
The members of the poxvirus family share a similar replicative cycle, which occurs in multiple stages in the cytoplasm of infected cells. The replicative cycle begins with binding of the virus to a glycosaminoglycan receptor on the surface of the host cell. After successfully binding to a host receptor, the viral particle enters the host cell. Poxviruses are enveloped and must undergo a two-step uncoating process upon entry to the cell in order to complete their replicative cycle. The first step in uncoating occurs as the viral particle enters the cell, resulting in removal of the outer membrane of the virion. The second step of uncoating reveals the core of the virus containing its linear double-stranded DNA genome to the host cell’s cytoplasmic environment. There are two phases of gene expression for viruses in the poxvirus family. The early genes, expressed first during the replicative cycle, encode nonstructural proteins to construct the machinery necessary to replicate the viral genome. One of these proteins is a DNA-dependent RNA polymerase. This protein allows the poxvirus to replicate in the host cell’s cytoplasm, which is a unique feature for a double-stranded DNA virus. Most double-stranded DNA viruses must utilize the host cell’s replicative machinery for at least part of their replicative cycle and thus replicate in the nucleus rather than the cytoplasm. The late genes, expressed after genome replication, encode structural proteins necessary to construct new virions. After all the viral components are synthesized by the infected host cell, new viral particles are assembled utilizing the cytoskeleton of the host cell and are released from the cell.
Four genera of poxvirus are capable of infecting humans: Orthopoxvirus, Parapoxvirus, Yatapoxvirus, and Molluscipoxvirus (see Table 9-1 ). This chapter focuses on the clinical and pathologic features of one member of the Parapoxvirus genus, the orf virus, and on the Molluscipoxvirus genus, since these include the most common poxvirus agents of human disease.
Orf Virus
Clinical Features
Prevalence
Orf virus is a parapoxvirus capable of infecting goats and sheep as well as humans. It is endemic to Northern California and rural areas around the world. It affects primarily people who handle sheep and goats occupationally, but it may infect people without a history of direct animal contact through fomite transmission. Additionally, outbreaks of orf infection may occur following religious ceremonies involving the ceremonial butchering of lambs or goats.
Etiology
Orf virus causes a disease commonly referred to as orf. The name orf derives from the Anglo-Saxon word for cattle, which is a misnomer because transmission to or from cattle has never been reported. It was first reported as a human infection by George Peterkin in 1937. It has many descriptive names including ecthyma contagiosum, contagious pustular dermatosis, infectious pustular dermatosis, farmyard pox, ovine pustular dermatitis, scabby mouth, and sore mouth.
Humans can become infected with orf virus via exposure to infected lesions on animals or through exposure to contaminated fomites such as fences, barn enclosures, or even wool shears. The orf virus is capable of surviving both heat and drying forces, and fomite transmission has been documented years after possible deposition of the virus from infected animals. Orf virus can also survive in the soil for at least 6 months. Humans who handle infected sheep or goat carcasses may also become infected. Human-to-human transmission has been reported in one case.
Molecular Biology
The parapoxviruses have a unique appearance on electron microscopy that distinguishes them from other members of the poxvirus family. Most poxviruses are brick shaped to oval with criss-crossing tubercles that make the virion resemble a ball of wool, but the parapoxviruses have a spiral coat that is appreciable on electron microscopy. The viral particle is between 200 and 380 nanometers in length.
Orf virus produces several gene products that enable it to evade immune control both in animals and people. There are known viral proteins elaborated, which inhibit interferon as well as granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) by interfering with receptor binding, thus preventing full activation of the innate and adaptive immune response and allowing uninhibited elaboration of orf viral particles. Interestingly, interferon gamma production is associated with resolution of infection.
Orf Virus—Fact Sheet
Definition
- ■
Parapoxvirus causing orf disease.
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Disease is also known as ecthyma contagiosum, contagious pustular dermatosis, infectious pustular dermatosis, farmyard pox, ovine pustular dermatitis, scabby mouth, and sore mouth.
Epidemiology
- ■
Orf primarily affects people who handle sheep and goats occupationally, but it may infect people without a history of direct animal contact through fomite transmission. Outbreaks may occur following religious ceremonies involving the ceremonial butchering of lambs or goats.
Clinical Features
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Orf may present as single or multiple lesions on exposed skin typically including the hands, wrists, forearms, or face.
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There are four clinical stages to disease: maculopapular, targetoid, acute weeping, and regenerative dry stages.
Prognosis and Therapy
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Orf is typically a self-limited, single-organ system infection.
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Secondary bacterial infection of orf lesions is not uncommon.
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Supportive therapy with dressing changes and analgesia may be used when the number of skin lesions is limited.
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Cryotherapy and shave excision may speed resolution by destroying or removing virally infected cells and allowing for the host inflammatory and healing responses.
A live virus vaccine is used in livestock, principally among lambs, where it is administered via a scratch between the foreleg and chest. A characteristic orf lesion is produced at the site, which forms a scab containing infectious viral particles. The vaccine material and the scab formed on vaccinated animals are both capable of causing disease in humans and other sheep or goats.
Natural infection with orf virus results in long-lived immunity in humans. Orf antibody titers are detectable in the serum of patients naturally infected with the virus. Of note, previous exposure to the orthopoxvirus, smallpox, or the smallpox vaccination with vaccinia virus does not offer any protection from orf virus.
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