Background
More than 200 years ago, in one of the first demonstrations of vaccination, Edward Jenner inoculated a young English boy with cowpox material from a dairymaid and showed that the boy became resistant to smallpox. Today, cowpox is a rare disease, largely confined to small mammals on the European continent and in Great Britain, with occasional transmission to humans. Most cases present with a small number of vesicopustular lesions on the hands or face that subsequently ulcerate and develop a black eschar before spontaneously resolving. Rarely, cutaneous dissemination and even death may occur.
Pathophysiology
Cowpox is caused by the cowpox or catpox virus, a member of the orthopoxvirus family, which also includes smallpox and vaccinia.[1] The virus is believed to be acquired by direct contact with an infected animal, most often a cat in the case of humans, with lesions occurring where the virus gains access through broken skin.[2] Infection generally remains localized at the initial site of inoculation, although lymphatic spread in a sporotrichoid pattern and generalized skin infection have been reported.[3, 4, 5] Human-to-human transmission of cowpox has never been reported.
As a member of the Orthopoxvirus family, cowpox is a large double-stranded DNA virus that replicates in cell cytoplasm. Viral particles bind to plasma membrane receptors on host cells and then enter into the cytoplasm, where the viral genome is replicated and viral progeny are assembled. After new viral particles are assembled, the host cell lyses, releasing infectious virus, which can enter surrounding cells. Cowpox virus has no latent stage and does not integrate its DNA into the host genome.
Poxviruses use numerous strategies to evade the host immune system. These include production of homologues of mammalian tumor necrosis factor receptor, interleukin-1beta receptor, interleukin 18–binding protein, interferon-alpha/beta receptor, and interferon-gamma receptor, as well as a complement-binding protein and a caspase inhibitor.[6] These proteins are thought to neutralize the host's antiviral response by binding to cytokines and complement proteins and inhibiting their function. In addition, cowpox virus has been shown to inhibit intracellular transport of major histocompatibility class I molecules, allowing it to evade cytotoxic T cells.[7, 8]
Epidemiology
Frequency
United States
Cowpox has never been reported in the United States.
International
Cowpox is a rare infection of humans, with fewer than 150 human cases reported.[3, 9] Historically, most cases have been reported in Great Britain, with a smaller number from Germany, Belgium, the Netherlands, France, Sweden, Finland, Norway, and Russia. In 2001, 60 cases of possible cowpox were reported in Egypt, but this has not been confirmed.[9] Most cases occur in the late summer and fall.
Mortality/Morbidity
Human cowpox is usually a self-limited disease. The host immune response is usually sufficient to control the viral infection, and the only sequelae are scars at the site of the pox lesions. Of the 7 cases of severe generalized skin infection that have been reported, 4 of the patients had atopic dermatitis, one had Darier disease,[10] and one had hay fever.[4, 11] The only reported death associated with cowpox was in a patient with atopic dermatitis and allergic bronchial asthma who was receiving systemic steroids at the time of infection. After developing widespread cutaneous lesions, the patient died from pulmonary embolism. Autopsy failed to demonstrate viropathic effect in any internal organs, so it is unclear what role cowpox may have played in the patient's death.
Race
No racial predilection has been reported.
Sex
Equal numbers of male and female cases have been reported.
Age
Human cowpox is a disease of young people, with half of all cases occurring in individuals younger than 18 years. Young people may be at greater risk because of a propensity for close contact with animals, such as cats, or because of their not having been vaccinated for smallpox, which may confer some protection against cowpox.
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