Cowpox: an emerging zoonosis

Between mid-January and mid-February 2009, 33 human cases of cowpox were reportedly diagnosed in France (15 cases, 14 of which were in the north) and Germany (18 cases, 12 of which were in North-Rhine-Westphalia and six in Bavaria).

Sequence data of an amplified fragment from several cowpox virus (CPXV) isolates from both countries were found to be identical, indicative of a potential common source of infection. Further investigations led to the suspicion that the infected people — almost all of whom were children or young adults — were exposed to infected pet rats. The investigations of the pet rats to which the patients had been exposed suggested a common source of infection related to international trade by a rat breeder in a third European Union country.

The above event gained wide publicity within the EU and beyond. The potential of an introduced pathogen to infect people keeping wild or exotic mammalian pets had been demonstrated during the 2003 monkeypox outbreak in the United States, when the pathogen was imported with African rodents and introduced into pet shops. Though the CPXV is not known to be naturally circulating in the Western hemisphere, the international trade in pet animals and the recent growing trend to include rats among species kept as pets justify enhanced attention globally.

Background

Cowpox entered medical history with Edward Jenner’s publications “Inquiry” and “Further Observations on the Variolae Vaccinae” in 1798 and 1799. Jenner demonstrated the efficacy of cowpox virus (“true cowpox,” “variolae vaccinae”) scarification to induce a protective immunity against challenge with variola virus.

The designation cowpox virus refers to its association with pustular lesions on the teats of milking cows. Bovine cowpox was once a sporadic disease, until the early 1970s believed to be spread enzootically in cattle only. Zoonotic transmission to humans (milkers) has traditionally occurred via contact with infected cows. This concept has been gradually changing since. CPXV is member of the genus Orthopoxvirus within the family poxviridae. This virus is found only in Europe and regions of western Asia and is currently known to have a wide host range, with its main reservoir being wild rodents.

Despite the name of the virus, cattle are rarely infected, domestic cats being the species in which clinical disease is most often seen. Affected cats usually have multiple skin lesions, although respiratory and other signs also may be seen. In addition to cats, cows and rodents, infection is sometimes reported in other “accidental” hosts, including dogs, various mammals kept in zoos such as the felids cheetah, lion, lynx and ocelots as well as elephants, rhinoceros, anteaters and others.

Human infection, although rare, is more commonly reported than bovine infection, and can be often be traced to contact with an infected cat, or sometimes direct contact with rodents. The disease is self-limiting in immunocompetent human hosts (localized lesion) but it can be severe and even fatal in immunocompromised patients.

Cowpox in cattle

Bovine cowpox is extremely rare, and is limited to lesions on the teats of dairy cows. This probably reflects areas of skin most likely to be both damaged and to come into contact with rodent-contaminated material. In contrast to the disease in cats, cowpox virus does not appear to cause a systemic disease or more widespread skin lesions in cattle; the lesions are limited to the sites of the virus entry, after an incubation period of three to seven days. When bovine virus does occur, the disease can spread rapidly through the herd, probably on milking equipment. Lesions typically heal within one month. Milkers may develop fever and have lesions on the hands, arms or face.

Cowpox in cats

Cats, which are now the most commonly recognized host of CPXV, are believed to become infected when hunting. Most affected cats come from rural environments and are known to hunt rodents. Infection in cats has a marked seasonal incidence, with most cases occurring between September and November. Cat-to-cat transmission can also occur but usually results in only subclinical infection.

The most common route of entry appears to be through the skin, but oronasal infection is also possible. The viremic phase may be associated with pyrexia and depression and, during this period, virus can be isolated from various tissues, including the skin, turbinates (and sometimes lungs) and lymphoid organs. Widespread secondary skin lesions appear a few days after the onset of viremia. Most affected cats have a history of a single primary skin lesion, usually on the head, neck or a forelimb, often described as a small bite-like wound. The primary lesion can vary from a small, scabbed wound to a large abscess. About seven to 10 days after the appearance of the primary lesion, secondary lesions often begin to appear. Over two to four days, these develop into discrete, circular, ulcerated papules, which soon become covered by scabs. Healing is usually complete by about six weeks.

Many cats show no signs other than skin lesions, but about 20% may develop mild coryza or conjunctivitis. Most domestic cats recover uneventfully. In cheetahs, more severe pulmonary disease frequently occurs.

Presumptive and rapid diagnosis can be made in most cases from unfixed scab, exudate or biopsy material examined by electron microscopy for the characteristic brick-shaped orthopox virions. A more accurate and sensitive method of diagnosis is isolation of virus in cell culture or on chick chorioallantois. If no virus is isolated, fixed biopsy material for histologic examination and serum for antibody determination also can be sent to the laboratory.

Because it seems that infection in domestic cats is mainly sporadic and acquired from chance contact with infected wildlife reservoir, control measures probably are not indicated. In wildlife parks, where big cats are at risk from small wild rodents, especially where the disease has already occurred, vaccination may be considered. At present, management of outbreaks among large cats depends on prompt diagnosis and segregation of affected animals to reduce the possibility of cat-to-cat spread. Premises may be disinfected with hypochlorite bleach or detergents. At ambient temperatures, poxviruses are relatively resistant and may remain infective in dried crusts for months.

Cowpox in rodents

The CPXV has been the subject of extensive research in wild rodent populations since the mid 1990s. In Western Europe, field voles (Microtus agrestis), bank voles (Myodes glareolus) and wood mice (Apodemus sylvaticus) are accepted as being the main reservoir hosts of CPXV. In M. agrestis populations, the virus is endemic, and may play a role in regulating abundance. In Northern Europe, virus has been isolated from root voles (M. oeconomus). In Turkmenistan, antibody has been detected in 15% of suslicks (Spermophilus citellus) and 18% of giant gerbils (Rhombomys opimus), with very few virus isolates.

Cowpox infection in rodents is acute and lasts about four weeks, although it causes little obvious clinical disease. However, by extracting the host’s resources and/or inducing a nutritionally demanding immune response, infections in wild rodents may have sublethal effects that affect population dynamics. It has been shown that cowpox is associated with significantly diminished reproductive potential in wood mice and bank voles.

Rats (Rattus norvegicus) have been implicated several times as source of human infection. The first such case was published in 2002, when CPXV was isolated by Dutch investigators from the ulcerative eyelid lesions of a 14-year-old girl, who had cared for a clinically ill wild rat that later died. CPXV isolated from the rat showed complete homology with the girl’s virus. However, until recently rats were not regarded as a likely reservoir of CPXV. This was based both upon a surveillance carried out in Great Britain, as well as upon the assumption that if rats were reservoir hosts, the virus would be found world-wide.

The recent events in France and Germany should shed some additional light on the role of rats in the epidemiology of cowpox. In any event, a preliminary conclusion may be the need to advise immunompromised patients to avoid contact with domestic or wild rodents.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.

For more information:

• Pastoret P, Bennett M, Brochier B, et al. Animals, public health and the example of cowpox. Rev Sci Tech. 2000;19:23-32.