Human cowpox infections manifest in the form of a localized skin rash. Multiple papules may become visible a few days after infection, although cases of single lesions have been described. Papules turn into vesicles and affected individuals frequently present with fluid-filled, raised blisters on hands, arms and face. Because the infection requires direct contact with a carrier or an infected animal, other areas of the body are rarely affected. Vesicles may be surrounded by erythematous and edematous skin; they break easily and turn into bleeding ulcers that dry and are subsequently covered by purple-black eschar. Lymphadenopathy of regional lymph nodes may be noted.

More severe forms of cowpox virus infections can be observed in immunodeficient patients.

Lesions do not respond to antibiotic treatment but spontaneously heal after about two months.

Complications and additional symptoms may arise from secondary bacterial infection of ulcerated lesions.

Progressive vaccinia, a rare, potentially life-threatening dermatological condition associated with uncontrolled spread of the initial lesion, extensive ulceration and necrosis, has not yet been described in cowpox patients. This pathology is related to the vaccination of immunosuppressed patients with vaccinia virus strains, known as both vaccinia necrosum or vaccinia gangrenosum.

• Lymphadenopathy

  An 11-year-old girl had been suffering from 2 recently developed reddish ulcerated nodules on the right side of her neck and, concomitantly, from a very hard swelling as well as from painless lymphadenopathy. [ncbi.nlm.nih.gov]

  The eschar was 2 cm in diameter and was accompanied by expanding local erythema (Panel A) and submandibular lymphadenopathy. She had been treated empirically with antibiotics, but there was no improvement. [nejm.org]

  Eight days later, the patient was admitted to the hospital with a black necrotic scab on the internal surface of the right arm, regional lymphangitis, and axillar lymphadenopathies ( Figure 1, panel A). [wwwnc.cdc.gov]

  She presented with an inflammatory, erythematous swelling of the skin beneath the right ear and painless lymphadenopathy in the regional parotid and upper jugular lymph nodes. [academic.oup.com]

  There was no regional lymphadenopathy. Biopsy of the lesion revealed massive spongiosis and reticular degeneration at several places in epidermis with marked acute inflammatory dermal infiltrate [Figure - 2]. [ijdvl.com]

• Gangrene

  After antibiotic and fluid therapy, revision of the skin lesions and amputation of a gangrenous toe, the cat recovered. [ncbi.nlm.nih.gov]

• Sore Throat

  Other generalised symptoms from cowpox are fever, tiredness, vomiting, and sore throat. Eye complaints such as conjunctivitis, periorbital swelling and corneal involvement have been reported. Enlarged painful local lymph nodes may also develop. [dermnetnz.org]

  Furthermore, most of the reported patients have slight systemic symptoms, such as pyrexia, and they sometimes experience sore throat, influenza-like illness, and general malaise that lasts 3–10 days. [academic.oup.com]

• Respiratory Distress

  Over a few days, his condition deteriorated, and he developed multiple vesicopustular skin lesions and required an emergency tonsillectomy due to respiratory distress. [ncbi.nlm.nih.gov]

• Mild Clinical Course

  In contrast, a rather mild clinical course of cowpox was confirmed in a 49-year-old male farmer vaccinated against smallpox. Only a small eschar developed, and wound closure was complete after 6 weeks. [ncbi.nlm.nih.gov]

• Cellulitis of the Face

  In addition to the severe edematous cellulitis of the face, the clinical course was dominated by several areas of subcutaneous, necrotizing lymphadenitis, from one of which a huge abscess formed that had to be incised. [ncbi.nlm.nih.gov]

  Diagnosis was delayed for our patient, because the initial massive cellulitis of the face resembled a H. influenzae phlegmon; however, the results of cultures were negative. [academic.oup.com]

Anamnesis usually reveals close contact with rodents, cats or cows. If history of contact with these animals is negative, other mammals may be considered as possible carriers of the pathogen [6].

Cowpox virus particles may be isolated from vesicle fluid, wound fluid or eschar. Histological examination may reveal cytoplasmic inclusion bodies, such as type-A inclusion and Guarnieri bodies. While the latter are diagnostic for poxviridae, the former is produced only by a small number of species belonging to that family.

Samples may also be directly submitted to electron microscopic analysis to detect the presence of Orthopoxviridae, which are rather large, rectangular shaped virus particles. Although morphologic features allow differentiation of orthopoxvirus from other genera, electron microscopy is not suitable for differentiation of distinct species. Differentiation may only be achieved either by traditional viral culture or by application of modern molecular biological methods.

Cowpox viruses may be grown on the chorioallantoic membrane of chick embryos where they cause characteristic hemorrhagic lesions. In contrast, most other orthopoxvirus strains induce non-hemorrhagic lesions [9].

Polymerase chain reaction is the method of choice for biomolecular identification, where viral nucleic acids are isolated from samples or viral cultures. Classical DNA sequencing or restriction analysis may provide evidence for cowpox, as well as newer techniques such as multiplex polymerase chain reactions [1] [10].

Serological tests are not routinely done to confirm cowpox. From an epidemiological point of view, it may be of interest to submit the patient's pets to serological analysis in order to determine the source of infection.

• Cytoplasmic Inclusion Bodies

  The most significant pathological feature of cowpox is the presence of two types of cytoplasmic inclusion bodies: irregular B-type inclusion bodies, and numerous large, homogenous, acidophilic, A-type inclusion bodies. [web.stanford.edu]

  Histological examination may reveal cytoplasmic inclusion bodies, such as type-A inclusion and Guarnieri bodies. While the latter are diagnostic for poxviridae, the former is produced only by a small number of species belonging to that family. [symptoma.com]

Cowpox is a self-limiting disease. There is no definitive treatment though supportive treatment consisting of wound hygiene and prevention or treatment of secondary bacterial infections can be provided. In moderate to severe cases, patients may require bed rest or even hospitalization. Anti-vaccinia gammaglobulin and surgical interventions may be recommended for patients developing lesions as severe as progressive vaccinia.

Virustatics are not routinely administered. Compounds such as cidofovir and derivatives may be effective against orthopoxvirus strains, but they have serious side effects that are not outweighed by the potential benefits of an antiviral therapy [11] [12].

For safety reasons, patients should be advised that wound fluids are potentially infectious. Other persons should avoid direct contact even though direct transmission from human to human has not been reported.

The prognosis for this disease is excellent. Human cowpox infections are usually self-limiting, and dermatological lesions generally heal without leaving scars in immunocompetent patients.

On the other hand, the course of the disease may be more severe and prolonged in immunocompromised individuals, but long-term sequelae are not expected either. However, in some cases, scars may remain.

The cowpox virus, a member of the orthopoxvirus family, may be transmitted by many mammalian species. Although the disease is classically ascribed to contact with infected dairy cows, most recent human cases have been caused by pets, notably by rodents and, less frequently, cats [2] [3]. Presumably, cats are infected by rodents that carry the pathogen [4]. The virus may enter the human body via scratches, bites or previously existing wounds. Human-to-human transmission has never been reported.

Cowpox is a rare disease in humans. Although the individual risk for people in close contact with rodents, cats and cows may be somewhat elevated when compared with the remaining part of the population, the risk to contract this disease is still very low.

People who are vaccinated against smallpox seem to have a certain degree of immunity against cowpox.

For as of yet unknown reasons, most cases of cowpox are reported during the warm months of summer and fall.

Cowpox virus is distributed in large parts of Europe. However, most cases are recorded in Great Britain and have also been described in Central and Northern Europe and Russia. An isolated but rather large outbreak has been reported in Egypt [5]. Cowpox have neither been encountered in the Middle or Far East, in Asia, Australia nor in the United States [2].

Presumably, rodents serve as a reservoir for the viral pathogen. In Finland, an orthopoxvirus seroprevalence close to 100% has been observed in the elderly [6].

Most cowpox patients are children and adolescents. Considering the risk factors for contracting this disease, a higher incidence of abrasions or other skin lesions, closer contact with pets and lack of immunity provided by smallpox vaccines may serve as an explanation for this fact.

Cowpox is transmitted through direct contact with infected animals. Although an increased risk of infection after contact with skin ulcers of animals seems plausible, recent cases argue for the alternative hypothesis that asymptomatic carriers, particularly rodents, are as likely to transmit the causative virus.

The virus enters the skin through recently inflicted or previously existing skin lesions and does not generally spread from the site of infection. Extensive infections have been reported in rare cases, notably in immunodeficient patients. In these cases, the virus may spread through lymphatic vessels. While an atopic girl developed a severe, generalized eruption [6], a course as severe as post-vaccine encephalitis has not yet been described for the cowpox virus [7].

Cowpox causes skin lesions primarily by virus-mediated cell lysis. The virus attaches to the plasma membrane of host cells, enter their cytoplasm, replicate using their organelles for biosynthesis of viral proteins, assemble new virus particles, and finally exit their host cells after triggering their lysis. This cycle is then restarted in new host cells. Unlike herpesviridae or retroviridae, the cowpox virus neither establishes latent infections nor inserts their DNA into the host cell genome.

The cowpox virus also causes the release of immunomodulatory proteins. They induce the expression of decoy cytokine receptors and thus render interleukin-1β, tumor necrosis factor-α and interferons virtually ineffective. These pathogens also inhibit apoptosis in order to increase their chance for replication and evade complement-mediated lysis [8].

Infection with cowpox virus requires direct contact with carriers or infected animals. Therefore, skin lesions of pets, cattle or any other animals should not be handled without taking appropriate hygiene measures. In any case, hands should be washed after touching pets or livestock. Immunodeficient patients should avoid animal contact.

The overall incidence of cowpox might diminish further if awareness of this disease is raised in people who work with animals that may transmit the virus.

Cowpox patients should use wound dressings to avoid spreading the pathogen with vesicle fluids or eschar.

Cowpox is a zoonotic disease that mainly affects individuals who work in close contact with infected cows.

The causative agent of this disease is the cowpox virus, a member of the genus of orthopoxvirus. Other species of this genus include vaccinia virus and smallpox virus. Cowpox virus and vaccinia virus are very similar to each other and for some time, it has not been clear if they indeed constitute two distinct species. Additionally, it has been stated that both are able to induce cowpox, and the latter is sometimes also referred to as vaccinia. Currently, molecular biological techniques allow for a clear differentiation between both species [1].

Although there are enormous clinical differences between cowpox and smallpox, their antigenic similarities allowed for the vaccination disease and ultimately the eradication of smallpox. "Vaccine" and "vaccination" derive from the word vaccinia virus". Based on the observation that people who had suffered from cowpox did not contract smallpox, Edward Jenner vaccinated his son against smallpox in 1796 by using viruses taken from cowpox lesions.

Many species of mammals are susceptible to cowpox, but cows have been known to develop and spread the disease for centuries. Infected cows usually show dermatological lesions on udder and teats, which is why milkers develop characteristic ulcerating vesicles on the hands and forearms. Previously existing skin lesions facilitate viral infection. The disease is usually self-limiting and ulcers generally heal without scarring. However, serious systemic symptoms may manifest in immunodeficient patients.

Interestingly, newer research found rodents and cats to be the most frequent sources of human infection [2].

Cowpox is a zoonotic disease, which is a disease transmitted by animals. Traditionally, infections were ascribed to direct contact with infected livestock, which is where the disorder's name stems from.

Causes

Cowpox is an infectious disease caused by the cowpox virus, a virus closely related to the vaccinia virus and to the smallpox virus. In fact, observations that people who had cowpox were immune to smallpox prompted Edward Jenner to perform the very first vaccination at the end of the 18th century.

Cows may develop ulcerative lesions on udder and teats, which is why dairy farmers have historically constituted the largest group of cowpox patients . However, most recent infections with cowpox have been associated with rodents and cats. Rodents may carry the virus without showing any symptoms, whereas cats often develop large skin ulcers.

Symptoms

One or more papules form on hands, arms and face a few days after infection. Other body regions may be affected if they were in direct contact with the diseased animal. Within a few days, these papules turn into fluid-filled blisters, which break easily, ulcerate, and are subsequently covered by a purple to black eschar. The surrounding skin may be reddened and swollen.

The disease is self-limiting, which means that dermatological lesions heal without treatment within approximately two months. Most frequently, ulcers heal without leaving scars.

More severe courses may be observed in patients with weak immune systems.

Diagnosis

The physician will ask questions regarding close contact with animals, particularly rodents, cats and cows.

Samples will be taken from blisters, wound fluid or eschar for examination under a microscope or an attempt to grow the virus in viral cultures.

Samples may be observed with a classical microscope or with an electron microscope which allows very high magnification and direct visualization of virus particles. Even though the findings of these exams may prompt a strong suspicion for cowpox, this diagnosis needs to be re-confirmed by applying molecular biological techniques for definitive identification of the virus.

Treatment

There is no specific treatment for cowpox. However, the vast majority of infections with cowpox virus is self-limiting and only supportive therapy is necessary. The latter may consist of wound hygiene, prevention, and possibly treatment of secondary bacterial infections. In moderate to severe cases, bed rest is indicated.

Wound dressings are recommended to avoid virus spread through infectious fluids, but human-to-human transmission has never been reported.

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