Cowpox virus is an orthopoxvirus, a genus that also includes variola virus, the agent of smallpox, vaccinia virus, and monkeypox virus, now designated mpox. Despite its name, cowpox virus circulates primarily in wild rodents, with domestic cats serving as the most common bridge to human infection. In Europe, reported human cases have been sporadic and typically linked to contact with infected domestic animals, particularly felines that hunt rodents. The virus produces a localized infection at the site of inoculation, characterized by a lesion that progresses through macular, papular, vesicular, and pustular stages before crusting over, accompanied in many cases by fever, malaise, and painful swelling of the lymph nodes draining the affected region. Although most infections in immunocompetent individuals are self-limiting, the lesions can be extensive, slow to heal, and disfiguring, and severe or even fatal outcomes have been described in immunosuppressed patients.

The clinical course in the two Czech patients followed the classic pattern of orthopoxvirus infection but initially defied a precise etiological diagnosis. Both presented with vesiculopustular lesions on the shoulder, firm red swelling at the affected site, and regional lymphadenopathy. Laboratory workup revealed only low levels of inflammatory markers, a finding consistent with a viral rather than bacterial process. Initial microbiological investigations, however, were inconclusive. The patients were empirically treated with acyclovir, targeting a possible herpesvirus infection, and doxycycline, covering atypical bacterial pathogens, before being switched to symptomatic topical treatment once those agents failed to alter the course of disease. Over the following weeks, the lesions evolved into deep ulcers, a hallmark of cowpox that distinguishes it from the more superficial lesions of herpes or varicella-zoster infection, and eventually healed with scarring over a period of six to eight weeks.

The severity of the illness was underlined by the fact that one of the two patients required surgical excision of necrotic lymph nodes. Lymph node involvement in cowpox can be pronounced, and in some cases the draining nodes become so inflamed and necrotic that they mimic bacterial lymphadenitis or even malignancy. The need for surgical intervention in a young, otherwise healthy adult illustrates that cowpox, while rarely life-threatening in immunocompetent hosts, is far from a trivial infection. The prolonged healing time, the residual scarring, and the requirement for an operative procedure all contribute to a disease burden that clinicians in non-endemic regions may not anticipate when evaluating patients with unexplained vesiculopustular eruptions.

The epidemiological investigation quickly centered on the couple’s new pets. Four weeks before symptom onset, consistent with the typical incubation period for cowpox virus, the pair had purchased pet rats. Shortly afterward, all but one of the animals developed respiratory symptoms and died. Respiratory disease in rodents infected with cowpox virus is a recognized phenomenon, and die-offs in colonies of pet rats have been implicated in human cases elsewhere in Europe. The temporal association between the rats’ illness and the patients’ lesions, together with the localized inoculation-type lesions compatible with direct contact with the animals, raised strong suspicion of rat-associated transmission, although the source material notes that this link remains suspected rather than definitively proven through sequencing of virus from the animals themselves.

The laboratory odyssey that followed is perhaps the most instructive element of the report. Initial quantitative polymerase chain reaction testing for Orthopoxvirus DNA, performed on patient samples at the State Veterinary Institute, returned negative results. It was only almost a year later, when preserved specimens were reanalyzed at the Czech National Institute of Public Health, that cowpox virus DNA was detected in nearly all of the samples. This delayed confirmation speaks to several technical and systemic challenges. Orthopoxvirus qPCR assays vary in sensitivity depending on the specimen type, the stage of lesion evolution, and the viral load present. Swabs taken from crusted or healing lesions, or samples handled and stored under suboptimal conditions, can yield false negatives. Moreover, access to specialized orthopoxvirus diagnostics is limited in many European countries, particularly in settings where such infections have never been documented and where testing algorithms are not geared toward them.

The authors argue that these cases expose a critical gap at the interface of human medicine, veterinary medicine, and public health surveillance. Cowpox virus has a wide host range and circulates silently in wild rodent populations across Europe and parts of Asia. Human cases cluster where the reservoir intersects with domestic animals or, as suspected here, with the exotic pet trade. Pet rats have emerged as a recurring source of human infection in several countries, a development that tracks the growing popularity of fancy rats as companion animals. When a clinician in a country with no prior documented cases encounters a patient with an atypical pox-like lesion, cowpox rarely appears on the differential diagnosis, and laboratory infrastructure to confirm it may simply not be in routine use. The result, as this report demonstrates, can be a diagnostic delay measured in months.

The report also carries broader implications in the current era of renewed orthopoxvirus concern. The global mpox outbreaks of recent years have prompted many countries to expand orthopoxvirus testing capacity, and the Czech experience suggests that this capacity should be maintained and made broadly accessible rather than reserved for outbreak response. Distinguishing cowpox from mpox, varicella, disseminated herpes zoster, and other vesiculopustular conditions requires specific molecular diagnostics, and the public health response differs depending on the agent involved. Accurate identification matters not only for individual patient management but also for tracing potential sources, warning other people who may have been exposed to the same batch of animals, and monitoring whether the virus is establishing itself in new reservoir populations.

For clinicians, the practical lessons are concrete. A patient presenting with a hemorrhagic or ulcerating lesion that progresses through vesicular and pustular stages, accompanied by regional lymphadenopathy and only mild systemic symptoms, should prompt a careful occupational and recreational history, including contact with cats, rodents, and exotic pets. Travel history, contact with animals that have died, and the presence of similar illness in household animals are all relevant clues. When orthopoxvirus infection is suspected, collecting material from fresh vesicular lesions and coordinating directly with the reference laboratory can substantially improve the chances of a positive molecular result. Serological methods and additional molecular targets may be needed when initial PCR testing is negative but clinical suspicion remains high.

The Czech cases ultimately tell a story of successful resolution despite systemic friction. Both patients recovered, their lesions healed with scarring, and retrospective testing secured a laboratory diagnosis that had eluded the initial workup. But the authors emphasize that the delayed diagnosis resulted from limited access to appropriate diagnostic testing, and they call for improved laboratory diagnostics and closer collaboration among clinicians, microbiologists, public health authorities, and veterinary professionals. As the exotic pet trade continues to bring wild-derived pathogens into close contact with humans, and as orthopoxviruses command renewed global attention, the experience in the Czech Republic stands as a reminder that rare infections become inevitable somewhere, and that preparedness depends on the unglamorous work of maintaining diagnostic capacity and communication across disciplines before the first case arrives.

Subject of Research: Zoonotic cowpox virus infection transmitted from pet rats to two human patients in the Czech Republic

Article Title: First human cowpox infections in the Czech Republic: suspected transmission from pet rats

Article References: Dzupova, O., Jirincova, H., Gkalpakiotis, S., Bohac, P., Pierzynova, A., & Bartos, H. (2026). First human cowpox infections in the Czech Republic: suspected transmission from pet rats. Virology Journal. https://doi.org/10.1186/s12985-026-03312-0

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03312-0

Keywords: cowpox virus, Orthopoxvirus, zoonotic infections, pet rats, Czech Republic, qPCR diagnostics, vesiculopustular lesions, lymphadenopathy, One Health, virology, case report, public health