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Cowpox virus (CPXV) has an animal reservoir and is typically transmitted to humans by contact with infected animals. In 2017, CPXV infection of a pregnant woman in France led to the death of her fetus. Fetal death after maternal orthopoxvirus (smallpox) vaccination has been reported; however, this patient had not been vaccinated. Investigation of the patient's domestic animals failed to demonstrate prevalence of CPXV infection among them. The patient's diagnosis was confirmed by identifying CPXV DNA in all fetal and maternal biopsy samples and infectious CPXV in biopsy but not plasma samples. This case of fetal death highlights the risk for complications of orthopoxvirus infection during pregnancy. Among orthopoxviruses, fetal infection has been reported for variola virus and vaccinia virus; our findings suggest that CPXV poses the same threats for infection complications as vaccinia virus.

Poxvirus (PXV) infections are a common cause of cutaneous signs. In France, certain forms of poxvirus are frequent and benign (molluscum contagiosum), while others are rare but potentially serious (cowpox virus [CPXV]). Whereas only smallpox and molluscum contagiosum viruses have a human reservoir and are transmitted between humans, most poxvirus infections are zoonoses having only animal reservoirs. Only a small number of poxviruses are responsible for infection in humans, but the increasing number of new pets, some of which are exotic, coupled with the rapid rise in international travel are creating a greater risk of transmission of zoonotic PXV to new vectors and of spread of these diseases to new regions throughout the world. In France, molluscum contagiosum, orf and milkers' nodule give rise to numerous consultations and are well known to dermatologists. However, dermatologists must also be able to identify other parapoxviruses of similar presentation to orf; thus, CPXV and monkeypox are considered potentially emergent viruses with a high risk of epidemic and spread due to increasing international transport and the loss of the maximum protection against smallpox. Finally, despite its declared eradication, smallpox is currently being monitored because of the potential risk of reintroduction, whether accidentally or deliberately through bioterrorism., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Competing interests: None declared.

Cowpox virus (CPXV) infection is a reportable and potentially zoonotic disease that occurs sporadically in a variety of animals. During the past six decades, CPXV infection has been extensively researched and described in both domestic (cat, dog, horse, cattle) and zoo animals (e. g. elephant, rhinoceros, okapi). Of note, a review of the literature produced only three reports of CPXV in individual or small groups of South American camelids. The goal of this review was to describe the current knowledge as it relates to clinical features of CPXV infection in South American camelids and to compare the clinical manifestations with those described in other animal species. In alpacas and llamas, virus transmission occurs via direct contact with infected animals or oronasal infection through microlesions in the skin and mucous membranes. In its mild form, the disease is limited to certain regions of the body (head, neck, extremities or perineal region) and characterised by pustules or crusts. CPXV infection can also cause generalised and frequently lethal disease with multifocal to diffuse skin lesions (papules, pustules, crusts, ulcers) accompanied by virus replication in other organs. Conjunctivitis, stomatitis and rhinitis are seen commonly together with nonspecific clinical signs, including anorexia, listlessness and fever. As in other poxvirus infections, factors leading to an immunosuppression may contribute to the development of the clinical ma -nifestation of CPXV infection. There appear to be no specific manifestations of CPXV infection in South American camelids. More research is needed to fully understand the pathogenesis and epidemio logy of CPXV infection, particularly in South American camelids., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Schattauer GmbH.)

We investigated the first laboratory-confirmed human case of cowpox virus infection in Russia since 1991. Phylogenetic studies of haemagglutinin, TNF-α receptor-like protein and thymidine kinase regions showed significant differences with known orthopoxviruses, including unique amino-acid substitutions and deletions. The described cowpox virus strain, taking into account differences, is genetically closely related to strains isolated years ago in the same geographical region (European part of Russia and Finland), which suggests circulation of viral strains with common origin in wild rodents without spread over long distances and appearance in other parts of the world.

Case Series Summary: This case series documents five cases of pneumonia (with pleural effusion in three cases) caused by cowpox virus (CPxV) in domestic cats. Predisposition to pneumonia may have resulted from mixed infections in two cases (feline herpesvirus and Bordetella bronchiseptica in one cat, and Mycoplasma species in the other)., Relevance and Novel Information: As well as diagnostic confirmation by previously described methods of virus isolation from skin lesions, and demonstration of pox virions in skin samples using electron microscopy and inclusion bodies in histological preparations, this is the first report of diagnosis by virus isolation from bronchoalveolar lavage fluid or pleural fluid, and demonstration of inclusion bodies in cytological preparations. This is also the first series to report treatment with interferon omega (IFN-ω). Two cats survived, both of which had been treated with IFN-ω. As CPxV represents a serious zoonotic risk it is an important differential diagnosis of pneumonia in cats., (© ISFM and AAFP 2015.)

Cowpox in humans is a rare zoonotic disease; its recognition is therefore problematic due to the lack of clinical experience. The differential diagnosis includes other poxvirus infections and also infections with herpesviruses or selected bacteria. The clinical course can be complicated and the improvement may take weeks. Late diagnosis is one of the causes of unnecessary combined antibiotic therapy or surgical intervention. A case of cowpox after a cat scratch in a 15-year-old girl is presented, with a summary of the available clinical data on cowpox infections.

Infection of non-human primates (NHPs) such as rhesus and cynomolgus macaques with monkeypox virus (MPXV) or cowpox virus (CPXV) serve as models to study poxvirus pathogenesis and to evaluate vaccines and anti-orthopox therapeutics. Intravenous inoculation of macaques with high dose of MPXV (>1-2×10(7) PFU) or CPXV (>10(2) PFU) results in 80% to 100% mortality and 66 to 100% mortality respectively. Here we report that NHPs with positive detection of poxvirus antigens in immune cells by flow cytometric staining, especially in monocytes and granulocytes succumbed to virus infection and that early positive pox staining is a strong predictor for lethality. Samples from four independent studies were analyzed. Eighteen NHPs from three different experiments were inoculated with two different MPXV strains at lethal doses. Ten NHPs displayed positive pox-staining and all 10 NHPs reached moribund endpoint. In contrast, none of the three NHPs that survived anticipated lethal virus dose showed apparent virus staining in the monocytes and granulocytes. In addition, three NHPs that were challenged with a lethal dose of MPXV and received cidofovir treatment were pox-antigen negative and all three NHPs survived. Furthermore, data from a CPXV study also demonstrated that 6/9 NHPs were pox-antigen staining positive and all 6 NHPs reached euthanasia endpoint, while the three survivors were pox-antigen staining negative. Thus, we conclude that monitoring pox-antigen staining in immune cells can be used as a biomarker to predict the prognosis of virus infection. Future studies should focus on the mechanisms and implications of the pox-infection of immune cells and the correlation between pox-antigen detection in immune cells and disease progression in human poxviral infection.

Clinical and epidemiological aspects of cats with cowpox in Germany from the years 2004 to 2010 are described and discussed. Questionnaires were sent to veterinarians and owners of affected cats identified with the help of a number of pathology laboratories. Of 69 mailed questionnaires, 45 veterinary and 26 owner questionnaires were returned and a total of 46 feline poxcases were evaluated. The cases were distributed all over Germany although there was an accumulation of cases in specific geographic areas. The clinical and epidemiological observations match those of other studies. The majority of cats were outdoor cats, came from a rural environment and developed clinical signs in late summer or autumn. All cats showed skin lesions which were predominantly localized on the anterior part of the body, 61% of the cats showed other clinical signs in addition to the skin lesions. Approximately half of the cats lived in a multi-pet household, but in only one case clinical signs typical for cowpox were observed in another cat of the household. In two cases a cat-to-human transmission was assumed. In addition, to evaluate the prevalence of pox virus infections in outdoor cats in areas with previous reports of such infections, 92 apparently unaffected outdoor cats were tested for orthopoxvirus antibodies using an indirect immunofluorescence assay. Sixteen (17%) of the tested serum samples were seropositive against orthopoxvirus (titre between 1:20 and 1:40).This is a higher serum prevalence than in previously published studies from Germany. A possible explanation is selection of a population of outdoor cats from regions with previous known clinical cases.

Cowpox virus infection of humans is an uncommon, potentially fatal, skin disease. It is largely confined to Europe, but is not found in Eire, or in the USA, Australasia, or the Middle or Far East. Patients having contact with infected cows, cats, or small rodents sporadically contract the disease from these animals. We report here clinical aspects of 8 patients from the Munich area who had purchased infected pet rats from a local supplier. Pet rats are a novel potential source of local outbreaks. The morphologically distinctive skin lesions are mostly restricted to the patients' necks, reflecting the infected animals' contact pattern. Individual lesions vaguely resemble orf or Milker's nodule, but show marked surrounding erythema, firm induration and local adenopathy. Older lesions develop eschar, leaving slow-healing, deep ulcerative defects after eschar separation. Severe flu-like illness may be present in the acute phase. Smallpox-vaccinated patients tend to develop less severe reactions and heal more quickly. The differential diagnosis may include other localized orthopoxvirus infections, herpes simplex, bacterial infection, anthrax, foreign body granuloma, and primary tuberculosis. Dermatologists should be aware of the diagnostic and therapeutic algorithms for handling this disease.

A pet rat derived cowpox virus strain, which was also the source of human infections, was used to infect young Wistar and fancy rats. After an incubation period of 6 days the animals developed a severe, often fatal disease with high amounts of virus detected in oropharyngeal secretions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The present report describes a case of generalized cowpox virus infection with necrotizing facial dermatitis in a cat and a likely transmission to an animal keeper. The viral aetiology was confirmed by histopathology, immunohistochemistry, PCR, virus isolation, DNA sequencing and electron microscopy. Histopathological examination of the cat's skin revealed a severe, necrotizing dermatitis with ballooning degeneration and hyperplasia of epithelial cells with pathognomonic cytoplasmic eosinophilic inclusion bodies. Additionally, at post-mortem examination, a systemic poxvirus infection was detected affecting pancreas, thymus, lymph node, liver and lung. The human patient's skin biopsy revealed an ulcerative dermatitis with epidermal hyperplasia and ballooning degeneration. Serological investigation displayed a high orthopoxvirus-specific antibody titre in the human patient. Environmental factors increase the natural reservoir host population for cowpox viruses, such as voles, which results in a higher risk of infection for cats and subsequently for humans. Due to this zoonotic potential, a cowpox virus infection must be considered as an aetiological differential in cases of necrotizing dermatitis in cats., (© 2011 The Authors. Journal compilation © 2011 ESVD and ACVD.)

Background: The number of recorded human cowpox cases are recently increasing. The symptoms caused by cowpox virus (CPXV) in a number of human cases are close to the symptoms characteristic of the orthopoxviral human infections caused by monkeypox or smallpox (variola) viruses. Any rapid and reliable real-time PCR method for distinguishing cowpox from smallpox and monkeypox is yet absent., Objectives: The aim of this study was to develop a quick and reliable real-time TaqMan PCR assay for specific detection of cowpox virus and to determine the sensitivity and specificity of this method., Study Design: Based on aligned nucleotide sequences of orthopoxviruses, we found a virus-specific region in the CPXV genome and selected the oligonucleotide primers and hybridization probe within this region. The specificity of the developed method was tested using a panel of various orthopoxvirus (OPV) DNAs. The sensitivity was determined using the recombinant plasmid carrying a fragment of CPXV DNA and genomic DNA of the CPXV strain GRI-90., Results: The analytical specificity of this method was determined using DNAs of 17 strains of four OPV species pathogenic for humans and amounted to 100%. The method allows 6 copies of plasmid DNA and 20 copies of CPXV DNA in the reaction mixture to be detected., Conclusion: A quick and reliable TaqMan PCR assay providing for a highly sensitive and specific detection of CPXV DNA was developed., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

A 40-year-old Asian circus elephant developed mouth and trunk ulcers. Three weeks later, her 19-year-old animal warden noticed a vesicle on his forearm, evolving into a scab. Identical cowpox strains were isolated from lesions of the elephant and the warden. Cowpox virus could no longer be isolated after the scab disappeared, but PCR still revealed orthopox DNA. Healing was complete seven weeks later, leaving a 1 cm scar., (Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this article is to make physicians of all specialties aware of the possible variations of clinical course in human cowpox infection. This has been a matter of current interest since the detection of a first cluster of infections among owners of white pet rats in the Krefeld area in the spring of 2008. Two further cases arose in the Krefeld area in November 2008, and there have since been multiple further reports from various regions in Germany and the neighboring countries., Method: The authors report on the first six documented cases of infection with cowpox virus among young persons owning pet rats, with both typical and atypical clinical courses., Results: The clinical, molecular biological, and serological findings confirmed cowpox virus infection in all six cases. The DNA sequence of the cowpox virus hemagglutinin gene was identical in all patients. The infections had arisen after direct contact with pet rats., Conclusions: Molecular genetic analysis of the cases described here suggests that the observed occurrence of cowpox virus infection among human beings and pet rats in multiple geographical areas represents a unitary epidemiological event that has not yet come under control. Further cases can be expected.

The authors report three human cases of cowpox infection, among farm workers who were manually milking infected cows, in the microregion of Itajubá, Minas Gerais. The diagnostic techniques used were: isolation of samples similar to the vaccinia virus, from skin lesion secretions; polymerase chain reaction; electronic microscopy; and antibodies for Orthopoxvirus in the patients' blood.

A 21-year-old immunocompetent woman developed a cowpox infec-tion,while working as a veterinarian's assistant in a rural area. She had never received vaccinia immunization and came in contact with a fatally-infected house cat. Under symptomatic treatment, the infection remained localized to one cheek and cleared over 3 weeks with substantial dermal-subcutaneous tissue destruction. Orthopoxvirus detection by PCR is a modern diagnostic standard, in addition to identification by negative-contrast electron microscopy. A promising therapeutic option is cidofovir, but this virostatic drug is not yet approved for the treatment of cowpox.

Infections with orthopoxviruses usually lead to cross-protection among all species of the family. This has been a prerequisite for successful eradication of smallpox. Here we report the rare case of a 17-year-old male, who survived a generalised cowpox virus infection of unusual severity but surprisingly did not show a proper seroconversion. Only a very weak antibody production was observed in early and late serum samples, which initially appeared to be cowpox virus specific in immunofluorescence. No neutralising antibodies were detected and in Western blotting antibody specificity was restricted to the orthopoxvirus H3L protein only. The patient had been hospitalised for alcohol and cannabis intoxication 2 months prior to the orthopoxvirus infection and high levels of cannabinoids have been found repeatedly in the urine and upon one occasion also benzodiazepines. As these substances are known to interfere with antibody production and no immunodeficiencies were detected, drug-induced immunosuppression can be suspected as the most likely cause. Therefore a possible link between "soft" drug use and sufficient immunosuppression to warrant alterations in vaccine policies using live virus vaccines like smallpox vaccine should be further studied.

Background: Several poxviruses can infect humans and cause diseases of varying severity. Besides the eradicated Variola virus that induced high mortality rates, numerous further human pathogenic orthopoxviruses are potentially fatal but generally cause less severe infections. While infection-related viremia was described for Variola virus and seems to be rare for Monkeypox virus, it is still debated for Vaccinia virus. So far, viremia in Cowpox virus-infected humans has not been reported., Objectives: To estimate the potential risk of Cowpox virus to disseminate and develop severe infections, two Cowpox virus patients were examined for viremia., Study Design: Whole blood, serum and fluid from virus-induced lesions were analyzed by serology or quantitative real-time PCR., Results: Real-time PCR and sequence analysis of the hemagglutinin gene confirmed Cowpox virus in the lesions of both patients. Serology performed on serum obtained at the same time as the lesion specimens demonstrated orthopoxvirus-specific IgG and IgM antibodies, indicating a recent orthopoxvirus infection. In addition, Cowpox virus DNA was detectable in whole blood, but not in serum, as late as week 4 post-infection., Conclusions: In contrast to observations following vaccination with Vaccinia virus, DNAemia in patients with localized symptoms of a Cowpox virus infection does not seem to be a rare event. However, its relevance for Cowpox virus pathogenicity has to be elucidated.

Concurrent infection with cowpox and feline parvovirus was diagnosed in a 5-month-old male European Short Hair cat. Microscopical examination of the facial skin, ears and foot pads revealed multifocal to coalescing, ulcerative to necrotizing dermatitis and panniculitis with ballooning epidermal degeneration and eosinophilic cytoplasmic inclusion bodies. Immunohistochemistry, polymerase chain reaction testing and virus isolation confirmed infection with a strain of cowpox virus similar to that isolated from a cat in Germany 5 years previously. Lymphoid tissues were depleted and there was catarrhal enteritis caused by feline parvovirus as confirmed by immunohistochemistry and in-situ hybridization. This co-infection did not result in a more severe and rapid course of the poxvirus-associated disease.

We describe a patient with facial cellulitis/erysipelas due to cowpox virus inoculation in the respiratory epithelium of the nose. A cytopathic agent was isolated in cell culture, and the diagnosis of cowpox was confirmed by electron microscopy and polymerase chain reaction. The most likely source of infection was exposure to the family cats. 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. Hyperbaric oxygen treatment was provided to prevent development of dermal necrosis. The healing process in the numerous areas of lymphadenitis was markedly protracted, and 1 persisting node (which yielded positive results on polymerase chain reaction) had to be excised 2 years after onset of disease. This is the first reported case of inoculation of cowpox virus in the respiratory mucosa of the nose. It resulted in a clinical course totally different than that for inoculation in the skin. We also present a short review of findings on orthopoxvirus infection that focuses on the chain of transmission.