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Cowpox virus is considered to be a re-emerging zoonotic pathogen and a public health threat due to increasing numbers of cases in humans and animals in Europe over the past decade, including within the United Kingdom (UK). We present epidemiological data and diagnostic features of 27 recent, naturally occurring cowpox cases in zoo and wild animals across the UK, including the first reports of cowpox in two snow leopards (Panthera uncia), a Bengal tiger (Panthera tigris tigris), three Chilean pudus (Pudu puda), a Malayan tapir (Tapirus indicus) and a Eurasian otter (Lutra lutra), and the first reports of Orthopoxvirus infection in a lar gibbon (Hylobates lar), a Southern tamandua (Tamandua tetradactyla) and an aardvark (Orycteropus afer). This study provides a detailed overview of cowpox infections in a wide range of non-domestic animal species, presents a range of methods for diagnosis and demonstrates the value of retrospective analysis of pathology surveillance in revealing epidemiological links., (Copyright © 2023 University of Liverpool, UK. Published by Elsevier Ltd.. All rights reserved.)

Cowpox viruses (CPXVs) exhibit the broadest known host range among the Poxviridae family and have caused lethal outbreaks in various zoo animals and pets across 12 Eurasian countries, as well as an increasing number of human cases. Herein, we review the history of how the cowpox name has evolved since the 1700s up to modern times. Despite early documentation of the different properties of CPXV isolates, only modern genetic analyses and phylogenies have revealed the existence of multiple Orthopoxvirus species that are currently constrained under the CPXV designation. We further chronicle modern outbreaks in zoos, domesticated animals, and humans, and describe animal models of experimental CPXV infections and how these can help shaping CPXV species distinctions. We also describe the pathogenesis of modern CPXV infections in animals and humans, the geographic range of CPXVs, and discuss CPXV-host interactions at the molecular level and their effects on pathogenicity and host range. Finally, we discuss the potential threat of these viruses and the future of CPXV research to provide a comprehensive review of CPXVs.

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.

Cowpox virus (CPXV), genus Orthopoxvirus , family Poxviridae , is a zoonotic pathogen in Eurasian wild rodents. High seroprevalences have been reported previously for vole and murine species in Europe. In contrast, viral DNA was only rarely detected, and very few reservoir-derived CPXV isolates exist. In this study, CPXV DNA and CPXV-reactive antibodies were monitored in wild small mammals for 5 years in four German federal states. Screening of liver tissues of 3966 animals by CPXV real-time PCR (qPCR) revealed five voles of two species positive for CPXV DNA. Two positive bank voles ( Myodes glareolus ) and two positive common voles ( Microtus arvalis ) originated from two plots in Baden-Wuerttemberg. One positive bank vole originated from Mecklenburg-Western Pomerania. None of the small mammals from Thuringia and North Rhine-Westphalia was positive in the qPCR. CPXV antigen-based indirect immunofluorescence assays of 654 highly diluted chest cavity fluid samples detected two bank voles and two common voles from the same sites in Baden-Wuerttemberg to be highly seroreactive. Five animals were CPXV DNA positive, and four other animals were orthopoxvirus seropositive. Our study indicates both a very low prevalence and a patchy occurrence of CPXV in common and bank voles and absence in other rodent and shrew species in Germany. The multiple detection of infected voles at one site in Baden-Wuerttemberg and continued detection in a region of Mecklenburg-Western Pomerania classify these regions as potential endemic foci.

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.)

Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012-2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been described in South American camelids (SACs) only three times, all four herds were investigated to gain a deeper understanding of CPXV epidemiology in alpacas. The different herds were investigated twice, and various samples (serum, swab samples, and crusts of suspicious pox lesions, feces) were taken to identify additionally infected animals. Serum was used to detect CPXV-specific antibodies by performing an indirect immunofluorescence assay (iIFA); swab samples, crusts, and feces were used for detection of CPXV-specific DNA in a real-time PCR. In total, 28 out of 107 animals could be identified as affected by CPXV, by iIFA and/or PCR. Herd seroprevalence ranged from 16.1% to 81.2%. To investigate the potential source of infection, wild small mammals were trapped around all alpaca herds. In two herds, CPXV-specific antibodies were found in the local rodent population. In the third herd, CPXV could be isolated from a common vole ( Microtus arvalis ) found drowned in a water bucket used to water the alpacas. Full genome sequencing and comparison with the genome of a CPXV from an alpaca from the same herd reveal 99.997% identity, providing further evidence that the common vole is a reservoir host and infection source of CPXV. Only in the remaining fourth herd, none of the trapped rodents were found to be CPXV-infected. Rodents, as ubiquitous reservoir hosts, in combination with increasingly popular alpacas, as susceptible species, suggest an enhanced risk of future zoonotic infections., Competing Interests: The authors declare no conflict of interest.

Cowpox virus infections in captive cheetahs (Acinonyx jubatus) with high morbidity and mortality have already been reported in the UK and Russia in the 1970s. However, most of the reported cases have been singular events. Here, we report a total of five cowpox virus outbreaks in cheetahs in the same safari park in Denmark between 2010 and 2014. Nine cheetahs showed varying severity of clinical disease; two of them died (22%). All episodes occurred between August and October of the respective year. No other carnivores kept at the same institution nor the keepers taking care of the animals were clinically affected. The clinical picture of cowpox was confirmed by extensive laboratory investigations including histopathological and molecular analyses as well as cell culture isolation of a cowpox virus. High anti-orthopoxvirus antibody titers were detected in all 9 diseased cheetahs compared to seven contact cheetahs without clinical signs and 13 cheetahs not in direct contact. Additionally, whole genome sequencing from one sample of each cluster with subsequent phylogenetic analysis showed that the viruses from different outbreaks have individual sequences but clearly form a clade distinct from other cowpox viruses. However, the intra-clade distances are still larger than those usually observed within clades of one event. These findings indicate multiple and separate introductions of cowpox virus, probably from wild rodent populations, where the virus keeps circulating naturally and is only sporadically introduced into the cheetahs. Sero-positivity of voles (Arvicola amphibious) caught in zoo grounds strengthens this hypothesis. As a consequence, recommendations are given for medical and physical management of diseased cheetahs, for hygienic measures as well as for pre-shipment isolation before cheetah export from zoo grounds.

Buffalopox is a contagious viral disease affecting milch buffaloes (Bubalus Bubalis) and, rarely, cows. The disease has zoonotic implications, as outbreaks are frequently associated with human infections, particularly in the milkers. Buffalopox is associated with high morbidity (80%). The clinical symptoms of the disease are characterized by wartline lesions on the udder, teats, inguinal region, base of the ears, and over the parotid. In the severe form, generalized rash is observed. Although the disease does not lead to high mortality, it has an adverse effect on the productivity and working capacity of the animals resulting in large economic losses. The outbreaks of buffalopox occurred frequently in India, Pakistan, Bangladesh, Nepal, Iran, Egypt, and Indonesia, where buffaloes are reared as milch animals. The buffalopox is closely related with other Orthopoxviruses. In particular, it is close to the vaccinia virus. There is a view that the buffalopox virus might be derived from the vaccinia virus. It is possible that it became pathogenic to humans and animals through adaptive evolution of the genome by obtaining the virulence genes. PCR is performed for the C18L gene for the purpose of specific detection and differentiation of the buffalopox virus from other orthopoxviruses. The C18L gene encodes the ankyrin repeat protein, which determines the virus host range. The open reading frame of this gene is only 150-nucleotide long as against 453 nucleotide in the vaccinia virus, 756 - in the camelpox virus, and 759 - in the cowpox virus. It can be concluded that a systematic study based on the epidemiology of the virus, existence of reservoirs, biological transmission, and the molecular organization of the buffalopox virus from buffalo, cow, and humans may pave the way to a better understanding of the circulating virus and contribute to the control of the disease using the suitable diagnostic and prophylactic measures.

Vaccinia virus (VACV) has had an important role for humanity because of its use during the smallpox eradication campaign. VACV is the etiologic agent of the bovine vaccinia (BV), an emerging zoonosis that has been associated with economic, social, veterinary and public health problems, mainly in Brazil and India. Despite the current and historical VACV importance, there is little information about its circulation, prevalence, origins and maintenance in the environment, natural reservoirs and diversity. Brazilian VACV (VACV-BR) are grouped into at least two groups based on genetic and biological diversity: group 1 (G1) and group 2 (G2). In this study, we went to the field and investigated VACV clonal diversity directly from exanthemous lesions, during BV outbreaks. Our results demonstrate that the G1 VACV-BR were more frequently isolated. Furthermore, we were able to co-detect the two variants (G1 and G2) in the same sample. Molecular and biological analysis corroborated previous reports and confirmed the co-circulation of two VACV-BR lineages. The detected G2 clones presented exclusive genetic and biological markers, distinct to reference isolates, including VACV-Western Reserve. Two clones presented a mosaic profile, with both G1 and G2 features based on the molecular analysis of A56R, A26L and C23L genes. Indeed, some SNPs and INDELs in A56R nucleotide sequences were observed among clones of the same virus population, maybe as a result of an increased mutation rate in a mixed population. These results provide information about the diversity profile in VACV populations, highlighting its importance to VACV evolution and maintenance in the environment.

Cowpox virus (CPXV) was isolated from a fatal outbreak among cotton-top tamarins. Samples from healthy common marmosets in contact were also CPXV genome positive. The CPXV isolated from the cotton-top tamarins exhibited a unique hemagglutinin sequence. Pathogenicity investigations using a Wistar rat model characterized the isolate as low pathogenic.

We investigated 4 related human cases of cowpox virus infection reported in France during 2011. Three patients were infected by the same strain, probably transmitted by imported pet rats, and the fourth patient was infected by another strain. The 2 strains were genetically related to viruses previously isolated from humans with cowpox infection in Europe.

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.

Background: Cowpox virus is an Orthopoxvirus that can cause infections in humans and a variety of animals. Infections occur in Eurasia; infections in humans and animals have not been reported in the United States. This report describes the occurrence of the first known human case of laboratory-acquired cowpox virus infection in the United States and the ensuing investigation., Methods: The patient and laboratory personnel were interviewed, and laboratory activities were reviewed. Real-time polymerase chain reaction (PCR) and serologic assays were used to test the patient's specimens. PCR assays were used to test specimens obtained during the investigation., Results: A specimen from the patient's lesion tested positive for cowpox virus DNA. Genome sequencing revealed a recombinant region consistent with a strain of cowpox virus stored in the research laboratory's freezer. Cowpox virus contamination was detected in 6 additional laboratory stocks of viruses. Orthopoxvirus DNA was present in 3 of 20 environmental swabs taken from laboratory surfaces., Conclusions: The handling of contaminated reagents or contact with contaminated surfaces was likely the mode of transmission. Delays in recognition and diagnosis of this infection in a laboratory researcher underscore the importance of a thorough patient history-including occupational information-and laboratory testing in facilitating a prompt investigation and application of control and remediation measures.

Features of spread of cowpox in the contemporary conditions are examined. A decrease of population immunity to pox in the population of Russia caused by cancellation of pox immunization, hidden circulation of cowpox virus in various species of rodents, as well as lack of vigilance to pathogenic orthopoxviurses in healthcare workers were noted to create the real preconditions for the emergence of infection of humans caused by cowpox virus. Thereby presence of means of express laboratory diagnostics of cowpox and means of effective medical protection for the prevention of development of this disease in the population of Russia becomes an actual necessity.

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.

Cowpox virus (CPXV) was isolated from skin lesions of a llama on a farm in Italy. Transmission electron microscopy showed brick-shaped particles consistent with orthopoxviruses. CPXV-antibodies were detected in llama and human serum samples; a CPXV isolate had a hemagglutinin sequence identical to CPXV-MonKre08/1-2-3 strains isolated from banded mongooses in Germany.

Public health threats are increasingly triggered by events which span across international, national and state level jurisdictions. Innovative surveillance methods are needed to ensure adequate and timely response to such threats. In January 2009 the Department of Infectious Disease Epidemiology at the Robert Koch Institute (RKI) established a system of weekly telephone conferences with all competent authorities of the German federal states to identify, discuss and respond to infectious disease events in real-time. A regular and structured platform was developed for use between participants from state level public health authorities, the military and the RKI. During the first three quarters, 46 infectious diseases were covered, including mandatory reports of measles and meningococcal meningitis and outbreaks of cowpox, which does not have to be notified in Germany. Results of a targeted evaluation and a consistently high attendance rate both indicate that the teleconference has met additional needs for supplemental information exchange among participants. The telephone conference has proven to be a useful resource for rapid and direct communication, coordination and evaluation of signals for public health events in Germany.

Recent cowpox virus (CPXV) infections of humans in Europe transmitted from cats and pet rats have risen public awareness of this rare zoonosis. Based on serosurveys wild rodents are regarded as primary reservoir hosts. Cats can become infected while hunting and could therefore serve as a sentinel for CPXV strains circulating in wild rodents. In a retrospective study we analysed 73 formalin-fixed paraffin-embedded skin samples from cats with a histologically proven CPXV infection. Specimens had been collected in different parts of Germany during 2000-2008. Following DNA extraction part of the hemagglutinin gene was amplified and sequenced from 72 samples. A phylogenetic analysis was inferred resulting in a total of 21 different CPXV genetic variants. The geographic distribution was imposed on a map., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Often described as an extremely rare zoonosis, cowpox virus (CPXV) infections are on the increase in Germany. CPXV is rodent-borne with a broad host range and contains the largest and most complete genome of all poxviruses, including parts with high homology to variola virus (smallpox). So far, most CPXV cases have occurred individually in unvaccinated animals and humans and were caused by genetically distinguishable virus strains., Methodology/principal Findings: Generalized CPXV infections in banded mongooses (Mungos mungo) and jaguarundis (Herpailurus yagouaroundi) at a Zoological Garden were observed with a prevalence of the affected animal group of 100% and a mortality of 30%. A subsequent serological investigation of other exotic animal species provided evidence of subclinical cases before the onset of the outbreak. Moreover, a time-delayed human cowpox virus infection caused by the identical virus strain occurred in a different geographical area indicating that handling/feeding food rats might be the common source of infection., Conclusions/significance: Reports on the increased zoonotic transmission of orthopoxviruses have renewed interest in understanding interactions between these viruses and their hosts. The list of animals known to be susceptible to CPXV is still growing. Thus, the likely existence of unknown CPXV hosts and their distribution may present a risk for other exotic animals but also for the general public, as was shown in this outbreak. Animal breeders and suppliers of food rats represent potential multipliers and distributors of CPXV, in the context of increasingly pan-European trading. Taking the cessation of vaccination against smallpox into account, this situation contributes to the increased incidence of CPXV infections in man, particularly in younger age groups, with more complicated courses of clinical infections.

Recent studies have provided evidence that endemic pathogens may affect dynamics in animals. However, such studies have not typically considered that infected individuals might have a preceding underlying poor condition. We examined whether individuals in poor condition are more likely to become infected by an endemic pathogen, using as a system the dynamics of cowpox virus in field voles. With data from monthly sampled vole populations, a nested case-control study evaluated whether susceptible individuals with poorer condition had higher probabilities of contracting cowpox. The influence of condition was found to be considerable, especially for males. At times when a susceptible male with good body condition had a relatively low probability of becoming infected, a susceptible male with poor body condition was twice as likely to contract cowpox; if this male was also anaemic, the chances were almost quadrupled. We discuss the care needed when interpreting the findings of wildlife disease studies.

The seasonality of recurrent epidemics has been largely neglected, especially where patterns are not driven by forces external to the population. Here, we use data on cowpox virus in field voles to explore the seasonal patterns in wildlife (variable abundance) populations and compare these with patterns previously found in humans. Timing in our system was associated with both the number and the rate of recruitment of susceptible hosts. A plentiful and sustained supply of susceptible hosts throughout the summer gave rise to a steady rise in infected hosts and a late peak. A meagre supply more limited in time was often insufficient to sustain an increase in infected hosts, leading to an early peak followed by a decline. These seasonal patterns differed from those found in humans, but the underlying association found between the timing and the supply of susceptible hosts was similar to that in humans. We also combine our data with a model to explore these differences between humans and wildlife. Model results emphasize the importance of the interplay between seasonal infection and recruitment and suggest that our empirical patterns have a relevance extending beyond our own system.

We describe a cluster of cowpox virus (CPXV) infections in humans that occurred near Munich, Germany, around the beginning of 2009. Previously, only sporadic reports of CPXV infections in humans after direct contact with various animals had been published. This outbreak involved pet rats from the same litter.

In early 2009, four human cases of cowpox virus cutaneous infection in northern France, resulting from direct contact with infected pet rats (Rattus norvegicus), were studied. Pet rats, originating from the same pet store, were shown to be infected by a unique virus strain. Infection was then transmitted to humans who purchased or had contact with pet rats.

Summary: In histories of smallpox and vaccination, little attention has been paid to their progress in the southern latitudes. In this paper, I focus on the appearance of smallpox around Sydney Cove in 1789 and the introduction of cowpox (vaccine) to New South Wales in 1804. I demonstrate the connections, historical and virological, between the two events and examine the role of variolation in the spread of smallpox and in anticipating vaccination. I argue that imported "variolous matter," perhaps obtained in Cape Town, may have been the source of infection in the catastrophic epidemic among the Aborigines in 1789. I likewise examine the means by which vaccine was brought to Australia in relation to comparable initiatives around the Indian Ocean. I assess the significance of the early history of vaccination in Australia in relation to subsequent developments and as a remarkable demonstration of the global reach of the new prophylactic.

Detailed results on the dynamics of cowpox virus infection in four natural populations of the field vole, Microtus agrestis, are presented. Populations were sampled every 4 weeks (8 weeks in mid-winter) for 6 years. The purpose was to examine the relationships between overall or susceptible host abundance (N, S) and both the number of infected hosts (I) and the prevalence of infection (I/N). Overall, both I and I/N increased with N. However, evidence for a threshold abundance, below which infection was not found, was at best equivocal in spite of the wide range of abundances sampled. Cross-correlation analyses reflected annual and multi-annual cycles in N, I, S and I/N, but whereas N was most strongly correlated with contemporary values of I and I/N, in the case of S, the strongest correlations were with values 1 to 2 months preceding the values of I and I/N. There was no evidence for a 'juvenile dilution effect' (prevalence decreasing with abundance as new susceptibles flush into the population) and only weak evidence of a time-delayed effect of abundance on the number infected. We argue that these effects may occur only in systems with characteristics that are not found here. Transfer function analyses, which have been neglected in epidemiology, were applied. These models, with ln(S) as the input parameter, in spite of their simplicity, could be linked closely to conventional formulations of the transmission process and were highly effective in predicting the number infected. By contrast, transfer function models with ln(N) as the input parameter were less successful in predicting the number infected and/or were more complex and more difficult to interpret. Nonetheless, overall, we contend that while monitoring numbers susceptible has most to offer, monitoring overall abundance may provide valuable insights into the dynamics of infection.

A new outbreak of Vaccinia virus was observed in Southwest region of São Paulo State, Brazil. The disease was observed in four small dairy farms with manual milking. Lesions were detected in cattle and in humans previously vaccinated and not vaccinated against smallpox. Although several reports of Vaccinia virus outbreaks have been occurring in Brazil, it was not yet reported in this region. This outbreak reinforces the viral circulation in our country. The disease in persons previously vaccinated and not vaccinated against smallpox reinforces the absence of immunity, the risk to the human health, and the need for more epidemiologic and immunologic studies.

The physiological and immunological state of an animal can be influenced by current infections and infection history. Consequently, both ongoing and previous infections can affect host susceptibility to another parasite, the biology of the subsequent infection (e.g. infection length) and the impact of infection on host morbidity (pathology). In natural populations, most animals will be infected by a succession of different parasites throughout the course of their lives, with probably frequent concomitant infections. The relative timing of different infections experienced by a host (i.e. the sequence of infection events), and the effects on factors such as host susceptibility and host survival, can only be derived from longitudinal data on individual hosts. Here we review some of the evidence for the impact of co-infection on host susceptibility, infection biology and pathology focusing on insights obtained from both longitudinal studies in humans and experiments that explicitly consider the sequence of infection. We then consider the challenges posed by longitudinal infection data collected from natural populations of animals. We illustrate their usefulness using our data of microparasite infections associated with field vole (Microtus agrestis) populations to examine impacts on susceptibility and infection length. Our primary aim is to describe an analytical approach that can be used on such data to identify interactions among the parasites. The preliminary analyses presented here indicate both synergistic and antagonistic interactions between microparasites within this community and emphasise that such interactions could have significant impacts on host-parasite fitness and dynamics.

Purpose of Review: Human cowpox, a rare zoonotic infection, evokes a self-limited disease, except for immunocompromised and eczematous patients, particularly children, where it can become severe. The causative agent, cowpox virus, is distributed in Europe, west former USSR, and adjacent areas of Northern and Central Asia, with an increasing number of reports in Europe. The purpose of this paper is to review cowpox with an emphasis on its epidemiology and management., Recent Findings: Numerous reports of human cowpox affecting young people in Europe indicate that lack of smallpox vaccination, which has been abandoned since 1977, may render the population more vulnerable to cowpox virus. The ownership of wild and exotic animal pets is becoming more popular, and the range of recognized wild and domestic animal hosts is expanding,, Summary: Cowpox as a human emerging zoonotic hazard raises public health concerns as well as a question about the production of effective vaccine and antiviral agents.

1. Cowpox virus is an endemic virus circulating in populations of wild rodents. It has been implicated as a potential cause of population cycles in field voles Microtus agrestis L., in Britain, owing to a delayed density-dependent pattern in prevalence, but its impact on field vole demographic parameters is unknown. This study tests the hypothesis that wild field voles infected with cowpox virus have a lower probability of survival than uninfected individuals. 2. The effect of cowpox virus infection on the probability of an individual surviving to the next month was investigated using longitudinal data collected over 2 years from four grassland sites in Kielder Forest, UK. This effect was also investigated at the population level, by examining whether infection prevalence explained temporal variation in survival rates, once other factors influencing survival had been controlled for. 3. Individuals with a probability of infection, P(I), of 1 at a time when base survival rate was at median levels had a 22.4% lower estimated probability of survival than uninfected individuals, whereas those with a P(I) of 0.5 had a 10.4% lower survival. 4. At the population level, survival rates also decreased with increasing cowpox prevalence, with lower survival rates in months of higher cowpox prevalence. 5. Simple matrix projection models with 28 day time steps and two stages, with 71% of voles experiencing cowpox infection in their second month of life (the average observed seroprevalence at the end of the breeding season) predict a reduction in 28-day population growth rate during the breeding season from lambda = 1.62 to 1.53 for populations with no cowpox infection compared with infected populations. 6. This negative correlation between cowpox virus infection and field vole survival, with its potentially significant effect on population growth rate, is the first for an endemic pathogen in a cyclic population of wild rodents.

1. Little is known about the dynamics of pathogen (microparasite) infection in wildlife populations, and less still about sources of variation in the risk of infection. Here we present the first detailed analysis of such variation. 2. Cowpox virus is an endemic sublethal pathogen circulating in populations of wild rodents. Cowpox prevalence was monitored longitudinally for 2 years, in populations of field voles exhibiting multiannual cycles of density in Kielder Forest, UK. 3. The probability that available susceptible animals seroconverted in a given trap session was significantly positively related to host density with a 3-month time lag. 4. Males were significantly more likely to seroconvert than females. 5. Despite most infection being found in young animals (because transmission rates were generally high) mature individuals were more likely to seroconvert than immature ones, suggesting that behavioural or physiological changes associated with maturity contribute to variation in infection risk. 6. Hence, these analyses confirm that there is a delayed numerical response of cowpox infection to vole density, supporting the hypothesis that endemic pathogens may play some part in shaping vole cycles.

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.

The possible role of pathogens in rodent population cycles has been largely neglected since Elton's 'epidemic hypothesis' of 1931. To revisit this question, 12 adjacent, cyclic but out-of-phase populations of field voles (Microtus agrestis) in North East England were studied and the initial results are presented here. The prevalences of antibodies to cowpox virus and of clinical signs of Mycobacterium microti infection (vole tuberculosis) showed delayed (not direct) density dependence (with a lag of three to six months). This did not result from changes in population structure, even though there were such changes associated with the different phases of the cycle. The prevalences rose as vole numbers rose, and peaked as numbers declined. The apparent lag in the numerical response of infection prevalence to changes in host abundance is consistent with the hypothesis that diseases, singly or in combination, play a hitherto underestimated role in the dynamics of cyclic populations.

Background and Objective: In the last few years, outbreaks of an apparently specific dermatosis occurred during the months of late summer and early autumn in our locality. Our aim in this study was to reveal the underlying etiology of this dermatosis., Subjects and Methods: Sixty patients with the disease were studied clinically, epidemiologically, histopathologically, and ultrastructurally., Results: The results of all methods suggest that the dermatosis is most probably a human cowpox infection. Electron microscopy showed unenveloped cowpox virons., Conclusions: This apparently specific dermatosis is due to human cowpox infection. Future investigations will be needed to better define this important zoonosis frequently passed by cats to humans and carried by rodents.

Cowpox is an orthopoxvirus infection endemic in European wild rodents, but with a wide host range including human beings. In this longitudinal study we examined cowpox in two wild rodent species, bank voles Clethrionomys glareolus and wood mice Apodemus sylvaticus, to investigate the dynamics of a virus in its wild reservoir host. Trapping was carried out at 4-weekly intervals over 3 years and each animal caught was uniquely identified, blood sampled and tested for antibodies to cowpox. Antibody prevalence was higher in bank voles than in wood mice and seroconversion varied seasonally, with peaks in autumn. Infection was most common in males of both species but no clear association with age was demonstrated. This study provides a model for studying other zoonotic infections that derive from wild mammals since other approaches, such as one-off samples, will fail to detect the variation in infection and thus, risk to human health, demonstrated here.

Public attitudes towards animals are often contradictory. In developed countries where the problem of food security has been solved to a large degree, public concern is concentrated on food safety and animal welfare, along with a debate on the social status of both domestic and wild animals. Zoonoses are often the focal point of these concerns. In developing countries (which often have the greatest biodiversity), wildlife constitutes an uncontrollable source of often unknown zoonoses. The authors attempt to analyse the link between animals and public health. Special attention is given to the example of cowpox, a disease which has been recognised as a zoonosis for more than two centuries but the epidemiology of which has recently been rediscovered.

Five case reports on cowpox virus infections in cats, humans, and for the first time in a horse are presented. It becomes obvious that in most cases the diagnosis cowpox is suspected rather late, although fast and reliable diagnostic tools such as pathohistological examination and polymerase chain reaction are available. The threat of a zoonotic transmission mainly through cats is gaining importance. Although wild rodents have been claimed to be the reservoir and source for cowpox viruses in cats, very little is known about the epidemiology of cowpox virus. Based on the different genome organizations found in the German isolates, we conclude that various subtypes of cowpox virus are circulating in Germany at one time.

It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats.

We report the first isolation of cowpox virus from a domestic cat in Norway, and the first confirmed isolation of cowpox virus from a human case in Norway. These two Norwegian cowpox virus isolates, as well as two Swedish human isolates, were partially characterized and compared with each other and with cowpox virus Brighton and vaccinia virus strain Western Reserve. Restriction enzyme analysis of the genomes revealed differences between all six viruses examined, but suggested that the two Norwegian isolates are closely related, as are the two Swedish isolates. Restriction endonuclease digestion of genomic DNA demonstrated that one of the Swedish isolates and the two Norwegian isolates have larger genomes than vaccinia virus strain Western Reserve, but smaller than cowpox Brighton. All four Scandinavian isolates lacked a 72 base-pair region within the A-type inclusion body protein gene which is present in the prototype cowpox virus Brighton.

In 1994, a human and a feline case of cowpox virus infection appeared in the western part of Norway. Cowpox has not been diagnosed with certainty in Norway since the beginning of this century, when it was associated with the use of cowpox virus as a vaccine against smallpox. The human infection manifested as a spontaneously emerged, severe ulceration at the medial angle of the right eye in a 37-y-old woman, and developed into a relatively severe dermatitis. The ulcer healed slowly, leaving a scar. The feline infection was represented by a febrile, dehydrated and anorectic 6-months-old non-pedigree short-hair, with crater-like ulcers all over the body. After antibiotic and fluid therapy, revision of the skin lesions and amputation of a gangrenous toe, the cat recovered. Electron microscopy of the isolates and cultivation of virus on chorioallantoic membrane of chicken embryos confirmed the suspicion of cowpox virus infection.

Only few human cowpox/catpox infections have been reported until now. The diagnosis of bland localized infections may be missed, if this disease is not well known. However, early diagnosis of localized cowpox/catpox infections is important, since at least immunocompromised patients are at risk of potential lethal generalization similar to generalized variola vera. Using a typical case report, the characteristics of the disease, as well as the current aspects of epidemiology, diagnosis and therapy are summarized. The characteristic finding of intracytoplasmatic inclusion bodies by light microscopy can be demonstrated in a human biopsy-specimen for the first time and greatly facilitated the diagnosis.

Human cowpox is a rare but relatively severe infection of interest because of its links with Edward Jenner and the introduction of smallpox vaccine and, more recently, because of re-evaluation of the epidemiology of the infection. This indicates that cowpox is not enzootic in cattle, relegates the cow to a minor role, and emphasizes the importance of feline cowpox as a source of human infection and of wildlife as virus reservoirs. The evidence available suggests that the virus is of low infectivity for humans and should not become an increasing problem despite the cessation of smallpox vaccination and increasing numbers of immunocompromised individuals.