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A key aim in epidemiology is to understand how pathogens spread within their host populations. Central to this is an elucidation of a pathogen's transmission dynamics. Mathematical models have generally assumed that either contact rate between hosts is linearly related to host density (density-dependent) or that contact rate is independent of density (frequency-dependent), but attempts to confirm either these or alternative transmission functions have been rare. Here, we fit infection equations to 6 years of data on cowpox virus infection (a zoonotic pathogen) for 4 natural populations to investigate which of these transmission functions is best supported by the data. We utilize a simple reformulation of the traditional transmission equations that greatly aids the estimation of the relationship between density and host contact rate. Our results provide support for an infection rate that is a saturating function of host density. Moreover, we find strong support for seasonality in both the transmission coefficient and the relationship between host contact rate and host density, probably reflecting seasonal variations in social behavior and/or host susceptibility to infection. We find, too, that the identification of an appropriate loss term is a key component in inferring the transmission mechanism. Our study illustrates how time series data of the host-pathogen dynamics, especially of the number of susceptible individuals, can greatly facilitate the fitting of mechanistic disease models.

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.

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. 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. 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.

The transmission dynamics of the cowpox virus infection have been quantified in two mixed populations of bank voles (Clethrionomys glareolus) and wood mice (Apodemus sylvaticus), through analyses of detailed time-series of the numbers of susceptible, infectious and newly infected individuals. The cowpox virus is a zoonosis which circulates in these rodent hosts and has been shown to have an adverse effect on reproductive output. The transmission dynamics within species is best described as frequency dependent rather than density dependent, contrary to the 'mass action' assumption of most previous studies, both theoretical and empirical. Estimation of a transmission coefficient for each species in each population also allows annual and seasonal variations in transmission dynamics to be investigated through an analysis of regression residuals. Transmission between host species is found to be negligible despite their close co-habitation. The consequences of this for the combining ability of hosts as zoonotic reservoirs, and for apparent competition between hosts, are discussed.

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.

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.

There have been virtually no studies of 'who acquires infection from whom' in wildlife populations, but patterns of transmission within and between different classes of host are likely to be reflected in the spatiotemporal distribution of infection among those host classes. Here, we use a modified form of K-function analysis to test for space-time interaction among bank voles and wood mice infectious with cowpox virus. There was no evidence for transmission between the two host species, supporting previous evidence that they act as separate reservoirs for cowpox. Among wood mice, results suggested that transmission took place primarily between individuals of the opposite sex, raising the possibility that cowpox is sexually transmitted in this species. Results for bank voles indicated that infected females might be a more important source of infection to either sex than are males. The suggestion of different modes of transmission in the two species is itself consistent with the apparent absence of transmission between species.