A longitudinal study of an endemic disease in its wildlife reservoir: cowpox and wild 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.

Transmission dynamics of a zoonotic pathogen within and between wildlife host species.

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 cohabitation. The consequences of this for the combining ability of hosts as zoonotic reservoirs, and for apparent competition between hosts, are discussed.

Cowpox: reservoir hosts and geographic range.

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.

Edward Jenner's Inquiry; a bicentenary analysis.

Edward Jenner's famous Inquiry was published 200 years ago. Probably few now know on what evidence he based his claims but most will be aware that they initiated controversy which to some extent still continues. This paper briefly reviews the Inquiry, analysing its merits and faults. Jenner's claims were based on slender experimental evidence and some of the information presented was incomplete and misleading. However Jenner's role in the introduction of vaccination was seminal and others could only test and extend his ideas. His reputation as the initial promoter of vaccination is justified.

The effect of cowpox virus infection on fecundity in bank voles and wood mice.

Although epidemic infectious diseases are a recognized cause of changes in host population dynamics, there is little direct evidence for the effect of endemic infections on populations. Cowpox virus is an orthopoxvirus which is endemic in bank voles (Clethrionomys glareolus), wood mice (Apodemus sylvaticus) and field voles (Microtus agrestis) in Great Britain. It does not cause obvious signs of disease nor does it affect survival, but in this study we demonstrate experimentally that it can reduce the fecundity of bank voles and wood mice by increasing the time to first litter by 20-30 days. The pathogenic mechanisms causing this effect are at present not known, but this finding suggests that natural subclinical infection could have a considerable effect on the dynamics of wild populations.

Cowpox in British voles and mice.

Serosurveys indicate that bank voles, field voles and woodmice are probably reservoir hosts of cowpox virus in western Europe, although virus has not yet been isolated from these species. In this study, bank voles, field voles, woodmice and laboratory mice were shown to be susceptible to combined intradermal and subcutaneous inoculation with 3-20 plaque-forming units (pfu) of cowpox virus. Bank and field voles, but not laboratory mice, were also susceptible to combined oral and nasal inoculation with 50 pfu. Few clinical signs were seen and virus was generally recovered only from inoculation sites. Bank voles were not susceptible to injection of ectromelia virus (5000 pfu) into the skin (as described above). These results provide information on which further pathogenesis and transmission studies can be based, and support the view that the orthopoxvirus antibody detected in British wild voles and woodmice indicates infection with cowpox virus. However, further investigation of the pathogenesis of cowpox in these species is needed to understand better the epidemiology of the disease.

Cowpox: a re-evaluation of the risks of human cowpox based on new epidemiological information.

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.

The Jenner bicentenary: the introduction and early distribution of smallpox vaccine.

This review describes the background to Jenner's first vaccination, his later work, and the dissemination of information about vaccination and the vaccine itself. Although based on relatively slender evidence, Jenner's theories were basically sound and he merits the credit given him. Given the circumstances, particularly the slow speed of travel and the lack of information about the duration of immunity, vaccination became established very quickly in many countries.