Derrick Baxby

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 viruss 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.

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

Potential use of non-replicating vectors as recombinant vaccines

Avipoxviruses, members of the Poxvirus family, are naturally restricted in that productive replication takes place only in avian species. Recent work has described the construction of Avipox recombinants using fowlpox and canarypox viruses. Preparation of recombinant fowlpox viruses which express immunogens from avian pathogens and successful vaccination of poultry have been reported. Recombinant fowlpox and canarypox viruses which express immunogens from mammalian pathogens have also been described and have been demonstrated to provide protective immunity on inoculation in non-avian species. This is a surprising result. Such non-replicating expression vectors provide the possibility of developing safe, effective vaccines which combine the advantages of killed and live vaccines.

Serological evidence for the reservoir hosts of cowpox virus in British wildlife

The reservoir host of cowpox virus in Western Europe is not known, but epidemiological evidence from human and feline infections indicates that the virus is probably endemic in small wild rodents. Therefore, serum and tissue samples were collected from a variety of wild British mammals and some birds, and tested for evidence of Orthopoxvirus infection. Antibody reacting with cowpox virus was detected in 9/44 (20%) bank voles (Clethrionomys glareolus), 8/24 (33%) field voles (Microtus agrestis), 17/86 (20%) wood mice (Apodemus sylvaticus) and 1/44 house mice (Mus musculus), but in no other animal species tested. Although virus was not isolated from any animal, this serological survey, together with other evidence, suggests that bank and field voles and wood mice are the main reservoir hosts of cowpox virus in Great Britain.

Selective decontamination of the digestive tract: 13 years on, what it is and what it is not

Selective decontamination of the digestive tract (SDD) is a prophylactic strategy designed to prevent or minimise the impact of both endogenous and exogenous infections by potentially pathogenic micro-organisms (PPM) in patients admitted to the intensive care unit (ICU). It was introduced in 1983 and has received considerable attention, especially in Europe, some of it favourable and some critical. By mid-1996, SDD had been assessed in 46 controlled trials and evaluated by various reviews. On balance, when properly used, SDD significantly reduces infectious morbidity, in particular respiratory tract infections by 65% and mortality by 20% [1, 2]. Despite being the best ever evaluated manoeuvre in intensive care medicine and one of the few interventions subjected to scientific and statistical appraisal, SDD is still controversial due to issues including the following: (a) five negative SDD trials, which are always mentioned in discussion, (b) the moderate irapact on mortality and (c) the fear of the emergence of antimicrobial resistance, despite the lack of any evidence after one decade [3]. However, our concern here is with those who have been disappointed with or even explicitly critical of SDD while at the same time failing to recognise the full SDD protocol or realise inherent limitations. Despite the need for precise definition of the terms used in describing and analysing SDD, there is still some ambiguity, to which we have unfortunately contributed. Here, we take the opportunity, provided by the 13th anniversary of the introduction of SDD, to clarify the definition in the hope that future ambiguity and confusion may be prevented.

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.

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.

An outbreak of cowpox in captive cheetahs: virological and epidemiological studies.

This paper describes virological and epidemiological features of an infection which killed two of three affected cheetahs at Whipsnade Park in 1977. Two animals had profuse skin lesions and the third had an acute haemorrhagic pneumonia. The outbreak was shown to be caused by cowpox virus. Cowpox virus is believed to circulate in small wild animals, but the source of infection was not traced despite virological and serological tests on 93 captive and 102 wild animals. Sub-clinical infections did not occur in susceptible contact cheetahs. Immune globulin did not influence the outcome and smallpox vaccine does not take in cheetahs. Management of any future outbreak will rely on prompt diagnosis and segregation of infected animals.

Edward Jenner's inquiry; a bicentenary analysis

Edward Jenners 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. Jenners claims were based on slender experimental evidence and some of the information presented was incomplete and misleading. However Jenners 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.