J. Med. Microbiol. - Vol.
45 (1996), 157-158
0 1996 The Pathological Society of Great Britain and Ireland
ED IT0 R IA L
cowpox
On 14 May 1796, Edward Jenner inoculated James
Phipps, an 8-year-old boy, with cowpox material
obtained from a lesion on a local dairy maid, Sarah
Nelmes. Two months later, Phipps was inoculated with
smallpox lesion material but did not develop smallpox.
Although earlier accounts of cowpox, and even
vaccination, exist, it was Jenner’s Inquiry, of 1798
[l], together with his Further Observations [2]
published the following year, that contained the first
thorough descriptions of bovine and human cowpox.
These reports formed the basis for our understanding of
the natural history of cowpox for much of the
following two centuries, and only since the mid-
1970s has this traditional view of cowpox, as an
endemic disease of cattle, been challenged.
Cowpox virus has been isolated only in Europe and
some contiguous regions of Western Asia [3]. Clinical
bovine infection is rare [4, 51: the prevalence of
Orthopoxvirus antibody in British cattle is only 0.7%
[6], and we are not aware of any virologically
confirmed bovine cases in the UK since 1976.
Furthermore, human infections can only rarely be
traced to contact with cattle, infected or otherwise
[4,7]. In contrast, pseudocowpox (also known as
milker’s nodule or paravaccinia), caused by a Para-
poxvirus very closely related to orf virus of sheep, is
endemic world-wide in cattle, and human infection is
an occupational disease of farm workers [S].
Over the last 20 years, evidence has accumulated that
the reservoir hosts of cowpox virus are wild rodents,
with infection endemic in different species in different
areas of its geographic range. In Turkmenia, ground
squirrels (Citellus fulvus) and giant gerbils (Rhomb-
omys opimus) appear to be the reservoir hosts, based
on serology and virus isolation [9, 101. In Eastern
Europe, virus has also been isolated from root voles
(Microtus oeconomus) [ll], while in the UK and
western continental Europe, Orthopoxvirus antibody
has been detected in bank voles (Clethrionomys
glareolus), field voles (Microtus agrestis) and wood-
mice (Apodemus sylvaticus) [ 12- 141. Although cow-
Correspondence should be sent to: Dr M. Bennett, Depart-
ment of Veterinary Clinical Science and Animal Husbandry,
University of Liverpool, PO Box 147, Liverpool L69 3BX.
pox virus has not been isolated from any rodent
species in Western Europe, bank and field voles and
woodmice are susceptible to very low doses of virus
by skin and oronasal inoculation, and bank voles are
resistant to infectious ectromelia, the other main
Orthopoxvirus of rodents (unpublished observations).
Experimentally infected voles and woodmice develop
little obvious clinical disease, and the mechanisms of
transmission in wild and captive populations of the
reservoir hosts are being studied currently. Antibody
studies in the UK, where cowpox is the only reported
Orthopoxvirus, are relatively easy to interpret, but in
central Europe, where other, antigenically similar,
orthopoxviruses may circulate [151, identification of
the responsible virus can be difficult.
Felids are also susceptible to cowpox. Clinical
infection is most frequently diagnosed in the domestic
cat [16, 171, but several outbreaks have also occurred
in other cat species held in European zoological
collections [18]. Affected domestic cats often have a
history of a single original lesion, sometimes de-
scribed as a bite-like wound, on the head or a
forelimb, but widespread secondary skin lesions
resulting from a cell-associated viraemia have usually
developed by the time that the cat is presented for
veterinary attention [ 161. During the viraemic period,
large amounts of virus can also be isolated from the
lungs and turbinates of infected cats, although clinical
respiratory disease is rare. Most affected domestic cats
come from rural areas, are known to hunt rodents, and
are seen in the autumn: all features consistent with
transmission from a rodent host while hunting. Cat-to-
cat transmission can occur, but is rare, and serological
surveys confirm that cats are not a reservoir host of
cowpox.
One or two cases of human cowpox are reported each
year in the UK, and there is only a low prevalence of
Orthopoxvirus antibody, even though smallpox vacci-
nation might be expected to cause ‘false’ positive
results. The clinical and epidemiological features have
recently been reviewed [7]. There is usually a single
lesion at the site of inoculation, most often on a hand
or on the face. Multiple inoculations sometimes occur,
and immunocompromised patients may exhibit more
widespread lesions. Most affected individuals are
systemically ill, and around one-third are admitted to
158 EDITORIAL
hospital. Rare fatal cases have been described [19].
Over half of all recent cases have been traced to
contact with an infected cat [7], but the virus is
probably not very infectious to man, and cat-to-man
transmission can be readily avoided by basic hygienic
precautions. Like feline cowpox, the human disease is
most frequently seen in the autumn, probably reflect-
ing the incidence of feline cases and the size and
activity of rodent populations. Immunisation with
smallpox vaccine is unlikely to protect against
infection and the development of a primary lesion,
but may prevent the development of more severe
cowpox [20]. Thus, the decline in Orthopoxvirus
immunity after the cessation of smallpox vaccination
is unlikely to affect the incidence of human cowpox.
Cowpox has also been described in various zoo
animals including elephants, rhinoceroses, anteaters,
okapis and white rats [3, 101. One case in a pet dog
has been described [17]. Serological surveys of foxes
(Vulpes vulpes) in the UK, and some Benelux
countries have revealed no evidence of infection in
foxes [14], but surveys in central Europe have
detected a low prevalence of relatively low titre
antibody [21]. These differences may reflect the
different assays used, or variation in the host ranges
of virus strains. Experimentally, foxes are susceptible
to skin inoculation only with very high doses of a
British strain of cowpox virus [22], but little work has
been done to compare the host range and virulence of
geographically distinct cowpox viruses. A Russian
isolate appeared to be much more pathogenic for
domestic cats than British isolates [23], and cowpox
viruses are known to differ in both biological proper-
ties (such as ceiling temperature of growth, haemag-
glutinin production and heat inactivation) and
restriction maps. Isolates from the extremes of the
geographic range (i.e., British and Turkmenian strains)
show the greatest variation. The largest variety of
strains in any one area is found in central Europe,
suggesting a central European origin for cowpox virus.
Cowpox virus is not the only Orthopoxvirus with a
rodent reservoir. Monkeypox is endemic in squirrels
(Funisciurus spp. and Heliosciurus spp.) in West and
Central Africa [24]; in the western USA an Ortho-
poxvirus circulates in wild voles (Microtus californi-
cus) [25]. Uncharacterised poxviruses occur in other
rodents, and the reservoir hosts of several orthopox-
viruses, for example buffalopox [26], are unknown.
Thus cowpox, as well as being of interest in its own
right, may provide a useful, and accessible, model for
understanding the epidemiology of other orthopox-
viruses, some of which, like cowpox, are zoonotic.
M. BENNETT and D. BAXBY*
Departments of Veteiinary Clinical Science and
Animal Husbandry and Medical Microbiology and
Genitourinary Medicine,
University of Liverpool, PO Box 147, Liverpool L69 3BX
References
1. Jenner E. An inquiry into the causes and effects of the variolae
vaccinae, a disease discovered in some of the western countries
of England, particularly Gloucestershire, and known by the
name of the cowpox. London, Sampson Low. 1798.
2. Jenner E. Further observations on the variolae vaccinae or
cowpox. London, Sampson Low. 1799.
3. Baxby D, Bennett M. Cowpox virus. In: Webster RG, Granoff
A (eds) Encyclopedia of virology, vol 1. London, Academic
Press. 1994: 261-267.
4. Baxby D. Is cowpox misnamed? A review of 10 human cases.
BMJ 1977; 1: 1379-1381.
5 . Gibbs EPJ, Johnson RH, Collings DF. Cowpox in a dairy herd
in the United Kingdom. Vet Rec 1973; 92: 56-64.
6. Baxby D, Osborne AD. Antibodies in natural bovine cowpox.
J Hyg 1979; 83: 425448.
7. Baxby D, Bennett M, Getty B. Human cowpox 1969-93; a
review based on 54 cases.‘Br J Dermatol 1994; 131: 598407.
8. Baxby D, Bennett M. Poxvirus zoonoses. J Med Microbiol
1996 (in press).
9. Marennikova SS. Field and experimental studies of poxvirus
infections in rodents. Bull World Health Organ 1979; 57: 461-
464.
10. Marennikova SS, Shelukhina EA, Efremova El! New outlook
on the biology of cowpox virus. Acta Virol 1984; 57: 437444.
11. Lvov SD, Gromashevskyi VL, Marennikova S S et al. Poxvirus
isolation from Microtus oeconomus Pal. 1776 in Colsky
peninsula. Vopr Virus01 1988; 1: 92-94.
12. Kaplan C, Healing TD, Evans N, Healing L, Prior A. Evidence
of infection by viruses in small British field rodents. J Hyg
1980; 84: 285-294.
13. Crouch AC, Baxby D, McCracken CM, Gaskell RM, Bennett
M. Serological evidence for the reservoir hosts of cowpox
virus in British wildlife. Epidemiol Znfect 1995; 115: 185-191.
14. Boulanger D, Crouch A, Brochier B et al. Serological survey
of Orthopoxvirus infection in wild mammals in Belgium and
assessment of the risk of hybridisation between recombinant
vaccinia virus and wild orthopoxviruses in the field. Vet Rec
1996 (in press).
15. Mahnel H, Holejsovsky J, Bartak P, Czerny C-P. [Congenital
‘ectromelia’ in fir-bearing animals caused by Orthopoxvirus
muris.] Kongenitale ‘Ektromelie’ bei Pelztieren durch Ortho-
poxvirus muris. Tierarztl Prax 1993; 21: 469-172.
16. Bennett M, Gaskell CJ, Baxby D, Gaskell RM, Kelly DF,
Naidoo J. Feline cowpox viruses infection. J Small Anim Pract
1990; 31: 167-173.
17. Bomhard D, von Pfleghaar S, Mahnel H. Zur Epidemiologie,
Klinik, Pathologie und Virologie der Katzen-Pocken-Infektion.
Kleintierpraxis 1992; 37: 2 19-230.
18. Baxby D, Ashton DG, Jones DM, Thomsett LR. An outbreak
of cowpox in captive cheetahs: virological and epidemiological
studies. J Hyg 1982; 89: 365-372.
19. Czerny C-P, Eis-Hubinger AM, Mayr A, Schnewies KE, Pfeiff
B. Animal poxviruses transmitted from cat to man: current
event with lethal end. Zentralbl Veterinarmed 1991; 38: 421-
431.
20. Baxby D. Indications for smallpox vaccination: policies still
differ. Vaccine 1993; 11: 395-396.
21. Henning K, Czerny C-P, Meyer H, Muller T, Kramer M. A
seroepidemiological survey for orthopox virus in the red fox
(Vulpes vulpes). Vet Microbiol 1995; 43: 251-259.
22. Boulanger D, Brochier B, Crouch A et al. Comparison of the
susceptibility of the red fox (Vulpes vulpes) to vaccinia -
rabies recombinant virus and to cowpox virus. Vaccine 1995;
13: 215-219.
23. Zhukova OA, Tsanava SA, Marennikova SS. Experimental
infection of domestic cats by cowpox virus. Acta Virol 1992;
36: 329-331.
24. Khodakevich L, Jezek Z, Kinzanzka K. Isolation of monkey-
pox virus from wild squirrel infected in nature. Lancet 1986;
1: 98-99.
25. Regnery DC. Isolation and partial characterization of an
Orthopoxvirus from a California vole (Microtus calijornicus).
Arch Virol 1986; 94: 159-162.
26. Dumbell K, Richardson M. Virological investigations of
specimens from buffaloes affected by buffalopox in Mahar-
ashtra State, India, between 1985 and 1987. Arch Virol 1993;
128: 257-267.