12:25am Thursday 02 April 2020

Cowpox virus: old friend but new foe

Despite the importance of cowpox in human medicine the virus has attracted relatively little attention and how the many forms of cowpox are related was until recently a matter of conjecture.  The issue has been clarified by a large international consortium headed by Darin Carroll at the Centers for Disease Control and Prevention in Atlanta, Georgia and including Jolanta Kolodziejek and Norbert Nowotny of the University of Veterinary Medicine, Vienna.  The scientists compared the complete genome sequences of twelve different isolates of the cowpox virus, using sophisticated computer methods to prepare a phylogeny or family tree of the various forms.

Their first finding was that “cowpox” may actually comprise a number of distinct species.  The researchers found a high degree of variation between samples, with the sequences clustering into five distinct “clades” or groups, each of which could be considered to represent a separate species.  This is in contrast to prevailing wisdom, which considers cowpox to be a disease with a single causative agent.  The second surprising finding was that the strains used in smallpox vaccines were most closely related to cowpox virus isolates from Russia, Finland and Austria rather than to samples from England.  This suggests that commercial smallpox vaccines were not derived from Jenner’s original strain but instead from somewhere in central or eastern Europe.

The last reported case of smallpox was in 1977 and in 1979 the World Health Organization declared that the disease had been eradicated.  To date, smallpox is the only human viral disease to have been fully eradicated.  Because smallpox is no longer a threat and because vaccination against it was occasionally associated with unpleasant side-effects, wide scale vaccination ceased in the early 1980s and fewer people are now immune to smallpox and related viruses, such as monkeypox and cowpox.  As a consequence, these diseases are increasingly recorded in man.  The incidence of monkeypox in the Democratic Republic of the Congo (the country with the most cases) has risen twenty-fold since the 1980s and 2003 saw a serious outbreak of the disease in the US.

As Jenner noted in the 18th century, the cowpox virus is also readily transmitted to man.  Despite its name, cowpox no longer occurs in cows but wild mice and voles represent a source of infection:  Nowotny cites a recent study in Austria that revealed that “about 1 in 6 mice carries the cowpox virus.  As a result, the virus can be transmitted to domestic cats (at least, to those that hunt mice) and we and others have shown that it can then be passed on to humans” and the decades since the cessation of vaccination have witnessed a significant rise in the incidence in humans.  The majority of cases stem from Great Britain (a nation of dog-lovers, perhaps, although cats are also popular pets) with the remainder restricted to Europe, apart from a single case in Israel.  The disease is unpleasant but not generally fatal, except in immunocompromised patients.  As Nowotny says, “diagnosis of cowpox is relatively straightforward – in humans as well as in animals – but it is important that doctors and vets consider the possibility when they see patients with lesions.”

The paper Chasing Jenner’s Vaccine: Revisiting Cowpox Virus Classification by Darin S. Carroll, Ginny L. Emerson, Yu Li, Scott Sammons, Victoria Olson, Michael Frace, Yoshinori Nakazawa, Claus Peter Czerny, Morten Tryland, Jolanta Kolodziejek, Norbert Nowotny, Melissa Olsen-Rasmussen, Marina Khristova, Dhwani Govil, Kevin Karem, Inger K. Damon and Hermann Meyer is published in the online journal PloS one (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023086).


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