[Zoonotic vaccinia in Colombia: Cumulative evidence of the emergence of poxviruses in the world]. / Vaccinia zoonótica en Colombia: evidencia acumulativa de la emergencia de los poxvirus en el mundo.

The recent occurrence of vaccinia virus infections in humans and animals in Colombia, together with that reported for this and other species of the genus Orthopoxvirus in some South American, African, Asian and European countries, is supporting evidence of the emergence and re-emergence of the genus. This fact has become of great interest for public health around the world due to its biological and an epidemiological features, as was in the past the variola virus, one of its representatives. The emergence and re-emergence of the genus Orthopoxvirus may be a consequence of stopping vaccination against the variola virus in the 1970s and 1980s. This vaccination unsuspectedly induced cross-protective immunity to other species of that genus. This is a review of the history, biology and epidemiology of the main species of the genus Orthopoxvirus, together with its clinical presentation, social context and public health impact in the past, present and future.

La reciente ocurrencia de infecciones por el virus vaccinia en animales y humanos en distintos lugares de la geografía colombiana, sumadas a otras por éste y por otros virus pertenecientes al género Orthopoxvirus (familia Poxviridae), ocurridas en algunos países de Suramérica, África, Asia y Europa se convierten en evidencia de la inminente emergencia y re-emergencia de este género, con características biológicas y epidemiológicas que le confieren gran interés para la salud pública del mundo, como lo fue en el pasado una de sus especies representativas: el virus de la viruela. Esta emergencia y re-emergencia parecen estar relacionadas con la suspensión en las décadas de los 70s y 80s de las campañas de vacunación contra la viruela, las cuales; insospechadamente estuvieron protegiendo a la población, no únicamente contra este virus, sino contra otros del mismo género. En el presente artículo se hace una revisión de la biología y epidemiología de los principales miembros del género Orthopoxvirus, su presentación clínica, antecedentes históricos, contexto social, e impacto en la salud pública mundial en el pasado, presente y a futuro.

Therapy and short-term prophylaxis of poxvirus infections: historical background and perspectives.

The era of antiviral chemotherapy started more than 50 years with the findings by Domagk and his colleagues that thiosemicarbazones showed activity against vaccinia virus. One of the derivatives, methisazone, was even investigated in the prophylaxis of smallpox. With the successful implementation of the smallpox vaccine, the use of methisazone was not further pursued. Should there be a threat of smallpox or other poxvirus infections, that could not be immediately controlled by vaccination, a therapeutic intervention could be envisaged based on several therapeutic strategies targeted at such cellular enzymes as IMP dehydrogenase, SAH hydrolase, OMP decarboxylase and CTP synthetase, as well as viral enzymes such as the DNA polymerase. Most advanced as a therapeutic or early prophylactic modality to tackle poxvirus infection is cidofovir, which was found active (i) in vitro against all poxviruses studied so far; (ii) in vivo, against vaccinia and cowpox virus infections in experimental animal models; as well as (iii) some human poxvirus infections, such as molluscum contagiosum. In case of an inadvertent poxvirus epidemic, antiviral therapy (i.e. with cidofovir) will offer the possibility to provide short-term prophylaxis, or therapy. Cidofovir should also allow to treat severe complications of vaccination as may happen in for example immunosuppressed patients.

[Smallpox and smallpox virus--200 years since the first vaccination in Norway]. / Kopper og koppevirus--200 år siden første vaksinasjon i Norge.

In December 1801, the first vaccination against smallpox in Norway took place. Vaccine material came from Denmark, England, Ireland, and other countries; it was also obtained from a few local cowpox cases. What mattered was the effect, not the origin. Several reports indicate that variola virus itself, the cause of smallpox, was also used for human vaccination after passages through cows and horses. A vaccine institute for production of vaccine in calves was established in Kristiania in 1891. Cowpox was once a rare disease in cattle, but a total of 70,985 bovine cases were reported between 1889 and 1928. The source of infection was thought to be humans vaccinated against smallpox. Pox-like diseases were also registered in horses, pigs, sheep, goats and dogs at that time. Compulsory vaccination continued in Norway until 1976; smallpox is now eradicated. During the last decades, however, cowpox virus infections have re-emerged among zoo animals, domestic cats and humans in Western Europe, with small wild rodents and shrews as wildlife reservoirs. Vaccinia virus is also met with new interest as a vector in recombinant vaccines. Given the fact that the human population no longer has immunity against orthopoxviruses and the new possible exposure through pets and wildlife, it may be appropriate to reflect on poxvirus history in Norway in the light of the present situation.

Adventures with poxviruses of vertebrates.

Because they were the largest of all viruses and could be visualised with a light microscope, the poxviruses were the first viruses to be intensively studied in the laboratory. It was clear from an early date that they caused important diseases of humans and their domestic animals, such as smallpox, cowpox, camelpox, sheeppox, fowlpox and goatpox. This essay recounts some of the early history of their recognition and classification and then expands on aspects of research on poxviruses in which the author has been involved. Studies on the best-known genus, Orthopoxvirus, relate to the use of infectious ectromelia of mice as a model for smallpox, embracing both experimental epidemiology and pathogenesis, studies on the genetics of vaccinia virus and the problem of non-genetic reactivation (previously termed 'transformation') and the campaign for the global eradication of smallpox. The other group of poxviruses described here, the genus Leporipoxvirus, came to prominence when the myxoma virus was used for the biological control of Australian wild rabbits. This provided a unique natural experiment on the coevolution of a virus and its host. Future research will include further studies of the many immunomodulatory genes found in all poxviruses of vertebrates, since these provide clues about the workings of the immune system and how viruses have evolved to evade it. Some of the many recombinant poxvirus constructs currently being studied may come into use as vaccines or for immunocontraception. A field that warrants study but will probably remain neglected is the natural history of skunkpox, raccoonpox, taterapox, yabapox, tanapox and other little-known poxviruses. A dismal prospect is the possible use of smallpox virus for bioterrorism.

Historical vignette: a life with poxviruses and publishers.

Although I started science investigating the physical anthropology of Australian aboriginals and then spent six years in the Australian Army during the 1939-45 war, largely working on malaria control, the poxviruses have been the focal point of my research--at the bench, in the field, on committees, and in front of my word processor. I have had a relatively short period as a scientist at the bench, just over twenty years out of the sixty years since I graduated. For the last thirty years the pipette has been replaced by the pen and the word processor, and contacts with publishers have become an important element in my life. My pilgrim's progress, from mousepox through myxomatosis to vaccinia and then smallpox, has been helped by what can only be described as good luck, coming in many guises. I have been fortunate in many ways; in my father and mother and the genes and family life they gave me; in my wife, who was an immense source of support until her death in 1995; in the people whom I met during the Second World War; and in my close association with three great scientists, Macfarlane Burnet, René Dubos, and Howard Florey. I had the good fortune to be appointed, as a young and inexperienced virologist, to one of the best research jobs in the world, as a professor in the Australian National University. I have been very lucky in having had the opportunity to exploit a series of scientific gold mines; in turn, malaria, during the War, then mousepox, an unexploited virus because its use was forbidden in the United States, then, after a brief flirtation with mycobacteria, myxomatosis, an unparalleled natural experiment of evolution in action, and finally the most impressive achievement in public health in world history, the global eradication of smallpox. My last job in the University before retirement provided me with the opportunity to do something about the most important problems confronting humankind: the degradation of the environment, driven by the explosion in human numbers and their ever-growing use of resources. Each of these activities has provided opportunities to establish and maintain close friendships with scientists all over the world.

Mousepox (infectious ectromelia): past, present, and future.

Mousepox is an orthopoxvirus infection of mice that was discovered in laboratory mice in England in 1930. Depending upon mouse genotype, it may produce a severe disease with acute hepatitis and high mortality, a generalized rash in animals that survive longer, or a trivial inapparent infection. It has long been enzootic in breeding stocks of mice in Europe, Japan, and China but not in North America and Australia. However, it has been imported into the USA on several occasions, sometimes causing severe epizootics. It may contaminate or replace various viruses that are passaged in mice and may be transferred between mouse stocks in intact mice or in mouse tumors or tissues. Vaccination with vaccinia virus provides protection and has been used to eradicate virus from mouse colonies. Depopulation and sterilization of infected animal quarters my be required.