It is 30 years since the last recorded case of naturally acquired smallpox. The eradication of this terrible disease which caused the deaths of hundreds of millions over the centuries, could raise the possibility that cowpox virus, which played an important part in the fight against smallpox, could be taking advantage of the removal of its more virulent relative to cause some problems of its own. A recent report from Germany on case reports of cowpox poses the question of a link between the end of smallpox vaccination and an increase in human cowpox cases.
To look at the role of these two viruses in the history of medicine and immunology, we must go back to the eighteenth century to find Edward Jenner, cowpox and his fight against smallpox. Jenner, sometimes called the Father of immunology was born in Berkley Gloucester in 1746. He studied medicine in London before returning to Berkley to practice. Smallpox was a major cause of death at that time, particularly dangerous for children. Jenner developed a theory based on the folklore, what we would now call indigenous knowledge, that milkmaids who suffered the mild disease of cowpox never contracted smallpox. In 1796 he carried out an experiment on an eight-year-old boy, James Phipps, in which he collected pus from a cowpox pustule and inserted it into an incision on the boy’s arm. Phipps became immune to smallpox. Jenner described his findings in a paper submitted to the Royal Society in 1797, but found considerable resistance to his ideas, and was told that he needed more evidence. Jenner experimented on several other children, including his own 11-month-old son, and in 1798 the results were finally published. Jenner coined the word vaccine from the Latin ‘vacca’ for cow. Popular resistance to vaccination continued and a famous satirical cartoon of 1802 showed people who had been vaccinated sprouting cow’s heads.
The British Anti-Vaccination Society published this cartoon in 1802 to satirize Edward Jenner and "the Wonderful Effects of the New Inoculation."
The practice of immunization wasn’t entirely new. The process of variolation was developed in the 10th century in China and India. It involved taking pus from the pocks of someone suffering from smallpox and inoculating healthy people with it, to create a mild case of the disease and giving lifelong immunity afterwards. Variolation carried the risk of death from the infection, but at a time when smallpox was rife the odds made it worthwhile; about 0.5-2% may have died after variolation, compared with 20-30% after natural smallpox. Although, a major disadvantage of the practice was that variolated people could pass on severe smallpox to others.
Smallpox has been a scourge of humans for centuries. There was physical evidence of smallpox, a pustular rash, on the mummified body of Pharaoh Ramesses V of Egypt, who died in 1157 BC. The disease was taken by traders from Egypt to India during the 1st millennium BC, and from there it swept into China in the 1st century AD reaching Japan in the 6th century. Returning crusaders provided a way for smallpox to spread through Europe in the 11th and 12th centuries. Smallpox was particularly devastating when brought to new naive populations. The demise of the Aztec and Inca civilizations in the 16th century had as much to do with smallpox brought by the Spanish Conquistadors, as it did to their swords and guns. The native populations of North, South and Central Americas had no immunity to the disease, unlike the European colonists, and the disease swept through their populations. In the 18th century smallpox decimated the aborigines when it reached Australia, the last corner of the world to have previously escaped its ravages.
Smallpox was finally eradicated in the 1970s, with the last natural case recorded in a man in Somalia in 1977. In 1966 D. A. Henderson was appointed to lead the WHO, and he played an important role in the global campaign to eradicate smallpox. Henderson and his team developed a strategy of containment and surveillance. When an outbreak was identified a WHO team would arrive, vaccinate and isolate those who were ill and trace and vaccinate all their contacts. Effectively they ring-fenced the disease until it had no way of moving on to its next victim. The eradication teams also actively hunted down the disease, travelling with a ‘recognition card’ showing a baby with smallpox, to explain to people what the illness looked like. Rewards were offered to encourage reporting of cases.
The eradication of smallpox is one of the great achievements in medical history and one that the WHO can be truly proud. However, could the decline of immunity to the smallpox virus have an unfortunate (though relatively small) side effect? Cases of cowpox are rare in humans, but could the reduced resistance as a consequence of the end of smallpox vaccination let the cowpox virus in?
Cowpox virus, like the smallpox virus is a member of the genus Orthopoxvirus in the sub-family Chordopoxvirinae of the family Poxviridae. Cowpox is really misnamed as cattle are not the main hosts: it occurs predominantly in rodents. Cowpox virus has a broad host range and has been isolated from cats, dogs, elephants and humans as well as bovines. Genome sequence analysis has suggested that cowpox virus is closest to a hypothetical ancestral poxvirus from which other orthopoxviruses have evolved.
In a report in Eurosurveillance by A. Nitsche and G. Pauli a number of human cases of cowpox are described in Germany even though the disease does not appear to be present in German cattle. It seems that cats are the main culprits for spreading the disease to people. Patients usually show local exanthema on arms and legs or in the face, often in the area of the eyes, probably acquired as smear infections, and most cases have a pronounced lymphadenopathy. In addition to this, infected people often display influenza-like symptoms, headache, nausea and myalgia after an incubation period of between seven and 12 days. The disease can be very serious in immunosuppressed patients as they can develop lethal systemic disease that resembles a variola infection.
Orthopoxviruses in general can be detected by either electron microscopy or serology, but for a rapid differentiation between different orthopoxviruses it is best to use DNA sequencing. Other existing assays are based on RFLP analysis of PCR amplicons of various poxvirus genes, but are less informative and slower. There is no approved antiviral therapy against poxviruses currently available, so it is important that people who come into contact with animals that could be infected, especially cats with slow-healing skin lesions, are therefore advised to protect themselves. Hygienic procedures need to be followed (such as wearing gloves) when treating both animals and humans with cowpox.
There is more than 300 records on cowpox in the CAB Abstracts Database covering the virology of the virus, infections in cattle and its transmission to humans from cats, rodents and other animals.