MicrobiologyBytes

Human disease attributable to variola virus (VARV), the etiologic agent of smallpox, has been reported in human populations for more than 2,000 years. VARV is unique among orthopoxviruses in that it is an exclusively human pathogen. Because it has a large, slowly evolving DNA genome, researchers were able to construct a phylogeny of VARV by analyzing single nucleotide polymorphisms (SNPs) from genome sequences of 47 VARV isolates with broad geographic distributions. The results reveal two primary VARV clades, which are likely to have diverged from an ancestral African rodent-borne variola-like virus either 16,000 or 68,000 years before present (YBP), depending on which historical records (East Asian or African) are used to calibrate the molecular clock. One primary clade was represented by the Asian VARV major strains, the more clinically severe form of smallpox, which spread from Asia either 400 or 1,600 YBP. The other primary clade included both alastrim minor, a phenotypically mild smallpox described from the Americas, and isolates from West Africa. This clade diverged from an ancestral VARV either 1,400 or 6,300 YBP.
Observations of smallpox-typical skin rashes on Egyptian mummies dating from 1100 to 1580 B.C. gave credibility to theories that ancient Egypt was an early (and perhaps the earliest) smallpox endemic region. However, smallpox researchers noted that “The most striking thing about smallpox is its absence from the books of the Old and New Testaments, and also from the literature of the Greeks and Romans. Such a serious disease as variola major is very unlikely to have escaped a description by Hippocrates if it existed.” Historical records from Asia describe evidence of smallpox-like disease in medical writings from ancient China (1122 B.C.) and India (as early as 1500 B.C.). The earliest unmistakable description of smallpox first appears in the 4th century A.D. in China, the 7th century A.D. in India and the Mediterranean, and the 10th century A.D. in southwestern Asia. These early Asian descriptions could indicate that pandemic smallpox originated in East Asia. Sequence analysis indicates that divergence between VARV and rodent poxviruses occurred from 16,000 YBP to 68,000 YBP, and that VARV seems to have evolved from a pathogen of African rodents and subsequently spread out of Africa.
On the origin of smallpox: Correlating variola phylogenics with historical smallpox records
PNAS USA 2007 104:15787-15792

What does this all mean?

• In spite of concerns about bioterrorism, smallpox is no longer a major human pathogen, but understanding the origin of this disease, which has been of major importance for most of human history, offers glimpses into how we might rapidly understand new emerging diseases as they appear.
• For a long time it has been generally believed the the most probable origin for smallpox virus was in Asia, but as with yellow fever and HIV, this new research seems to show that smallpox originally came out of Africa.

Bluetongue is a highly infectious virus disease of ruminants. Cattle and goats are major hosts of the virus, but in these species infection is usually asymptomatic despite high virus levels, allowing the disease to circulate in the absence of any symptoms. Sheep and deer are usually the only species to exhibit symptoms of infection. Bluetongue infections are marked by a high fever, excessive salivation, swelling of the face and tongue and cyanosis of the lips and tongue (turning blue). Infected animals become lame and listless. Ulcers appear around the mouth, nose and eyes. Then the neck may start to swell, followed by the head. The animal becomes lame, starts bleeding internally and breathing becomes difficult. The incubation period for bluetongue is 5-20 days. The mortality rate is normally low, but infected animals lose condition and there is a high mortality rate of 70% or more in susceptible breeds of sheep (due to secondary bacterial infections). While infected animals can recover, productivity is reduced with milk yields in dairy herds dropping by about 40%.

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Bluetongue virus (BTV) is a Reovirus of the genus Orbivirus. The virus is transmitted by midges, in particular Culicoides imicola and a few other species. Of more than 1,400 species of midges known world-wide, only around 20 culicoid species are known to be involved in transmission of bluetongue virus. Bluetongue can also be transmitted directly from one animal to another through semen and transplacentally. Bluetongue occurs in Australia, the USA, Africa, the Middle East, Asia and Europe, generally between latitudes 35°S and 50°N. It occurs around the Mediterranean in summer, subsiding when temperatures drop in winter. In Europe the disease has been spreading north since October 1998, possibly as a result of climate change. In August 2006 bluetongue spread to the Netherlands, then Belgium, Germany, Holland, and Luxembourg. The first ever case of bluetongue in the UK was reported in Suffolk on 23rd September 2007. On 28th September 2007 Defra confirmed that bluetongue is now endemic in the UK.

Unlike foot and mouth disease, bluetongue cannot be controlled by culling of infected livestock alone. Since midges form a reservoir of infection in endemic areas, you would also need to kill all the midges to eradicate the disease. Another complication is there are at least 24 distinct serotypes of the virus (based on the lack of cross neutralisation). Vaccination against one serotype does not usually confer protection against any of the other serotypes. The antigenic diversity of Bluetongue virus is due to both antigenic drift (accumulation of point mutations) and antigenic shift (reassortment of individual gene segments). The virus which has affected northern Europe and the UK is known as BTV8.

Live attenuated BTV vaccines containing a weakened form of the live virus are cheap, easy to produce and can be administered in a single dose. They are effective in controlling clinical outbreaks of bluetongue. However, the disadvantages of attenuated BTV vaccines are:

• Risk of reassortment with virulent wild viruses which potentially could give rise to new virulent strains.
• Potential for reversion to virulence both in the vertebrate host and in vector insects.
• Attenuated BTV can cross the placenta and pregnant ruminants vaccinated with attenuated vaccines may suffer foetal loss.
• Existing vaccines are designed for sheep; there is little data on their safety and effectiveness in other species.

There have been attempts to develop inactivated (killed) whole virus vaccines for BTV for the past 25 years, but none have yet been produced commercially. Inactivated vaccines are they more expensive to produce than attenuated vaccines and also require at least two doses with an adjuvant to generate a protective immune response. Bluetongue virus is not usually contagious for humans, and meat and dairy products pose no hazard. However, there is some concern over the potential spread via blood from infected people.

Bluetongue: Latest News

Related:

• Will bluetongue come to the UK on the wind in 2007?
• Sheep virus ‘low risk to the UK’

• 23rd September: A suspected new case of foot-and-mouth is being investigated on the Hampshire-West Sussex border. Bluetongue is confirmed on a farm in Suffolk.

• 21st September: Another case of foot-and-mouth disease was confirmed on a farm in the Egham area of Surrey. Around 40 cattle were culled on the premises, which are within the existing 3km protection zone.

• 18th September: Defra confirms fifth infected premises since the start of the outbreak.

• 14th September: Defra announces that a second farm in Surrey is affected, imposes new protection and surveillance zone and confirms that sequencing tests of the virus have shown it to be type 01 BFS67, the same strain of virus responsible for the August outbreak.

• 12th September: Defra confirms a new case of FMD in Surrey.

• 8th September: The last restrictions imposed on livestock movement in the UK following the foot-and-mouth disease outbreak were lifted, but the earliest the UK can achieve international foot-and-mouth disease-free status is 7th November.

• August 2007: On 3rd August Defra confirmed an outbreak of foot and mouth disease on a farm near Guildford in Surrey. Defra confirmed that the FMDV strain found in Surrey is most similar to strains used in international diagnostic laboratories and in vaccine production, including at the Pirbright site shared by the Institute of Animal Health (IAH) and Merial Animal Health Ltd, a pharmaceutical company. The present indications are that this strain is an O1 BFS67-like virus, isolated in the 1967 Foot and Mouth Disease outbreak in Great Britain. This strain is present at the IAH and was used in a batch manufactured in July 2007 by the Merial facility. On a precautionary basis Merial has agreed to voluntarily halt vaccine production. Defra confirms a second case of foot and mouth on a farm within the 3km protection zone. Between 50 and 100 cows on the affected farm have been culled. As expected, the Health and Safety Executive’s initial report concludes that “there is a strong probability that the FMDV strain involved in the farm outbreak originated from the IAH or the Merial sites”. The letter to the Minister says “There is no reason to prevent the Institute for Animal Health from operating providing that all the usual biosecurity protocols are followed rigorously” but that “The situation regarding Merial is less clear cut, and I would advise that further work be done before any operations involving live pathogens are restarted. As the report indicates there are doubts about the integrity of the drainage system, including pipe work which leads to the final effluent treatment plant”. The report also says “Release by human movement must also be considered a real possibility. Further investigation of the above issues is required and is being urgently pursued”. Chief veterinary officer Debby Reynolds told a news conference she had ordered livestock on a third farm in Surrey to be culled on suspicion the disease may have spread.

Defra: Interactive map

10 Facts About Foot and Mouth Disease:

1. Foot-and-mouth disease (FMD) is a highly infectious disease of hoofed animals (ungulates) such as cattle, sheep, goats and pigs. It can also infect elephants, rats, and hedgehogs.
2. The symptoms of FMD are fever followed by the development of vesicles (blisters) chiefly in the mouth and on the feet.
3. Affected animals suffer weight loss from which they do not recover for several months, and in cows milk production can decline significantly. Although most animals eventually recover from FMD the disease can be fatal, especially in newborn animals.
4. Foot and mouth disease is caused by a Picornavirus.
5. FMD has an incubation period of 2-14 days before symptoms appear. The virus can survive in dry faecal material for 14 days in summer, in slurry for six months in winter, in urine for 39 days and on the soil for up to 28 days.
6. Some infected animals remain asymptomatic carriers of FMD which can transmit the disease to other animals.
7. The last major outbreak of foot and mouth disease in the UK in 2001 led to the slaughter of between 6.5 to 10 million animals and is estimated to have cost the country up to £8.5 billion.
8. The United States, Canada, Australia, Japan, Indonesia and Korea are currently free of FMD, but the disease is present in Eastern Europe, Asia, Africa and South America.
9. Vaccination against FMD is difficult because there are seven serotypes of the virus and a vaccine for one serotype does not protect against any others. Vaccination only provides temporary immunity. Defra Decision Tree for Disease Control Strategies against FMD
10. Humans can be infected with foot-and-mouth disease through close contact with infected animals, but this is extremely rare and human infections are not fatal. Because the virus that causes FMD is sensitive to stomach acid, it cannot spread to humans via consumption of infected meat or milk.