The epidemic of the extremely powerful strain of small pox that swept Foula, in the Shetland Isles, wiped out more than 90 per cent of its population in 1720.
It is said that only six people were left on the island to bury the dead, such was the devastation it caused.
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No one has been quite sure how small pox ended up on Foula, but shipwrecked sailors are known to have transmitted the deadly illness in other cases.
Foula's remote location - it sits almost 30 miles to the west of the Shetland mainland - meant that there was no immunity to the disease at all.
Hard winters and lack of food are also thought to have been contributing factors to the ferocity of its effect.
The death rates on Foula hasve been compared to those experienced by Native Americans who were afflicted with smallpox, given the complete lack of resistance to the illness.
Vomiting blood, stomach haemorrhage and blood poisoning were the hallmarks of the disease.
After the epidemic, the island was repopulated with people from the Shetland mainland.
It has been speculated that this shift in population was to fundamentally alter the way of life on Foula.
In 1884, the Glasgow Herald reported: "The Norse language, it is said, lingered longer in Foula than in any other island in Shetland, and I conjecture that the visitation of small-pox, which in 1720 almost destroyed the whole population, was the means of changing the tongue, as the vacuum caused by the epidemic was filled up by a rush of immigrants from the mainland.
"To this terrible scourge may also be attributed the paucity of old traditions. The best memories probably perished."
The disease returned to the island in 1760 and a period of inoculation was introduced but the high fee of two or three guineas, only ten or twelve people took it up.
Nine years later 1769, the disease spread again but a higher uptake of inoculation slowed down the death rate.
Locals conjured up their own protections from the disease. In Shetland, John Williamson - described in accounts as a 'jack of all trades' - is said to have treated thousands of people.
"Williamson claimed that his technique was to dry smallpox scabs over a peat fire and bury them from seven or eight years before using them to inoculate patients," one account said.
In 1853, the Vaccination Act made the inoculation of young babies against small pox compulsory.
The Scotsman, three years later, reported on the struggle to get islanders of Foula complying with the immunisation programme, with parents to pay half a Crown to get their children protected.
The report described angry scenes as mothers accused the registrar and medical officer of being "robbing swindlers ....for seeking half a crown for scratching their bairns".
The report added: "The officials confess that they were never so hard put all their lives , and were thankful that the brawny arms of the furies , which were brandished disagreeably close to their noses , were not used in ducking them in the loch."
Around 40 people live on Foula today.