Khan, 39, hailed as a "national hero" by the health ministry, had been moved to a treatment ward run by the medical charity Médecins Sans Frontières in the far north of Sierra Leone.
He died on Tuesday afternoon, less than a week after his diagnosis was announced, and on the same day that the president, Ernest Bai Koroma was due to visit his treatment centre in the north-eastern town of Kailahun.
"It is a big and irreparable loss to Sierra Leone as he was the only specialist the country had in viral haemorrhagic fevers," said the chief medical officer, Brima Kargbo.
The west African airline Asky has suspended flights to and from Sierra Leone and Liberia as concern over the spread of the virus has increased since the first death was reported last week in Nigeria's coastal city of Lagos, home to 21 million people.
Togo-based Asky said it would no longer take on food in Guinea, where the outbreak was first identified. It said passengers leaving the Guinean capital, Conakry, would be checked for signs of the disease before departure. The airline added that medical teams would be deployed to screen passengers in transit through its Lome hub. The Lagos victim was a Liberian who travelled to Nigeria on Asky via Lomé.
Nigeria's largest carrier, Arik Air, has suspended flights to Liberia and Sierra Leone because of the Ebola risk.
The fatality rate of the current outbreak is around 60%, although the disease can kill up to 90% of those who catch it.
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