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The World Health Organization said one case of hantavirus infection had been confirmed, with five more suspected cases under investigation.
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It reported one confirmed and five suspected cases aboard the MV Hondius ship, which was travelling from Argentina to Cape Verde.
One UK national aged 69 is in intensive care in Johannesburg, South Africa. Local officials told the BBC he had the virus. The UK Foreign Office told the BBC it was monitoring reports, and ready to support British nationals.
Hantavirus is usually passed to humans from rodents via their faeces, saliva or urine. It can cause severe respiratory illness. Rarely, it can be transmitted between people.
The MV Hondius is run by tour company Oceanwide Expeditions.
According to an itinerary on its website, MV Hondius departed from Ushuaia in southern Argentina on 20 March and completed its journey on 4 May in Cape Verde, where it is anchored outside the capital, Praia.
It is described as a 107.6m (353ft) polar cruise ship, with space for 170 passengers in 80 cabins, along with 57 crew members, 13 guides and one doctor.
Foster Mohale, a spokesperson for South Africa's health ministry, told the BBC there were about 150 tourists from various countries aboard the vessel.
Before the WHO confirmation of three deaths, Mohale told the BBC that at least two people had died.
He said the man, aged 70, and the woman, aged 69, were a Dutch couple.
The health official said the man suddenly became ill, developing fever, headache, abdominal pain and diarrhoea. He died on arrival on the island of St Helena, a British territory in the South Atlantic.
The woman also became ill on board and was evacuated to South Africa, where she died in a Johannesburg hospital.
The third person who died was also Dutch and efforts were under way to repatriate their body, along with a guest "closely associated" with them, Oceanwide Expeditions said.
It also confirmed two crew members required urgent medical care, but authorities in Cape Verde had not given authorisation for them to disemba
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