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Both patients reportedly contracted the disease in Nigeria before traveling to England and were diagnosed on days apart. There is no known British connection between the two patients, said PHE Tuesday.
The second patient is treated in a unit specializing in infectious diseases at Royal Liverpool University Hospital, after being transferred from Blackpool Victoria Hospital.
It comes after a Nigerian resident was diagnosed with the disease in Cornwall last week. The infection has never been diagnosed in the UK, said PHE.
According to PHE, monkeypox is a rare viral infection that usually only leads to mild illness and does not spread easily. Its symptoms include fever, muscle aches and rashes. People usually recover within a few weeks, although this can lead to serious illness in some cases.
PHE said they were contacting a number of people who could have been in contact with patients, including other passengers who traveled with the first patient on their flight from Nigeria.
"It is very unusual to see two cases in a relatively short period of time, and we are working hard to get in touch with people, including health workers, who might have been in contact with the deputy director of the National Office of Infection. PHE, said in a statement.
"We know that in September 2017, Nigeria experienced a huge outbreak of monkeypox," he added. "It is likely that monkeypox continues to circulate in Nigeria and could therefore affect travelers returning from this part of the world".
"The patient is being cared for by our infectious and tropical diseases unit, with highly qualified staff who are experienced in treating a variety of infectious diseases," he said.
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