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The illness, which causes fever, headaches and a cough, has so far affected people of all ages including children.
The cases have occurred in the region of Panzi, which has limited health facilities and lies around 700 kilometres (435 miles) southeast of the capital, Kinshasa.
"An unknown public health event" detected since October 24 has "already caused the deaths of 27 people out of a total of 382 people affected", the National Institute of Public Health said in a report dated late Tuesday and sent to AFP.
According to local authorities, the number could however be higher.
"Civil society and the head doctor of the Panzi health zone have reported the loss of 67 lives," provincial health minister Apollinaire Yumba said.
A team of epidemiologists has been sent to the area, he added, urging people not to panic and to limit their movements.
"Entering and leaving this health zone must be limited," Yumba said.
He added that people must "avoid greeting each other by shaking hands, regularly washing hands".
The World Health Organization told AFP it was working with Congolese authorities "to understand the situation".
"We have dispatched a team to the area to collect samples for laboratory investigations," the UN health body said.
The DRC, one of the poorest countries in the world, has in recent months been at the epicentre of an outbreak of mpox, with more than 1,000 deaths.
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