"There is an epidemic in Madagascar which is currently affecting five districts (out of 112). Eighty-six people have been inflicted by the plague, of which 39 have died," said the ministry in a statement read to AFP.
A doctor in the ministry in Antananarivo said 90 per cent of the cases were diagnosed as pneumonic plague, a vicious strain, which can kill within three days, leaving little time for antibiotics to work.
The first person died before November but government only officially declared the existence of a plague on November 23.
The plague has been blamed on an infestation of rats in residential areas due to uncontrolled deforestation.
In its statement the government urged anyone suffering fever and headaches to consult a health practitioner, saying drugs to treat the plague were available free of charge.
Affected districts are in the north, northeast, southeast and the centre of the island nation.