The cause of the death of Yusra Afaq, a doctor in a government-run hospital, last week has been identified as Crimean-Congo haemorrhagic fever.
The remaining four deaths, which occurred over the last six weeks, were also caused by haemorrhagic fever; but the exact type is still unknown, said Naushad Sheikh, Permanent Secretary at the health ministry of southern Sindh province.
Karachi is the capital of Sindh province.
"The hospitals in Karachi have been put on high alert after 45 more cases of haemorrhagic fever were reported," Sheikh told Reuters on Saturday.
Doctors say headaches and vomiting, followed by bleeding through the nose, mouth and ears are the symptoms of haemorrhagic fever. The illness is often accompanied by hepatitis and pulmonary failure.
Shabbir Ahmad Qaimkhani, provincial health minister, said doctors had been instructed to take special protective measures while dealing with patients after Afaq's death.
"All the patients of haemorrhagic fever are in isolation wards to minimise chances of spread of the disease," Qaimkhani said.
Four people were killed in the southwestern province of Baluchistan last year because of Crimean-Congo haemorrhagic fever.
Locally called Congo virus fever, the disease is endemic in parts of Pakistan, Afghanistan, Iran, Saudi Arabia, southern Europe and most of north Africa.
The disease is spread by ticks from animals to humans, or from humans to humans.