Houses were reduced to rubble and bodies swathed in blankets lay on the ground after the magnitude 6.1 earthquake, photographs on Afghan media showed.
An unknown number of people remained stuck under rubble and in outlying areas, photos showed.
Health and aid workers said rescue operations were complicated by difficult conditions including rains, landslides and many villages being nestled in inaccessible hillside areas.
“Many people are still buried under the soil. The rescue teams of the Islamic Emirate have arrived and with the help of local people are trying to take out the dead and injured,” a health worker at one of Paktika’s main hospitals said.
Mounting a rescue operation will prove a major test for the hard-line Islamist Taliban authorities, who took over the country last August after two decades of war and have been cut off from much international assistance because of sanctions.
A spokesman for the United Nations Office for the Coordination of Humanitarian Affairs (UNOCHA) said it was sending teams in addition to ambulances and helicopters sent by the Taliban-led ministry of defence, which was leading rescue efforts.
“Although search and rescue efforts are ongoing, heavy rain and wind is hampering efforts with helicopters reportedly unable to land this afternoon,” he said via email.
“The death toll is likely to rise as some of the villages are in remote areas in the mountains and it will take some time to collect details,” interior ministry official Salahuddin Ayubi said.
Wednesday’s quake was the deadliest in Afghanistan since 2002.
It struck about 44km from the southeastern city of Khost, near the border with Pakistan, the US Geological Survey (USGS) said.
Shaking was felt by about 119 million people in Pakistan, Afghanistan and India, the European-Mediterranean Seismological Centre (EMSC) said on Twitter, but there were no immediate reports of damage or casualties in Pakistan.
The EMSC put the earthquake’s magnitude at 6.1 although the USGC said it was 5.9.
Most of the confirmed deaths were in the eastern province of Paktika, where 255 people were killed and more than 200 injured, Ayubi added.
In the province of Khost, 25 were dead and 90 had been taken to hospital.
Haibatullah Akhundzada, the supreme leader of the ruling Taliban, offered his condolences in a statement.
Adding to the challenge for Afghan authorities is recent flooding in many regions, which the disaster agency said had killed 11, injured 50 and blocked stretches of highway.
The disaster comes as Afghanistan grapples with a severe economic crisis since the Taliban took over as US-led international forces withdrew from the country.
In response to the Taliban takeover, many countries imposed sanctions on Afghanistan’s banking sector and cut billions of dollars in development aid.
Humanitarian aid has continued, however, from international agencies such as the United Nations.
A foreign ministry spokesman said the Taliban would welcome international help.
Several countries, including neighbouring Pakistan and Iran said they were sending humanitarian aid including food and medicine.
Large parts of South Asia are seismically active because a tectonic plate known as the Indian plate is pushing north into the Eurasian plate.
In 2015, an earthquake struck the remote Afghan northeast, killing several hundred people in Afghanistan and nearby northern Pakistan.
In January, an earthquake struck western Afghanistan, killing more than 20 people.
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