Within a 15-minute period on Tuesday morning, at least three schools were targeted in Nangarhar's capital, Jalalabad.
As children recently returned to school after their summer vacation, two girls' high schools were targeted. While first responders and families rushed to the scene, a second improvised explosive device (IED) was detonated, killing a 12-year-old boy and injuring several other children, and men.
Meanwhile, explosive experts located and diffused an IED placed by terrorists next to a third school.
Guterres said the UN "stands with the people and government of Afghanistan as they strive for peace and reconciliation".
"Our deepest sympathy is with the victims, families and the Afghan people," said Tadamichi Yamamoto, the UN Special Representative for Afghanistan and head of UNAMA.
"The bombings of schools and the killing of children are among the most egregious and repulsive acts of terrorism which violate international humanitarian law," Yamamoto said.
The blast came less than a week after a suicide attack killed more than 20 people in the Afghan capital of Kabul.
Most of Tuesday's civilian casualties occurred in the Mohmandara district of Nangarhar when a suicide attacker detonated explosives among a crowd demonstrating against a local Afghan police commander. At least 20 died at the scene, and more than 60 were injured.
Jalalabad and other parts of Nangarhar have recently witnessed multiple deliberate attacks against civilians. Since June, Nangarhar schools have been pointedly targeted in retaliation for operations by Government and allied forces in the area.
"I feel profound indignation at this latest wave of attacks deliberately targeting civilians. The planners must face justice," said the special representative.
UNAMA reminded all warring parties to uphold their obligations to protect civilians and called upon them to comply with international humanitarian law and immediately cease targeting civilians, including schools.
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