Pakistani political party activists burn an effigy during a protest against U.S. drone attacks in Bannu on Nov. 17, 2013. Pakistan reacted angrily earlier this month to a U.S. drone attack that killed Pakistani Taliban chief Hakimullah Mehsud, saying the strike had sabotaged peace talks with the insurgents. (KARIM ULLAH/AFP/Getty Images)

American and Pakistani officials sharply disagreed Thursday about whether an Islamic school was struck by a U.S. drone, in an unusual attack that inflamed tensions over the CIA drone campaign.

According to Pakistani officials, three missiles were fired into a compound in Khyber ­Pakhtunkhwa province about 5 a.m. local time Thursday, a rare strike outside the Pakistani tribal areas near the Afghan border that are usually targeted by U.S drones.

Pakistani officials say the drone hit a madrassa, or Islamic seminary, killing six people, including two teachers. The dead included Maulvi Ahmad Jan and Maulvi Hameedullah, who were top surrogates for Sirajuddin Haqqani, the second in command of the Haqqani militant group, which has ties to al-Qaeda.

A U.S. official disputed that the strike was aimed at a madrassa. Instead, the official said, the target was a compound associated with the Haqqani network, which is accused of multiple attacks against American forces in Afghanistan.

The official, who spoke on the condition of anonymity, acknowledged that a madrassa was in the vicinity but said it was not damaged. U.S. officials have seen no indication of civilian casualties, he said.

Umar Khan Bangash, a local politician who lives in the area, said the missile hit the 15-room seminary. He and other Pakistani officials said the madrassa is frequently used by refugees from Afghanistan and suspected militants affiliated with the Haqqani network.

Citing intelligence sources, the Reuters news agency reported that Sirajuddin Haqqani was spotted at the seminary as recently as two days before the attack.

Haqqani is wanted by the United States for a 2008 attack on a Kabul hotel that killed six people, including one American, according to the FBI.

Pakistani officials, who spoke on the condition of anonymity to discuss the matter freely, said Haqqani was not at the compound during the attack.

The Haqqani network is considered one of the most ruthless militant groups in the region and operates training camps in Pakistan.

Sirajuddin Haqqani’s brother, Nasiruddin, who was also a leader of the group, was fatally shot two weeks ago under mysterious circumstances as he left a market on the outskirts of Islamabad, the Pakistani capital.

The body of Nasiruddin Haqqani was removed from the scene before police arrived and was buried by relatives, Pakistani officials said.

It is unclear who killed him.

Thursday’s drone attack could further complicate relations between the United States and some Pakistani leaders, as well as intensify debate within this country over an appropriate response to the strikes.

Although the United States has carried out dozens of drone strikes in tribal areas in northwest Pakistan, provincial officials said Thursday’s attack was the first in other areas in more than five years.

Even before the strike, Imran Khan and other political leaders in Khyber Pakhtunkhwa were planning to protest the U.S. drone campaign by halting NATO convoys that cross the province to reach landlocked Afghanistan.

Khan said Thursday that he plans to go ahead with his plan and is organizing a rally for Saturday that could briefly disrupt some NATO supplies.

“This is a declaration of war against the people of Pakistan,” said Shireen Mazari, a spokeswoman for Khan’s Movement for Justice party.

Prime Minister Nawaz Sharif also issued a statement Thursday condemning drone strikes, calling them a violation of Pakistan’s sovereignty.

But Sartaj Aziz, Sharif’s foreign policy adviser, told Pakistani lawmakers Wednesday that the prime minister intends to honor the agreement that permits NATO forces to use Pakistani roads through at least 2015.

In recent days, officials in Khyber Pakhtunkhwa have struggled to contain sectarian violence between Shiite and Sunni Muslim residents. At least three people have been killed, causing the army to deploy in several cities.

“I don’t understand why a drone at this time,” said Sheraz Paracha, a spokesman for the chief minister of Khyber Pakhtunkhwa. “This will further incite the people here.”

Miller reported from Washington. Tim Craig in Kabul contributed to this report.