JALALABAD, Afghanistan -- Hundreds shouted "Death to America." Some in the angry crowd burned an effigy of President Bush, others threw stones at a U.S. military convoy.

Police fired on the demonstrators Wednesday, trying to stifle the biggest display of anti-American anger in Afghanistan since U.S.-led forces ousted the ruling Taliban militia 3 1/2 years ago. Four people were killed and 71 injured.

The source of their rage? A report in Newsweek that interrogators desecrated Islam's holy book, the Quran, at the U.S. prison at Guantanamo Bay Cuba. U.S. officials said they were investigating.

There were no reports of American casualties in the protests, which quickly spread Wednesday to four Afghan provinces.

The violence was centered in Jalalabad, a city 80 miles east of the capital, Kabul.

Mobs smashed car and shop windows and attacked government offices, the Pakistani consulate and the offices of two U.N. agencies. Smoke billowed from the consulate and a U.N. building. More than 50 foreign aid workers were reportedly evacuated.

Protests may expand

The protests may expand into neighboring Pakistan, where a coalition of hard-line Islamic parties said it would hold nationwide demonstrations Friday over the alleged desecration of the Quran.

Many of the 520 inmates in Guantanamo are Pakistanis and Afghans captured after the Sept. 11 attacks. Despite both governments' support of the U.S.-led war on terrorism, suspicion lingers in the conservative Muslim nations about the American military.

Growing urban unrest could pose another security challenge for the U.S.-backed Afghan government, which is already battling a reinvigorated Taliban insurgency. About 18,000 U.S. troops are in Afghanistan, fighting rebels and searching for Taliban and al-Qaida leaders, including Osama bin Laden.

President Hamid Karzai, who travels to Washington this month for talks with Bush, played down the violence.

"It is not the anti-American sentiment, it is a protest over news of the desecration of the holy Quran," Karzai told reporters after talks with NATO officials in Brussels, Belgium.

"Afghanistan is now a democratic country, people can come out and protest and demonstrate and express themselves," Karzai said. "It also shows that Afghanistan's institutions, the police, the army, are not yet ready to handle protests and demonstrations."

The brief article in the May 9 edition of Newsweek reported that interrogators at Guantanamo placed Qurans on toilets to rattle suspects, and in at least one case "flushed a holy book down the toilet."

"This allegation is contrary to our respect for cultural customs and fundamental belief in the freedom of religion," Pentagon spokesman Lt. Cmdr. Flex Plexico said.

Last weekend, Pakistan's government said it was "deeply dismayed" about the report and registered its disapproval to Washington. Many Afghans read Pakistani papers and understand Pakistani broadcasts; access to satellite TV has mushroomed since the fall of the Taliban in late 2001.

The report of the alleged Quran desecration at Guantanamo has had little impact in the Arab world, however. The news stations Al-Jazeera and Al-Arabiyya reported the protests in Afghanistan and said the U.S. was investigating. Little mention was made in Islamic Web forums where militants often comment on news reports.

Aid workers in Jalalabad suggested conservative clerics had been agitating for days in the mosques of the city, which lies in a Pashtun-dominated area that once welcomed the Taliban and al-Qaida.

"They take things like that (reported abuse of the Quran) and link it to the U.S. presence here," said Phil Halton of the Afghan NGO Security Organization. "It's a familiar theme."

The unrest in Jalalabad began Tuesday, when protesters burned an effigy of Bush. It flared again Wednesday, when more than 1,000 university and high school students marched through the city and stoned a convoy of U.S. military vehicles.

The American troops fired into the air to force the crowd back and quickly left the scene, provincial intelligence chief Sardar Shah said.

U.S. military spokeswoman Lt. Cindy Moore said American forces were ordered to their camps but had no information on whether any of them were caught up in the unrest.

Associated Press Television News footage showed Afghan troops firing dangerously low over the heads of fleeing demonstrators.

The Interior Ministry said four people were killed and that the 71 injured included six police officers.

Deputy provincial health chief Mohammed Ayub Shinwari said most of the injured were students. He said two of the dead had been shot and many of the injured also had suffered bullet wounds.

"There is a lot of damage to the city, they have burned a lot of things," Shah said. "These are the enemies of peace and stability in Afghanistan who don't want people to be able to get on with their lives in peace."

Students held similar protests in three other provinces -- Laghman, Khost and Wardak -- but there were no reports of violence.

Wednesday was not the first time Pakistan's diplomatic missions have been targeted in Afghanistan. The two countries' bilateral relations have historically been strained by border disputes.

An Afghan opposition leader claimed the demonstration reflected frustration at the role of the United States and Karzai's plans for military ties, which could include long-term U.S. bases.

"From the beginning, people have disagreed with these things, but when the government makes one announcement after another, people lose patience and explode," said former presidential candidate Mohammed Mohaqeq.

Afghan leaders have long complained of heavy-handed search operations and the deaths of civilians in U.S. operations. They have also called for the release of those still held at Guantanamo, the naval base on Cuba where the United States is detaining more than 500 prisoners from its war on terror.

Some men who have been released from Guantanamo have accused their American jailers of defacing Qurans as part of the alleged psychological and physical abuse they endured during interrogation.

"They did everything to us -- they tortured our bodies, they tortured our minds, they tortured our ideas and our religion," former prisoner Mohamed Khan told The Associated Press a year ago when he was among two dozen Afghans sent home.

State Department spokesman Richard Boucher said Wednesday that U.S. personnel assigned to Guantanamo go through training to ensure they understand the procedures for protecting the rights and dignity of detainees.

"There is an opportunity to worship. People can get copies of the Quran. They get prayer beads," he added.

"The call to prayer is played over camp loudspeakers at the appropriate times every day. And the detainees have stenciled arrows pointing in the direction of Mecca so people are afforded the opportunity to pray as they wish."

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Associated Press writers Stephen Graham in Kabul and George Gedda in Washington contributed to this report.