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Three other people were also injured when the bomber blew himself up as contractors left the offices of the US Protection and Investigations security company, close to a Canadian military base.
The early morning attack is the sixth suicide bombing to happen in the Kandahar region in nine days.
The two Americans are believed to have been contractors working for the company. Asmatullah Alizai, provincial police chief, said that four of the other dead were Afghan policemen and one was a translator.
USPI, a Texan-based company, is one of the biggest security firms working in Afghanistan, where it has operated since 2002. It employs 45 expatriates and hundreds of Afghans.
There have been six suicide bombings in the Kandahar region since November 27, when two Canadian soldiers were killed by militants. The Taleban has launched a number of roadside and suicide bombings this year and the growing insurgency has killed up to 4,000 people.
Despite the recent attacks Nato said today that the number of coordinated insurgency attacks across the country has decreased.
Last month there were 449 major attacks, which is almost half the number of those in September when there were 869, according to Brigadier Richard Nugee, the chief spokesman for NATO's International Security Assistance Force.
However, speaking at a news conference in Kabul, Brigadier Nugee said that militants were instead resorting to suicide bomb attacks.
"By using suicide bombs, they are being forced into a desperate tactic which in the long run will work against them because the people of Afghanistan will go against them," he said.
Meanwhile, in the eastern city of Jalalabad a man wearing a vest and belt packed with explosives was arrested, the Afghanistan intelligence agency announced.
The man allegedly confessed that he had crossed the border from Pakistan to carry out a suicide bombing attack and that his family would have been paid about $20,000 for his attack. He said he was hired by a cleric from a religious school in Pakistan, the agency said.
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