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A suicide bomber has killed a US diplomat and two other people in a suicide attack near the US consulate in Karachi, Pakistani police say.
Many more were hurt in the blast, which tore through a car park near the consulate in a high-security zone.
The blast comes two days before US President George Bush visits Pakistan. He says his trip will go ahead.
US National Security Adviser Stephen Hadley said there was some evidence the diplomat was deliberately targeted.
The BBC's Jonathan Beale, travelling with the president, says the attack will only increase security concerns as Mr Bush prepares to visit Pakistan.
Mr Bush is currently in India. He is due to hold talks in Islamabad, 1,100km (690 miles) north of Karachi, on Saturday.
"Terrorists and killers are not going to prevent me from going to Pakistan. My trip to Pakistan is an important trip," Mr Bush told reporters in Delhi.
He confirmed the killing of the US diplomat.
Police in Karachi said they believed a suicide bomber had rammed a car packed with high-intensity explosives into the diplomat's vehicle.
The force of the blast hurled the vehicle into the air and across a seven-foot-high concrete barrier, police said.
Karachi police chief Niaz Sadiqui told a press conference: "We have reached the conclusion that it was a suicide attack, and we have found body parts of the attacker."
Official police spokesman Deputy Inspector Zubair Mahmood said a consulate employee and a paramilitary ranger had died along with the US diplomat.
Initial reports suggested there had been two bombs, but police now say a small second blast may have been a petrol tank exploding as a result of the first blast.
About 50 people were reported to have been injured.
A bomb disposal expert said it was one of the most powerful explosions the city had seen. It left a crater 2m (six feet) deep.
There has been no indication yet who is behind the attack.
If it was directed at the US consulate, it could have been carried out by Islamists opposed to Mr Bush's trip, the BBC's Barbara Plett in Islamabad says.
Investigators are reportedly seeking video surveillance footage from the scene.
The explosion happened in the car park of the Marriott Hotel, several windows of which were shattered by the blast.
History of attacks
The BBC's Aamer Ahmed Khan says most people use the rear entrance of the hotel because the road in front of the hotel is part of the US consulate's high-security zone.
"We are investigating the motives behind the blasts but apparently it coincided with the visit of Bush," Salahuddin Haider, a spokesman for the provincial government, is quoted as saying by the AFP news agency.
Karachi has experienced previous attacks against Western targets.
In June 2002, 12 people were killed when a suicide-bomber detonated a vehicle laden with explosives outside the same US consulate that was hit on Thursday.
Members of an Islamic militant group were convicted of carrying out that bombing and an earlier attack on the Sheraton hotel which killed 11 French engineers.Source:http://news.bbc.co.uk/1/hi/world/south_asia/4765170.stm