The wins followed Republicans' reconquest of another House seat earlier this fall that had been lost to Democrats.
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In the 2nd Congressional District, which includes most of New Orleans, Republican attorney Anh "Joseph" Cao won 50 percent of the vote to Jefferson's 47 percent and will become the first Vietnamese-American in Congress. His only previous political experience was an unsuccessful 2007 bid for a seat in the state legislature.
In the 4th Congressional District in western Louisiana, Republican John Fleming squeaked past Democrat Paul Carmouche in the race to replace retiring 10-term Rep. Jim McCrery, R-La. Only a few hundred votes separated the two.
Republicans made an aggressive push to take the 2nd District seat from the 61-year-old Jefferson, who has pleaded not guilty to charges of bribery, laundering money and misusing his congressional office.
"The people of the 2nd District have spoken," Cao, 41, told supporters at a restaurant near the French Quarter. "We want new direction. We want action. We want accountability."
In a speech that was gracious but stopped short of concession, Jefferson blamed low voter turnout for his showing and said supporters may have thought he was a shoo-in after he won a Nov. 4 primary in the predominantly black and heavily Democratic district.
"I think people just ran out of gas a bit," he said. "People today flat didn't come out in large numbers."
Greg Rigamer, a New Orleans political consultant, said his analysis showed turnout in predominantly white sections of the district was double that in black areas. He said that helped push Cao to victory over Jefferson, who became Louisiana's first black congressman since Reconstruction when he took office in 1991.
"This is quite a feat," Rigamer said of Cao's victory.
New Orleans voters had long been loyal to Jefferson, re-electing him in 2006 even after news of the bribery scandal broke. Late-night TV comics made him the butt of jokes after federal agents said they found $90,000 in alleged bribe money hidden in his freezer.
"People are innocent until proven guilty," said Faye Leggins, 54, an educator and Democrat who moved back to the city six months ago and still has fresh memories of Hurricane Katrina. She voted for Jefferson on Saturday. "He has enough seniority, so he can do a lot to redevelop this city."
But Republicans argued the scandal had cost Jefferson his clout in Congress. Election Day brought excitement to the state's usually low-key Vietnamese-American community, said David Nguyen, 45, a store manager and Cao supporter.
"The Vietnamese aren't much into politics," he said.
Cao came to the United States as a child after the fall of Saigon in 1975 and went on to earn degrees in philosophy, physics and law.
Both the 2nd and 4th Congressional District races were postponed because of Gustav, which struck in September.
In the 4th District, Republican Fleming, a physician, had 48 percent of the vote to 47 percent for Carmouche, the Democrat. Two minor party candidates split the remaining vote.
Both candidates had help from national heavyweights as Republicans tried to maintain their hold on the district and Democrats looked to add to the seats they gained Nov. 4. President-elect Barack Obama recorded a radio ad for Carmouche, while Vice President Dick Cheney helped Fleming with fundraising.
The national GOP also backed Cao, an immigration lawyer, with a barrage of advertising portraying Jefferson as corrupt.
Prosecutors contend Jefferson used his influence as chairman of the congressional Africa Investment and Trade Caucus to broker deals in Nigeria, Ghana, Cameroon and other African nations on behalf of those who bribed him.
The 2007 indictment claims Jefferson received more than $500,000 in bribes and demanded millions more between 2000 and 2005, including the $90,000 found in the freezer of his Washington home. Jefferson denies wrongdoing.
No trial date has been set.