Those killed in the dawn accident near Kasserine included the lorry driver, the ministry said, adding that around 15 cars also caught fire.
Initial findings showed the truck driver was unable to brake and his vehicle hit the bus and several cars as he sped out of control before slamming into an electricity pylon.
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Dozens of injured were taken to hospital in Kasserine, as emergency crews worked to extract others still trapped in the wreckage.
Photos shared on social media showed columns of thick black smoke rising from the scene of the accident, and national television broadcast images of burnt cars.
As of the end of May, 528 people had died in road accidents in the North African country of some 11 million inhabitants since the beginning of the year.
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