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The five-member family, hailing from Anad in the Thiruvananthapuram district, was on its way to the international airport in Nedumbassery to see off a relative.
Quoting local people, the police said the car rammed into the lorry which came from the opposite direction. The car was completely damaged in the impact of the collision.
All the four died on the spot and one person who was seriously injured, was rushed to a nearby hospital, they added.