"Eight armed men on motorcycles opened fire on a bus at Safoora Chorangi, Gulistan-e-Johar area of Karachi, killing at least 41 passengers," a police official said.
The death toll could further rise as about 20 others are seriously injured. The injured and dead were shifted to various hospitals by rescue workers.
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Nobody has taken responsibility for the attack, however the Taliban and groups like Lashkar-e-Jhangvi are known to often carry out such attacks.
Police and Rangers arrived at the scene and started manhunt.
More than 60 people were on the board the bus which was carrying the people of Ismaili community from Al-Azhar Garden area of the city to their place of worship near Aysha Manzil, police said.
Ismaili community is a branch of Shia Muslims and they are considered very peaceful people.
The attack came a day after Prime Minister Nawaz Sharif visited Kabul and declared that enemies of Afghanistan are also enemies of Pakistan.
Pakistan has seen a rise in sectarian violence in recent years particularly against minority Shias who represent around 20 per cent of the country's Muslim population.
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