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Around 10 cars of a passenger train derailed near a town in the southern province of Sindh, roughly 275 km (171 miles) from the country's largest city Karachi, it was reported.
"This is quite a big accident," railway minister Khawaja Saad Rafique told reporters.
The derailment of the Hazara Express happened near Sahara railway station close to Nawabshah city in the southern Sindh province.
"According to the information so far, 28 passengers have been killed and many are injured," Khawaja Saad Rafique told reporters, adding at least 1,000 people were aboard the Hazara Express when it came off the tracks.
The Hazara Express is a daily passenger train that leaves the port city of Karachi in the south and takes around 33 hours to reach Havelian in Khyber Pakhtunkhwa province, some 1,600 kilometres north.