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Essex Police said the people were all pronounced dead at the scene in an industrial park in Grays, east of London. Early indications suggest the victims are 38 adults and one teenager.
A 25-year-old man from Northern Ireland has been arrested on suspicion of murder.
“This is a tragic incident where a large number of people have lost their lives,” Essex Police chief superintendent Andrew Mariner said in a statement.
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The police said they were alerted by the ambulance service shortly before 1:40am (0040 GMT) following the discovery of a truck container with people inside at the Waterglade Industrial Park.
“We are in the process of identifying the victims. However I anticipate that this could be a lengthy process,” said Mariner.
“We believe the lorry is from Bulgaria,” said Mariner.
He said it was thought the truck entered Britain on Saturday at Holyhead on the northwest tip of Wales — one of the main ports for ferries from Ireland.
“We have arrested the lorry driver in connection with the incident who remains in police custody as our enquiries continue.”