The Spain goalkeeper picked up a leg muscle problem and could see his campaign in Brazil brought to a premature end less than a week after the start of the tournament
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But now the former Atletico Madrid man could miss the remainder of the group stage after suffering a gluteal injury which forced him to sit out of training.
De Gea underwent medical scans on Sunday, and it is feared that a significant strain will end his tournament, with initial reports in Spain suggesting he will be out for at least 10 days.
Casillas' poor showing in Salvador on Friday led to the first-choice keeper accepting culpability for the loss, and some in the media have questioned his place in the side. However, if De Gea is forced to leave the camp as a result of his injury, only Pepe Reina remains at Del Bosque's disposal as a potential replacement.
Spain currently sit bottom of Group B, and will take on Australia following their clash with Chile at the Maracana on Wednesday.