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The in-form Swansea City star is said to have suffered a muscle strain while training with the team on Saturday.
Ayew played a key role in Ghana’s 2-0 win against Sudan in Cape Coast last week, scoring both goals.
The Black Stars will face the Northeast African country again in Khartoum in on Tuesday, November 17.
READ ALSO: AFCON Qualifiers: Fatau Dauda earns Ghana call-up for Sudan clash
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Andre Ayew
But in a statement, the Ghana Football Association (GFA) said Ayew will play no part in that game due to injury.
“Black Stars captain Andre Ayew has been ruled out of the trip to Sudan for the second leg of the 2021 AFCON qualifier due to injury,” the statement said.
“The Swansea City midfielder suffered a muscle strain at the team’s training session on Saturday, ruling him out of the squad for the trip.
“He is expected to return to Swansea to undergo further tests to assess the extent of injury.”
Meanwhile, Legon Cities goalkeeper Fatau Dauda has earned a late call-up for Ghana’s upcoming game against Sudan.
Dauda has been called to replace first-choice goalkeeper Richard Ofori, who has been suspended for the game.Ofori picked up a second card in the qualifiers during Ghana’s 2-0 win against Sudan in Cape Coast last week, culminating in a suspension.
Ghana currently sits top of Group C of the 2021 AFCON qualifiers with nine points from three games.