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Tottenham star Yves Bissouma looked in agony as a foul forced him to be stretchered off just nine seconds into his first outing of the season.
Bissouma, 29, has not featured this campaign for Spurs after persistently turning up late for training over the summer.
But he looked like he might revive his season on Sunday as he came on for Mali against Madagascar in their 4-1 World Cup qualifying win.
The midfielder was brought on in the 67th minute with Mali 3-0 up but he was hacked down just nine seconds after play resumed and writhed on the floor in pain.
Bissouma had made an instant impact, intercepting a pass and looking to start a counter-attack before he was stopped in his tracks by an agricultural challenge.
He appeared to be gesturing at his left ankle and covered his face as team-mates gathered around him. He tried to get up to walk off the pitch independently but was unable to.
Bissouma was stretchered off for Mali just seconds into his first appearance of the season, and was visibly distressed.
Get well soon, Biss 🤍❤️🩹 pic.twitter.com/oydQtSnB5C
Tottenham midfielder Yves Bissouma got injured nine seconds after his entry into Mali's 4-1 in over Madagascar
Bissouma, 29, was hacked down in a rash challenge shortly after coming on as a substitute
The midfielder is seen celebrating Tottenham's Europa League title in May
It marks another major blow for Bissouma, who may have been hoping that international involvement could catapult him into Thomas Frank's plans.
He suffered a long-term ankle injury in the 2022-23 season, missing 17 games as a result, and the fear is that he could be set for another lengthy lay-off, though that has not been confirmed.
Bissouma was axed from Spurs' squad for the UEFA Super Cup defeat by Paris Saint-Germain and subsequently left out of their Champions League group.
When available he has been heavily involved in their last three seasons since joining for £25million from Brighton. He started in their Europa League final victory against Manchester United in May.
However, he will have to pull up his socks to get a look in under Frank.
Explaining the Malian's exclusion for the UEFA Super Cup, Frank said: 'Bissouma isn't here because of disciplinary reasons. He's been late several times and the latest time was just one too many.
'You need to give your players a lot of love, also have demands, and there also need to be consequences. This time there was a consequence.'
Over the summer, Bissouma was linked with a move away from the club.
Daily Mail Sport previously reported how Roma and Fenerbahce had expressed an interest in Bissouma, while Galatasaray were also keen.
