Yohan Blake has been ruled out of defending his 100m world title due to a hamstring injury, the Jamaican's manager Cubie Seegobin revealed.
The gold medallist from 2011 has not run a competitive 100m in 2013 and is the latest high profile withdrawal from the Word Championships in Moscow next month.
American Tyson Gay and fellow-Jamaican Asafa Powell were revealed to have tested positive for banned substance oxilofrine over the weekend, with both athletes expected to miss the meet in Russia.
"This decision was made after continual assessment and re-evaluations since his withdrawal from the Jamaican Senior Championships," said Seegobin.
"Yohan has made vast improvement, although the injury sustained in April of this year has prevented him from attaining the necessary fitness levels that we have grown accustomed to seeing in his competition performances."
Blake has run just once this year, labouring to a 200m win in his homeland in June. He was automatically entered for the 100m event as the reigning world champion, but was already set to miss the 200m after failing to attend the Jamaican trials.
Jamaica's Nesta Carter, who has run the fastest legitimate time of the year in Madrid, and American Justin Gatlin, bronze medallist from the London 2012 Olympic Games, will be the main challengers to favourite Usain Bolt.
The six-time Olympic champion, who qualified at the Jamaican trials with a time of 9.94 seconds, was disqualified from the 100m final in Daegu in 2011 after a false-start, allowing compatriot Blake to claim the title.
The news is a further boost to Britain's Jason Basaolu, who ran a personal best at the British Championships in Birmingham last weekend and is likely to go into the event as the third fastest man of 2013 in the field.