Adam Yates sits in the Orica-Scott hotel on Sunday evening along Italy's eastern coast in Le Marche with a DNF instead of a second place overall behind Nairo Quintana (Movistar).
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The team says “it’s disappointing,” but that he had to abandon after falling sick with a fever during the fifth stage to Fermo.
The Brit placed ninth overall in 2015 and looked ready for a podium finish this year when the race ends on Tuesday.
On Saturday's stage four, on Monte Terminillo, he battled with Quintana and Team Sky's Geraint Thomas to finish third on the summit finish. On the following day, instead, a fever finished him.
"He had stomach problems at the start and they developed really quickly during the stage and then he already has a fever now," sports director Matt White said.
"It's disappointing because he definitely deserved the podium here, but there's some things you can control and some things you can't, and illness is definitely something you can't.
Yates placed ninth in 2015 and in 2016 looked ready for a repeat performance until they annulled the summit finish stage due to bad weather.
He placed third on the queen stage of the 2017 edition and moved into the white jersey. All that remained were three stages.
"He's definitely disappointed. We don't know where he got it from, I'm not sure. It materialised quickly. It's disappointing," White added.
"He was just not feeling good from the start and it just got gradually worsened. He hopped off and by the time he got back to the bus [at the finish] he already had a fever."
On Monday, he will travel to his apartment in Andorra. He will recover for couple of days before preparing for the Volta a Catalunya, which he will race with his twin brother Simon.
The two are building for the Giro d’Italia this May.
Simon Yates also suffered despite winning a stage in Paris-Nice this week. Today, he fought at the back of the main group in France.
"Simon had diarrhoea the night before. The night that he won, he only slept for a couple of hours and was quite sick in a different way," said White.
"He left it quite weak yesterday and will just be happy to finish off Paris-Nice. He had a good win in the week and will need some time to recover after going deep."
