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The Nairobi club had hoped to build on a 5-0 triumph over Anse Reunion in the Seychelles this month -- their first victory in the competition after two earlier appearances resulted in four losses and no goals.
But Ivorian Vincent Die Foneye broke the deadlock on 30 minutes in Cairo, Ahmed Omran scored a second before half-time and Ahmed Raouf completed a comfortable victory five minutes from time.
Engineering company club ENPPI dominated the match and poor finishing robbed them of a bigger victory margin against the only Kenyan club to win a CAF competition.
The last-32 first leg result leaves ENPPI well positioned to advance ahead of the early April return game in Nairobi as they strive to become the first Egyptian winners of the second-tier African club championship.
A further 15 fixtures are scheduled for later Saturday and Sunday with CS Sfaxien of Tunisia -- the only side to win the Confederation Cup twice -- hosting Gamtel from Gambia.