Ismaily failed to preserve a comfortable 2-0 first-leg advantage after slumping to a stunning 4-0 loss to Kenyan side Sofapaka to exit the CAF Confederation Cup from the preliminaries.
Harras El-Hodoud spared Egyptian blushes in Africa's secondary competition after holding Ethiopia's Dedebit to a 1-1 draw later on Saturday for a 5-1 aggregate win.
Ismaily were expected to seal smooth progress to the round of 16 after easing to home victory two weeks ago but were humiliated in the second leg to bow out at the first hurdle.
To rub salt into the wounds, star midfielder Hosni Abd-Rabou sustained what appeared a serious head injury. He was substituted after five minutes before being taken to hospital for medical checks.
Central midfielder Amr El-Sulaya was also replaced before the break after picking up an ankle injury.
Sofapaka scored three times in 11 first-half minutes to overturn the first-leg deficit and leave Ismaily’s hopes of advancing to the next round in tatters.
Congolese striker Bob Mugalia opened the scoring on 26 minutes before doubling the hosts’ advantage seven minutes later.
Titus Mulama added the third on 37 minutes as Sofapaka made the most of some disastrous defending from Ismaily, whose only African triumph was in 1969 when they won the Champions League.
Any hopes Ismaily had of going through were shattered deep in stoppage time when Sofapaka’s Patrick Kagogo completed the rout.
The defeat will increase pressure on Ismaily’s Dutch coach Mark Wotte, who was heavily criticized when the team failed to get beyond the Champions League’s group stage last season.
The three-time Egyptian champions, however, still have the domestic league to play for. They lie second in the table with 29 points, three behind leaders Zamalek.
In Ethiopia, Ismaily's compatriots El-Hodoud advanced to the next round after striker Ahmed Abdel-Ghani scored in the dying minutes to salvage a 1-1 draw with Dedebit. El-Hodoud, who were eliminated from the Confederation Cup group stage in the past three seasons, thrashed their opponents 4-0 in the first leg.
In other matches, Unfashionable Moroccan side FUS Rabat -- shock winners of the Confederation Cup last year -- progressed to the last-16 third round despite a 2-1 loss to Toure Kunda in Senegal.
Mansour Abdelilah opened the scoring close to half-time for FUS, who took a 2-0 advantage into the game, and the home team hit back through goals from Ame Diallo and Cheikh Samb with Thierno Thioune fluffing a penalty in between.
JS Kabylie of Algeria, another former African champion seeking the 660,000-dollar first prize, showed their mettle with a 2-1 victory over surprise qualifiers Tevragh Zeina in Mauritania.
Chemseddine Nessakh, who scored the lone first-leg goal that gave the 'Canaries' a brittle advantage, was the Algerian star with a goal in each half before Ould Moktar converted a penalty in Nouakchott.
Rafik Abdessamad struck twice in the final 20 minutes as Difaa al-Jadida of Morocco overturned a two-goal first-leg deficit against Olympique Beja of Tunisia by winning 3-0 with Adil Karouchi the other scorer.
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