The Great Plague of 542 is thought to be the most devastating event that struck the Mediterranean, even more so than the Black Death of 1347. Both were caused by bubonic plague, which was able to establish a foothold through a small drop in global temperatures, and then recurred in several smaller pandemics over the next few centuries.
It is theorised that the 542 plague was able to hit the Mediterranean from its possibly Ethiopian genesis point thanks to a violent eruption of the volcano Krakatoa a few years earlier, which dropped global temperatures just enough to enable the plague to descend from the cool Ethiopian highlands to wreak havoc upon the warmer lands of the Mediterranean, Persia and Europe. Either way though, the method of the plague's arrival is irrelevant; my POD is that, thanks to an eruption of Krakatoa in 298AD, bubonic plague arrives in Alexandria in 302AD.
The following year, the Emperor Diocletian begins his great persecution of the Christians. He is cheered to discover that many of the Christians of the Greek Isles, who sit aside the Alexandrian/Balkan trade lanes, are suffering from a mysterious, devastating illness, which disfigures them horribly; clearly a sign from the Gods that the Christians should be wiped out. However, as the year 303 progresses, Diocletian is disturbed to hear that the "Christian disease" is increasingly jumping to Roman legionaries too, and from them, across the entire Empire.
In 304, the plague hits the Imperial capitals at Milan and Nicomedia. First from Antioch, Diocletian recieves reports that tens of thousands of people are dying every day, before the Prefects of Alexandria and Carthage report the same thing, and finally, the buboes reach Rome. The Christians, cheered, call the plague the "Fury of the Wrath of God"; sent by the Lord to purge the pagans, and to take the Christian people to join Him in Heaven. In August, they recieve the most cheering piece of news yet; the Emperor Diocletian is dead, struck down by the deadly plague.
By the end of 304, the plague has died down, yet the effects have been devastating. The Roman Empire's pre-plague population of 100,000,000 has collapsed to something like 70,000,000 people. Both of the senior Emperors, Diocletian and Maximian, were dead, as was the Caesar Constantius. Thus, the Emperor Galerius, a great millitary victor, became, briefly, sole ruler of the Roman Empire.
Galerius was a noted enemy of Christianity, but he was also a superstitious man. Shortly after re-establishing the Tetrachy by naming Constantine, son of the Caesar Constantius, as co-Augustus, he completed halted the persecution of Christians, as a way of appeasing the Christian God. This done, he headed eastwards to Antioch at full speed, to deflect an opportunistic Persian attack on the ravaged Roman Empire. In this, the Emperor Galerius was succesful; he scored a second major victory, and was able to keep the territorial concessions of 298.
Galerius reigns for another twelve years, but is eventually toppled by his western rival, Constantine, when Galerius' Caesar and nephew, Maximinus Daia, escapes an attempted assassination by his paranoid uncle. Constantine uses this as a pretext to march on Nicomedia in 316, but events prove to overtake him. A small, but crucially timed, outbreak of plague bursts out around the Sea of Marmara, killing the Emperor. Constantine's Christian allies are quick to point out the Hand of God in this, as destroying all enemies of Christianity. Constantine and Maximinus are duly impressed, and convert to Christianity officially at the town of Byzantium, which has survived the worst ravages of the outbreak.
Thoughts on this?