The Antonine plague burst onto the Roman Empire's radar very early into their calendar: with the first recorded outbreak being in 165 CE. This is during the Golden Age of the Roman Empire, but during the reign of the last of the 5 Good Emperors.
The Antonine Plague has been seen as the mark of the demise of the Romans, as it caused a massive stir in the general populus. This pandemic consisted of two outbreaks. The first was mild in comparison to the second. The first outbreak affected the city of Rome more than anywhere else in the Roman Empire. The second outbreak, however, spread to the furthest reaches of the Empire. The Antonine Plague is considered a pandemic due to the fact that the Romans controlled much of the inhabited world at the time of this plagues' beginning.
After a few milennia, historians and scientists were able to figure out what caused the Antonine Plague. They combined their knowledge of "modern" diseases with the writings of an ancient Greek physician called Galen. With their combined knowledge, they were able to confirm that the cause of the Antonine Plague was most likely Smallpox.