Francis died at only 45 years of age. Later in life his vision slowly deteriorated, sometimes to the point of complete blindness. Due to the pain in his eyes, Brother Elias insisted he seek treatment. So they traveled to Rieti and Francis underwent the excruciating cauterization procedure, but his sight never improved. While nobody can look back and diagnose whether Francis simply died from years under harsh living conditions, an STD, or some other kind of disease, we do know that before turning his life over to God he pretty much indulged in every kind of pleasure life offered. To put it simply, Francis had a lot of sex. Now, considering both the general lack of knowledge about STDs and the inability to protect oneself (outside of abstinence), I can't imagine how anyone could get away with even a moderately sexually active lifestyle with catching something. And at least one common STD, Cytomegalovirus, can result in blindness. Considering his relatively young age at death, you can't rule out the possibility.
Of course, we'll never know for sure and ultimately it doesn't matter, but I do feel that if it is true, such a death only makes Francis' story that much more dramatic and relevant in an age of widespread sexual confusion and promiscuity. It's also a powerful testimony to Francis' redemption from his old "life" to eternal life in Christ. Francis could have died for the world and all the temporal pleasures it offered him, but he chose Christ and died for Christ, teaching his brothers by word and example right to the very end. And perhaps an early death was God's gift to Francis, to finally be taken from this world and into Heaven.