Plague

In 1918, the influenza pandemic took the lives of more people than died in World War I; it was the most devastating epidemic recorded in world history.  It infected 500 million people around the world, including people on remote Pacific islands and in the Arctic, and resulted in the deaths of 50 to 100 million. You could not hide.

In two years, a fifth of the world's population was infected. The flu was most deadly for people ages 20 to 40, unusual for influenza which is usually a killer of the elderly and young children. It infected 28% of all Americans (Tice). An estimated 675,000 Americans died of influenza during the pandemic, ten times as many as in the world war. Of the U.S. soldiers who died in Europe, half of them fell to the influenza virus and not to the enemy. An estimated 43,000 servicemen mobilized for WWI died of influenza (Crosby). 

Compare this to the Black Death. The Black Death is estimated to have killed 30–60% of Europe's total population. In total, the plague may have reduced the world population from an estimated 450 million down to 350–375 million in the 14th century. It took 200 years for the world population to recover to its previous level. The plague recurred as outbreaks in Europe until the 19th century.

The most widely accepted estimate for the Middle East, including Iraq, Iran and Syria, during this time, is for a death rate of about a third. The Black Death killed about 40% of Egypt's population. Half of Paris's population of 100,000 people died. In Italy, the population of Florence was reduced from 110,000–120,000 inhabitants in 1338 down to 50,000 in 1351. At least 60% of the population of Hamburg and Bremen perished, and a similar percentage of Londoners may have died from the disease as well. In London approximately 62,000 people died between the years between 1346 and 1353. Before 1350, there were about 170,000 settlements in Germany, and this was reduced by nearly 40,000 by 1450. In 1348, the plague spread so rapidly that before any physicians or government authorities had time to reflect upon its origins, about a third of the European population had already died. In crowded cities, it was not uncommon for as much as 50% of the population to die. The disease bypassed some areas, and the most isolated areas were less vulnerable to contagion. Monks and priests were especially hard-hit since they cared for victims of the Black Death.
Caregivers always die first.

(couple of sources, incl wiki)