[7] The first began with the Plague of Justinian, which ravaged the Byzantine Empire and surrounding areas in 541 and 542; the pandemic persisted in successive waves until the middle of the 8th century.

The second began with the Black Death, which killed at least one third of Europe's population in a series of expanding waves of infection from 1346 to 1353; this pandemic recurred regularly until the 19th century.

The first was primarily bubonic and was carried around the world through ocean-going trade, through transporting infected persons, rats, and cargoes harboring fleas.

An influx of new people because of political conflicts and global trade led to the spread of the disease throughout the world from Asia to the rest of Europe, to reach Africa and the Americas.

The third pandemic of plague originated in the area after a rapid influx of Han Chinese to exploit the demand for minerals, primarily copper, in the second half of the 19th century.

People brought the fleas and rats back into growing urban areas, where small outbreaks sometimes reached epidemic proportions.

Although William McNeil and others believe the plague to have been brought from the interior to the coastal regions by troops returning from battles against the Muslim rebels, Benedict suggested evidence to favor the growing and lucrative opium trade, which began after about 1840.

[29] His discoveries led in time to modern treatment methods, including insecticides, the use of antibiotics and eventually plague vaccines.

[33] The British colonial government in India pressed medical researcher Waldemar Haffkine to develop a plague vaccine.

[35] In 1897 and 1903, two conventions were held known as International Sanitary Conferences; the first in Venice and the second in Paris, to help deal with threat of the new outbreaks of the bubonic plague.

[35] Burning was used often to deal with the Plague as it was believed to be the most effective way to eliminate strains of the disease from places inhabited by the infected.

[36] In many instances, the third plague pandemic either revealed or exacerbated major social conflicts and racial inequalities.

[37] Because of this, the British authorities often ended up enforcing western hygiene and medical practices and radical quarantine measures in countries and provinces such as India, South Africa and Hong Kong.

[35] In America when the plague reached San Francisco, the medical board of the city implemented a strict quarantine of the entire Chinatown district after discovering only one case of the plague; this has led historians to question whether this measure was motivated by racial bias among medical professionals.