Outbreaks of plague continued in Asia throughout the 1800s. The third pandemic wave began in Southern China in 1865, spreading south and west. Between 1894 and 1929 there were over 24,000 cases in Hong Kong. From Hong Kong it entered the ports of India, where at least 12 million people died over 20 years.

By the end of the 1800s, developments in bacteriology and infection control meant that medical researchers were able to observe and investigate the disease in detail for the first time.

A team of European scientists was sent to colonial Hong Kong in the 1890s to study the epidemic. French-Swiss bacteriologist Alexandre Yersin isolated the bacterium that caused the disease in 1897, and it was named Yersinia pestis after him.

In 1898 Paul Louis Somond established the mechanism for transmission was via fleas, which transferred bacteria from infected hosts to the non-infected through their bites. The fleas were transported around the world overland and on ships by black rats.

Known as house rats or ship rats, black rats liked to live in close proximity to humans. When the rats died the fleas moved onto human hosts. The fleas also infested clothing and could be carried to other locations in that way.