[8] Y. pestis spreads through the lymphatic vessels of the infected human until it reaches a lymph node, where it causes acute lymphadenitis.

The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness, and spitting or vomiting of blood.

The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases, mortality is nearly 100%.

[21] For this reason, if a person receives antibiotics before a sample is collected for laboratory testing, they may have a false negative culture and a positive PCR result.

[21] In 2020, a study about rapid diagnostic tests that detect the F1 capsule antigen (F1RDT) by sampling sputum or bubo aspirate was released.

However, when using the rapid test, both positive and negative results need to be confirmed to establish or reject the diagnosis of a confirmed case of plague and the test result needs to be interpreted within the epidemiological context as study findings indicate that although 40 out of 40 people who had the plague in a population of 1000 were correctly diagnosed, 317 people were diagnosed falsely as positive.

[24][25] He conducted a massive inoculation program in British India, and it is estimated that 26 million doses of Haffkine's anti-plague vaccine were sent out from Bombay between 1897 and 1925, reducing the plague mortality by 50–85%.

The United States CDC thus only recommends vaccination for (1) all laboratory and field personnel who are working with Y. pestis organisms resistant to antimicrobials: (2) people engaged in aerosol experiments with Y. pestis; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).

[27] A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.

[7] In cases of surgical mask shortages, patient overcrowding, poor ventilation in hospital wards, or other crises, pre-exposure prophylaxis might be warranted if sufficient supplies of antimicrobials are available.

[7] Postexposure prophylaxis should be considered for people who had close (<6 feet), sustained contact with a patient with pneumonic plague and were not wearing adequate personal protective equipment.

[7] Antimicrobial postexposure prophylaxis also can be considered for laboratory workers accidentally exposed to infectious materials and people who had close (<6 feet) or direct contact with infected animals, such as veterinary staff, pet owners, and hunters.

[2] In 2022 the possible origin of all modern strands of Yersinia pestis DNA was found in human remains in three graves located in Kyrgyzstan, dated to 1338 and 1339.

Bacteria today affecting marmots in Kyrgyzstan, are closest to the strand found in the graves, suggesting this is also the location where plague transferred from animals to humans.

Han dynasty general Huo Qubing is recorded to have died of such contamination while engaging in warfare against the Xiongnu[citation needed].

[34] In 1347, the Genoese possession of Caffa, a great trade emporium on the Crimean peninsula, came under siege by an army of Mongol warriors of the Golden Horde under the command of Jani Beg.

After a protracted siege during which the Mongol army was reportedly withering from the disease, they decided to use the infected corpses as a biological weapon.

This event might have led to the transfer of the Black Death via their ships into the south of Europe, possibly explaining its rapid spread.

[35] During World War II, the Japanese Army developed weaponized plague, based on the breeding and release of large numbers of fleas.

During the Japanese occupation of Manchuria, Unit 731 deliberately infected Chinese, Korean and Manchurian civilians and prisoners of war with the plague bacterium.

Members of the unit such as Shiro Ishii were exonerated from the Tokyo tribunal by Douglas MacArthur but 12 of them were prosecuted in the Khabarovsk War Crime Trials in 1949 during which some admitted having spread bubonic plague within a 36-kilometre (22 mi) radius around the city of Changde.

Scientists who worked in USSR bio-weapons programs have stated that the Soviet effort was formidable and that large stocks of weaponised plague bacteria were produced.