Even in 2021, bubonic plague continues to exist in nature, and there are generally a few thousand human cases per year. Going back to the beginning of the 20th century, it is estimated that there were roughly one million cases per year in 1907. Within two decades, this number had fallen below one fifth of this level to 170,000 cases per year in the 1920s, and in the 1940s it was just over 20,000 per year. By the mid-20th century, it had fallen below 5,000 cases per year, but the rapid decrease in cases observed in the first half of the 1900s did not continue through the second half of the century. Even in 2019, there was one case of plague recorded in the United States. How infection occurs Yersinia pestis is the bacteria that causes the plague virus, and it is most commonly spread by rats and their fleas. The disease survives by fleas infecting rats, which in turn infect other fleas; the majority of rats survive the disease, which facilitates its spread; this is known as the "enzootic cycle ". Interestingly, the disease is usually fatal for the fleas, as it blocks their "stomachs" and causes them to starve; as the fleas get hungrier, they attempt to feed on more hosts, spreading the disease more rapidly. When the rats die, the parasitic fleas then search for a new host, which means that other animals (particularly mammals) are susceptible to this virus. While rat fleas can not survive on other hosts for very long, they can infect other (including human) fleas with the virus. The most common way for humans to contract the plague however, is when a rat flea bites its human host; during this process the flea simultaneously regurgitates Yersinia pestis bacteria into the wound, and this causes bubonic plague. Humans can then spread the disease among one another by coming into contact with the infected tissue or fluids of an infected person, or from the transfer of fleas. Continued existence of the plague Plague is extremely difficult to eradicate in nature, as rodent communities in the wild provide natural reservoirs for the disease to spread. In previous centuries, rats had much more frequent contact with humans for a variety of reasons; houses were more often made of wood (which made infestations easier), public spaces were much dirtier, and the presence of rats was tolerated more. As the understanding of epidemiology grew in the 20th century, this greatly reduced the frequency of plague in human populations. Unlike human diseases such as smallpox, which was eradicated through vaccination and other medical advancements, basic sanitation and the extermination of rats have been the driving force behind the decline of plague.

The Black Death was the largest and deadliest pandemic of Yersinia pestis recorded in human history, and likely the most infamous individual pandemic ever documented. The plague originated in the Eurasian Steppes, before moving with Mongol hordes to the Black Sea, where it was then brought by Italian merchants to the Mediterranean. From here, the Black Death then spread to almost all corners of Europe, the Middle East, and North Africa. While it was never endemic to these regions, it was constantly re-introduced via trade routes from Asia (such as the Silk Road), and plague was present in Western Europe until the seventeenth century, and the other regions until the nineteenth century. Impact on Europe In Europe, the major port cities and metropolitan areas were hit the hardest. The plague spread through south-western Europe, following the arrival of Italian galleys in Sicily, Genoa, Venice, and Marseilles, at the beginning of 1347. It is claimed that Venice, Florence, and Siena lost up to two thirds of their total population during epidemic's peak, while London, which was hit in 1348, is said to have lost at least half of its population. The plague then made its way around the west of Europe, and arrived in Germany and Scandinavia in 1348, before travelling along the Baltic coast to Russia by 1351 (although data relating to the death tolls east of Germany is scarce). Some areas of Europe remained untouched by the plague for decades; for example, plague did not arrive in Iceland until 1402, however it swept across the island with devastating effect, causing the population to drop from 120,000 to 40,000 within two years. Reliability While the Black Death affected three continents, there is little recorded evidence of its impact outside of Southern or Western Europe. In Europe, however, many sources conflict and contrast with one another, often giving death tolls exceeding the estimated population at the time (such as London, where the death toll is said to be three times larger than the total population). Therefore, the precise death tolls remain uncertain, and any figures given should be treated tentatively.

Although the Black Death peaked in Europe between 1348 and 1351, plague was almost always present in Britain for the next four centuries. In most years, plague was a dormant threat that affected very few people, and diseases such as smallpox and influenza were much more widespread; however, bubonic plague was prone to outbreaks that could decimate populations in a few short years. In London, plague outbreaks occurred every few decades, usually with death tolls in the tens of thousands. The duration and severity of these epidemics varied, sometimes having high death tolls but subsiding quickly, while others had relatively lower death tolls but could last for a number of years. As London's population and density also grew drastically during this period, plague affected the city differently in the sixteenth and seventeenth centuries. Great Plague of London The final major plague epidemic observed in Britain took place in 1665 and 1666. It became known as the "Great Plague" as it was the last of its kind in Britain, and its death toll eclipsed all other epidemics in the preceding century (although it was much smaller than that of the Black Death). The plague lasted for eighteen months, and had a reported death toll of more than 70,000 in this time; although modern historians estimate that the actual death toll exceeded 100,000. At its peak in September 1665, it is reported that there were more than 7,000 deaths per week, although this may have also been much higher due to the limited records kept at the time. Another reason for the lack of accurate records relating to this epidemic is because of the Great Fire of London in 1666. The fire started on September 02. 1666, and destroyed almost all of the city within the walls, leaving thousands homeless. Historians continue to debate the fire's significance, some citing that it destroyed the unsanitary dwellings where infected rats lived and drove them from the city, while others claim that the timings were purely coincidental and that the epidemic had already begun to subside in February.

The Third Plague Epidemic began in the mid-1800s in Yunnan, China, (an area that is still a natural reservoir for the Yersinia pestis bacteria) and had a huge death toll across Asia in the next century. While plague was confined to the Yunnan region for some decades, the mass displacement and social upheaval caused by the Taiping Rebellion saw millions flee the area , bringing the disease to other parts of the country. A plague epidemic then emerged in British-controlled Hong Kong in 1894, where merchants then unknowingly transported infected rats to other parts of the empire along various trade routes. Arrival in Bombay The first Indian cases were reported in Bombay (present-day Mumbai), and the Bombay Presidency suffered more losses than any other region in India (although there were some individual years where the state of Punjab reported more deaths). As with most disease or famine outbreaks in the region, the British authorities were slow to react, and their eventual response was in many ways too late. In some cases authorities even facilitated the spread of the disease; with multiple accounts of the military forcing healthy people into quarantine camps, evicting and burning homes of the afflicted, or by using such excessive force that the public would refuse medical help. Spread in India Lack of understanding among the Indian public was also to their own detriment. Some religions in India forbid the killing of rats, while some people simply refused to acknowledge that they were sick. As the plague in Bombay spiraled out of control, many fled to other parts of the country, taking the plague with them. It is estimated that there were over one million deaths in India by 1902, and almost one million further deaths in 1903 alone. The first four months of 1904 also saw over half a million deaths, almost matching the entire total for 1902. Plague would remain endemic to India for the next few decades, and there are varying reports of up to 10 or 12 million total plague deaths in this time. The public health measures taken to combat the plague in the early 20th century would mark the beginnings of India's public health system, and some of the quarantine measures put in place by the colonial government were even used in 2020 during the outbreak of the COVID-19 pandemic.

BackgroundPlague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone–no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease–how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.Methodology/Principal findingsThis systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints–the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.Conclusions/SignificanceThis systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial’s results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.

The successful reconstruction of an ancient bacterial genome from archaeological material presents an important methodological advancement for infectious disease research. The reliability of evolutionary histories inferred by the incorporation of ancient data, however, are highly contingent upon the level of genetic diversity represented in modern genomic sequences that are publicly accessible, and the paucity of available complete genomes restricts the level of phylogenetic resolution that can be obtained. Here we add to our original analysis of the Yersinia pestis strain implicated in the Black Death by consolidating our dataset for 18 modern genomes with single nucleotide polymorphism (SNP) data for an additional 289 strains at over 600 positions. The inclusion of this additional data reveals a cluster of Y. pestis strains that diverge at a time significantly in advance of the Black Death, with divergence dates roughly coincident with the Plague of Justinian (6th to 8th century AD). In addition, the analysis reveals further clues regarding potential radiation events that occurred immediately preceding the Black Death, and the legacy it may have left in modern Y. pestis populations. This work reiterates the need for more publicly available complete genomes, both modern and ancient, to achieve an accurate understanding of the history of this bacterium.

The region of present-day China has historically been the most populous region in the world; however, its population development has fluctuated throughout history. In 2022, China was overtaken as the most populous country in the world, and current projections suggest its population is heading for a rapid decline in the coming decades. Transitions of power lead to mortality The source suggests that conflict, and the diseases brought with it, were the major obstacles to population growth throughout most of the Common Era, particularly during transitions of power between various dynasties and rulers. It estimates that the total population fell by approximately 30 million people during the 14th century due to the impact of Mongol invasions, which inflicted heavy losses on the northern population through conflict, enslavement, food instability, and the introduction of bubonic plague. Between 1850 and 1870, the total population fell once more, by more than 50 million people, through further conflict, famine and disease; the most notable of these was the Taiping Rebellion, although the Miao an Panthay Rebellions, and the Dungan Revolt, also had large death tolls. The third plague pandemic also originated in Yunnan in 1855, which killed approximately two million people in China. 20th and 21st centuries There were additional conflicts at the turn of the 20th century, which had significant geopolitical consequences for China, but did not result in the same high levels of mortality seen previously. It was not until the overlapping Chinese Civil War (1927-1949) and Second World War (1937-1945) where the death tolls reached approximately 10 and 20 million respectively. Additionally, as China attempted to industrialize during the Great Leap Forward (1958-1962), economic and agricultural mismanagement resulted in the deaths of tens of millions (possibly as many as 55 million) in less than four years, during the Great Chinese Famine. This mortality is not observable on the given dataset, due to the rapidity of China's demographic transition over the entire period; this saw improvements in healthcare, sanitation, and infrastructure result in sweeping changes across the population. The early 2020s marked some significant milestones in China's demographics, where it was overtaken by India as the world's most populous country, and its population also went into decline. Current projections suggest that China is heading for a "demographic disaster", as its rapidly aging population is placing significant burdens on China's economy, government, and society. In stark contrast to the restrictive "one-child policy" of the past, the government has introduced a series of pro-fertility incentives for couples to have larger families, although the impact of these policies are yet to materialize. If these current projections come true, then China's population may be around half its current size by the end of the century.