Timeline of typhus

This is a timeline of typhus, describing major events such as epidemics and key medical developments.

Year/period	Key developments
Early history	Vague descriptions of a typhus–like disease are documented by the Greeks.[1]
Middle Ages	European literature describes recognizable descriptions of typhus.[2]
15th century	Epidemic typhus and murine typhus rage in Europe. No distinction is made between different forms of typhus at the time.[3]
17th–19th century	Devastating epidemics of typhus occur intermittently throughout Europe.[2]
1930s	First vaccine for typhus is developed.[4][2]
1940s	The development of the powerful pesticide DDT highly contributes to elimination of body louse, the typhus vector, with remarkable consequences on the epidemiology of typhus at a global scale.[2]
1950–1980	Large epidemics of louse-borne typhus become less frequent and its geographical distribution decline due to improvements in living standards.[5]
1990s	Louse-borne typhus re-emerges in foci associated with poor sanitary conditions (such as in prisons and refugee camps) and a colder climates in mountainous regions. Outbreaks are reported in the rural highlands of Central and South America (especially in Peru) and Africa (Burundi, Uganda, Ethiopia, Nigeria and Rwanda). Sporadic cases or small suspected outbreaks are identified in Northern Africa, Russia and Kazakhstan, and among homeless populations in developed countries.[5]
Recent years	According to the World Health Organization, the current death rate from typhus is about one out of every 5,000,000 people per year. Only a few areas of epidemic typhus exist today.[6]

Full timeline

Reported cases of louse-borne typhus in American countries, for the period 1949-1958.[7] The notable decrease in cases correlates with the development of DDT implementation in the 1940s and 1950s.[2]

Reported cases of flea-borne typhus (murine) in American countries for the period 1949-1958.[7]

Number of Scrub typhus cases in South Korea during 2001-2013, reflecting an incidence increase in modern times in a developed country.[8]

Number of Scrub typhus cases by month in South Korea during 2001-2013, showing its seasonal behavior. The majority of cases occurred in October and November.[8]

Year/period	Type of event	Event	Present day geographical location
460 BC	Medical development	Greek physician Hippocrates defines typhus as "fever with a confused state of the intellect (...) a tendency to stupor".[3]	Greece
430 BC	Epidemic	The Athenian Plague is the first pestilence that might be attributed to louse-borne typhus. Athenian historian Thucydides describes a typhus-like disease so devastating that contributed ultimately to the downfall of Athens.[1]	Greece
313 BC	Medical development	Chinese clinical manual Zhouhofang describes first clinical accounts of scrub typhus (called "Tsutsugamushi disease").[3]	China
1489	Epidemic	One of the first written descriptions of typhus (probably epidemic) describes rash, sores, delirium, and about 17,000 deaths of Spanish troops, during the Granada War.[9][4]	Spain
1546	Medical development	Italian physician Girolamo Fracastoro publishes De contagione et contagiosis morbis where he differentiates typhus from plague.[3]	Italy
1655	Epidemic	Typhus is first recorded in Mexico (the country would suffer a total of 22 typhus epidemics between 1655 and 1918).[10]	Mexico
1759	Report	English authorities estimate about 25% of all prisoners in England dying of gaol fever (epidemic typhus) per year.[9]	United Kingdom
1760	Medical development	The disease is named typhus, from the Greek smoke or stupor because of the symptom of delirium that can develop.[9] In Montpellier, French physician François Boissier de Sauvages de Lacroix creates the clinical term typhus exanthematique for epidemic typhus.[3]	France, Europe
1762	Medical development	Scottish physician James Lind promotes hygienic measures during typhus outbreaks to reduce mortality.[3]	United Kingdom
1810	Medical development	Japanese physician Hakuju Hashimoto first describes a condition resembling typhus, setting the basis of the name "tsutsugamuchi disease", combining the terms tsutsuga (disease, harm, noxious), and muchi (insect/creature).[3][11]	Japan
1812	Epidemic	About as many as 300,000 French soldiers are estimated to perish from typhus, outnumbering the fewer than 100,000 losing their lives in battle, during the French invasion of Russia.[4]	Russia
1829	Medical development	French physician Pierre Charles Alexandre Louis differentiates typhus fever from typhoid fever.[1]	France
1830–1839	Epidemic	Typhus outbreaks kill over 100,000 people.[9]	Ireland
1837	Scientific development	American physician William Wood Gerhard shows that typhus and typhoid, though they often share symptoms, are separate and distinct contagions. Gerhard distinguishes enteric fevers (i.e. typhoid) from ricketsial fevers (i.e. typhus).[12][3]	United States
1837–1873	Epidemic	Typhus outbreaks are recorded in Philadelphia, Concord, Baltimore, and Washington, D.C..[9]	United States
1843	Scientific development	Craigie and Hendersen differentiate relapsing fevers clinically and pathologically from epidemic typhus.[3]
1847	Epidemic	The 1847 North American typhus epidemic is caused by a massive Irish emigration, during the Great Famine. More than 20,000 people die.[13]	Canada
1858	Medical development	British physicist Charles Murchison associates typhus epidemics with poor hygienic standards.[3]
1878	Medical development	Theobald Palm publishes in Europe first account of Japanese Tsutsugamuchi disease (scrub typhus).[3]
1898	Medical development	During an outbreak of atypical typhus, Brill describes the case of 17 patients with an illness resembling typhoid fever. This condition becomes known as Brill's disease. By 1950, researchers would show by clinical and serological data that the cause of Brill's disease was rickettsia prowazekii, the same agent responsible for epidemic typhus.[14][14][3]	United States
1906	Scientific development	Howard Ricketts and Russel Wilder discover the causative agent and transmission vector (dermacentor variabilis) of Rocky Mountain spotted fever (also known as tick typhus).[3]
1908	Scientific development	Schüffner describes 'pseudo-typhoid' in Sumatra, which later would reveal to be tsutsugamuchi disease (scrub typhus).[3]	Indonesia
1909	Scientific development	French bacteriologist Charles Nicolle, working at Pasteur Institute, correctly hypothesizes that lice are the vectors for transmitting typhus from person to person. Although Nicolle does not succeed in developing a vaccine against the disease, his discovery helpes greatly on the Western Front during the First World War, when delousing stations are established. Nicolle is awarded the Nobel Prize in Physiology or Medicine in 1928.[4]	Tunis
1910	Scientific development	Smithson describes a disease resembling typhus in Australia.[3][15]	Australia
1910	Scientific development	American pathologist Howard Taylor Ricketts along with Russel M. Wilder, first discovers rickettsiae (named after him) in the blood of epidemic typhus patients in Mexico.[3]	Mexico
1910	Scientific development	Conor and Bruch describe boutonneuse fever (also called Indian tick typhus or Mediterranean spotted fever) in Tunis.[3]	Tunisia
1911	Scientific development	McNaught describes an anomalous form of 'para-typhoid' in South Africa, with suspected tick transmission. The condition, consisting of fever and profuse rash, would later reveal to be two forms: Mediterranean spotted fever and African tick bite typhus.[3]	South Africa
1913	Scientific development	McKenchie describes a typhus-like fever in the Himalayan foothills.[16][3]	India
1916	Scientific development	Brazilian pathologist Henrique da Rocha Lima, discovers the cause of epidemic typhus, describing pathogen rickettsia prowazekii in honor of Howard Taylor Ricketts and Stanislaus von Prowazek, both of whom contracted typhus in the course of their investigations and died.[1][9]	Germany
1916	Scientific development	Austrian–Bohemian bacteriologist Edmund Weil and Polish microbiologist Arthur Felix first describe the later so–called Weil–Felix test, an agglutination test for the diagnosis of rickettsial infections. Weil and Felix establish that typhus fever develops agglutinins for certain strains of proteus, namely proteus OX19 and X2.[1][17]
1917	Scientific development	Neill uses blood from cases of typhus fever in Texas and injects it in the peritoneum of male guinea pigs, leading to scrotal swelling and inflammation, along with hemorrhage. This would later be known as Neill-Mooser's reaction, due to the extension of the experiment my Mooser in 1928.[18]
1922	Scientific development	Hone describes a new form of endemic typhus (OX19 positive) in Australia. The responsible pathogen would later reveal to be rickettsia honei.[19][20][3]	Australia
1922	Epidemic	Typhus epidemic reaches its peak in Soviet territory, with some 25 to 30 million cases in Russia.[21]	Russia
1923	Medical development (prevention)	Cyanide-based pesticide Zyklon B is developed. The product would become notorious for its use by Nazi Germany to conduct mass killings of Jews and other prisoners during the Final Solution.[22]	Germany
1923	Scientific development	American epidemiologist Kenneth F. Maxcy describes murine typhus as an endemic form of sporadic typhus in the United States. Maxcy suggests that murine typhus might occur in the absence of lice and is not necessarily imported from outside the country.[23]	United States
1924	Scientific development	Fletcher distinguishes scrub typhus from murine typhus.[3]
1926	Scientific development	American epidemiologist Kenneth F. Maxcy, after studying typhus in the Southern United States, suggests that fleas (xenopsylla cheopis) might be the vectors of typhus into humans. Maxcy's theory would be validated by two different groups in 1931.[18]
1926	Scientific development	Fletcher and Lesslar create the term "tropical typhus".[19][3]
1930	Scientific development	Scrub typhus, a form of typhus caused by the intracellular parasite Orientia tsutsugamushi, is first isolated and identified.[24]	Japan
1930	Scientific development	Nagayo demonstrates ricketsia tsutsugamuchi for the first time inside cells.[3]
1931	Scientific development	Dyer proves typhus is transmitted by rat fleas (xenopsylla cheopis).[3]
1933	Medical development	Polish biologist Rudolf Weigl develops the first human immunization against typhus. Weigl would first grow healthy lice for about twelve days by having uninfected lice feed on humans once a day for about 30 to 45 minutes, keeping the lice in small cages and strapping them to the thighs or calves of the human “feeders” allowing the lice to grow. Then he would inject the lice with rickettsia prowazekii, further allowing the lice to grow for an additional five days on human “feeders” who had been given the vaccine. Finally he would extract and grind up the lice’s midguts into a paste, which would become the vaccine. Weigl's method becomes so successful that the few human testers who developed typhus, including Weigl himself, all quickly would recover from the disease.[4]	Poland
1934	Medical development	American microbiologist Hans Zinsser suggests that so called Brill's disease represents a recrudescence of epidemic typhus originally acquired in Europe (the condition would be renamed Brill–Zinsser disease).[14] The same year, Zinsser develops a vaccine (made of killed rickettsiae) for immunization against Typhus.[25]	United States
1938	Scientific development	American bacteriologist H. R. Cox demonstrates that bacterium rickettsia prowazekii could be cultivated most satisfactorily in the yolk sacs of chick embryos.[1][26]
1943	Scientific development	American major Harry Plotz and others describe a method that would permit differentiation between epidemic typhus and murine typhus.[1]	United States
1945		German diarist Anne Frank dies of typhus.[27]	Germany
1945		"Operation Tyburn" is launched. The first mass production of scrub typhus vaccine starts.[3]
1959–1975		Vietnam War. Scrub typhus is one of the major causes of fevers of unknown origin.[3]	Vietnam
1960	Scientific development	German researcher F. Weyer shows that the typhus responsible rickettsial pathogen multiplies in the gut of the crab louse.[1][28][29]	Germany
1978	Epidemic	Murine typhus breaks out in Kuwait. 254 cases are reported by the World Health Organization.[25]	Kuwait
1996	Epidemic	Murine typhus breaks out in Portugal.[25]	Portugal
1997	Epidemic	The most important outbreak of epidemic typhus occurs in Burundi and involves more than 40,000 patients.[30]	Burundi
2000	Epidemic	Scrub typhus reemerges in Maldives and Palau.[3]	Maldives, Palau
2001	Epidemic	Murine typhus breaks out in Nepal. 50% of 756 disease cases are found to have antibodies against rickettsia typhi.[25]	Nepal
2001–2013	Epidemic	A rapid increase in the incidence of patients with scrub typhus is observed in South Korea, with the majority of cases reported in the western and southern coast. An almost four-fold increase in the number of patients is observed in 2013 (10,485 cases) compared to 2001 (2,637 cases).[8]	South Korea
2013	Epidemic	Twelve patients with murine typhus are identified in Galveston, Texas. An isolate from 1 patient confirms to be Rickettsia typhi. This reemergence would emphasize the importance of vector control and awareness of this disease by local physicians and public health officials.[31]	United States

See also

• Timeline of plague
• Timeline of measles

References

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