Editing African trypanosomiasis (section)

==History==
{{See also|Tsetse fly#History}}African trypanosomes can be traced back to prehistoric times. After analyzing and reconstructing the genes that encode for small subunit ribosomal RNA, researchers find that Salivarian trypanosomes, which includes African trypanosomes, separated from other trypanosomes approximately 300 million years ago.<ref>{{Cite journal |last1=Haag |first1=Jochen |last2=O'hUigin |first2=Colm |last3=Overath |first3=Peter |date=1998-03-01 |title=The molecular phylogeny of trypanosomes: evidence for an early divergence of the Salivaria |url=https://linkinghub.elsevier.com/retrieve/pii/S0166685197001850 |journal=Molecular and Biochemical Parasitology |volume=91 |issue=1 |pages=37–49 |doi=10.1016/S0166-6851(97)00185-0 |pmid=9574924 |issn=0166-6851}}</ref> Eventually, the African trypanosomes became parasites found in the digestive system, likely a precursor for early insects. Since tsetse flies emerged about 35 million years ago, the transmission of trypanosomes to mammals has occurred*. This immense period of exposure to trypanosomes may serve as the reason for most African wildlife species being tolerant of trypanosomiasis with no symptoms.<ref>{{Cite journal |last=Lambrecht |first=Frank L. |date=1985-11-01 |title=Trypanosomes and Hominid Evolution: Tsetse flies and trypanosomes may have played a role in early hominid evolution |url=https://academic.oup.com/bioscience/article-abstract/35/10/640/221201?redirectedFrom=fulltext |journal=BioScience |volume=35 |issue=10 |pages=640–646 |doi=10.2307/1309990 |jstor=1309990 |issn=0006-3568}}</ref> In addition to wild life, African trypanosomes have affected human evolution in sub-Saharan regions of Africa. Humans have evolved to be resistant to all other African Trypanosome species except T. b. Gambiense and T. b. Rhodesiense.<ref name=":1" /> [[File:Davidbruce.JPG|thumb|In 1903, [[David Bruce (microbiologist)|David Bruce]] recognized the tsetse fly as the arthropod vector.]]
The condition has been present in Africa for millions of years.<ref name=":1">{{cite journal | vauthors = Steverding D | title = The history of African trypanosomiasis | journal = Parasites & Vectors | volume = 1 | issue = 1 | page = 3 | date = February 2008 | pmid = 18275594 | pmc = 2270819 | doi = 10.1186/1756-3305-1-3 | doi-access = free }}</ref> In contrast to arboreal primates who are susceptible to trypanosomiasis, humans, with the exception of T. b. gambiense and T. b. rhodesiense infections are resistant to the parasite serving as an evolutionary mark in the [[evolutionary divergence]] of early hominid natural selection.<ref name=":1"> </ref>
Because of a lack of travel between Indigenous people, sleeping sickness in humans had been limited to isolated pockets. Due to the increasing amount of deaths caused by the disease, the first accounts of African sleeping sickness came from doctors on slave ships who were implored by slave traders to investigate this disease. [[Arab slave trade]]rs entered central Africa from the east, following the [[Congo River]], bringing parasites along. Gambian sleeping sickness travelled up the Congo River, and then further east.<ref name=Strong165/>

An Arab writer of the 14th century left the following description in the case of a sultan of the Mali Kingdom: "His end was to be overtaken by the sleeping sickness (''illat an-nawm'') which is a disease that frequently befalls the inhabitants of these countries, especially their chieftains. Sleep overtakes one of them in such a manner that it is hardly possible to awake him."<ref name=Strong165>{{cite book| vauthors = Strong RP |title=Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases|date=1944|publisher=The Blakiston company|location=York, PA|page=165|edition=Seventh}}</ref>

The British [[naval surgeon]] [[John Atkins (naval surgeon)|John Atkins]] described the disease on his return from [[West Africa]] in 1734:<ref name="Strong165" />
{{blockquote|The Sleepy Distemper (common among the Negroes) gives no other previous Notice, than a want of Appetite 2 or 3 days before; their sleeps are sound, and Sense and Feeling very little; for pulling, drubbing or whipping will scarce stir up Sense and Power enough to move; and the Moment you cease beating the smart is forgot, and down they fall again into a state of Insensibility, drivling constantly from the Mouth as in deep salivation; breathe slowly, but not unequally nor snort. Young people are more subject to it than the old; and the Judgement generally pronounced is Death, the Prognostik seldom failing. If now and then one of them recovers, he certainly loses the little Reason he had, and turns Ideot...}}

French naval surgeon [[Marie-Théophile Griffon du Bellay]] treated and described cases while stationed aboard the [[hospital ship]] ''Caravane'' in [[Gabon]] in the late 1860s.<ref name= "ecole nav">{{cite web|url=http://ecole.nav.traditions.free.fr/officiers_griffon_theophile.htm|title=Médecin|website=ecole.nav.traditions.free.fr}}</ref>

In 1901, a devastating epidemic erupted in [[Uganda]], killing more than 250,000 people,<ref>{{cite journal | vauthors = Fèvre EM, Coleman PG, Welburn SC, Maudlin I | title = Reanalyzing the 1900-1920 sleeping sickness epidemic in Uganda | journal = Emerging Infectious Diseases | volume = 10 | issue = 4 | pages = 567–573 | date = April 2004 | pmid = 15200843 | doi = 10.3201/eid1004.020626 | doi-access = free }}</ref> including about two-thirds of the population in the affected lakeshore areas. According to ''The Cambridge History of Africa'', "It has been estimated that up to half the people died of sleeping-sickness and [[smallpox]] in the lands on either bank of the lower river [[Congo River|Congo]]."<ref>{{cite book | vauthors = Fage JD |title=The Cambridge History of Africa: From the earliest times to c. 500 BC |url=https://books.google.com/books?id=8DSa_viBgsgC&pg=PA748 |date=5 September 1985 |publisher=Cambridge University Press |isbn=978-0-521-22803-9 |page=748 |url-status=live |archive-url=https://web.archive.org/web/20150318211755/http://books.google.com/books?id=8DSa_viBgsgC&pg=PA748 |archive-date=18 March 2015}}</ref>

The causative agent and [[vector (epidemiology)|vector]] were identified in 1903 by [[David Bruce (microbiologist)|David Bruce]], and the [[subspecies]] of the protozoa were differentiated in 1910. Bruce had earlier shown that ''T. brucei'' was the cause of a similar disease in horses and cattle that was transmitted by the [[tsetse fly]] (''Glossina morsitans'').<ref name=Strong165/>

The first effective treatment, [[atoxyl]], an [[arsenic]]-based drug developed by [[Paul Ehrlich]] and [[Kiyoshi Shiga]], was introduced in 1910, but blindness was a serious side effect.

[[Suramin]] was first synthesized by Oskar Dressel and Richard Kothe in 1916 for [[Bayer]]. It was introduced in 1920 to treat the first stage of the disease. By 1922, Suramin was generally combined with tryparsamide (another pentavalent organoarsenic drug), the first drug to enter the nervous system and be useful in the treatment of the second stage of the gambiense form. Tryparsamide was announced in the ''Journal of Experimental Medicine'' in 1919 and tested in the [[Belgian Congo]] by [[Louise Pearce]] of the [[Rockefeller University|Rockefeller Institute]] in 1920. It was used during the grand epidemic in West and Central Africa on millions of people and was the mainstay of therapy until the 1960s.<ref name=Steverding>{{cite journal | vauthors = Steverding D | title = The development of drugs for treatment of sleeping sickness: a historical review | journal = Parasites & Vectors | volume = 3 | issue = 1 | page = 15 | date = March 2010 | pmid = 20219092 | pmc = 2848007 | doi = 10.1186/1756-3305-3-15 | doi-access = free }}</ref> American medical missionary [[Arthur Lewis Piper]] was active in using tryparsamide to treat sleeping sickness in the Belgian Congo in 1925.<ref>{{cite journal | vauthors = Klingman JD | title = Arthur Lewis Piper, M.D.: a medical missionary in the Belgian Congo | journal = Journal of Community Health | volume = 19 | issue = 2 | pages = 125–146 | date = April 1994 | pmid = 8006209 | doi = 10.1007/BF02260364 | s2cid = 37502216 }} Periodicals Archive Online accessed 15 October 2013.</ref>

[[Pentamidine]], a highly effective drug for the first stage of the disease, has been used since 1937.<ref name=Mag2012>{{cite book| vauthors = Magill AJ | chapter = Leishmaniasis | veditors = Magill AJ, Strickland GT, Maguire JH, Ryan ET, Solomon T |title=Hunter's Tropical Medicine and Emerging Infectious Disease|date=2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-4043-7|page=723|edition=9th| chapter-url = https://books.google.com/books?id=x15umovaD08C&pg=PA723}}</ref> During the 1950s, it was widely used as a [[prophylactic]] agent in western Africa, leading to a sharp decline in infection rates. At the time, eradication of the disease was thought to be at hand.<ref name="Steverding"/>

The organoarsenical [[melarsoprol]] (Arsobal) developed in the 1940s is effective for people with second-stage sleeping sickness. However, 3–10% of those injected have reactive [[encephalopathy]] (convulsions, progressive coma, or psychotic reactions), and 10–70% of such cases result in death; it can cause [[brain damage]] in those who survive the encephalopathy. However, due to its effectiveness, melarsoprol is still used today. Resistance to melarsoprol is increasing, and combination therapy with nifurtimox is currently under research.<ref name="Wery">{{Cite journal |last=Wéry |first=M. |date=August 1994 |title=Drug used in the treatment of sleeping sickness (human African trypanosomiasis: HAT) |url=https://linkinghub.elsevier.com/retrieve/pii/0924857994900124 |journal=International Journal of Antimicrobial Agents |language=en |volume=4 |issue=3 |pages=227–238 |doi=10.1016/0924-8579(94)90012-4|pmid=18611614 }}</ref>

[[Eflornithine]] (difluoromethylornithine or DFMO), the most modern treatment, was developed in the 1970s by Albert Sjoerdsma and underwent clinical trials in the 1980s. The drug was approved by the United States [[Food and Drug Administration]] in 1990.<ref>{{cite book | chapter = Eflornithine |title=Handbook of Drugs for Tropical Parasitic Infections | vauthors = Hellgren U, Ericsson O, AdenAbdi Y, Gustafsson LL |page=60 |isbn=978-0-203-21151-9 | chapter-url = https://books.google.com/books?id=DYc7bY-egLEC&q=difluoromethylornithine%20developed%20Sjoerdsma&pg=PA60|date=2003-05-20 | publisher = CRC Press }}</ref> [[Aventis]], the company responsible for its manufacture, halted production in 1999. In 2001, Aventis, in association with the [[World Health Organization]], signed a five-year agreement to manufacture and donate the drug.<ref>{{Cite news |last=Boseley |first=Sarah |last2= |first2= |date=2001-05-07 |title=Drug firm wakes up to sleeping sickness |url=https://www.theguardian.com/world/2001/may/07/medicalscience.businessofresearch |access-date=2025-03-03 |work=The Guardian |language=en-GB |issn=0261-3077}}</ref>

In addition to sleeping sickness, previous names have included negro lethargy, maladie du sommeil (Fr), Schlafkrankheit (Ger), African lethargy,<ref name=TMHP>{{cite-TMHP|African Lethargy, Sleeping Sickness, or Congo trypanosomiasis; Trypanosoma gambiense}}, pp. 20–21.</ref> and Congo trypanosomiasis.<ref name=TMHP/><ref>{{cite book| vauthors = Strong RP |title=Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases|date=1944|publisher=The Blakiston company|location=York, PA|page=164|edition=Seventh}}</ref>

<gallery caption="The British-led ''Sleeping Sickness Commission'' collecting tsetse flies, Uganda and [[Nyasaland]], 1908–1913">
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