African trypanosomiasis historical perspective: Difference between revisions

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{{African trypanosomiasis}}
{{African trypanosomiasis}}
{{CMG}}; {{AOEIC}} Pilar Almonacid
{{CMG}}; {{AOEIC}} Pilar Almonacid, {{ADG}}
==Overview==
African trypanosomiasis has been present in Africa for thousands of years. In 1903, David Bruce identified the [[vector]] of causative agent. In 1910, the differentiation between the [[subspecies]] of the [[protozoa]] was established.


==Historical Perspective==
==Historical Perspective==
[[Suramin]] was introduced in 1920 to treat the first stage of the disease.   By 1922, Suramin was generally combined with Tryparsamide (another pentavalent organo-arsenic drug) in the treatment of the second stage of the gambiense form. It was used during the grand epidemic in West and Central Africa in millions of people and was the mainstay of therapy until 1969.  
*In 1841, Valentin, a professor of [[physiology]], discovered a trypanosome-like [[flagellate]] for the first time in the [[blood]] of a trout.<ref name="pmid15145378">{{cite journal |vauthors=Cox FE |title=History of sleeping sickness (African trypanosomiasis) |journal=Infect. Dis. Clin. North Am. |volume=18 |issue=2 |pages=231–45 |year=2004 |pmid=15145378 |doi=10.1016/j.idc.2004.01.004 |url=}}</ref>
*In 1843, Gruby gave a detailed description of [[trypanosomes]] based on the work done independently by Gluge and Mayer in the [[blood]] of frogs.
*In 1891, Nepveu identified [[trypanosomes]] for the first time in human [[blood]].
*In 1898, Brault suggested [[trypanosomes]] as the cause of [[sleeping sickness]].
*In 1901, Forde and Dutton described [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']] in human [[blood]] for the first time.
*In 1902, the First and Second [[Sleeping Sickness]] Commissions led by Low and Bruce were conducted in Uganda.
*In 1902, Castellani identified [[trypanosomes]] in the [[cerebrospinal fluid]] of patients suffering from [[sleeping sickness]] for the first time.
*In 1903, David Bruce recognized the [[tsetse fly]] as the [[arthropod]] [[Vector (biology)|vector]].
*In 1905, Bruce suggested that [[Tsetse fly|tsetse flies]] transmit trypanosomes mechanically.
*In 1909, Kleine demonstrated the cyclical transmission of trypanosomes in [[Tsetse fly|tsetse flies.]]
*In 1910, Stevens and Fantham identified [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiens''e]] as the cause of acute [[sleeping sickness]].
*In 1914, Ritz described the [[antigenic variation]] of [[trypanosomes]].
*In 1969, Vickerman described the coat of [[trypanosomes]] as the source of [[antigenic variation]].


[[Pentamidine]], a highly effective drug for the first stage of the disease, has been used since 1939. During the fifties, it was widely used as a [[prophylactic]] agent in Western Africa, leading to a sharp decline in infection rates. At the time, it was thought that eradication of the disease was at hand.
== Landmark Events in Treatment Strategies ==
 
* In 1902, Laveran and Mesnil discovered that sodium arsenite can be used to kill [[trypanosomes]].
The organo-arsenical [[melarsoprol]] (Arsobal) was developed in the 1940s, and is effective for patients with second stage sleeping sickness. However, 3 - 10% of those injected have reactive [[encephalopathy]] (convulsions, progressive coma, or psychotic reactions), and 10 - 70% die; it can cause [[brain damage]] in those that 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.
* In 1945, [[DDT]] was used for the first time in controlling [[Tsetse fly|tsetse flies]].
 
* In 1949, [[melarsoprol]] was used for the first time as an anti-trypanosome drug.
[[Eflornithine]] (difluoromethylornithine or DFMO), the most modern treatment, was developed in the 1970s by Albert Sjoerdsmanot and underwent clinical trials in the 1980s. The drug was approved by the United States [[Food and Drug Administration]] in 1990, but [[Aventis]], the company responsible for its manufacture, halted production in 1999. In 2001, however, Aventis, in association with [[Médecins Sans Frontières]] and the [[World Health Organization]], signed a long-term agreement to manufacture and donate the drug.
* In 1992, [[eflornithine]] was used for the treatment of human [[Sleeping sickness (patient information)|sleeping sickness]].
 
The genome of the parasite has been decoded and several proteins have been identified as potential targets for drug treatment. The decoded DNA also revealed the reason why generating a vaccine for this disease has been so difficult. ''T. brucei'' has over 800 genes that manufacture proteins that the disease mixes and matches to evade immune system detection.<ref>{{cite journal |author=Berriman M, Ghedin E, Hertz-Fowler C, ''et al'' |title=The genome of the African trypanosome Trypanosoma brucei |journal=Science |volume=309 |issue=5733 |pages=416-22 |year=2005 |pmid=16020726 |doi=10.1126/science.1112642 |url=http://www.sciencemag.org/cgi/content/full/309/5733/416}}</ref>
 
An international research team working in the Democratic Republic of the Congo, Southern Sudan and Angola involving Immtech International and University of North Carolina at Chapel Hill have completed a [[Phase IIb]] clinical trial and commenced a [[Phase III]] trial in 2005 testing the efficacy of the first oral treatment for Sleeping Sickness, known at this point as "DB289".
<ref>{{cite news
  |first=David
  |last=Williamson
  |title=Compound might defeat African sleeping sickness, clinical trial beginning this month
  |date=August 25, 2005
  |publisher=University of North Carolina
  |url=http://usinfo.state.gov/xarchives/display.html?p=washfile-english&y=2005&m=August&x=20050826160501cmretrop0.7327387&t=livefeeds/wf-latest.html
}}</ref>
<ref>{{cite news
  |author=Staff
  |page=5
  |title=Clinical Trials Update
  |date=September 15, 2005
  |publisher=[[Genetic Engineering News]]
}}</ref>
 
Recent findings indicate that the parasite is unable to survive in the bloodstream without its [[flagellum]]. This insight gives researchers a new angle with which to attack the parasite.<ref>{{cite web | title=African Sleeping Sickness Breakthrough | url=http://domino.lancs.ac.uk/info/LUNews.nsf/I/448E635736B6B25A8025714700317FD1 | accessdate=April 7 | accessyear=2006 }}</ref>
 
A new treatment based on a truncated version of the apolipoprotein L-1 of [[high density lipoprotein]] and a nanobody has recently been found to work in mice, but has not been tested in humans.<ref>
[[New Scientist]], [http://www.newscientist.com/channel/health/mg19526181.400-cholesterol-secret-of-our-killer-blood.html 25 Aug. 2007, pp. 35-7]
</ref>


==References==
==References==
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Latest revision as of 20:19, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

Overview

African trypanosomiasis has been present in Africa for thousands of years. In 1903, David Bruce identified the vector of causative agent. In 1910, the differentiation between the subspecies of the protozoa was established.

Historical Perspective

Landmark Events in Treatment Strategies

References

  1. Cox FE (2004). "History of sleeping sickness (African trypanosomiasis)". Infect. Dis. Clin. North Am. 18 (2): 231–45. doi:10.1016/j.idc.2004.01.004. PMID 15145378.