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| {{CMG}}; {{AOEIC}} Pilar Almonacid | | {{CMG}}; {{AOEIC}} Pilar Almonacid |
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| ==Overview==
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| African trypanosomiasis has been present in Africa since at least the 14th century, and probably for thousands of years before that. The causative agent and vector were not identified until 1902–1903 by [[David Bruce (microbiologist)|Sir David Bruce]], and the differentiation between protozoa was not made until 1910. 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. Numerous drugs designed to treat the disease have been introduced since then.
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| There have been three severe epidemics in Africa over the last century: one between 1896 and 1906, mostly in Uganda and the Congo Basin, one in 1920 in several African countries, and one that began in 1970 and is still in progress. The 1920 epidemic was arrested due to mobile teams systematically screening millions of people at risk. The disease had practically disappeared between 1960 and 1965. After that success, screening and effective surveillance were relaxed and the disease has reappeared in endemic form in several foci over the last thirty years.
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| <ref>{{cite paper
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| |author=WHO Media centre
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| |title=Fact sheet N°259: African trypanosomiasis or sleeping sickness
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| |date=2001
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| |url=http://www.who.int/mediacentre/factsheets/fs259/en/index.html
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| }}</ref>
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| ==Historical Perspective==
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| ===Drug Developments===
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| [[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.
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| [[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.
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| 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.
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| [[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.
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| ===Biological Understanding of African Trypanosomiasis===
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| 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>
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| 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>
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| 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>
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| [[New Scientist]], [http://www.newscientist.com/channel/health/mg19526181.400-cholesterol-secret-of-our-killer-blood.html 25 Aug. 2007, pp. 35-7]
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| </ref>
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| ===Research===
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| 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".
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| <ref>{{cite news
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| |first=David
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| |last=Williamson
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| |title=Compound might defeat African sleeping sickness, clinical trial beginning this month
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| |date=August 25, 2005
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| |publisher=University of North Carolina
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| |url=http://usinfo.state.gov/xarchives/display.html?p=washfile-english&y=2005&m=August&x=20050826160501cmretrop0.7327387&t=livefeeds/wf-latest.html
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| }}</ref>
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| <ref>{{cite news
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| |author=Staff
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| |page=5
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| |title=Clinical Trials Update
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| |date=September 15, 2005
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| |publisher=[[Genetic Engineering News]]
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| }}</ref>
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| ==References== | | ==References== |