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| __NOTOC__
| | ==Medical therapy== |
| | ===Uncomplicated strongylidiasis=== |
| | *''Strongyloides stercoralis'' |
| | :* Preferred regimen (1): [[Ivermectin]] 200 μg/kg/day PO q24h for 2 days |
| | :* Note: For immunocompromised patients several treatment courses at 2-week intervals is recommended. |
| | :* Alternative regimen (1): [[Thiabendazole]] 1.5 g PO q24h for 2 consecutive days. |
| | :* Note: The maximum dosage is 3 g/d every 2 days (this dosage is likely to be toxic and needs to be reduced) |
| | :* Note: Cure rates as high as 87% to 94%, but the drug may not be effective in the disease that is disseminated beyond the gastrointestinal tract. |
| | :* Note: Many patients have gastrointestinal adverse effects, it is used rarely in the U.S. because of adverse effects |
| | :* Alternative regimen (2): [[Albendazole]] 400 mg PO bid for 3 days |
|
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|
| {{CMG}}<br>
| | ===Complicated strongyloidiasis (Disseminated or hyper-infection syndrome)=== |
| {{SK}} sleeping sickness, Human African trypanosomiasis
| | :* Preferred regimen (1): [[Ivermectin]] 200 μg/kg/d PO q24h orally for at least 7 to 10 days (until larvae are no longer detected in stool, sputum, or urine) |
| ==Overview== | | :* Note: For hyper-infection and disseminated disease, adding albendazole (400 mg PO bid for 7 days) to ivermectin may be warranted. |
| Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection with protozoan parasites belonging to the genus Trypanosoma. They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harbouring human pathogenic parasites.Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. For reasons that are so far unexplained, in many regions where tsetse flies are found, sleeping sickness is not. Rural populations living in regions where transmission occurs and which depend on agriculture, fishing, animal husbandry or hunting are the most exposed to the tsetse fly and therefore to the disease. The disease develops in areas ranging from a single village to an entire region. Within an infected area, the intensity of the disease can vary from one village to the next.
| |
| ==Overview==
| |
| 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.
| |
| <ref>{{cite paper
| |
| |author=WHO Media centre
| |
| |title=Fact sheet N°259: African trypanosomiasis or sleeping sickness
| |
| |date=2001
| |
| |url=http://www.who.int/mediacentre/factsheets/fs259/en/index.html
| |
| }}</ref>
| |
| | |
| ==Historical Perspective==
| |
| ===Drug Developments===
| |
| [[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.
| |
| | |
| [[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.
| |
| | |
| 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.
| |
| | |
| [[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.
| |
| | |
| ===Biological Understanding of African Trypanosomiasis===
| |
| 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>
| |
| | |
| 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>
| |
| | |
| ===Research===
| |
| 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>
| |
| | |
| ==Pathophysiology==
| |
| ===Transmission===
| |
| *The disease is mostly transmitted through the bite of an infected tsetse fly but there are other ways in which people are infected:
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| *Mother-to-child infection: the trypanosome can cross the placenta and infect the fetus.
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| *Mechanical transmission through other blood-sucking insects is possible, however, it is difficult to assess its epidemiological impact.
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| *Accidental infections have occurred in laboratories due to pricks with contaminated needles.
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| *Transmission of the parasite through sexual contact has been documented.
| |
| Human African trypanosomiasis takes 2 forms, depending on the parasite involved:
| |
| ===Trypanosoma brucei gambiense===
| |
| *Trypanosoma brucei gambiense is found in 24 countries in west and central Africa.
| |
| *This form currently accounts for 97% of reported cases of sleeping sickness and causes a chronic infection.
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| *A person can be infected for months or even years without major signs or symptoms of the disease.
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| *When more evident symptoms emerge, the patient is often already in an advanced disease stage where the central nervous system is affected.
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| ===Trypanosoma brucei rhodesiense ===
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| *Trypanosoma brucei rhodesienseis found in 13 countries in eastern and southern Africa.
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| *Nowadays, this form represents under 3% of reported cases and causes an acute infection.
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| *First signs and symptoms are observed a few months or weeks after infection.
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| *The disease develops rapidly and invades the central nervous system. Only Uganda presents both forms of the disease, but in separate zones.
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| ===American trypanosomiasis or Chagas disease===
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| *Another form of trypanosomiasis occurs mainly in Latin America.
| |
| *The causal organism belongs to a different Trypanosoma subgenus and is transmitted by a different vector.
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| ===Animal trypanosomiasis===
| |
| *Other parasite species and sub-species of the Trypanosoma genus are pathogenic to animals and cause animal trypanosomiasis in wild and domestic animals.
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| *In cattle the disease is called Nagana.
| |
| *Trypanosomiasis in domestic animals, particularly in cattle, is a major obstacle to the economic development of affected rural areas.
| |
| | |
| Animals can host the human pathogen parasites, especially T.b. rhodesiense, of which domestic and wild animals are an important reservoir. Animals can also be infected with T.b. gambiense and act as a reservoir to a lesser extent. However the precise epidemiological role of the animal reservoir in the gambiense form of the disease is not yet well known.
| |
| | |
| Major human epidemics
| |
| There have been several epidemics in Africa over the last century:
| |
| | |
| one between 1896 and 1906, mostly in Uganda and the Congo Basin;
| |
| one in 1920 in a number of African countries; and
| |
| the most recent epidemic started in 1970 and lasted until the late 1990s.
| |
| The 1920 epidemic was controlled thanks to mobile teams which carried out the screening of millions of people at risk. By the mid-1960s, the disease was under control with less than 5000 cases reported in the whole continent. After this success, surveillance was relaxed, and the disease reappeared, reaching epidemic proportions in several regions by 1970. The efforts of WHO, national control programmes, bilateral cooperation and nongovernmental organizations (NGOs) during the 1990s and early 21st century reversed the curve.
| |
| | |
| Since the number of new human African trypanosomiasis cases reported between 2000 and 2012 dropped by 73%, the WHO neglected tropical diseases roadmap targeted its elimination as a public health problem by 2020.
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| | |
| Disease burden
| |
| | |
| Sleeping sickness threatens millions of people in 36 countries in sub-Saharan Africa. Many of the affected populations live in remote rural areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission.
| |
| | |
| In 1998, almost 40 000 cases were reported, but estimates were that 300 000 cases were undiagnosed and therefore untreated.
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| During the most recent epidemic the prevalence reached 50% in several villages in Angola, the Democratic Republic of the Congo, and South Sudan. Sleeping sickness was the first or second greatest cause of mortality in those communities, even ahead of HIV/AIDS.
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| In 2009, after continued control efforts, the number of cases reported dropped below 10 000 (9878) for the first time in 50 years. This decline in number of cases has continued with 2804 new cases reported in 2015, the lowest level since the start of systematic global data-collection 76 years ago. The estimated number of actual cases is below 20 000 and the estimated population at risk is 65 million people.
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| Current disease distribution
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| The disease incidence differs from one country to another as well as in different parts of a single country.
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| | |
| In the last 10 years, over 70% of reported cases occurred in the Democratic Republic of the Congo (DRC).
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| The DRC is the only country that currently reports more than 1000 new cases annually and accounts for 84% of the cases reported in 2015.
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| Central African Republic is the only country that declared between 100 and 200 new cases in 2015.
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| Countries such as Angola, Burkina Faso, Cameroon, Chad, Congo, Côte d'Ivoire, Equatorial Guinea, Gabon, Gjana, Guinea, Malawi, Nigeria, South Sudan, Uganda, United Republic of Tanzania, Zambia and Zimbabwe are reporting fewer than 100 new cases per year.
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| Countries like Benin, Botswana, Burundi, Ethiopia, Gambia, Guinea Bissau, Kenya, Liberia, Mali, Mozambique, Namibia, Niger, Rwanda, Senegal, Sierra Leone, Swaziland and Togo have not reported any new cases for over a decade. Transmission of the disease seems to have stopped in some of these countries but there are still some areas where it is difficult to assess the exact situation because the unstable social circumstances and/or difficult accessibility hinder surveillance and diagnostic activities.
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| ==Epidemiology and demographics==
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| There are two subspecies of the parasite Trypanosoma brucei that cause disease in humans. The clinical features of the infection depend on the subspecies involved. The two subspecies are found in different regions of Africa. At present, there is no overlap in their geographic distribution.
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| | |
| T. b. rhodesiense (East African sleeping sickness) is found in focal areas of eastern and southeastern Africa. Each year a few hundred cases are reported to the World Health Organization. Over 95% of the cases of human infection occur in Tanzania, Uganda, Malawi, and Zambia. Animals are the primary reservoir of infection. Cattle have been implicated in the spread of the disease to new areas and in local outbreaks. A wild animal reservoir is thought to be responsible for sporadic transmission to hunters and visitors to game parks. Infection of international travelers is rare, but it occasionally occurs. In the U.S., one case per year, on average, is diagnosed. Most cases of sleeping sickness imported into the U.S. have been in travelers who were on safari in East Africa.
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| | |
| T. b. gambiense (West African sleeping sickness) is found predominantly in central Africa and in limited areas of West Africa. Most of the sleeping sickness in Africa is caused by this form of the parasite. Epidemics of sleeping sickness have been a significant public health problem in the past, but the disease is reasonably well-controlled at present, with 7,000-10,000 cases reported annually in recent years. Over 95% of the cases of human infection are found in Democratic Republic of Congo, Angola, Sudan, Central African Republic, Chad, and northern Uganda. Humans are the important reservoir of infection, although the parasite can sometimes be found in domestic animals (e.g., pigs, dogs, goats). Imported infection in the U.S. is extremely rare, and most cases have occurred in African nationals who have immigrated rather than in returning U.S. travelers.
| |
| | |
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| *=Epidemiology and Demographics==
| |
| <!-- Image with unknown copyright status removed: [[Image:Sleepinggeographic.jpg|thumb|200px|right|Geographic distribution vector for sleeping sickness cases.]] -->
| |
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| According to recent estimates, the disability adjusted life years (9 to 10 years) (DALYs) lost due to sleeping sickness are 2.0 million.<ref>{{cite paper
| |
| |author=World Health Organization (Geneva)
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| |title=World Health Report 2000: Health Systems Improving Performance
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| |date=2000
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| |url=http://www.who.int/tdr/diseases/tryp/direction.htm#Refs
| |
| }}</ref>
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| Recent estimates indicate that over 60 million people living in some 250 foci are at risk of contracting the disease, and there are about 300,000 new cases each year.<ref>{{cite paper
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| |author=WHO Expert Committee on Control and Surveillance of African trypanosomiasis (Geneva)
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| |title=WHO Technical Report Series,No.881
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| |date=1998
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| |url=http://www.who.int/tdr/diseases/tryp/direction.htm#Refs
| |
| }}</ref>
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| The disease has been recorded as occurring in 36 countries, all in sub-Saharan Africa.
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| Humans are the main reservoir for ''Trypanosoma brucei gambiense'', but this species can also be found in pigs and other animals. Wild game animals and cattle are the main reservoir of ''T. b. rhodesiense''.
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| | |
| Horse-flies (Tabanidae) and Stomoxydinae possibly could play a role by mechanical transmission (in special situations) not only of [[Nagana]] (the animal form of sleeping sickness) but also of the human disease form.<ref>{{cite journal
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| |author=Cherenet T, Sani RA, Panandam JM, Nadzr S, Speybroeck N, van den Bossche P
| |
| |title=Seasonal prevalence of bovine trypanosomosis in a tsetse-infested zone and a tsetse-free zone of the Amhara Region, north-west Ethiopia
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| |journal=[[The Onderstepoort journal of veterinary research]]
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| |year=2004 |volume=71 | issue=4 | pages= 307–312
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| |url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15732457&query_hl=1
| |
| }}</ref>
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| ===East African Trypanosomiasis===
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| Worldwide, approximately 40,000 new cases of both East and West African trypanosomiasis are reported to the [[World Health Organization]] each year. However, many cases are not reported due to a lack of infrastructure and the true number of new cases is undoubtedly much higher. Since 1967, thirty-six cases of East African trypanosomiasis have been reported within the United States, all among individuals who had traveled to Africa.
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| East African trypanosomiasis is found in parts of Eastern and Central Africa, including Uganda, Kenya, Tanzania, Malawi, Ethiopia, Zaire, Zimbabwe, and Botswana. Areas where infection is spread are largely determined by the location of the infected [[tsetse fly]] and wild animal population.
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| ===West African Trypanosomiasis===
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| West African trypanosomiasis can be contracted in parts of Western and Central Africa. The tsetse fly lives only in Africa; areas where infection is spread are largely determined by where the infected tsetse fly is found.<ref>
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| http://www.cdc.gov/ncidod/dpd/parasites/trypanosomiasis/factsht_ea_trypanosomiasis.htm#what
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| http://www.cdc.gov/ncidod/dpd/parasites/trypanosomiasis/factsht_wa_trypanosomiasis.htm</ref>
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| ==History and symptoms==
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| In the first stage, the trypanosomes multiply in subcutaneous tissues, blood and lymph. This is also called haemo-lymphatic stage, which entails bouts of fever, headaches, joint pains and itching
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| In the second stage the parasites cross the blood-brain barrier to infect the central nervous system. This is known as the neurological or meningo-encephalic stage. In general this is when more obvious signs and symptoms of the disease appear: changes of behaviour, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature. Without treatment, sleeping sickness is considered fatal although cases of healthy carriers have been reported.
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| {| class="wikitable"
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| !
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| !Symptoms
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| |-
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| |First stage (hemo-lyphatic stage)
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| * Fever
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| * Headaches
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| * Joint pains and itching
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| |-
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| |Second stage (neurological or meningo-encephalic stage)
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| * Changes of behaviour
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| * Confusion
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| * Sensory disturbances
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| * Poor coordination
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| * Disturbance of the sleep cycle,
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| |}
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| ==Diagnosis==
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| *Definitive diagnosis rests on the observation of trypanosomes by microscopy.
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| *In T. b. rhodesiense infection, the identification of suspected cases relies on the clinical presentation and a history of exposure. The level of parasitemia is relatively high, particularly in the first stage of disease, and trypanosomes can be found in blood.
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| *In centrifuged blood, the parasite sediments just above the white cells, and examination of buffy coat will increase sensitivity. Slides stained with Giemsa can be used, but it is easiest to find the parasite by microscopic examination of fresh wet preparations, because the trypanosomes are motile and attract the eye. Delay between sampling and microscopy should be minimized, because trypanosomes will lose motility within a few hours. Parasites can also be found in fluid expressed in trypanosomal chancres and in lymph node aspirates. Serologic testing is not used for the diagnosis of T. b. rhodesiense infection.
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| Detecting trypanosomes in T. b. gambiense infection is more difficult.
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| ==Serology==
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| *The card agglutination test for trypanosomiasis/T. b. gambiense is a serologic screening test used for mass population screening in endemic areas of Africa. It is not available in the U.S.
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| *The test is not specific enough for confirmation of infection, but it is helpful in identifying suspect cases.
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| *For parasitologic confirmation, a posterior cervical lymph node (if present) is punctured and the fluid examined. The yield in lymph node examination varies from about 40% to 80%.
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| *Trypanosomes can also be found in blood, however, the yield is low, and concentration techniques (e.g. buffy coat examination, miniature anion-exchange centrifugation technique) are helpful. Serial examinations on consecutive days may be needed.
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| *Treatment decisions are based on the stage of the disease. Every patient diagnosed with African trypanosomiasis must undergo a lumbar puncture for the examination of CSF. *The most widely used criteria for defining second stage disease are the observation of trypanosomes in CSF or a white cell count of 6 or higher. Other indications of second stage disease include elevated protein and an increase in nonspecific IgM in CSF.
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| Disease management is made in 3 steps:
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| *Screening for potential infection. This involves using serological tests (only available for T.b.gambiense) and checking for clinical signs - especially swollen cervical lymph nodes.
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| *Diagnosing by establishing whether the parasite is present in body fluids.
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| *Staging to determine the state of disease progression. This entails examining the cerebrospinal fluid obtained by lumbar puncture.
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| Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated and risky treatment procedures
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| ==Treatment==
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| The type of treatment depends on the disease stage. The drugs used in the first stage are safer and easier to administer than those for second stage. Also, the earlier the disease is identified, the better the prospect of a cure. The assessment of treatment outcome requires follow up of the patient up to 24 months and entails laboratory exams of body fluids including cerebrospinal fluid obtained by lumbar puncture, as parasites may remain viable for long periods and reproduce the disease months after treatment. Treatment success in the second stage depends on drugs that cross the blood-brain barrier to reach the parasite. Such drugs are toxic and complicated to administer. In total five different drugs are used for the treatment of sleeping sickness. These drugs are donated to WHO by manufacturers and distributed free of charge to disease endemic countries.
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| Medical treatment of African trypanosomiasis should begin as soon as possible and is based on the infected person’s symptoms and laboratory results. Medication for the treatment of African trypanosomiasis is available through the [[CDC]]. Pentamidine isethionate and suramin (under an investigational New Drug Protocol from the CDC Drug Service) are the drugs of choice to treat the hemolymphatic stage of West and East African Trypanosomiasis, respectively. Melarsoprol is the drug of choice for late disease with central nervous system involvement (infections by T.b. gambiense or T. b. rhodiense).
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| Hospitalization for treatment is necessary. Periodic follow-up exams that include a [[spinal tap]] are required for 2 years. If a person fails to receive medical treatment for African trypanosomiasis, death will occur within several weeks to months.
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| ==Pathogenesis==
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| there is modulation of the exposed surface antigens of the parasite. Metacyclic trypanosomes in the tsetse fly and bloodstream forms in mammalian and human hosts have proteins on their surface known as major variant surface glycoprotein (VSG). Each trypanosome is covered with approximately 10 million copies of a single VSG [33].
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| Innate immunity — Innate immunity against T. brucei is due to the trypanolytic activity of apolipoprotein L-I (APOL1), which is bound to high-density lipoproteins in human serum [34]. This protein is taken up in the parasite by endocytosis and triggers osmotic swelling of the lysosomal compartment with subsequent cell death [35]. The importance of the APOL1 protein in innate immunity has been demonstrated by the onset of human disease when parasites have acquired resistance to APOL1 [34] or when patients have mutations in the APOL1 gene [36].
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| Evasion of host defense — T. brucei parasites can evade destruction by the mammalian host immune response in the bloodstream by periodically switching their VSG, a phenomenon known as antigenic variation [37,38]. This results in characteristic waves of parasitemia during human African trypanosomiasis (HAT) infection. Trypanosomes express a different VSG during each successive wave of parasitemia and change their surface VSG each time the host begins to mount an effective immune response. In this way, the parasite is able to stay one step ahead of the host's immune response [39]. This process also leads to nonspecific activation of the host humoral immune response, which can induce false-positive antibody-based tests used to diagnose other infections [25].
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| Other mechanisms enabling T. brucei parasites to survive despite host immune defenses include their ability to grow in the presence of high levels of interferon-gamma and to avoid complement-mediated destruction [40]. One study identified two different genotypes of the parasite circulating simultaneously in the same patient [41].
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| Immune response — Antigenic variation leads to nonspecific polyclonal B cell activation during infection and immunoglobulin M is produced in large quantities. Immune complexes form, and secondary hyperplasia of the reticuloendothelial system occurs, particularly involving the spleen and lymph nodes. This process may lead to downregulation of the immune system. Therefore, generalized suppression of humoral and cellular immune responses may be seen in advanced stages of the disease [42].
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| The relative contribution of immune complex deposition, inflammatory infiltrates, vascular infiltration, and direct parasite invasion to organ damage in African trypanosomiasis is uncertain; it is likely that the pathogenesis of HAT reflects a complex combination of these mechanisms
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| ==Medical Therapy==
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| ===Antimicrobial Regimen===
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| :* ''' Sleeping sickness'''<ref>{{cite web|title=African Trypanosomiasis| url= http://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html}}</ref>
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| ::* 1. '''East african trypanosomiasis'''
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| :::* 1.1 '''T. b. rhodesiense, hemolymphatic stage'''
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| ::::* 1.1.1 '''Adult '''
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| :::::* Preferred regimen: [[Suramin]] 1 gm IV on days 1,3,5,14, and 21
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| ::::* 1.1.2 '''Pediatric'''
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| :::::* Preferred regimen: [[Suramin]] 20 mg/kg IV on days 1, 3, 5, 14, and 21
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| :::* 1.2 '''T. b. rhodesiense, CNS involvement'''
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| ::::* 1.2.1 '''Adult'''
| |
| :::::* Preferred regimen: [[Melarsoprol]] 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
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| ::::* 1.2.2 '''Pediatric'''
| |
| :::::* Preferred regimen: [[Melarsoprol]] 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days
| |
| ::* 2. '''West african trypanosomiasis'''
| |
| :::* 2.1 '''T. b. gambiense, hemolymphatic stage'''
| |
| ::::* 2.1.1 '''Adult'''
| |
| :::::* Preferred regimen: [[Pentamidine]] 4 mg/kg/day IM/ IV for 7-10 days
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| ::::* 2.1.2 '''Pediatric'''
| |
| :::::* Preferred regimen: [[Pentamidine]] 4 mg/kg/day IM/IV for 7-10 days
| |
| :::::* Note (1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
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| :::::* Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
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| :::* 2.2 '''T. b. gambiense, CNS involvement'''
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| ::::* 2.2.1 '''Adult'''
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| :::::* Preferred regimen: [[Eflornithine]] 400 mg/kg/day IV qid for 14 days
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| ::::* 2.2.2 '''Pediatric'''
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| :::::* Preferred regimen: [[Eflornithine]] 400 mg/kg/day IV qid for 14 days
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| :::::* Note (1): [[Eflornithine]] should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
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| :::::* Note (2): The safety of [[Eflornithine]] in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. [[Eflornithine]] is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
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| | |
| ==Prevention==
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| Wear protective clothing, including long-sleeved shirts and pants. The tsetse fly can bite through thin fabrics, so clothing should be made of medium-weight material.
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| Wear neutral-colored clothing. The tsetse fly is attracted to bright colors and very dark colors.
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| Inspect vehicles for tsetse flies before entering. The flies are attracted to moving vehicles.
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| Avoid bushes. The tsetse fly is less active during the hottest period of the day. It rests in bushes but will bite if disturbed.
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| Use insect repellant. Though insect repellants have not proven effective in preventing tsetse fly bites, they are effective in preventing other insects from biting and causing illness.
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| ==Screening==
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| *Instances of sleeping sickness are being reduced by the use of the [[sterile insect technique]].
| |
| *Systematic [[Screening (medicine)|screening]] of communities in identified foci is the best approach as case-by-case screening is not practically possible in highly endemic regions.
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| *Systematic screening may be in the form of mobile clinics or fixed screening centres where teams travel daily to the foci.
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| *The nature of gambiense disease is such that patients don't seek treatment early enough because the symptoms at that stage are not evident or serious enough to warrant seeking medical attention, considering the remoteness of some affected areas. Also, diagnosis of the disease is difficult and most health workers may not be able to detect it.
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| *Systematic screening allows early-stage disease to be detected and treated before the disease progresses, and removes the potential human reservoir.<ref>{{cite web
| |
| |title=Strategic Direction for African Trypanosomiasis Research
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| |work=Special Programme for Research and Training in Tropical Diseases
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| |url=http://www.who.int/tdr/diseases/tryp/direction.htm
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| |accessdate=2006-03-01
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| }}</ref>
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