View source for African trypanosomiasis

{{Short description|Parasitic disease also known as sleeping sickness}}
{{Redirect2|Sleeping sickness|Sleep fever|other uses|Sleeping sickness (disambiguation)}}
{{About|the human disease|the disease affecting animals|Animal trypanosomiasis}}
{{cs1 config|name-list-style=vanc}}
{{Use dmy dates|date=September 2024}}
{{Infobox medical condition
| name = African trypanosomiasis
| synonyms = Sleeping sickness, African sleeping sickness
| alt =
| caption = Trypanosoma forms in a [[blood film|blood smear]]
| image_size =
| image = Trypanosoma sp. PHIL 613 lores.jpg
| field = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms = '''Stage 1''': Fevers, headaches, itchiness, joint pains<ref name=WHO2013/><br />'''Stage 2''': [[Insomnia]], [[confusion]], [[Ataxia]]<ref name=Lancet2013/><ref name=WHO2013/>
| complications =
| onset = 1–3 weeks post exposure<ref name=Lancet2013/>
| duration =
| types = ''[[Trypanosoma brucei gambiense]]'' and ''[[Trypanosoma brucei rhodesiense]]''<ref name=WHO2020/>
| causes = ''[[Trypanosoma brucei]]'' spread by [[tsetse fly|tsetse flies]]<ref name=WHO2020/>
| risks =
| diagnosis = [[Blood smear]], [[lumbar puncture]]<ref name=Lancet2013/>
| differential =
| prevention =
| treatment =
| medication = [[Fexinidazole]], [[pentamidine]], [[suramin]], [[melarsoprol]], [[eflornithine]], [[nifurtimox]]<ref name=WHO2020/>
| prognosis = Fatal without treatment<ref name=WHO2020/>
| frequency = 977 (2018)<ref name=WHO2020/>
| deaths = 3,500 (2015)<ref name=GBD2015De/>
}}
<!-- Definition and cause -->

'''African trypanosomiasis''' is an insect-borne [[parasitic]] infection of humans and other animals.<ref name="WHO2020" />

Human African trypanosomiasis (HAT), also known as '''African sleeping sickness''' or simply '''sleeping sickness''', is caused by the species ''[[Trypanosoma brucei]]''.<ref name=WHO2020/> Humans are infected by two types, ''Trypanosoma brucei gambiense'' and ''Trypanosoma brucei rhodesiense''.<ref name=WHO2020/> ''Trypanosoma brucei gambiense'' causes over 92% of reported cases.<ref name="WHO2013">{{cite web 
| url = https://www.who.int/mediacentre/factsheets/fs259/en/
| title = Fact sheet N°259: Trypanosomiasis, Human African (sleeping sickness) 
| author = WHO Media Centre 
| publisher = [[World Health Organization]] 
| date = March 2014 
| access-date = 25 April 2014 
| url-status = live 
| archive-url = https://web.archive.org/web/20140426104752/http://www.who.int/mediacentre/factsheets/fs259/en/ 
| archive-date = 26 April 2014 
}}</ref>
Both are usually transmitted by the bite of an infected [[tsetse fly]] and are most common in rural areas.<ref name=WHO2020/>

<!-- Signs and symptoms -->
Initially, the first stage of the disease is characterized by fevers, headaches, itchiness, and joint pains, beginning one to three weeks after the bite.<ref name=WHO2013/><ref name=Lancet2013/> Weeks to months later, the second stage begins with confusion, poor coordination, numbness, and trouble sleeping.<ref name=Lancet2013/> Diagnosis involves detecting the parasite in a [[blood smear]] or lymph node fluid.<ref name=Lancet2013/> A [[lumbar puncture]] is often needed to tell the difference between first- and second-stage disease.<ref name=Lancet2013/>

<!-- Prevention and treatment -->
Prevention of severe disease involves screening the at-risk population with blood tests for ''Trypanosoma brucei gambiense''.<ref name=WHO2020/> Treatment is easier when the disease is detected early and before neurological symptoms occur.<ref name=WHO2020/> The use of [[pentamidine]] or [[suramin]] treats the hemolymphatic stage of ''T. Brucei'' infection but if the disease progresses to the neurological stage dosages of [[eflornithine]] or a combination of [[nifurtimox]] and eflornithine can serve as a treatment for late-stage African Sleeping Disease.<ref name=Lancet2013>{{cite journal | vauthors = Kennedy PG | title = Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness) | journal = The Lancet. Neurology | volume = 12 | issue = 2 | pages = 186–194 | date = February 2013 | pmid = 23260189 | doi = 10.1016/S1474-4422(12)70296-X | s2cid = 8688394 }}</ref><ref name=WHO2020/> [[Fexinidazole]] is a more recent treatment that can be taken by mouth, for either stage of ''Trypanosoma brucei gambiense''.<ref name=WHO2020>{{cite web |title=Trypanosomiasis, human African (sleeping sickness) |url=https://www.who.int/en/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness) |publisher=World Health Organization |access-date=14 May 2020}}</ref> While [[melarsoprol]] works for both types, it is typically used only for ''Trypanosoma brucei rhodesiense'', due to its serious side effects.<ref name=WHO2020/> Without treatment, sleeping sickness typically results in death.<ref name=WHO2020/>

<!-- Epidemiology and History-->
The disease occurs regularly in some regions of [[sub-Saharan Africa]] with the population at risk being about 70 million in 36 countries.<ref name=Sim2012>{{cite journal | vauthors = Simarro PP, Cecchi G, Franco JR, Paone M, Diarra A, Ruiz-Postigo JA, Fèvre EM, Mattioli RC, Jannin JG | display-authors = 6 | title = Estimating and mapping the population at risk of sleeping sickness | journal = PLOS Neglected Tropical Diseases | volume = 6 | issue = 10 | article-number = e1859 | year = 2012 | pmid = 23145192 | pmc = 3493382 | doi = 10.1371/journal.pntd.0001859 | doi-access = free }}</ref> An estimated 11,000 people are currently infected with 2,800 new infections in 2015.<ref name=GBD2015Pre>{{cite journal | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 | collaboration = GBD 2015 Disease and Injury Incidence and Prevalence Collaborators | display-authors = 6 | vauthors = Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, Carter A, Casey DC, Charlson FJ, Chen AZ, Coggeshall M, Cornaby L, Dandona L, Dicker DJ, Dilegge T, Erskine HE, Ferrari AJ, Fitzmaurice C, Fleming T, Forouzanfar MH, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Hay SI, Johnson CO, Kassebaum NJ, Kawashima T, Kemmer L }}</ref><ref name=WHO2013/> In 2018 there were 977 new cases.<ref name=WHO2020/> In 2015 it caused around 3,500 deaths, down from 34,000 in 1990.<ref name=GBD2015De>{{cite journal | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/s0140-6736(16)31012-1 | collaboration = GBD 2015 Mortality and Causes of Death Collaborators | display-authors = 6 | vauthors = Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, Casey DC, Charlson FJ, Chen AZ, Coates MM, Coggeshall M, Dandona L, Dicker DJ, Erskine HE, Ferrari AJ, Fitzmaurice C, Foreman K, Forouzanfar MH, Fraser MS, Fullman N, Gething PW, Goldberg EM, Graetz N, Haagsma JA, Hay SI, Huynh C, Johnson CO, Kassebaum NJ, Kinfu Y, Kulikoff XR }}</ref><ref name=Loz2012>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA | display-authors = 6 | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–2128 | date = December 2012 | pmid = 23245604 | pmc = 10790329 | doi = 10.1016/S0140-6736(12)61728-0 | hdl-access = free | s2cid = 1541253 | hdl = 10536/DRO/DU:30050819 }}</ref> More than 80% of these cases are in the [[Democratic Republic of the Congo]].<ref name=WHO2013/> Three major outbreaks have occurred in recent history: one from 1896 to 1906 primarily in [[Uganda]] and the [[Congo Basin]], and two in 1920 and 1970, in several African countries.<ref name=WHO2013/> It is classified as a [[neglected tropical disease]].<ref name=NTD2017>{{cite web|title=Neglected Tropical Diseases|url=https://www.cdc.gov/globalhealth/ntd/diseases/index.html|publisher=Centers for Disease Control and Prevention|access-date=28 November 2014|date=6 June 2011|url-status=live|archive-url=https://web.archive.org/web/20141204084219/http://www.cdc.gov/globalhealth/ntd/diseases/index.html|archive-date=4 December 2014}}</ref> Other animals, such as cows, may carry the disease and become infected in which case it is known as nagana or [[animal trypanosomiasis]].<ref name=WHO2013/>

==Signs and symptoms==
African trypanosomiasis symptoms occur in two stages: 1) the hemolymphatic stage and 2) the neurological stage. The hemolymphatic stage refers to the period when parasites are present in the blood and lymphatic system, prior to central nervous system involvement. The neurological stage, also called the meningoencephalitic phase, begins when Trypanosoma parasites cross the blood–brain barrier and invade the central nervous system.<ref name="pmid15304634" /><ref name="www.cdc.gov_2020">{{cite web|date=2020-04-28|title=CDC – African Trypanosomiasis – Disease|url=https://www.cdc.gov/parasites/sleepingsickness/disease.html|access-date=2020-08-11|publisher=Centers for Disease Control and Prevention}}</ref> In addition to the hemolymphatic stage neurological symptoms can still present themselves, resulting in a difficulty in distinguishing the two stages based on clinical features alone.<ref name="www.cdc.gov_2020" />

The disease has been reported to present with atypical symptoms in infected individuals who originate from non-endemic areas (e.g., travelers). The reasons for this are unclear and may be genetic. Delayed or missed diagnosis in infected individuals who originate from non-endemic areas (travelers) has been reported symptoms including higher susceptibility and quicker progression of advanced stages of the disease. The reasons for this are unclear, but certain symptoms, such as high fever, could be due to genetic factors or a lack of previous exposure to non-human-pathogenic forms of trypanosomes.<ref name="Travelers">{{Cite journal |last1=Urech |first1=Karin |last2=Neumayr |first2=Andreas |last3=Blum |first3=Johannes |date=2011-11-01 |editor-last=Ghedin |editor-first=Elodie |title=Sleeping Sickness in Travelers - Do They Really Sleep? |journal=PLOS Neglected Tropical Diseases |language=en |volume=5 |issue=11 |article-number=e1358 |doi=10.1371/journal.pntd.0001358 |doi-access=free |issn=1935-2735 |pmc=3206012 |pmid=22069503}}</ref> The low number of such cases may also have skewed findings. In such persons, the infection is said to present mainly as fever with gastrointestinal symptoms (e.g., diarrhea and jaundice) and with [[lymphadenopathy]] rarely developing.<ref name="Kennedy_2019">{{cite journal | vauthors = Kennedy PG, Rodgers J | title = Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis | journal = Frontiers in Immunology | volume = 10 | page = 39 | date = 2019-01-25 | pmid = 30740102 | pmc = 6355679 | doi = 10.3389/fimmu.2019.00039 | doi-access = free }}</ref>

=== Trypanosomal ulcer ===

Systemic disease is sometimes presaged by a trypanosomal [[ulcer]] developing at the site of the infectious fly bite within 2 days of infection. The ulcer is most commonly observed in T. b. rhodesiense infection and rarely in T. b. gambiense infection, where ulcers are more common in persons from non-endemic areas.<ref name="www.cdc.gov_2020" />

=== Hemolymphatic phase ===
The incubation period is 1–3 weeks for ''T. b. rhodesiense,'' and longer (but less precisely characterised) in ''T. b. gambiense'' infection. The first/initial stage, known as the hemolymphatic phase, is characterized by non-specific, generalised symptoms<ref name="www.cdc.gov_2020" /> like: [[Intermittent fever|fever (intermittent)]], headaches (severe),<ref name="www.cdc.gov_2019">{{cite web|date=2019-04-22|title=CDC – African Trypanosomiasis – General Information – East African Trypanosomiasis FAQs|url=https://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-east.html|access-date=2020-08-11|publisher=Centers for Disease Control and Prevention}}</ref> [[Arthralgia|joint pains]], [[itch]]ing,<ref name="pmid15304634" /><ref name="www.cdc.gov_2020" /> weakness, malaise, fatigue, weight loss, lymphadenopathy, and [[hepatosplenomegaly]].<ref name="www.cdc.gov_2020" />

Diagnosis may be delayed due to the vagueness of initial symptoms. The disease may also be mistaken for [[malaria]] (which may occur as a co-infection).<ref name="Kennedy_2019" />

==== Intermittent fever ====

Fever is intermittent, with attacks lasting from a day to a week, separated by intervals of a few days to a month or longer.<ref name="pmid15304634" /><ref name="www.cdc.gov_2020" /> Episodes of fever become less frequent throughout the disease.<ref name="www.cdc.gov_2020" />

==== Lymphadenopathy ====

Invasion of the circulatory and lymphatic systems by the parasite is associated with severe [[Lymphadenopathy|swelling of lymph nodes]], often to tremendous sizes.<ref name="pmid15304634" /> Posterior cervical lymph nodes are most commonly affected; however, axillary, inguinal, and epitrochlear lymph node involvement may also occur.<ref name="www.cdc.gov_2020" /> [[Winterbottom's sign]] is a clinical finding involving swollen lymph nodes at the base of the skull or along the back of the neck, particularly characteristic of T. b. gambiense infections.<ref name="pmid15304634">{{cite journal | vauthors = Lundkvist GB, Kristensson K, Bentivoglio M | title = Why trypanosomes cause sleeping sickness | journal = Physiology | volume = 19 | issue = 4 | pages = 198–206 | date = August 2004 | pmid = 15304634 | doi = 10.1152/physiol.00006.2004 | s2cid = 17844506 }}</ref><ref name="www.cdc.gov_2020" />

==== Other features ====

Those affected may additionally present with: skin rash,<ref name="www.cdc.gov_2019" /> haemolytic anaemia, hepatomegaly and abnormal liver function, splenomegaly, endocrine disturbance, cardiac involvement (e.g., pericarditis and congestive heart failure), and ophthalmic involvement.<ref name="Kennedy_2019" />

<gallery widths="200" heights="200">
File:PMC5373517 pntd.0005324.g001.png|Ulcer of human African trypanosomiasis<ref name=":0">{{cite journal | vauthors = Gómez-Junyent J, Pinazo MJ, Castro P, Fernández S, Mas J, Chaguaceda C, Pellicé M, Gascón J, Muñoz J | display-authors = 6 | title = Human African Trypanosomiasis in a Spanish traveler returning from Tanzania | journal = PLOS Neglected Tropical Diseases | volume = 11 | issue = 3 | article-number = e0005324 | date = March 2017 | pmid = 28358876 | pmc = 5373517 | doi = 10.1371/journal.pntd.0005324 | doi-access = free }}</ref>
File:AcuteSleepingSickness.jpg|Typical fine-spotted pink rash of acute African trypanosomiasis on the skin of the abdomen ("trypanid rash")<ref name=Paul2014>{{cite journal | vauthors = Paul M, Stefaniak J, Smuszkiewicz P, Van Esbroeck M, Geysen D, Clerinx J | title = Outcome of acute East African trypanosomiasis in a Polish traveller treated with pentamidine | journal = BMC Infectious Diseases | volume = 14 | page = 111 | date = February 2014 | pmid = 24571399 | pmc = 3941560 | doi = 10.1186/1471-2334-14-111 | doi-access = free }}</ref>
File:SSHemorragicRash.jpg|Numerous [[ecchymoses|spots of bleeding into the skin]] of the leg in a person infected with ''T. b. rhodesiense''<ref name=Paul2014/>
</gallery>

=== Neurological phase ===
The second phase of the disease, the [[neurological disorder|neurological phase]] (also called the ''meningoencephalic stage''<ref name="www.cdc.gov_2020" />), begins when the parasite invades the [[central nervous system]] by passing through the [[blood–brain barrier]].<ref name="pmid15304634" /> Progression to the neurological phase occurs after an estimated 21–60 days in case of ''T. b. rhodesiense'' infection, and 300–500 days in case of ''T. b. gambiense'' infection.<ref name="www.cdc.gov_2020" />

In actuality, the two phases of African trypanosomiasis—the hemolymphatic stage and the neurological stage—often overlap, and their clinical features can be nonspecific or evolve gradually, making it difficult to distinguish them based on symptoms alone.<ref name=":03">{{Cite journal |last=Kennedy |first=Peter |date=25 January 2019 |title=Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis |journal=Frontiers in Immunology |volume=10 |page=39 |doi=10.3389/fimmu.2019.00039 |doi-access=free |pmid=30740102 |pmc=6355679 }}</ref> While signs such as enlarged lymph nodes and intermittent fever are more characteristic of the early stage, and neuropsychiatric symptoms such as sleep disturbances, confusion, or motor abnormalities suggest progression to the later stage, these indicators are not definitive. Consequently, to accurately determine the stage of the disease, specifically to determine central nervous system involvement, a [[lumbar puncture]] is performed to analyze the [[Cerebrospinal fluid|cerebrospinal fluid (CSF)]].<ref name=":03" /> The detection of trypanosome parasites in the CSF confirms that the infection has progressed to the neurological phase. This assessment is crucial because treatment protocols differ depending on whether or not the central nervous system has been affected. In the later stage, more intensive drugs that can cross the [[Blood–brain barrier|blood-brain barrier]] are necessary to eliminate the parasites from the brain and spinal cord.

==== Sleep disorders ====
Sleep-wake disturbances are a leading feature of the neurological stage<ref name="pmid15304634" /><ref name="Maxfield_2020">{{cite book | vauthors = Maxfield L, Bermudez R | chapter = Trypanosomiasis (Trypansomiasis)|date=2020| chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK535413/| title = StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=30571034|access-date=2020-08-11 }}</ref> and give the disease its common name of "sleeping sickness".<ref name="pmid15304634" /><ref name="www.cdc.gov_2020" /><ref name="Maxfield_2020" /> Infected individuals experience a disorganized and fragmented sleep-wake cycle.<ref name="pmid15304634" /> Those affected experience [[sleep inversion]] resulting in daytime sleep<ref name="pmid15304634" /> and somnolence,<ref name="www.cdc.gov_2020" /> and nighttime periods of wakefulness<ref name="pmid15304634" /> and insomnia.<ref name="www.cdc.gov_2020" /> Additionally, those affected also experience episodes of sudden sleepiness.<ref name="www.cdc.gov_2020" />

This sleeping impairment is also related to disruptions of [[circadian rhythm]], the body's internal clock, which regulates rhythmic behavior, including metabolic patterns in cells.<ref name="Filipa2">{{Cite journal |last1=Rijo-Ferreira |first1=Filipa |last2=Carvalho |first2=Tânia |last3=Afonso |first3=Cristina |last4=Sanches-Vaz |first4=Margarida |last5=Costa |first5=Rui M |last6=Figueiredo |first6=Luísa M. |last7=Takahashi |first7=Joseph S. |date=2018-01-04 |title=Sleeping sickness is a circadian disorder |journal=Nature Communications |language=en |volume=9 |issue=1 |page=62 |doi=10.1038/s41467-017-02484-2 |issn=2041-1723 |pmc=5754353 |pmid=29302035|bibcode=2018NatCo...9...62R }}</ref> Studies indicate ''[[Trypanosoma brucei|T. brucei]]'' alters the oscillatory expression of clock genes in the [[Suprachiasmatic nucleus|suprachiasmatic nuclei (SCN)]], among other brain regions, charged with circadian regulation.<ref name=":0222">{{Cite journal |last1=Cavadini |first1=G. |last2=Farkas |first2=I |last3=Saez |first3=M. |last4=Brunner |first4=M. |last5=Kerekes |first5=T. |last6=Jäkel |first6=M. |date=2007 |title=TNF-α suppresses the expression of clock genes by interfering with E-box-mediated transcription |journal=Proceedings of the National Academy of Sciences  |volume=104 |issue=31 |pages=12843–12848 |doi=10.1073/pnas.0701466104 |doi-access=free |pmid=17646651 |via=PNAS|pmc=1937554 }}</ref> This alteration of expression may be moderated by the host's immune responses, such as parasitic activity and inflammation resulting from elevated [[TNF-α|TNF-α levels]].<ref name=":0222" />

====Neurological/Neurocognitive symptoms====

Neurological symptoms include: [[tremor]], general muscle weakness, [[hemiparesis]], [[paralysis]] of a limb,<ref name="Brun10" /> abnormal muscle tone, gait disturbance, ataxia, speech disturbances, paraesthesia, hyperaesthesia, anaesthesia, visual disturbance, abnormal reflexes, seizures, and coma.<ref name="www.cdc.gov_2020" /> [[Parkinsonism|Parkinson]]-like movements might arise due to non-specific movement disorders and speech disorders.<ref name="Brun10" />

====Psychiatric/Behavioural symptoms====

Individuals may exhibit psychiatric symptoms, which can sometimes dominate the clinical presentation. These symptoms include aggressiveness, [[apathy]],<ref name="www.cdc.gov_2020" /><ref name="Brun10" /> irritability, [[Psychosis|psychotic]] reactions<ref name="Brun10">{{cite journal | vauthors = Brun R, Blum J, Chappuis F, Burri C | title = Human African trypanosomiasis | journal = Lancet | volume = 375 | issue = 9709 | pages = 148–159 | date = January 2010 | pmid = 19833383 | doi = 10.1016/S0140-6736(09)60829-1 | hdl-access = free | s2cid = 39433996 | hdl = 10144/114145 }}</ref> and [[hallucination]]s, [[anxiety]], [[emotional lability]], [[confusion]], [[mania]], attention deficit, and [[delirium]].<ref name="www.cdc.gov_2020" />

=== Advanced/Late disease and outcomes ===
Without treatment, the disease is invariably fatal, with progressive mental deterioration leading to coma, systemic organ failure, and death. An untreated infection with ''[[Trypanosoma brucei rhodesiense|T. b. rhodesiense]]'' will cause death within months<ref>{{cite web |title=East African Trypanosomiasis FAQs |date=29 August 2012 |work=Parasites – African Trypanosomiasis (also known as Sleeping Sickness) |publisher=Centers for Disease Control and Prevention |url=https://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-east.html |url-status=live |archive-url=https://web.archive.org/web/20170711152023/https://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-east.html |archive-date=11 July 2017}}</ref> whereas an untreated infection with ''[[Trypanosoma brucei gambiense|T. b. gambiense]]'' will cause death after several years.<ref>{{cite web |title=West African Trypanosomiasis FAQs |date=29 August 2012 |work=Parasites – African Trypanosomiasis (also known as Sleeping Sickness) |publisher=Centers for Disease Control and Prevention |url=https://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-west.html |url-status=live |archive-url=https://web.archive.org/web/20170619152521/https://www.cdc.gov/parasites/sleepingsickness/gen_info/faqs-west.html |archive-date=19 June 2017}}</ref> Damage caused in the neurological phase is irreversible.<ref name="allafrica.com">{{cite web |title=Uganda: Sleeping Sickness Reaching Alarming Levels |date=11 May 2008 |work=New Vision |url=http://allafrica.com/stories/200805120552.html |url-status=live |archive-url=https://web.archive.org/web/20080521173159/http://allafrica.com/stories/200805120552.html |archive-date=21 May 2008}}</ref>

== Circadian rhythm interactions ==

[[Circadian rhythm]], an intrinsic clock that mediates rhythm of biological function, is affected by African trypanosomiasis.<ref name=":0222"/> ''[[Trypanosoma brucei|T. brucei]]'' alters the rhythmic activity of clock genes in [[basal forebrain]], [[hypothalamus]], [[thalamus]], [[locus coeruleus]], [[brainstem]], etc
.<ref name=":0222"/> Both parasitic activity and inflammation induced by elevated [[TNF-α|TNF-α levels]] impairs oscillatory expression within the host.<ref name=":0222"/> These disruptions to regulate circadian gene expression are evidenced to contribute to key symptoms of African trypanosomiasis, such as fragmented sleep, temperature changes, and abnormal hormone release.

=== Effect on circadian rhythm ===
Most organisms implement internal timing mechanisms to regulate the homeostasis of the body with the environment. These mechanisms, called [[circadian clock]]s, regulate pathways in core processes, where in mammals the primary circadian clock is the [[Suprachiasmatic nucleus|suprachiasmatic Nucleus (SCN)]]. The SCN's ability to serve as the organism's primary internal clock and send signals to adjacent clocks to collectively synchronize them can be affected by a variety of factors. Certain factors that induce inflammation, such as viruses, bacteria, or parasites, can disrupt the interactions between a cell's circadian clock and the central pacemaker. The parasite aims to modify certain aspects of its host's behavior in a way that favors its survival and probability of transmission. To counteract this, the internal clock on hosts' immune cells anticipates the time of infection by the parasite and thus optimizes its cellular defenses or susceptibility to infection. In the case of [[Trypanosoma brucei]], the parasite takes advantage of the host immune cells' dependence on rhythmic regulation; it attacks the internal clock of the cells to improve its survival and multiplication.

African sleeping sickness mainly disrupts the [[Sleep-wake cycle|sleep/wake cycle]] alongside body temperature and hormonal regulation. After treatment, the sleep-wake cycle can revert to normal, indicating that the parasites are responsible for circadian rhythm alteration rather than neuronal damage.<ref name="Filipa2" />

Sleeping sickness disrupts both sleep timing and architecture. The underlying causes were investigated in a mouse model where ''T. brucei'' infected mice had a reduced ability to maintain [[Rapid eye movement sleep|REM sleep]] and an inability to respond homeostatically to sleep deprivation. There were also reduced electrophysiological responses, electrical activity produced by the nervous system and heart, and behavioral changes. This presented a likelihood to ''T. brucei'' altering homeostatic adenosine signaling in addition to the inflammatory responses generated from the infection.<ref name="adenosine">{{Cite journal |last1=Rijo-Ferreira |first1=Filipa |last2=Bjorness |first2=Theresa E. |last3=Cox |first3=Kimberly H. |last4=Sonneborn |first4=Alex |last5=Greene |first5=Robert W. |last6=Takahashi |first6=Joseph S. |date=2020-11-25 |title=Sleeping Sickness Disrupts the Sleep-Regulating Adenosine System |journal=The Journal of Neuroscience |language=en |volume=40 |issue=48 |pages=9306–9316 |doi=10.1523/JNEUROSCI.1046-20.2020 |issn=0270-6474 |pmc=7687053 |pmid=33097636}}</ref>

=== Effect of inflammation on circadian rhythm regulation ===
Inflammation modifies circadian physiology through altered homeostatic regulation. This is promoted by the response of the SCN to [[Inflammatory cytokine|proinflammatory cytokines]] that most notably causes phase shifts in locomotor rhythms, seen in mice. 
<ref name="Leone">{{Cite journal |last1=Leone |first1=M. Juliana |last2=Marpegan |first2=Luciano |last3=Duhart |first3=José M. |last4=Golombek |first4=Diego A. |date=July 2012 |title=Role of Proinflammatory Cytokines on Lipopolysaccharide-Induced Phase Shifts in Locomotor Activity Circadian Rhythm |url=http://www.tandfonline.com/doi/full/10.3109/07420528.2012.682681 |journal=Chronobiology International |language=en |volume=29 |issue=6 |pages=715–723 |doi=10.3109/07420528.2012.682681 |pmid=22734572 |issn=0742-0528|url-access=subscription }}</ref><ref name="two clocks" />

In a studied mouse model, the response to a ''T. brucei'' infection was analyzed, where inflammatory molecules such as the proinflammatory cytokine interferon, [[Interferon gamma|IFN-γ]], were released in positive correlation with a greater severity of sleeping sickness. The influence of IFN-γ on the circadian timing system and the altered SCN function was observed.<ref name = pmid15304634/>

Pro-inflammatory cytokines are released during an inflammatory response, generating reactions that alter the circadian clock. Cytokines such as [[Tumor necrosis factor|TNF-alpha]] and [[Interleukin-1 family|IL-1]] are associated with sleep sickness-related symptoms such as fever, fatigue, and sleep disturbances. The role of these cytokines is currently being explored; however, the sites of ''T. brucei'' infection generally involve an influx of inflammatory cells, which introduces its potential role in disrupting sleeping rhythms.<ref name = "pmid15304634"/><ref name = ":0222"/><ref name="two clocks">{{Cite journal |last1=Rijo-Ferreira |first1=Filipa |last2=Takahashi |first2=Joseph S. |date=2020-10-02 |title=Sleeping Sickness: A Tale of Two Clocks |journal=Frontiers in Cellular and Infection Microbiology |volume=10 |doi=10.3389/fcimb.2020.525097 |doi-access=free |issn=2235-2988 |pmc=7562814 |pmid=33134186}}</ref>

=== Circadian cycle in trypanosoma ===

Trypanosoma brucei is an extracellular parasite that disrupts the host's circadian clock with its own intrinsic clock. ''T. brucei'' can regulate its metabolism at two different stages in vitro. The genes that function with a circadian rhythm in ''T. brucei'' exhibit maximum expression at two different phases in a day.<ref name = Rijo-Ferreira/>

Instead of a traditional [[Transcription translation feedback loop|transcription and translation feedback loop model]], ''T. brucei'' has its genome primarily organized into polycistronic units (PCUs) that are already transcribed [[Messenger RNA|mRNA]] molecules and has most of its gene expression regulated post-transcription, including cycling genes.<ref name = Rijo-Ferreira/>

''T. brucei'' has a circadian oscillating [[transcriptome]] that is most likely entrained to the tsetse daily biting pattern for the most effective parasitic transmission and triggers metabolic parasitic changes.<ref name="Rijo-Ferreira">{{Cite journal |last1=Rijo-Ferreira |first1=Filipa |last2=Pinto-Neves |first2=Daniel |last3=Barbosa-Morais |first3=Nuno L. |last4=Takahashi |first4=Joseph S. |last5=Figueiredo |first5=Luisa M. |date=2017-03-13 |title=Trypanosoma brucei metabolism is under circadian control |journal=Nature Microbiology |language=en |volume=2 |issue=6 |page=17032 |doi=10.1038/nmicrobiol.2017.32 |issn=2058-5276 |pmc=5398093 |pmid=28288095}}</ref>

==Cause==
[[File:AfrTryp LifeCycle.svg|thumb|upright=1.8|The life cycle of the ''Trypanosoma brucei'' parasites]]
''Trypanosoma brucei gambiense'' accounts for the majority of African trypanosomiasis cases, with humans as the primary reservoir for transmission. In contrast, ''Trypanosoma brucei rhodesiense'' is primarily zoonotic, with accidental human infections.<ref name=Fra2014>{{cite journal | vauthors = Franco JR, Simarro PP, Diarra A, Jannin JG | title = Epidemiology of human African trypanosomiasis | journal = Clinical Epidemiology | volume = 6 | pages = 257–275 | date = 2014 | pmid = 25125985 | pmc = 4130665 | doi = 10.2147/CLEP.S39728 | doi-access = free }}</ref> The epidemiology of African trypanosomiasis is dependent on the interactions between the parasite (trypanosome), the vector ([[tsetse fly]]), and the host.<ref name="Fra2014"/>

===''Trypanosoma brucei (T. brucei)''===
{{Main|Trypanosoma brucei}}

There are two subspecies of the parasite responsible for starting the disease in humans. ''[[Trypanosoma brucei gambiense]]'' causes the disease in West and Central [[Africa]], whereas ''[[Trypanosoma brucei rhodesiense]]'' has a limited geographical range and is responsible for causing the disease in East and Southern Africa. In addition, a third subspecies of the parasite known as ''[[Trypanosoma brucei brucei]]'' is responsible for affecting animals but not humans.<ref name=Brun10/>

Humans are the main reservoir for ''T. b. 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''. These parasites primarily infect individuals in sub-Saharan Africa because that is where the vector (tsetse fly) is located. The two human forms of the disease also vary greatly in intensity. ''T. b. gambiense'' causes a [[chronic (medicine)|chronic condition]] that can remain in a passive phase for months or years before symptoms emerge, and the infection can last about three years before death occurs.<ref name=Brun10/>

''T. b. rhodesiense'' is the [[acute (medicine)|acute]] form of the disease, and death can occur within months since the symptoms emerge within weeks, and it is more virulent and faster developing than ''T. b. gambiense''. Furthermore, trypanosomes are surrounded by a coat that is composed of [[variant surface glycoprotein]]s (VSG). These proteins protect the parasite from any lytic factors that are present in human plasma. The host's immune system recognizes the glycoproteins present on the coat of the parasite, leading to the production of different [[antibodies]] (IgM and IgG).<ref name=Brun10/>

These antibodies will then act to destroy the parasites that circulate in the blood. However, from the several parasites present in the plasma, a small number of them will experience changes in their surface coats, resulting in the formation of new VSGs. Thus, the antibodies produced by the immune system will no longer recognize the parasite, leading to proliferation until new antibodies are created to combat the novel VSGs. Eventually, the immune system will no longer be able to fight off the parasite due to the constant changes in VSGs, and infection will arise.<ref name=Brun10/>

===Vector===
{| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
!Type
!''Trypanosoma''
!Distribution
!''V''ector
|-
|Chronic
|''[[Trypanosoma brucei gambiense|T. brucei gambiense]]''
|Western Africa
|''G. palpalis''
''G. tachinoides''

''[[Glossina fuscipes|G. fuscipes]]''

''G. morsitans''
|-
|Acute
|''[[Trypanosoma brucei rhodesiense|T. brucei rhodesiense]]''
|Eastern Africa
|''G. morsitans''
''G. swynnertoni''

''G. pallidipes''

''G. fuscipes''
|}
[[File:Glossina morsitans MKL Bd. 16 1890 (128536499).jpg|thumb|Drawing of a tsetse fly from 1890]]
The [[tsetse fly]] (genus ''Glossina'') is a large, brown, biting fly that serves as both a host and vector for the [[Trypanosoma brucei|trypanosome]] parasites. While taking blood from a mammalian host, an infected tsetse fly injects metacyclic trypomastigotes into the skin tissue. Metacyclic trypomastigotes are the infectious form of the parasite that develops in the salivary glands of the vector and is transmitted through the bite. From the bite, parasites first enter the lymphatic system and then pass into the bloodstream. Inside the mammalian host, they transform into bloodstream trypomastigotes and are carried to other sites throughout the body, reach other body fluids (e.g., lymph, spinal fluid), and continue to replicate by [[binary fission]].<ref>{{cite journal | vauthors = Jamabo M, Mahlalela M, Edkins AL, Boshoff A | title = Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies | journal = International Journal of Molecular Sciences | volume = 24 | issue = 15 | article-number = 12529 | date = August 2023 | pmid = 37569903 | pmc = 10420020 | doi = 10.3390/ijms241512529 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wamwiri FN, Changasi RE | title = Tsetse Flies (Glossina) as Vectors of Human African Trypanosomiasis: A Review | journal = BioMed Research International | volume = 2016 | article-number = 6201350 | date = 2016 | pmid = 27034944 | pmc = 4789378 | doi = 10.1155/2016/6201350 | doi-access = free }}</ref><ref name="transcript">{{Cite journal |last1=Christiano |first1=Romain |last2=Kolev |first2=Nikolay G. |last3=Shi |first3=Huafang |last4=Ullu |first4=Elisabetta |last5=Walther |first5=Tobias C. |last6=Tschudi |first6=Christian |date=October 2017 |title=The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion |journal=Molecular Microbiology |language=en |volume=106 |issue=1 |pages=74–92 |doi=10.1111/mmi.13754 |issn=0950-382X |pmc=5607103 |pmid=28742275}}</ref>

The entire life cycle of African trypanosomes is represented by extracellular stages. A tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host. The parasites then transform into procyclic trypomastigotes, specifically in the fly's midgut, multiply by binary fission, leave the midgut, and transform into epimastigotes. The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission.<ref name="d672">{{cite web | title=Trypanosomiasis, African | website=CDC | date=2018-06-08 | url=https://www.cdc.gov/dpdx/trypanosomiasisafrican/index.html | access-date=2024-06-18}}</ref>

The entire life cycle of the fly takes about three weeks. In addition to the bite of the [[tsetse fly]], the disease can be transmitted by:
* Mother-to-child infection: the trypanosome can sometimes cross the placenta and infect the fetus.<ref>{{cite journal | vauthors = Olowe SA | title = A case of congenital trypanosomiasis in Lagos | journal = Transactions of the Royal Society of Tropical Medicine and Hygiene | volume = 69 | issue = 1 | pages = 57–59 | year = 1975 | pmid = 1170654 | doi = 10.1016/0035-9203(75)90011-5 }}</ref>
* Laboratories: accidental infections, for example, through the handling of blood of an infected person and organ transplantation, although this is uncommon.
* Blood transfusion
* [[Human sexual activity|Sexual contact]]<ref name="rocha">{{cite journal | vauthors = Rocha G, Martins A, Gama G, Brandão F, Atouguia J | title = Possible cases of sexual and congenital transmission of sleeping sickness | journal = Lancet | volume = 363 | issue = 9404 | page = 247 | date = January 2004 | pmid = 14738812 | doi = 10.1016/S0140-6736(03)15345-7 | s2cid = 5311361 }}</ref>
[[Horse-fly|Horse-flies]] ([[Horse-fly|Tabanidae]]) and [[stable fly|stable flies]] ([[Muscidae]]) possibly play a role in the transmission of [[nagana]] (the animal form of sleeping sickness) and the human disease form.<ref>{{cite journal | vauthors = 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 | journal = The Onderstepoort Journal of Veterinary Research | volume = 71 | issue = 4 | pages = 307–312 | date = December 2004 | pmid = 15732457 | doi = 10.4102/ojvr.v71i4.250 | doi-access = free | hdl = 2078.1/104329 | hdl-access = free }}</ref> Studies have noted a strain of Tetste fly [[Glossina palpalis]] that has proved to pose a public health challenge in animal livestock because of a high carrier rate of DNA of trypanosome parasites. further studies can observe the carrier rate across a range of domestic animals in addition to determining the prevalence and risk factors of nagana in different seasons and establish seasonal variation in animal trypanosomiasis transmission.<ref name="pigs in Ghana">{{Cite journal |last1=Tweneboah |first1=Austine |last2=Rosenau |first2=Jana |last3=Addo |first3=Kofi Agyapong |last4=Addison |first4=Thomas Kwame |last5=Ibrahim |first5=Mahamat Alhadj Moussa |last6=Weber |first6=Judith Sophie |last7=Kelm |first7=Soerge |last8=Badu |first8=Kingsley |date=2024-06-05 |title=The Transmission of Animal African Trypanosomiasis in Two Districts in the Forest Zone of Ghana |url=https://www.ajtmh.org/view/journals/tpmd/110/6/article-p1127.xml |journal=The American Journal of Tropical Medicine and Hygiene |volume=110 |issue=6 |pages=1127–1136 |doi=10.4269/ajtmh.23-0329 |issn=0002-9637 |pmc=11154048 |pmid=38697074}}</ref>

=== Pathophysiology ===
[[Tryptophol]] is a chemical compound produced by the trypanosomal parasite in sleeping sickness, which induces sleep in humans.<ref>{{cite journal | vauthors = Cornford EM, Bocash WD, Braun LD, Crane PD, Oldendorf WH, MacInnis AJ | title = Rapid distribution of tryptophol (3-indole ethanol) to the brain and other tissues | journal = The Journal of Clinical Investigation | volume = 63 | issue = 6 | pages = 1241–1248 | date = June 1979 | pmid = 447842 | pmc = 372073 | doi = 10.1172/JCI109419 }}</ref>

==Diagnosis==
[[File:Afric tryp 1a DPDxi.jpg|thumb|upright=1.3|Two areas from a blood smear from a person with African trypanosomiasis, thin blood smear stained with [[Giemsa stain|Giemsa]]: typical trypomastigote stages (the only stages found in people), with a posterior kinetoplast, a centrally located nucleus, an undulating membrane, and an anterior flagellum. The two ''Trypanosoma brucei'' subspecies that cause [[human trypanosomiasis]], ''T. b. gambiense'' and'' T. b. rhodesiense'', are indistinguishable morphologically. The trypanosomes' length range is 14 to 33 μm; source: CDC.]]

The gold standard for diagnosis is the identification of trypanosomes in a sample by microscopic examination. Samples that can be used for diagnosis include [[ulcer]] fluid, lymph node aspirates, blood, [[bone marrow]], and, during the neurological stage, [[cerebrospinal fluid]]. Detection of trypanosome-specific antibodies can aid diagnosis. The sensitivity and specificity of these methods are too variable to be used alone for clinical diagnosis. Further, [[seroconversion]] occurs after the onset of clinical symptoms during a ''T. b. rhodesiense'' infection, so is of limited diagnostic use.<ref name="Lejon">{{Cite journal |last1=Lejon |first1=V. |last2=Jamonneau |first2=V. |last3=Solano |first3=P. |last4=Atchade |first4=P. |last5=Mumba |first5=D. |last6=Nkoy |first6=N. |last7=Bébronne |first7=N. |last8=Kibonja |first8=T. |last9=Balharbi |first9=F. |last10=Wierckx |first10=A. |last11=Boelaert |first11=M. |last12=Büscher |first12=P. |date=May 2006 |title=Detection of trypanosome-specific antibodies in saliva, towards non-invasive serological diagnosis of sleeping sickness |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3156.2006.01620.x |journal=Tropical Medicine & International Health |language=en |volume=11 |issue=5 |pages=620–627 |doi=10.1111/j.1365-3156.2006.01620.x |pmid=16640614 |issn=1360-2276}}</ref>

Trypanosomes can be detected from samples using two different preparations. A wet preparation can be used to look for the motile trypanosomes. Alternatively, a fixed (dried) smear can be stained using [[Giemsa]]'s or [[Field stain|Field]]'s technique and examined under a microscope. Often, the parasite is in relatively low abundance in the sample, so techniques to concentrate the parasites can be used before microscopic examination. For blood samples, these include centrifugation followed by an examination of the [[buffy coat]]; mini anion-exchange/centrifugation; and the quantitative buffy coat (QBC) technique. For other samples, such as spinal fluid, concentration techniques include centrifugation followed by an examination of the sediment.<ref name="Lejon" />

Three serological tests are also available to detect the parasite: the micro-CATT (card agglutination test for trypanosomiasis), wb-CATT, and wb-LATEX. The first uses dried blood, while the other two use whole blood samples. A 2002 study found the wb-CATT to be the most efficient for diagnosis, while the wb-LATEX is a better exam for situations where greater sensitivity is required.<ref name="pmid12481210">{{cite journal | vauthors = Truc P, Lejon V, Magnus E, Jamonneau V, Nangouma A, Verloo D, Penchenier L, Büscher P | display-authors = 6 | title = Evaluation of the micro-CATT, CATT/Trypanosoma brucei gambiense, and LATEX/T b gambiense methods for serodiagnosis and surveillance of human African trypanosomiasis in West and Central Africa | journal = Bulletin of the World Health Organization | volume = 80 | issue = 11 | pages = 882–886 | year = 2002 | pmid = 12481210 | pmc = 2567684 | url = http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862002001100008&lng=en&nrm=iso&tlng=en | url-status = live | archive-url = https://web.archive.org/web/20110919095402/http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862002001100008&lng=en&nrm=iso&tlng=en | archive-date = 19 September 2011 }}</ref>

==Prevention==
{{See also|Tsetse fly#Control techniques}}
[[File:PreventionSS.jpg|thumb|upright=1.3|Capture devices for tsetse flies, on shore and on a boat in Africa. Efforts to prevent sleeping sickness.<ref>{{cite journal | vauthors = Rayaisse JB, Salou E, Courtin F, Yoni W, Barry I, Dofini F, Kagbadouno M, Camara M, Torr SJ, Solano P | display-authors = 6 | title = Baited-boats: an innovative way to control riverine tsetse, vectors of sleeping sickness in West Africa | journal = Parasites & Vectors | volume = 8 | page = 236 | date = April 2015 | pmid = 25928366 | pmc = 4436790 | doi = 10.1186/s13071-015-0851-0 | doi-access = free }}</ref>]]
Currently, there are few medically related prevention options for African trypanosomiasis (i.e., no vaccine exists for immunity). Although the risk of infection from a tsetse fly bite is minor (estimated at less than 0.1%), the use of insect repellants, wearing long-sleeved clothing, avoiding tsetse-dense areas, implementing bush clearance methods, and wild game culling are the best options to avoid infection available for residents of affected areas.<ref name="Brun10"/>

Regular active and passive surveillance, involving detection and prompt treatment of new infections, and tsetse fly control, are the backbone of the strategy used to control sleeping sickness.<ref>{{Cite journal |last1=Franco |first1=Jose R. |last2=Priotto |first2=Gerardo |last3=Paone |first3=Massimo |last4=Cecchi |first4=Giuliano |last5=Ebeja |first5=Agustin Kadima |last6=Simarro |first6=Pere P. |last7=Sankara |first7=Dieudonne |last8=Metwally |first8=Samia B. A. |last9=Argaw |first9=Daniel Dagne |date=2024-04-16 |title=The elimination of human African trypanosomiasis: Monitoring progress towards the 2021–2030 WHO road map targets |journal=PLOS Neglected Tropical Diseases |language=en |volume=18 |issue=4 |article-number=e0012111 |doi=10.1371/journal.pntd.0012111 |issn=1935-2735 |pmc=11073784 |pmid=38626188 |doi-access=free}}</ref> Systematic [[screening (medicine)|screening]] of at-risk communities is the best approach, because case-by-case screening is not practical in endemic regions. Systematic screening may be in the form of mobile clinics or fixed screening centers where teams travel daily to areas with high infection rates. Such screening efforts are important because early symptoms are not evident or serious enough to prompt people with gambiense disease to seek medical attention, particularly in very remote areas. Also, diagnosis of the disease is difficult, and health workers may not associate such general symptoms with trypanosomiasis. 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 |url=https://www.who.int/tdr/diseases/tryp/direction.htm |archive-url=https://web.archive.org/web/20060322222639/http://www.who.int/tdr/diseases/tryp/direction.htm |archive-date=22 March 2006 |access-date=1 March 2006 |work=Special Programme for Research and Training in Tropical Diseases}}</ref> A single case of sexual transmission of West African sleeping sickness has been reported.<ref name="rocha" />

In July 2000, a resolution was passed to form the Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC). The campaign works to eradicate the tsetse vector population levels and subsequently the protozoan disease, by use of insecticide-impregnated targets, fly traps, insecticide-treated cattle, ultra-low dose aerial/ground spraying (SAT) of tsetse resting sites and the [[sterile insect technique]] (SIT).<ref name="Schofield2008">{{cite journal | vauthors = Schofield CJ, Kabayo JP | title = Trypanosomiasis vector control in Africa and Latin America | journal = Parasites & Vectors | volume = 1 | issue = 1 | page = 24 | date = August 2008 | pmid = 18673535 | pmc = 2526077 | doi = 10.1186/1756-3305-1-24 | doi-access = free }}</ref> The use of SIT in Zanzibar proved effective in eliminating the entire population of tsetse flies but was expensive and is relatively impractical to use in many of the endemic countries afflicted with African trypanosomiasis.<ref name="Brun2010">{{cite journal | vauthors = Brun R, Blum J, Chappuis F, Burri C | title = Human African trypanosomiasis | journal = Lancet | volume = 375 | issue = 9709 | pages = 148–159 | date = January 2010 | pmid = 19833383 | doi = 10.1016/S0140-6736(09)60829-1 | url = https://fieldresearch.msf.org/bitstream/10144/114145/1/091014_Brun_HAT_Lancet-2009-375-148_REVIEW.pdf | access-date = 25 September 2019 | hdl-access = free | quote = See pp. 154–5 | s2cid = 39433996 | archive-date = 27 August 2021 | archive-url = https://web.archive.org/web/20210827210340/https://fieldresearch.msf.org/bitstream/handle/10144/114145/091014_Brun_HAT_Lancet-2009-375-148_REVIEW.pdf;jsessionid=0B2E69D2637A7050EFDC83615468284D?sequence=1 | hdl = 10144/114145 }}</ref>

A pilot program in [[Senegal]] has reduced the tsetse fly population by as much as 99% by introducing male flies that have been sterilized by exposure to [[gamma ray]]s.<ref>{{cite news | vauthors = Paquette D |date=2019-05-31 |title=A U.S.-funded nuclear project to zap a killer fly into extinction is saving West Africa's cows |url=https://www.washingtonpost.com/world/africa/a-us-funded-nuclear-project-to-zap-a-killer-fly-into-extinction-is-saving-west-africas-cows/2019/05/31/12f92626-7713-11e9-a7bf-c8a43b84ee31_story.html |newspaper=[[The Washington Post]] |access-date=2019-06-01}}</ref><ref name="IAEA">{{cite web | title=The Tsetse Fly Eradication Project in Senegal Wins Award for Best Sustainable Development Practices | website=[[IAEA]] | date=23 July 2015 | url=http://www.iaea.org/newscenter/news/tsetse-fly-eradication-project-senegal-wins-award-best-sustainable-development-practices | access-date=2021-11-16}}</ref>

==Treatment==

The treatment depends on whether the disease is discovered in the first or second stage. A requirement for treatment of the second stage is that the drug passes the [[blood–brain barrier]].

===First Stage===
The treatment for first-stage disease is [[fexinidazole]] by mouth or [[pentamidine]] by injection for ''T. b. gambiense''.<ref name=WHO2020/> [[Suramin]] by injection was previously used for ''T. b. rhodesiense'',<ref name=WHO2020/> but fexinidazole has replaced this as the first-line treatment since 2024.<ref name=":2">{{Cite web |title=WHO delivers fexinidazole to Malawi and Zimbabwe – a long-awaited safer treatment for rhodesiense human African trypanosomiasis |url=https://www.who.int/news/item/07-02-2025-who-delivers-fexinidazole-to-malawi-and-zimbabwe---a-long-awaited-safer-treatment-for-rhodesiense-human-african-trypanosomiasis |access-date=2025-06-10 |website=www.who.int |language=en}}</ref> 

===Second Stage===
Fexinidazole may be used for the second stage of ''Trypanosoma brucei gambiense'', if the disease is not severe.<ref name=DRC2019>{{cite web |title=Fexinidazole, the first all-oral treatment for sleeping sickness, approved in the Democratic Republic of Congo – DNDi |url=https://www.dndi.org/2019/media-centre/press-releases/fexinidazole-sleeping-sickness-approved-democratic-republic-congo/ |website=dndi.org |date=29 January 2019 |access-date=4 November 2019}}</ref><ref name=WHO2020/> Otherwise a regimen involving the combination of [[nifurtimox]] and [[eflornithine]], [[nifurtimox-eflornithine combination treatment]], developed by the Drugs for Neglected Diseases initiative and partners,<ref name=":3">{{cite web | url=https://dndi.org/research-development/portfolio/nect/ | title=Nifurtimox-eflornithine combination therapy (NECT) | date=31 December 2003 }}</ref> or eflornithine alone appear to be more effective and result in fewer side effects.<ref name=Lut2013>{{cite journal | vauthors = Lutje V, Seixas J, Kennedy A | title = Chemotherapy for second-stage human African trypanosomiasis | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 6 | article-number = CD006201 | date = June 2013 | pmid = 23807762 | pmc = 6532745 | doi = 10.1002/14651858.CD006201.pub3 }}</ref> These treatments may replace [[melarsoprol]] when available.<ref name=Lut2013/><ref name=Lancet2013/> The combination has the benefit of requiring fewer injections of eflornithine.<ref name=Lut2013/>

Intravenous melarsoprol was previously the standard treatment for second-stage (neurological phase) disease and is effective for both types.<ref name=Lancet2013/> [[Melarsoprol]], which causes death in 5% of people who take it<ref name=Lancet2013/> and carries a risk of resistance development,<ref name=Lancet2013/> was previously the only treatment for second stage ''T.b. rhodesiense''. In 2024, it has been replaced by [[fexinidazole]] as the first-line treatment for sleeping sickness caused by ''T.b. rhodesiense''.<ref name=":2" />

'''Drug Development Projects'''.
A major challenge has been to find drugs that readily pass the blood–brain barrier. The latest drug that has come into clinical use is fexinidazol. Promising results have also been obtained with the benzoxaborole drug [[acoziborole]] (SCYX-7158), developed by the Drugs for Neglected Diseases initiative.<ref>{{cite web | url=https://dndi.org/research-development/portfolio/acoziborole/ | title=Acoziborole &#124; DNDi | date=31 December 2009 }}</ref> This drug is currently under evaluation as a single-dose oral treatment, which is a great advantage compared to currently used drugs. Another research field that has been extensively studied in ''Trypanosoma brucei'' is to target its nucleotide metabolism.<ref name="Hofer2023">{{cite journal | vauthors = Hofer A | title = Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids. | journal = FEMS Microbiology Reviews | volume = 47 | issue = 3 | article-number = fuad020 | date = 2022 | pmid = 37156497 | doi = 10.1093/femsre/fuad020 | doi-access = free | pmc = 10208901 }}</ref> The nucleotide metabolism studies have both led to the development of adenosine analogues looking promising in animal studies, and to the finding that downregulation of the P2 adenosine transporter is a common way to acquire partial drug resistance against the melaminophenyl arsenical and [[diamidine]] drug families (containing melarsoprol and pentamidine, respectively).<ref name="Hofer2023"/> Drug uptake and degradation are two major issues to consider to avoid drug resistance development.  In the case of nucleoside analogues, they need to be taken up by the P1 nucleoside transporter (instead of P2), and they also need to be resistant to cleavage in the parasite.<ref name="pmid27036940">{{cite journal | vauthors = Vodnala M, Ranjbarian F, Pavlova A, de Koning HP, Hofer A | title = Methylthioadenosine Phosphorylase Protects the Parasite from the Antitrypanosomal Effect of Deoxyadenosine: implications for the pharmacology of adenosine antimetabolites | journal = Journal of Biological Chemistry | volume = 291 | issue = 22 | pages = 11717–26 | date = 2016 | pmid = 27036940 | doi = 10.1074/jbc.M116.715615 | doi-access = free | pmc = 4882440 }}</ref><ref name="pmid28373184">{{cite journal | vauthors = Ranjbarian F, Vodnala M, Alzahrani KJ, Ebiloma GU, de Koning HP, Hofer A | title = 9-(2'-Deoxy-2'-Fluoro-β-d-Arabinofuranosyl) Adenine Is a Potent Antitrypanosomal Adenosine Analogue That Circumvents Transport-Related Drug Resistance | journal = Antimicrobial Agents and Chemotherapy | volume = 61 | issue = 6 | pages = e02719-16 | date = 2016 | pmid = 28373184 | doi = 10.1128/AAC.02719-16 | doi-access = free | pmc = 5444181 }}</ref>

==Prognosis==
If untreated, ''T. b. gambiense'' almost always results in death, with only a few individuals shown in a long-term 15-year follow-up to have survived after refusing treatment. ''T. b. rhodesiense'', being a more acute and severe form of the disease, is consistently fatal if not treated.<ref name=Lancet2013/>

Disease progression varies greatly depending on disease form. For individuals who are infected by ''T. b. gambiense'', which accounts for 92% of all of the reported cases, a person can be infected for months or even years without signs or symptoms until the advanced disease stage, where it is too late to be treated successfully. For individuals affected by ''T. b. rhodesiense'', which accounts for 2% of all reported cases, symptoms appear within weeks or months of the infection. Disease progression is rapid and invades the central nervous system, causing death within a short amount of time.<ref>{{cite web |title=Trypanosomiasis, human African (sleeping sickness) |date=March 2014 |publisher=World Health Organization |url=https://www.who.int/mediacentre/factsheets/fs259/en/ |url-status=live |archive-url=https://web.archive.org/web/20140426104752/http://www.who.int/mediacentre/factsheets/fs259/en/ |archive-date=26 April 2014}}</ref>

==Epidemiology==
[[File:African trypanosomiasis deaths 2002.svg|thumb|upright=1.4|Deaths per 100,000 [[population]] due to African trypanosomiasis by country in 2002<ref>[https://www.who.int/entity/healthinfo/statistics/bodgbddeathdalyestimates.xls WHO mortality and health data and statistics] {{webarchive|url=https://web.archive.org/web/20130116174540/http://www.who.int/healthinfo/statistics/bodgbddeathdalyestimates.xls |date=16 January 2013}}, accessed 10 February 2009.</ref>]]

In 2010, it caused around 9,000 deaths, down from 34,000 in 1990.<ref name="Loz2012"/> As of 2000, the disability-adjusted life-years (9 to 10 years) lost due to sleeping sickness are 2.0 million.<ref>{{cite report |author1=World Health Organization (Geneva)|title=World Health Report 2000: Health Systems Improving Performance |year=2000 |url=https://www.who.int/tdr/diseases/tryp/direction.htm#Refs|archive-url=https://web.archive.org/web/20060322222639/http://www.who.int/tdr/diseases/tryp/direction.htm#Refs|archive-date=22 March 2006}}</ref> From 2010 to 2014, there was an estimated 55 million people at risk for ''gambiense'' African Trypanosomiasis and over 6 million people at risk for ''rhodesiense'' African trypanosomiasis.<ref name="Franco_2017">{{cite journal | vauthors = Franco JR, Cecchi G, Priotto G, Paone M, Diarra A, Grout L, Mattioli RC, Argaw D | display-authors = 6 | title = Monitoring the elimination of human African trypanosomiasis: Update to 2014 | journal = PLOS Neglected Tropical Diseases | volume = 11 | issue = 5 | article-number = e0005585 | date = May 2017 | pmid = 28531222 | pmc = 5456402 | doi = 10.1371/journal.pntd.0005585 | doi-access = free }}</ref> In 2014, the World Health Organization reported 3,797 cases of Human African Trypanosomiasis when the predicted number of cases was to be 5,000. The number of total reported cases in 2014 is an 86% reduction from the total number of cases reported in 2000.<ref name="Franco_2017"/>

The disease has been recorded in 37 countries, all in sub-Saharan Africa. The Democratic Republic of the Congo is the most affected country in the world, accounting for 75% of the ''Trypanosoma brucei gambiense'' cases.<ref name=Fra2014/> In 2009, the population at risk was estimated at about 69 million, with one-third of this number being at a 'very high' to 'moderate' risk and the remaining two-thirds at a 'low' to 'very low' risk.<ref name="Sim2012"/> Since then, the number of people being affected by the disease has continued to decline, with fewer than 1000 cases per year reported from 2018 onwards.<ref>{{Cite journal |last1=Franco |first1=Jose R. |last2=Priotto |first2=Gerardo |last3=Paone |first3=Massimo |last4=Cecchi |first4=Giuliano |last5=Ebeja |first5=Agustin Kadima |last6=Simarro |first6=Pere P. |last7=Sankara |first7=Dieudonne |last8=Metwally |first8=Samia B. A. |last9=Argaw |first9=Daniel Dagne |date=2024-04-16 |title=The elimination of human African trypanosomiasis: Monitoring progress towards the 2021–2030 WHO road map targets |journal=PLOS Neglected Tropical Diseases |language=en |volume=18 |issue=4 |article-number=e0012111 |doi=10.1371/journal.pntd.0012111 |doi-access=free |issn=1935-2735 |pmc=11073784 |pmid=38626188}}</ref> Against this backdrop, sleeping sickness elimination is considered a real possibility, with the World Health Organization targeting the elimination of the transmission of the gambiese form by 2030.<ref name="Franco_2017"/><ref>World Health Organization. (2020). [Report of the third WHO stakeholders meeting on gambiense human African trypanosomiasis elimination: Geneva, 18–20 April 2018. [https://web.archive.org/web/20200715081626/https://www.who.int/trypanosomiasis_african/resources/9789240002296/en/] {{open access}}</ref> New treatments, such as single-dose [[acoziborole]], will be critical for elimination.<ref>{{Cite journal |last=Nuwer |first=Rachel |date=2025-01-09 |title=Why the last cases of sleeping sickness will be the hardest to eliminate |url=https://www.nature.com/articles/d41586-025-00013-6 |journal=Nature |language=en |doi=10.1038/d41586-025-00013-6 |pmid=39789138 |issn=1476-4687|url-access=subscription }}</ref> 

{| class="wikitable"
|-
! Trypanosoma brucei gambiense<ref>{{cite web |title=The Global Health Observatory – Human African trypanosomiasis (sleeping sickness) |url=https://www.who.int/data/gho/data/themes/topics/human-african-trypanosomiasis |access-date=8 July 2025 |publisher=[[World Health Organization]]}}</ref>
 ! 1990 !! 1991 !! 1992 !! 1993 !! 1994 !! 1995 !! 1996 !! 1997 !! 1998 !! 1999 !! 2000 !! 2001 !! 2002 !! 2003 !! 2004 !! 2005 !! 2006 !! 2007 !! 2008 !! 2009 !! 2010 !! 2011 !! 2012 !! 2013 !! 2014 !! 2015 !! 2016 !! 2017 !! 2018 !! 2019 !! 2020 !! 2021 !! 2022 !! 2023 
!2024
|-
| Angola || 1498 || 2094 || 2406 || 1796 || 1274 || 2441 || 6726 || 8275 || 6610 || 5351 || 4546 || 4577 || 3621 || 3115 || 2280 || 1727 || 1105 || 648 || 517 || 247 || 211 || 154 || 70 || 69 || 36 || 35 || 19 || 18 || 79 || 30 || 33 || 174 || 44 || 52
|10
|-
| Benin || 0 || 0 || 2 || 1 || 0 || 0 || 0 || 0 || 0 || 20 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0
|0
|-
| Burkina Faso || 27 || 27 || 20 || 17 || 18 || 13 || 12 || 1 || 15 || 15 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 1 || 0 || 0 || 0 || 0 || 0 ||0 ||0 ||0
|0
|-
| Cameroon || 86 || 69 || 21 || 3 || 20 || 21 || 17 || 10 || 54 || 32 || 27 || 14 || 32 || 33 || 17 || 3 || 15 || 7 || 13 || 24 || 16 || 15 || 7 || 6 || 7 || 6 || 6 || 5 || 7 || 17 || 2 || 11 || 7 || 11
|5
|-
| Central African Republic || 308 || 197 || 362 || 262 || 368 || 676 || 492 || 730 || 1068 || 869 || 988 || 718 || 572 || 539 || 738 || 666 || 460 || 654 || 1194 || 1054 || 395 || 132 || 381 || 59 || 194 || 147 || 124 || 76 || 57 || 86 || 39 || 44 ||110 || 104
|111
|-
| Chad || 20 || 221 || 149 || 65 || 214 || 315 || 178 || 122 || 134 || 187 || 153 || 138 || 715 || 222 || 483 || 190 || 276 || 97 || 196 || 510 || 232 || 276 || 197 || 195 || 95 || 67 || 53 || 28 || 12 || 16 || 17 ||15 ||18 ||7
|5
|-
| Congo || 580 || 703 || 727 || 829 || 418 || 475 || 474 || 142 || 201 || 91 || 111 || 894 || 1005 || 717 || 873 || 398 || 300 || 189 || 182 || 87 || 87 || 61 || 39 || 20 || 21 || 36 || 18 || 15 || 24 || 17 || 15 ||18 ||10 ||14
|26
|-
| Côte d'Ivoire || 365 || 349 || 456 || 260 || 206 || 326 || 240 || 185 || 121 || 104 || 188 || 92 || 97 || 68 || 74 || 42 || 29 || 13 || 14 || 8 || 8 || 10 || 9 || 7 || 6 || 3 || 0 || 3 || 2 || 1 || 0 ||1 ||0 ||0
|0
|-
| Democratic Republic of the Congo || 7515 || 5825 || 7757 || 11384 || 19021 || 18182 || 19342 || 25094 || 26318 || 18684 || 16951 || 17300 || 13816 || 11459 || 10339 || 10249 || 8013 || 8155 || 7318 || 7178 || 5624 || 5590 || 5968 || 5647 || 3205 || 2351 || 1769 || 1110 || 660 || 604 || 395 ||425 ||516 ||394
|330
|-
| Equatorial Guinea || 63 || 36 || 45 || 30 || 85 || 37 || 46 || 67 || 62 || 28 || 16 || 17 || 32 || 23 || 22 || 17 || 13 || 15 || 11 || 7 || 8 || 1 || 2 || 3 || 0 || 0 || 3 || 4 || 4 || 3 || 1 ||3 ||13 ||7
|12
|-
| Gabon || 80 || 45 || 33 || 80 || 61 || 20 || 32 || 11 || 6 || 38 || 45 || 30 || 26 || 26 || 49 || 53 || 31 || 30 || 24 || 14 || 22 || 17 || 9 || 17 || 10 || 9 || 10 || 9 || 16 || 8 || 11 ||18 ||21 ||12
|8
|-
| Ghana || 3 || 6 || 16 || 0 || 0 || 0 || 1 || 0 || 0 || 0 || 1 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 1 || 0 || 0 || 0 || 0 || 0 || 0 || 0 ||0 ||0 ||0
|0
|-
| Guinea || 52 || 29 || 24 || 27 || 26 || 33 || 38 || 88 || 99 || 68 || 52 || 72 || 132 || 130 || 95 || 94 || 48 || 69 || 90 || 79 || 68 || 57 || 70 || 78 || 33 || 29 || 107 || 140 || 74 || 69 || 36 ||28 ||30 ||24
|12
|-
| Mali || 0 || 0 || 0 || 27 || 17 || 11 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 ||0||0||0
|0
|-
| Nigeria || 24 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 27 || 14 || 14 || 26 || 31 || 10 || 21 || 3 || 0 || 0 || 0 || 2 || 3 || 2 || 0 || 0 || 0 || 1 || 0 || 0 || 0 || 0||0||0||0
|0
|-
| South Sudan || 67 || 58 || 28 || 62 || 69 || 56 || 157 || 737 || 1726 || 1312 || 1801 || 1919 || 3121 || 3061 || 1742 || 1853 || 789 || 469 || 623 || 373 || 199 || 272 || 317 || 117 || 63 || 45 || 17 || 12 || 17 || 11 || 15 ||10||30||50
|27
|-
| Togo || 2 || 0 || 0 || 0 || 0 || 3 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0||0||0||0
|0
|-
| Uganda || 2066 || 1328 || 2042 || 1764 || 1469 || 1062 || 981 || 1123 || 971 || 1036 || 948 || 310 || 604 || 517 || 378 || 311 || 290 || 120 || 198 || 99 || 101 || 44 || 20 || 9 || 9 || 4 || 4 || 0 || 1 || 2 || 1||0||0||0
|0
|-
| '''Total''' || 12756 || 10987 || 14088 || 16607 || 23266 || 23671 || 28736 || 36585 || 37385 || 27862 || 25841 || 26095 || 23799 || 19941 || 17100 || 15624 || 11372 || 10466 || 10380 || 9680 || 6973 || 6632 || 7091 || 6228 || 3679 || 2733 || 2131 || 1420 || 953 || 864 || 565 || 747 || 799 || 675
|546
|-
! Trypanosoma brucei rhodesiense
 ! 1990 !! 1991 !! 1992 !! 1993 !! 1994 !! 1995 !! 1996 !! 1997 !! 1998 !! 1999 !! 2000 !! 2001 !! 2002 !! 2003 !! 2004 !! 2005 !! 2006 !! 2007 !! 2008 !! 2009 !! 2010 !! 2011 !! 2012 !! 2013 !! 2014 !! 2015 !! 2016 !! 2017 !! 2018 !! 2019 !! 2020 !! 2021 !! 2022 !! 2023 
!2024
|-
|Ethiopia
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|No data
|6
|2
|0
|-
| Kenya || 91 || 8 || 4 || 2 || 1 || 0 || 2 || 5 || 14 || 22 || 15 || 10 || 11 || 0 || 0 || 0 || 1 || 0 || 0 || 1 || 0 || 0 || 2 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0 || 0
|0
|-
| Malawi || 228 || 195 || 143 || 53 || 31 || 15 || 8 || 7 || 10 || 11 || 35 || 38 || 43 || 70 || 48 || 41 || 58 || 50 || 49 || 39 || 29 || 23 || 18 || 35 || 32 || 30 || 37 || 7 || 15 || 91 || 89 || 49 || 24 || 16
|13
|-
| Mozambique || 3 || 7 || 24 || 10 || 16 || No data || No data || No data || No data || No data || No data || No data || 1 || No data || 1 || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data || No data
|No data
|No data
|No data
|No data
|-
| Uganda || 1417 || 832 || 606 || 503 || 342 || 497 || 178 || 217 || 283 || 283 || 300 || 426 || 329 || 338 || 335 || 473 || 261 || 119 || 138 || 129 || 112 || 84 || 71 || 43 || 70 || 28 || 10 || 13 || 4 || 5 || 2 || 2 || 0 || 0
|3
|-
| United Republic of Tanzania || 187 || 177 || 366 || 262 || 319 || 422 || 400 || 354 || 299 || 288 || 350 || 277 || 228 || 113 || 159 || 186 || 127 || 126 || 59 || 14 || 5 || 1 || 4 || 1 || 1 || 2 || 3 || 3 || 0 || 3 || 1 || 1 || 1 || 1
|0
|-
| Zambia || 7 || No data || 4 || 1 || 1 || 1 || 3 || No data || No data || 15 || 9 || 4 || 5 || 15 || 9 || 7 || 6 || 10 || 13 || 4 || 8 || 3 || 6 || 6 || 12 || 8 || 2 || 3 || 5 || 15 || 6 || 3 || 7 || 5
|18
|-
| Zimbabwe || No data || No data || No data || No data || 1 || No data || No data || 9 || No data || No data || No data || No data || No data || No data || No data || 3 || No data || No data || 0 || 3 || 2 || 4 || 9 || 1 || 3 || 3 || 1 || 1 || 0 || 2 || 0 || 0 || 0 || 0
|3
|-
| '''Total''' || 1933 || 1219 || 1147 || 831 || 710 || 935 || 591 || 583 || 606 || 619 || 709 || 755 || 617 || 536 || 552 || 707 || 453 || 305 || 259 || 187 || 154 || 111 || 101 || 85 || 115 || 68 || 52 || 27 || 24 || 116 || 98 ||55 ||38 ||24
|37
|}

==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 include 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|url-access=subscription }}</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|url-access=subscription }}</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 | hdl = 10568/61873 | hdl-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 |url-access=subscription }}</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">
File:Sleeping Sickness Commission photos Wellcome L0049104.jpg|alt=Images from The British-led Sleeping Sickness Commission collecting tsetse flies, Uganda and Nyasaland, 1908–1913
File:Sleeping sickness commission photos Wellcome L0049109.jpg
File:Sleeping sickness commission photos Wellcome L0049112.jpg
File:Sleeping Sickness Commission photos Wellcome L0049121.jpg
File:Sleeping sickness commission photos Wellcome L0049117.jpg
File:Sleeping sickness commission photos Wellcome L0049108.jpg
File:Sleeping sickness commission photos Wellcome L0049113.jpg
File:Sleeping sickness commission photos Wellcome L0049115.jpg
File:Sleeping Sickness Commission photos Wellcome L0049106.jpg
File:Sleeping sickness commission photos Wellcome L0049111.jpg
File:Sleeping sickness commission photos Wellcome L0049110.jpg
File:Sleeping sickness commission photos Wellcome L0049114.jpg
</gallery>

==Research==
The genome of the parasite has been [[whole genome sequencing|sequenced]] and several proteins have been identified as potential targets for drug treatment. Analysis of the genome also revealed the reason why generating a vaccine for this disease has been so difficult. ''T. brucei'' has over 800 genes and employs a mechanism of genetic variation, frequently changing its surface proteins to evade detection by the host's immune system.<ref>{{cite journal | vauthors = Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Böhme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, Macleod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE, El-Sayed NM | display-authors = 6 | title = The genome of the African trypanosome Trypanosoma brucei | journal = Science | volume = 309 | issue = 5733 | pages = 416–422 | date = July 2005 | pmid = 16020726 | doi = 10.1126/science.1112642 | s2cid = 18649858 | bibcode = 2005Sci...309..416B }}</ref>

Using a genetically modified form of a bacterium that occurs naturally in the gut of the vectors is being studied as a method of controlling the disease.<ref>{{cite journal | vauthors = Doudoumis V, Alam U, Aksoy E, Abd-Alla AM, Tsiamis G, Brelsfoard C, Aksoy S, Bourtzis K | display-authors = 6 | title = Tsetse-Wolbachia symbiosis: comes of age and has great potential for pest and disease control | journal = Journal of Invertebrate Pathology | volume = 112 Suppl | pages = S94-103 | date = March 2013 | pmid = 22835476 | pmc = 3772542 | doi = 10.1016/j.jip.2012.05.010 | bibcode = 2013JInvP.112S..94D }}</ref>

Recent findings indicate that the parasite cannot survive in the bloodstream without its [[flagellum]], a crucial appendage for movement and survival. 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 |access-date=7 April 2006 |archive-url=https://web.archive.org/web/20060513151344/http://domino.lancs.ac.uk/info/lunews.nsf/I/448E635736B6B25A8025714700317FD1 |archive-date=13 May 2006}}</ref>

[[Trypanosomiasis vaccine]]s are undergoing research.

The nifurtimox/eflornithine  combination treatment was developed by Drugs for Neglected Diseases initiative and partners.<ref name=":3" /> The results of a 2009 pivotal clinical trial sponsored by Drugs for Neglected Diseases initiative and Médecins Sans Frontières (MSF) showing that this  combination treatment was a safe and effective treatment for sleeping sickness were confirmed in a larger trial conducted in field conditions between 2009 and 2012.<ref>{{Cite journal |last1=Schmid |first1=Caecilia |last2=Kuemmerle |first2=Andrea |last3=Blum |first3=Johannes |last4=Ghabri |first4=Salah |last5=Kande |first5=Victor |last6=Mutombo |first6=Wilfried |last7=Ilunga |first7=Medard |last8=Lumpungu |first8=Ismael |last9=Mutanda |first9=Sylvain |last10=Nganzobo |first10=Pathou |last11=Tete |first11=Digas |last12=Mubwa |first12=Nono |last13=Kisala |first13=Mays |last14=Blesson |first14=Severine |last15=Mordt |first15=Olaf Valverde |date=2012-11-29 |title=In-Hospital Safety in Field Conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. b. gambiense Sleeping Sickness |journal=PLOS Neglected Tropical Diseases |language=en |volume=6 |issue=11 |article-number=e1920 |doi=10.1371/journal.pntd.0001920 |doi-access=free |issn=1935-2735 |pmc=3510081 |pmid=23209861}}</ref> 

Additionally, the [[Drugs for Neglected Diseases Initiative]] has contributed to the African sleeping sickness research by developing a compound called [[fexinidazole]]. This project was originally started in April 2007 and enrolled 749 people in the [[Democratic Republic of the Congo|DRC]] and [[Central African Republic]]. The results showed efficacy and safety in both stages of the disease, both in adults and children ≥ 6 years old and weighing ≥ 20&nbsp;kg.<ref>{{cite journal | vauthors = Mesu VK, Kalonji WM, Bardonneau C, Mordt OV, Blesson S, Simon F, Delhomme S, Bernhard S, Kuziena W, Lubaki JF, Vuvu SL, Ngima PN, Mbembo HM, Ilunga M, Bonama AK, Heradi JA, Solomo JL, Mandula G, Badibabi LK, Dama FR, Lukula PK, Tete DN, Lumbala C, Scherrer B, Strub-Wourgaft N, Tarral A | display-authors = 6 | title = Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial | journal = Lancet | volume = 391 | issue = 10116 | pages = 144–154 | date = January 2018 | pmid = 29113731 | doi = 10.1016/S0140-6736(17)32758-7 | s2cid = 46781585 | doi-access = free }}</ref> The [[European Medicines Agency]] approved it for first and second stage disease outside of Europe in November 2018.<ref>{{cite web|url=https://www.ema.europa.eu/documents/smop-initial/chmp-summary-opinion-fexinidazole-winthrop_en.pdf|title=CHMP Summary of Opinion – Fexinidazole Winthrop|access-date=19 November 2018}}</ref> The treatment was approved in the DRC in December 2018.<ref>{{cite web|url=https://www.dndi.org/2019/media-centre/press-releases/fexinidazole-sleeping-sickness-approved-democratic-republic-congo/|title=Fexinidazole, the first all-oral treatment for sleeping sickness, approved in Democratic Republic of Congo {{!}} DNDi|website=Drugs for Neglected Diseases initiative (DNDi)|date=29 January 2019|access-date=2019-06-04}}</ref> In August 2024, the World Health Organization recommended fexinidazole to replace suramin and melarsoprol as the first-line treatment for sleeping sickness caused by ''T.b. rhodesiense''.<ref name=":2" /> 

=== Clock gene expression induced by Infection with Trypanosoma brucei ===

Studies using transgenic rat models infected with Trypanosoma Brucei and maintained in a 12:12 LD cycle showed no significant effect on oscillations of Per1-luciferase expression or in real-time qPCR, in SCN tissue, significant alterations to circadian rhythms were present in the Pituitary, Pineal, and Spleen tissue. Pituitary gland tissue expressed a significantly shorter period of Per1-luc expression from infected rats. In the Pineal gland, Per1 and Bmal1 expressed diurnal differences in both infected and control mice, and Clock gene mRNA expression was significantly reduced, indicating an alteration in rhythmic pineal function. Real-time PCR analysis revealed a significantly reduced expression of Bmal1 mRNA in the spleen of infected rats.<ref name="Lundkvist, Gabriella B S">{{Cite journal |last1=Lundkvist |first1=Gabriella B. S. |last2=Sellix |first2=Michael T. |last3=Nygård |first3=Mikael |last4=Davis |first4=Erin |last5=Straume |first5=Marty |last6=Kristensson |first6=Krister |last7=Block |first7=Gene D. |date=April 2010 |title=Clock Gene Expression during Chronic Inflammation Induced by Infection with Trypanosoma brucei brucei in Rats |journal=Journal of Biological Rhythms |language=en |volume=25 |issue=2 |pages=92–102 |doi=10.1177/0748730409360963 |issn=0748-7304 |pmc=2897063 |pmid=20348460}}</ref>

===Funding===
For current funding statistics, human African trypanosomiasis is grouped with kinetoplastid infections. [[Kinetoplastida|Kinetoplastids]] refer to a group of flagellate protozoa.<ref name=G-finder/> Kinetoplastid infections include African sleeping sickness, [[Chagas]]' disease, and [[Leishmaniasis]]. Altogether, these three diseases accounted for 4.4 million [[disability adjusted life year]]s (DALYs) and an additional 70,075 recorded deaths yearly.<ref name=G-finder/> For kinetoplastid infections, the total global research and development funding was approximately $136.3 million in 2012. Each of the three diseases, African sleeping sickness, Chagas' disease, and Leishmaniasis each received approximately a third of the funding, which was about US$36.8 million, US$38.7 million, and US $31.7 million, respectively.<ref name=G-finder>{{cite web | vauthors = Moran M, Guzman J, Chapman N, Abela-Oversteengen L, Howard R, Farrell P, Luxford J |title=Neglected Disease Research and Development: The Public Divide. |url=http://www.policycures.org/downloads/GF_report13_all_web.pdf |publisher=Global Funding of Innovation for Neglected Disease |access-date=30 October 2016 |url-status=live |archive-url=https://web.archive.org/web/20160401190712/http://policycures.org/downloads/GF_report13_all_web.pdf |archive-date=1 April 2016}}</ref>

For sleeping sickness, funding was split into basic research, drug discovery, vaccines, and diagnostics. The greatest amount of funding was directed towards basic research of the disease; approximately US$21.6 million was directed towards that effort. As for therapeutic development, approximately $10.9 million was invested.<ref name=G-finder/>

The top funders for kinetoplastid infection research and development are public sources. About 62% of the funding comes from high-income countries, while 9% comes from low- and middle-income countries. High-income countries' public funding is the largest contributor to neglected disease research efforts. However, in recent years, funding from high-income countries has been steadily decreasing; in 2007, high-income countries provided 67.5% of the total funding, whereas, in 2012, high-income countries' public funds provided only 60% of the total funding for kinetoplastid infections. This downward trend leaves a gap for other funders, such as philanthropic foundations and private pharmaceutical companies, to fill.<ref name=G-finder/>

Much of the progress made in African sleeping sickness and neglected disease research as a whole is a result of the other non-public funders. One of these major sources of funding has come from foundations, which have increasingly become more committed to neglected disease drug discovery in the 21st century. In 2012, philanthropic sources provided 15.9% of the total funding.<ref name=G-finder/> The Bill and Melinda Gates Foundation has been a leader in providing funding for neglected diseases [[drug development]]. They have provided US$444.1 million towards neglected disease research in 2012. To date, they have donated over US$1.02 billion towards the neglected disease discovery efforts.<ref>{{cite web |title=Strategy Overview |date=2013 |work=Neglected Infectious Diseases |publisher=Bill and Melinda Gates Foundation |url=http://www.gatesfoundation.org/What-We-Do/Global-Health/Neglected-Infectious-Diseases#AreasofFocus |url-status=live |archive-url=https://web.archive.org/web/20151101024546/http://www.gatesfoundation.org/What-We-Do/Global-Health/Neglected-Infectious-Diseases#AreasofFocus |archive-date=1 November 2015}}</ref>

For kinetoplastid infections specifically, they have donated an average of US$28.15 million annually between the years 2007 to 2011.<ref name=G-finder/> They have labeled human African trypanosomiasis a high-opportunity target, meaning it is a disease that presents the greatest opportunity for control, elimination, and eradication, through the development of new drugs, vaccines, public health programs, and diagnostics. They are the second-highest funding source for neglected diseases, immediately behind the US National Institutes of Health.<ref name=G-finder/> At a time when public funding is decreasing and government grants for scientific research are harder to obtain, the philanthropic world has stepped in to push the research forward.{{citation needed|date=January 2023}}

Another important component of increased interest and funding has come from industry. In 2012, they contributed 13.1% total to the kinetoplastid research and development effort, and have additionally played an important role by contributing to public-private partnerships (PPP) as well as product-development partnerships (PDP).<ref name=G-finder/> A public-private partnership is an arrangement between one or more public entities and one or more private entities that exists to achieve a specific health outcome or to produce a health product. The partnership can exist in numerous ways; they may share and exchange funds, property, equipment, human resources, and intellectual property. These public-private partnerships and product development partnerships have been established to address challenges in the pharmaceutical industry, especially related to neglected disease research. These partnerships can help increase the scale of the effort toward therapeutic development by using different knowledge, skills, and expertise from different sources. These types of partnerships are more effective than industry or public groups working independently.<ref>{{cite book |chapter=Background Paper 8: 8.1 Public-Private Partnerships and Innovation |chapter-url=https://www.who.int/medicines/areas/priority_medicines/Ch8_1PPPs.pdf |title=Priority Medicines for Europe and the World Update Report |publisher=World Health Organization |year=2013 |url=https://www.who.int/medicines/areas/priority_medicines/en/ |archive-url=https://web.archive.org/web/20140820013255/http://www.who.int/medicines/areas/priority_medicines/en/ |archive-date=20 August 2014}}</ref>

==Other Animals and Reservoir==
{{Main|Animal trypanosomiasis}}
''Trypanosoma'' of both the ''rhodesiense'' and ''gambiense'' types can affect other animals such as cattle and wild animals.<ref name=WHO2013/> African trypanosomiasis has generally been considered an anthroponotic disease, and thus its control program was mainly focused on stopping the transmission by treating human cases and eliminating the vector. However, animal reservoirs were reported to possibly play an important role in the endemic nature of African trypanosomiasis, and for its resurgence in the historic foci of West and Central Africa.<ref name="BüscherBart2018">{{cite journal | vauthors = Büscher P, Bart JM, Boelaert M, Bucheton B, Cecchi G, Chitnis N, Courtin D, Figueiredo LM, Franco JR, Grébaut P, Hasker E, Ilboudo H, Jamonneau V, Koffi M, Lejon V, MacLeod A, Masumu J, Matovu E, Mattioli R, Noyes H, Picado A, Rock KS, Rotureau B, Simo G, Thévenon S, Trindade S, Truc P, Van Reet N | display-authors = 6 | title = Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination? | journal = Trends in Parasitology | volume = 34 | issue = 3 | pages = 197–207 | date = March 2018 | pmid = 29396200 | pmc = 5840517 | doi = 10.1016/j.pt.2017.11.008 | doi-access = free }}</ref><ref name="VourchakbéTiofack2020">{{cite journal | vauthors = Vourchakbé J, Tiofack ZA, Kante TS, Mpoame M, Simo G | title = Molecular identification of Trypanosoma brucei gambiense in naturally infected pigs, dogs and small ruminants confirms domestic animals as potential reservoirs for sleeping sickness in Chad | journal = Parasite | volume = 27 | page = 63 | year = 2020 | pmid = 33206595 | pmc = 7673351 | doi = 10.1051/parasite/2020061 | doi-access = free }} {{open access}}</ref>

== References ==
{{Reflist}}

== External links ==
{{Offline|med}}
{{Commons category}}
{{Scholia|topic}}
* {{cite web |title=A doctor's dream |url=https://stories.dndi.org/sleepingsickness-doctors-dream/ |website=stories.dndi.org |access-date=14 May 2020}}
* {{cite web |title=Sleeping sickness |publisher=[[Médecins Sans Frontières]] |url=http://www.doctorswithoutborders.org/news/issue.cfm?id=2401 |archive-url=https://web.archive.org/web/20131023233602/http://www.doctorswithoutborders.org/news/issue.cfm?id=2401 |archive-date=23 October 2013 }}
* [https://web.archive.org/web/20060219054150/http://www.lib.uiowa.edu/hardin/md/trypanosomiasisAfr.html Links to pictures of Sleeping Sickness] (Hardin MD/ [[University of Iowa]])
* {{cite book | vauthors = Hale Carpenter GD |title=A Naturalist on Lake Victoria, with an Account of Sleeping Sickness and the Tse-tse Fly |publisher=Unwin |year=1920 |url=https://archive.org/details/naturalistonlake00carp |oclc=2649363}}
{{Medical resources
| ICD10          = {{ICD10|B|56||b|50}}
| ICD9           = {{ICD9|086.5}}
| ICDO           =
| OMIM           =
| DiseasesDB     = 29277
| DiseasesDB_mult= {{DiseasesDB2|13400}}
| MedlinePlus    = 001362
| eMedicineSubj  = med
| eMedicineTopic = 2140
| MeshID         = D014353
}}
{{Protozoal diseases}}
{{Sleep}}
{{Diseases of poverty}}
{{Authority control}}

{{DEFAULTSORT:African Trypanosomiasis}}
[[Category:Health in Africa]]
[[Category:Insect-borne diseases]]
[[Category:Parasitic diseases]]
[[Category:Protozoal diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia infectious disease articles ready to translate]]
[[Category:Sleep disorders]]
[[Category:Tropical diseases]]
[[Category:Zoonoses]]
[[Category:African trypanosomiasis]]