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==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 = 257β275 | 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 that are responsible for starting the disease in humans. ''[[Trypanosoma brucei gambiense]]'' causes the diseases 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 act to 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:Tsetsemeyers1880.jpg|thumb|Drawing of a tsetse fly from 1880]] 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 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 | page = 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 | page = 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=74β92 |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 = 57β59 | 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, BrandΓ£o 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 = 307β312 | date = December 2004 | pmid = 15732457 | doi = 10.4102/ojvr.v71i4.250 | doi-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=1127β1136 |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 = 1241β1248 | date = June 1979 | pmid = 447842 | pmc = 372073 | doi = 10.1172/JCI109419 }}</ref>
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