Tripanosoma brucei: Versiyalar orasidagi farq

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„Trypanosoma brucei“ sahifasi tarjima qilib yaratildi
(Farq yoʻq)

25-Oktyabr 2022, 17:06 dagi koʻrinishi

Tripanosoma brucei - Afrikaning Sahroi Kabrida uchraydigan Trypanosoma jinsiga mansub parazit kinetoplastidlar turi. Odatda qon va to'qima hujayralarida hayot kechiradigan boshqa protozoa parazitlaridan farqli ravishda, u hujayradan tashqarida bo'lib, qon plazmasi va tana suyuqliklarida yashaydi.[1] U o'limga olib keladigan, ho'jayin orqali yuqadigan kasalliklarni keltirib chiqaradi. Bruceidan boshqa bu turga mansub parazitlar ham mavjud bo'lib, ular Afrika tripanosomiasi-odamlarda uyqu kasalligi keltirib chiqaradi, qoramol va otlarda hayvonlarning tripanosomiasi yoki nagana parazitlik qiladi.[2] Bu uchta kichik turga birlashtirilgan turlar majmuasi:T.b.brucei, T. b.gambiense va T. b.rhodesienselar hisoblanadi. Birinchisi odamdan boshqa sutemizuvchilarning paraziti bo'lib, nagana qo'zg'atadi, ikkinchisi esa zoonoz bo'lib, odamlar va hayvonlarda ham parazitlik qiladi va Afrika trpanosomiazini keltirib chiqaradi.

T. brucei sutemizuvchilar o'rtasida turli xil turlarga mansub hasharotlar tashuvchisi tomonidan tarqatiladi. Masalan: tsetse chivinlari(Glossina ). Hasharotlar qon bilan oziqlanish vaqtida tishlash orqali parazitni yuqtiradi. Parazitlar hayot aylanish jarayonida hasharotlar va sutemizuvchilar o'rtasida harakat qilganda murakkab morfologik o'zgarishlarga uchraydi. Sutemizuvchilarning qon oqimida parazit shakllari o'zlarining hujayra yuzasi oqsillari, antigenlik xususiyatlari o'zgaruvchan sirt glikoproteinlari bilan xo'jayin organizm immunitetidan himoyalanadi. Shuningdek, Brucei qon-miya to'sig'ini kesib o'tishi aniqlangan bir nechta patogenlardan biridir.[3] Parazit kasaliklaridan davolanishda yngi dori terapiyasini ishlab chiqishga shoshilinch ehtiyoj bor, chunki hozirgi davolashlar kerakli natijani bermayapti va bemor uchun o'limga olib kelishi mumkin.[4]


Parazit 1894-yilda ser Devid Bryus tomonidan kashf etilgan bo'lib, uning nomi 1899-yilda berilgan[5][6]

Tarix va kashfiyot

Dastlabki yozuvlar

Hayvonlardagi uyqu kasalligi qadimgi Misr yozuvlarida tasvirlangan. O'rta asrlarda arab savdogarlari Afrikaliklar va ularning itlari orasida uyqu kasalligining tarqalishini ta'kidladilar.[7] Bu XIX asrda Afrikaning janubiy va sharqiy qismidagi asosiy yuqumli kasallik hisoblangan.[8] Zulu Qirolligi(hozirgi Janubiy Afrikaning bir qismi) kasallikdan qattiq jabr ko'radi. Kasallik inglizlarga nagana nomi bilan ma'lum bo'ladi,[2] u zulucha so'z bo'lib, ruhiy tushkunlik degan ma'noni anglatgan. Afrikaning boshqa qismlarida Yevropaliklar buni "chivin kasalligi" deb atashgan.[9][10]

Uganda, Buruma orolida uyqu kasalligiga chalingan erkak.

1734-yilda ingliz dengiz jarrohi Jon Aktins inson uyqu kasalligining birinchi tibbiy tavsifini berdi. U Gvineyadagi "uyqusimon kasallik" deb atagan o'limlarni infektsiya bilan bog'lik ekanligini takidladi.[11] Yana bir ingliz shifokori Tomas Masterman Vinterbottom 1803-yilda Syerra-Leonedan kelgan simptomlarni aniqroq tavsiflab berdi.[12] Vinterbottom kasallikning asosiy xususiyatini servikal orqa limfa tugunlarining shishishi va bunday shishlar paydo bo'lgan qullar savdoga yaroqsiz deb ta'riflagan.[11] Kasallik alomalariga ko'ra bu "Winterbottom belgisi" deb nomlanadi.[13]

Parazitning kashfiyoti

Qirollik armiyasi tibbiyot korpusi 1894-yilda Janubiy Afrikada nagana kasalligini tekshirish uchun o'sha paytda Netleydagi armiya tibbiyot maktabida patologiya bo'yicha dotsent bo'lgan Devid Bryusni armiyada kapitan unvoni bilan tayinladi. Kasallik mahalliy qoramollar va Britaniya armiyasi otlari orasida tarqalgani aniqlandi. 1894-yil 27-oktabrda Bryus va uning mikrobiolog rafiqasi Meri Elizabet Bryus(qizlik ismi Stil) kasallik eng keng tarqalgan Ubombo tepaligiga ko'chib o'tdi.[14]

Tekshiruvning oltinchi kunida Bryus kasal sigirlarning qonidan parazitlarni aniqladi. U dastlab ularni o'ziga xos filariya(mayda dumaloq qurtlar) deb atadi, yil oxiriga kelib parazitlar "gematozoa"(protozoa) ekanligini va naganaga sabab bo'layotgani aniqladi. Bu Trypanosoma brucei ning ilk kashfiyoti edi.[15] Ilmiy nom Ingliz zoologlari Genri Jorj Plimmer va Jon Rouz Bredford tomonidan 1899-yilda printer xatosi tufayli Trypanosoma brucii nomi bilan yaratilgan.[16][17] Trypanosoma jinsini venger shifokori Devid Grubi 1843-yilda qurbaqalarda tajriba o'tkazib aniqlaydi.[18]

Epidemiyalar

Ugandada parazitni odam yuqtirgan birinchi holat 1898-yilda qayd etilgan[8] Undan keyin epidemiya 1900-yilda avj oldi.[19] 1901-yilga kelib, o'lim soni 20 000 ga yaqinlashib ahvol yanada bo'lgan holda og'irlashdi.[20] Yigirma yil davom etgan epidemiyada 250 mingdan ortiq odam halok bo'ldi.[19] Kasallik odatda "negro letargiya" nomi bilan mashhur.[21][22] Inson uyqu kasalligi va nagana o'xshashmi yoki bu ikki kasallik o'xshash parazitlardan kelib chiqqanmi, noma'lum.[23] Hatto Forde va Duttonning kuzatishlari ham tripanosomaning uyqu kasalligi bilan bog'liqligini aniqlab bera olmadi.[24]

Inson tripanosomalarining kashfiyoti

Britaniyalik mustamlakachi jarroh Robert Maykl Forde birinchi bo'lib odamda parazitni topdi. U buni 1901-yilda Gambiyaning Baturst shahridagi kasalxonaga yotqizilgan ingliz paroxod kapitanida aniqlaydi.[7] Uning 1902-yildagi hisoboti shuni ko'rsatadiki, parazit o'ziga xos filarial qurt ekanligi ma'lum bo'lgan.[12] Xuddi shu odamdan Fordening hamkasbi Jozef Everett Dutton uni Trypanosoma jinsiga mansub protozoa parazitini aniqladi.

Turlar

T. brucei turlar jamlanmasi boʻlib, unga quyida turlar kiradi:

  1. T. brucei gambiense- odamlarda sekin boshlangan surunkali tripanosomiaz kasalligini keltirib chiqaradi. Bu ko'pincha markaziy va g'arbiy Afrikada uchraydi, asosiy xo'jayini odamlar hisoblanadi.[25] 1973-yilda Devid Xerst Molyneux birinchi bo'lib yovvoyi va uy hayvonlarida ushbu shtammning infektsiyasini aniqlaydi.[26][27] 2002-yildan parazitni uy hayvonlar, jumladan, qoramollar ham yuqtirganligi haqida ma'lumotlar mavjud.[27] U barcha Afrika odamlarida tripanosomiaz kasalligining 98% da mavjuddir[28] va taxminan 100% o'limga olib kelgan.[29]
  2. T. brucei rhodesiense- odamlarda tez boshlanadigan o'tkir tripanosomiazni keltirib chiqaradi. Yuqori zoonoz parazit bo'lib, u Afrikaning janubiy va sharqiy qismida tarqalgan. Ov hayvonlari va chorva mollari asosiy xo'jayini hisoblanadi.[25][28]
  3. T. brucei brucei Trypanosomaning bir qancha boshqa turlari bilan birga asosan hayvonlar tripanosomiazini keltirib chiqaradi.T. b. brucei tripanosoma litik omil-1(TLF-1) tomonidan lizisga moyilligi tufayli odamlar uchun yuqumli emas.[30][31] Ammo u parazitning boshqa inson-infektsiyali kichik turlar bilan bog'liq va asosiy xususiyatlarga ko'ra o'xshahs bo'ladi.[32] Faqat kamdan-kam hollarda T. b. brucei odamga yuqadi.[33]

Tuzilishi

Tsetse chivinining o'rta ichakchasidagi protsiklik shakldagi SEM noto'g'ri rangli mikrografi . Hujayra tanasi to'q sariq rangda, flagellum esa qizil rangda. 84 piksel/mkm.

T. brucei tipik bir hujayrali eukaryotik hujayra boʻlib, uzunligi 8 dan 50 mkm gacha. Uning tanasi cho'zilgan va toraygan. Hujayra membranasi(pellikula deb ataladi) hujayra organellalarini(yadro, mitoxondriya, endoplazmatik retikulum, Golji apparati va ribosomalarni)o'rab turadi. Bundan tashqari, minglab mitoxondriyalar majmuasi bo'lgan kinetoplast deb ataladigan organella ham mavjud.[34] Kinetoplast bazal tana yonida joylashgan bo'lib, uni mikroskop ostida ajratib bo'lmaydi. Bazal tanasidan oldingi uchi tomon cho'zilgan bitta flagellum paydo bo'ladi. Tana yuzasi bo'ylab flagellum to'lqinli membranani hosil qiladi va hujayra membranasiga yopishadi. Old uchida faqat flagellumning uchi bo'sh bo'ladi.[35] Qon oqimi shaklining hujayra yuzasida turli xil sirt glikoproteinlarining(VSG) zich qatlami bo'lib, parazit tsetse pashshasining o'rta ichakchasidagi protsiklik fazaga differensiyalanganda bir xil darajada zich protsiklin qatlami bilan almashtiriladi.[36]

Tripanosomatidlarning oltita asosiy morfologiyasi. T.brucei hayotining turli bosqichlarida tripomastigota va epimastigota morfologik toifalariga kiradi.
Flagellar tuzilishi

Hayot sikli

Hayot sikli

T. brucei oʻzining hayot siklini tsets pashshasi(Glossina jinsi) va sutemizuvchilar: odamlar, qoramollar, otlar va yovvoyi hayvonlar doirasida yakunlaydi.[37]

Infeksiya tsetse pashshasi sutemizuvchilar terishini tishlaganida organizmga tushadi. Pashsha teri to'qimalariga metatsiklik tripomastigotalarni yuboradi. Tripomastigotlar limfa tizimiga va qon oqimiga kiradi. Dastlabki tripomastigotlar qisqa va dag'al bo'ladi(SS).[38] Ular tana yuzasida sirt glikoproteinlari deb ataladigan antigenik makromalekulalarni ishlab chiqarish orqali organizmning immunitet tizimidan himoyalangan.[1] Qon oqimiga kirgach, ular uzun va nozik shakllarga(LS) aylanadi. Keyin, ular ikkiga bo'linish yo'li bilan ko'payadi. Qiz hujayralarining ba'zilari yana kalta bo'lib qoladi.[39][40]Ulardan ba'zilari oraliq shakllar sifatida qolib, uzun va qisqa shakllar orasidagi o'tish bosqichini boshlaydi.[28] Uzun ingichka shakllar qon tomirlari endoteliyasiga kirib, ekstravaskulyar to'qimalarni, shu jumladan markaziy asab tizimi(CNS)[41] va homilador ayollarda yo'ldoshni bosib olishga qodir.[42]

Tsetse pashshasida

Faqat urg'ochilar infektsiya yuqtiruvchi anofelin chivinlari va qum chivinlaridan farqli ravishda, tsetse pashshalarining ikkala jinsi ham qon bilan oziqlanadi va teng ravishda tripanosomalarni tashiydi.[43] Qisqa va qo'pol tripomastigotlar(SS) qon bilan oziqlanadigan tsetse chivinlari tomonidan yuqtirib olinadi.[40][2]Tripomastigotlar pashshaning o'rta ichakchasiga kirib, protsiklik tripomastigotlarga aylanadi, chunki ular VSG'larini protsiklinlar deb ataladigan boshqa oqsil qoplamalari bilan almashtiradilar.[1] Pashsha qon tarkibidagi immunitet omillaridan ovqat hazm qilish tizimiga zarar yetkazganligi sababli, u infektsiyani bostirish uchun serpinlarni ishlab chiqaradi. GmmSRPN3, GmmSRPN5, GmmSRPN9 va ayniqsa GmmSRPN10 ni o'z ichiga olgan serpinlar keyinchalik o'rta ichak infektsiyasi uchun parazit tomonidan o'zlashtiriladi va ulardan qon tarkibidagi tripanolitik omillarni faolsizlantirish uchun ishlatiladi.Bu esa pashsha organizmini yashashga yaroqsiz holga keltiradi.[44]

Ko'payishi

Ikkiga bo'linish

Tripanosoma hujayra sikli (protsiklik shakl)

T. brucei koʻpayishi koʻpchilik eukariotlarga nisbatan boshqacha usulda kechadi. Yadro membranasi butunligicha qoladi. Mitoz jarayonida xromosomalar kondensatsiyalanmaydi. Bazal tana, aksariyat eukariotik hujayralarning sentrosomalaridan farqli, shpindelni tashkil qilishda rol o'ynamaydi va uning o'rniga kinetoplastning bo'linishida ishtirok etadi.[35]

  1. Bazal tanasi ko'payadi va ikkalasi ham kinetoplast bilan bog'langan bo'lib qoladi. Har bir bazal tanasi alohida flagellum hosil qiladi.
  2. Kinetoplast DNK sintezlanadi, keyin kinetoplast ikki bazal jismning ajralishi bilan birga bo'linadi.
  3. Yadro DNK sintezlanadi, yangi flagellum esa yoshroq, orqa, bazal tanadan cho'ziladi.
  4. Yadro mitozga uchraydi.
  5. Sitokinez oldingidan orqaga qarab o'tadi.
  6. Bo'linish abscision bilan yakunlanadi.

Meyoz

1980-yillarda T. brutsey rivojlanish bosqichlarining DNK tahlillari tsetse pashshasidagi tripomastigota meyoz, ya'ni jinsiy ko'payish bosqichidan o'tishini ko'rsatdi.[45] Ammo bu to'liq hayot sikli uchun har doim ham zarur emas.[46] Meyozga xos oqsillarning mavjudligi 2011-yilda aniqlangan.[47] Gaploid gametalar(meyozdan keyin hosil bo'lgan qiz hujayralar) 2014-yilda kashf etilgan. Gaploid tripomastigotaga o'xshash gametalar o'zlarining flagellalari orqali o'zaro ta'sir qilishi va hujayra sintezidan o'tishi mumkin(jarayon singamiya deb ataladi).[48][49] Shunday qilib, ikkiga bo'linishdan tashqari, T. brucei jinsiy yo'l orqali ko'payishi mumkin. Tripanosomalar Excavata superguruhiga mansub va eukariotlar orasidagi eng erta ajralib chiqadigan nasllardan biridir.[50] T. brutseyda jinsiy koʻpayishning kuzatilishi meyoz va jinsiy koʻpayish eukariotlarning ajdodlari va hamma joyda mavjud boʻlgan xususiyatlari degan gipotezani tasdiqlaydi.[51]

Infeksiya va patogenlik

Sutemizuvchilarning T. brucei infektsiyasining keyingi bosqichlarida parazit qon oqimidan ko'chib o'tib, limfa va miya suyuqliklarini zararlashi mumkin. Aynan mana shu to'qimalarga kirib borishi sabab parazitlar uyqu kasalligini keltirib chiqaradi.[38]

T. brucei qoʻshimcha ravishda, sutemizuvchilar oʻrtasida tana suyuqligi almashinuvi, masalan, qon quyish yoki jinsiy aloqa yoʻli bilan ham yuqishi mumkin, ammo bu juda kam uchraydi.[52][53] Yangi tug'ilgan chaqaloqlar infektsiyalangan onadan bolaga yuqishi mumkin(vertikal yoki konjenital uzatish).[54]

Kimyoterapiya

Afrika tripanosomiazni birinchi darajali davolash uchun odatda tavsiya etilgan to'rtta dori turlari mavjud: suramin 1921-yilda, pentamidin 1941-yilda, melarsoprol 1949-yilda va eflornitin 1990-yilda ishlab chiqilgan.[55][56] Bu dorilar to'liq samarali emas va odamlar uchun toksikdir.[57] Bundan tashqari, parazitlarda barcha dorilarga qarshi dori chidamliligi rivojlangan.[58] Dori-darmonlar cheklangan miqdorda qo'llaniladi, chunki ular T. brucei ning o'ziga xos shtammlariga va parazitlarning hayot sikli bosqichlariga qarshi samarali bo'ladi. Masalan, Suram faqat T. brucei ning birinchi bosqich infektsiyasida qo'llaniladi. Rhodensiense, pentamidin infektsiyaning birinchi bosqichi uchun, gambiense va eflornitin ikkinchi bosqichdagi T. brucei infektsiyasi uchun ishlatiladi. Melarsopol har ikkala infektsiya bosqichida parazitlarning ikki turiga qarshi samarali bo'lgan yagona dori[59], lekin juda zaharli bo'lib, davolanganlarning 5% miya shikastlanishidan vafot etadi( reaktiv ensefalopatiya).[60] Chagas kasalligi(Amerika tripanosomiazi) uchun tavsiya etilgan yana bir dori-nifurtimoks. U o'zi zaif dori, ammo melarsopol bilan birgalikda T. brucei ning ikkinchi bosqichli infektsiyasiga qarshi birinchi darajali dori sifatida ishlatiladi.[61][62]

Tarixiy jihatdan, mishyak va simob birikmalari 20-asrning boshlarida, ayniqsa hayvonlarning infektsiyalariga qarshi yaxshi natija bergan.


Evolyutsiya

Trypanosoma brucei gambiense ~ 10 000 yil oldin bitta nasldan paydo bo'lgan.[63] U aseksual ravishda rivojlanmoqda va uning genomi Meselson effektini ko'rsatadi.[63]

Genom

T. brutsey genomi quyidagilardan iborat:[64]

  • 1 dan 6 megabaza juftligidan iborat 11 juft katta xromosomalar .
  • 200 dan 500 kilobaza juftlikdan iborat 3-5 oraliq xromosoma.
  • 50 dan 100 kilobaza juftligidan iborat 100 ga yaqin minixromosomalar. Ular har bir gaploid genomda bir nechta nusxada mavjud bo'lishi mumkin.


Manbalar

  1. ↑ 1,0 1,1 1,2 Romero-Meza, Gabriela; Mugnier, Monica R. (2020). "Trypanosoma brucei". Trends in Parasitology 36 (6): 571–572. doi:10.1016/j.pt.2019.10.007. PMID 31757771. PMC 7375462. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=7375462.  Manba xatosi: Invalid <ref> tag; name ":9" defined multiple times with different content
  2. ↑ 2,0 2,1 2,2 "Cell-to-Cell Heterogeneity in Trypanosomes". Annual Review of Microbiology (Annual Reviews) 75 (1): 107–128. October 2021. doi:10.1146/annurev-micro-040821-012953. PMID 34228491.  Manba xatosi: Invalid <ref> tag; name "Luzak-et-al-2021" defined multiple times with different content
  3. ↑ "Passage of parasites across the blood-brain barrier". Virulence 3 (2): 202–212. 2012. doi:10.4161/viru.19178. PMID 22460639. PMC 3396699. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3396699. 
  4. ↑ "Treatment of human African trypanosomiasis--present situation and needs for research and development". The Lancet. Infectious Diseases 2 (7): 437–440. July 2002. doi:10.1016/S1473-3099(02)00321-3. PMID 12127356. 
  5. ↑ "Ubombo and the site of David Bruce's discovery of Trypanosoma brucei". Transactions of the Royal Society of Tropical Medicine and Hygiene 87 (4): 494–495. 1993. doi:10.1016/0035-9203(93)90056-v. PMID 8249096. 
  6. ↑ "Sir David Bruce's elucidation of the aetiology of nagana--exactly one hundred years ago". Transactions of the Royal Society of Tropical Medicine and Hygiene 88 (3): 257–258. 1994. doi:10.1016/0035-9203(94)90068-x. PMID 7974656. 
  7. ↑ 7,0 7,1 "The history of African trypanosomiasis". Parasites & Vectors 1 (1): 3. February 2008. doi:10.1186/1756-3305-1-3. PMID 18275594. PMC 2270819. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2270819.  Manba xatosi: Invalid <ref> tag; name ":04" defined multiple times with different content
  8. ↑ 8,0 8,1 "Sleeping sickness in Uganda: revisiting current and historical distributions". African Health Sciences 6 (4): 223–231. December 2006. PMID 17604511. PMC 1832067. https://www.ajol.info/index.php/ahs/article/view/6958.  Manba xatosi: Invalid <ref> tag; name ":1" defined multiple times with different content
  9. ↑ Medical and Veterinary Entomology, 2 (en), Academic Press, 2009 — 297 bet. ISBN 978-0-08-091969-0. 
  10. ↑ Preliminary Report on the Tsetse Fly Disease or Nagana, in Zululand. Durban (South Africa): Bennett & Davis, 1895 — 1 bet. 
  11. ↑ 11,0 11,1 "Human African trypanosomiasis of the CNS: current issues and challenges". The Journal of Clinical Investigation 113 (4): 496–504. February 2004. doi:10.1172/JCI34802. PMC 2214720. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2214720. 
  12. ↑ 12,0 12,1 "History of sleeping sickness (African trypanosomiasis)". Infectious Disease Clinics of North America 18 (2): 231–245. June 2004. doi:10.1016/j.idc.2004.01.004. PMID 15145378.  Manba xatosi: Invalid <ref> tag; name ":42" defined multiple times with different content
  13. ↑ "Hypothesis: the significance of Winterbottom's sign". The Journal of Tropical Medicine and Hygiene 94 (5): 338–340. October 1991. PMID 1942213. 
  14. ↑ Tropical Medicine: An Illustrated History of The Pioneers. Burlington (US): Elsevier Ltd., 2007 — 145–156 bet. ISBN 978-0-08-055939-1. 
  15. ↑ "Sir David Bruce, a pioneer of tropical medicine". British Journal of Hospital Medicine 67 (3): 158. March 2006. doi:10.12968/hmed.2006.67.3.20624. PMID 16562450. 
  16. ↑ Manba xatosi: Invalid <ref> tag; no text was provided for refs named Baker1995
  17. ↑ "Ueber die Entwickelung der Tsetseparasiten in Säugethieren [Preliminary note on the morphology and distribution of the parasite found in tsetse disease]" (de). Zeitschrift für Hygiene und Infektionskrankheiten 42 (1): 341–351. 1903. doi:10.1007/BF02217469. 
  18. ↑ "Trypanosomes" (en). Journal of the American Medical Association XLVIII (1): 1–10. 1907. doi:10.1001/jama.1907.25220270001001. 
  19. ↑ 19,0 19,1 "Reanalyzing the 1900-1920 sleeping sickness epidemic in Uganda". Emerging Infectious Diseases 10 (4): 567–573. April 2004. doi:10.3201/eid1004.020626. PMID 15200843. 
  20. ↑ Tropical Medicine: An Illustrated History of The Pioneers (en). London: Elsevier, 2007 — 133–135 bet. ISBN 978-0-08-055939-1. 
  21. ↑ "The Changes in the Central Nervous System of Two Cases of Negro Lethargy: Sequel to Dr. Manson's Clinical Report". British Medical Journal 2 (2033): 1666–1669. December 1899. doi:10.1136/bmj.2.2033.1666. PMID 20758763. PMC 2412509. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2412509. 
  22. ↑ "The 'Negro lethargy' in Uganda". Parasitology Today 12 (1): 41. January 1996. doi:10.1016/0169-4758(96)90083-6. PMID 15275309. 
  23. ↑ "The history of the association of Trypanosoma with sleeping sickness". British Medical Journal 2 (2241): 1565. 1903. doi:10.1136/bmj.2.2241.1565-a. PMC 2514975. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2514975. 
  24. ↑ "Zentralblatt für Bakteriologie--100 years ago: sleeping sickness--intoxication or infectious disease?". International Journal of Medical Microbiology 292 (3–4): 141–147. September 2002. doi:10.1078/1438-4221-00190. PMID 12398205. 
  25. ↑ 25,0 25,1 "The trypanosomiases". Lancet 362 (9394): 1469–1480. November 2003. doi:10.1016/S0140-6736(03)14694-6. PMID 14602444. 
  26. ↑ "Animal reservoirs and Gambian trypanosomiasis". Annales de la Société Belge de Médecine Tropicale 53 (6): 605–618. 1973. PMID 4204667. 
  27. ↑ 27,0 27,1 "Human African trypanosomiasis". Lancet 390 (10110): 2397–2409. November 2017. doi:10.1016/S0140-6736(17)31510-6. PMID 28673422. 
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  34. ↑ "Characterization of the novel mitochondrial genome replication factor MiRF172 in Trypanosoma brucei". Journal of Cell Science (The Company of Biologists) 131 (8): jcs211730. April 2018. doi:10.1242/jcs.211730. PMID 29626111. PMC 5963845. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5963845. 
  35. ↑ 35,0 35,1 „African animal trypanosomes“. Food and Agricultural Organization. Qaraldi: 2016-yil 28-yanvar. Manba xatosi: Invalid <ref> tag; name "fao" defined multiple times with different content
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  43. ↑ Rotureau, Brice; Van Den Abbeele, Jan (2013). "Through the dark continent: African trypanosome development in the tsetse fly". Frontiers in Cellular and Infection Microbiology 3: 53. doi:10.3389/fcimb.2013.00053. ISSN 2235-2988. PMID 24066283. PMC 3776139. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3776139. 
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  50. ↑ "Phylogenomic analyses support the monophyly of Excavata and resolve relationships among eukaryotic "supergroups"". Proceedings of the National Academy of Sciences of the United States of America 106 (10): 3859–3864. March 2009. doi:10.1073/pnas.0807880106. PMID 19237557. PMC 2656170. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2656170. 
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  52. ↑ „African Trypanosomes: epidemiology and risk factors“. Centers for Disease Control (2017-yil 2-may).
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  55. ↑ "Arsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis". Parasitology Research 90 (1): 71–79. May 2003. doi:10.1007/s00436-002-0799-9. PMID 12743807. 
  56. ↑ "Eflornithine for the treatment of human African trypanosomiasis". Parasitology Research 90 Supp 1: S49–S52. June 2003. doi:10.1007/s00436-002-0766-5. PMID 12811548. 
  57. ↑ "Current chemotherapy of human African trypanosomiasis". Parasitology Research 90 Supp 1: S10–S13. June 2003. doi:10.1007/s00436-002-0752-y. PMID 12811544. 
  58. ↑ "Drug resistance in human African trypanosomiasis". Future Microbiology 6 (9): 1037–1047. September 2011. doi:10.2217/fmb.11.88. PMID 21958143. 
  59. ↑ "A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis". Pathogens and Global Health 107 (5): 242–252. July 2013. doi:10.1179/2047773213Y.0000000105. PMID 23916333. PMC 4001453. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4001453. 
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  64. ↑ "Architecture of the Trypanosoma brucei nucleus during interphase and mitosis". Chromosoma 108 (8): 501–513. March 2000. doi:10.1007/s004120050402. PMID 10794572.  
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