1 1 Trypanosomiasis Trypanosomiasis Dwelle MD MPHTM MD MPHTM Terry L Dwelle Terry L
Trypanosomiasis Trypanosomiasis � African African trypanosomiasis trypanosomiasis � � Trypanosoma Trypanosoma brucei brucei gambiense gambiense � � Trypanosoma Trypanosoma brucei brucei rhodesiense rhodesiense � � American American trypanosomiasis trypanosomiasis � � Trypanosoma Trypanosoma cruzi cruzi � � Trypanosoma Trypanosoma rangeli rangeli � 2 2
Basic Hemoflaggelatology Hemoflaggelatology Basic � Found in the blood Found in the blood � � They are also called They are also called kinitoplastida kinitoplastida (contain (contain � kinetoplasts or modified mitochondria) or modified mitochondria) kinetoplasts � Basic forms Basic forms � � Amastigotes Amastigotes � � Promastigotes Promastigotes � � Epimastigotes Epimastigotes � � Trypomastigotes Trypomastigotes � � Metacyclic Metacyclic trypomastigotes trypomastigotes � 3 3
Amastigote (old (old Leishmania Leishmania stage) stage) Amastigote Kinetoplast (K) Axoneme (A) Nucleus (N) � Slightly oval (2 Slightly oval (2- -3 X 3 3 X 3- -4 microns) 4 microns) � � Axonemes Axonemes are like microtubules that are associated are like microtubules that are associated � with future flagellate motility with future flagellate motility � Found inside Found inside reticuloendothelial reticuloendothelial cells cells � � Multiplies by longitudinal binary fission Multiplies by longitudinal binary fission � � There is generally a small zone between the K and A There is generally a small zone between the K and A � 4 4
Promastigote (old (old leptomonas leptomonas stage) stage) Promastigote Volution Flagellum (F) Granules (VG) K A N Flagellar pocket (FP) � May have various shapes from short and fat to May have various shapes from short and fat to � long and thin long and thin � Occasionally see Occasionally see volutin volutin granules (VG) that granules (VG) that � represent waste products in the cytoplasm represent waste products in the cytoplasm 5 5
Epimastigote (old (old crithidia crithidia stage) stage) Epimastigote A K F N Posterior End Anterior End Undulating membrane (UM) � Varies in length (12 Varies in length (12- -75 microns) 75 microns) � � K is always anterior to the nucleus K is always anterior to the nucleus � � F pulls the body through tissues F pulls the body through tissues � � Epimastigote Epimastigote has an undulating membrane where the has an undulating membrane where the � promastigote doesn doesn’ ’t t promastigote � The undulating membrane causes the body to undulate The undulating membrane causes the body to undulate � 6 6
Trypomastigote and and Metacyclic Metacyclic Trypomastigote Trypomastigote Trypomastigote F A K Anterior Posterior UM N � This is the Trypanosome This is the Trypanosome � � The K is posterior to the N The K is posterior to the N vs vs the the Epimastigote Epimastigote with the N with the N � posterior to the K posterior to the K � Binary fission of the Binary fission of the Promastigote Promastigote, , Epimastigote Epimastigote and and � Trymastigote are the same (K first followed by the A, F, the N are the same (K first followed by the A, F, the N Trymastigote and then the cell) and then the cell) � Metacyclic Metacyclic Tryposmastigote Tryposmastigote is the same as the is the same as the tryposmastigote tryposmastigote � but is the infectious stage in the vector but is the infectious stage in the vector 7 7
African Trypanosomiasis Trypanosomiasis African � Known as African sleeping sickness Known as African sleeping sickness � � Endemic in 36 countries and affects from Endemic in 36 countries and affects from � 20,000 to 50,000 annually 20,000 to 50,000 annually � Untreated is universally fatal Untreated is universally fatal � � Animal infections may have more impact than Animal infections may have more impact than � human infections by decreasing the food human infections by decreasing the food supply (eg eg cattle, sheep, goats, pigs, chickens) cattle, sheep, goats, pigs, chickens) supply ( 8 8
African Trypanosomiasis Trypanosomiasis African Gambiense Rhodesiense 9 9 From Manson’s Tropical Diseases, pp 1172, Saunder’s 1996.
Trypanosoma Rhodesiense Rhodesiense Trypanosoma � East African upland East African upland savanahs savanahs � � Causes sporadic disease Causes sporadic disease � 10 10
Trypomastigote of of Rhodesiense Rhodesiense and and Gambiense Gambiense Trypomastigote F A K Anterior Posterior UM N � Trypanosome stage can Trypanosome stage can’ ’t be distinguished physically t be distinguished physically � from Gambiense Gambiense though biologically and though biologically and from biochemically different different biochemically � 14 14- -33 micrometers long 33 micrometers long � � Smaller Smaller kinetoplast kinetoplast than than Trypanosoma Trypanosoma cruzi cruzi � � T. R. is much less adapted to man therefore causing T. R. is much less adapted to man therefore causing � increased reaction and tissue damage and a much increased reaction and tissue damage and a much higher mortality than T. G. higher mortality than T. G. 11 11
12 12 Kinetoplast
Life Cycle Life Cycle � Host Host – – Animals ( Animals (eg eg bushbuck, bushbuck, hartebeeste hartebeeste, lion, hyena, cattle, , lion, hyena, cattle, � dogs, reedbuck, waterbuck, sheep, goats, etc.) occasionally dogs, reedbuck, waterbuck, sheep, goats, etc.) occasionally man man � Location Location – – Blood, Blood, LN LN’ ’s s, Spleen, CNS , Spleen, CNS � � Intermediate host Intermediate host – – Glossina Glossina moristans moristans group (prefers a dry group (prefers a dry � warm climate) warm climate) � Infective stage Infective stage – – metacyclic metacyclic trypomastigote trypomastigote � � The incubation period for T. R. is 3 The incubation period for T. R. is 3- -21 days and is usually 5 21 days and is usually 5- - � 14 days. T. G has an incubation period from months to years. 14 days. T. G has an incubation period from months to years. � Commonly seen in hunters, honey and firewood gatherers, Commonly seen in hunters, honey and firewood gatherers, � fisherman and tourists in game areas fisherman and tourists in game areas 13 13
Developmental Path Developmental Path Intermediate Vector Epimastigote Metacyclic Trypomastigotes Develops in the gut Glossina feeds on man Glossina feeds on man Trypanosoma Gambiense Local Tissue phase (1-2 weeks) Trypanosoma Rhodesiense I. Blood phase Human Phase II. Lymphnode phase III. CNS phase 14 14
Immunosuppression Immunosuppression 15 15 From Manson’s Tropical Diseases, pp 1187, Saunder’s 1996.
Immune Responses Immune Responses � Trypanosome populations have different Trypanosome populations have different � antigenic populations antigenic populations 16 16
Disease Disease I. Local Tissue – – T. chancre T. chancre – – painful boil with painful boil with I. Local Tissue interstitial inflammatory reaction interstitial inflammatory reaction II. Lymph- -node involvement node involvement – – hyperplasia of hyperplasia of II. Lymph endothelial linings of blood sinuses and endothelial linings of blood sinuses and perivascular infiltrates of leukocytes. Usually infiltrates of leukocytes. Usually perivascular rapid and fulminant fulminant course resulting in death course resulting in death rapid and within a few months within a few months III. CNS – – “ “sleeping sickness sleeping sickness” ” with headache, with headache, III. CNS paroxysmal fever, extreme weakness, rapid weight paroxysmal fever, extreme weakness, rapid weight loss, encephalomyelitis, mental deterioration, loss, encephalomyelitis, mental deterioration, coma, and death within 1 year coma, and death within 1 year 17 17
Disease Disease I. Local Tissue – – T. chancre T. chancre – – painful boil with painful boil with I. Local Tissue interstitial inflammatory reaction interstitial inflammatory reaction II. Lymph- -node involvement node involvement – – hyperplasia of hyperplasia of II. Lymph endothelial linings of blood sinuses and endothelial linings of blood sinuses and perivascular infiltrates of leukocytes. Usually infiltrates of leukocytes. Usually perivascular rapid and fulminant fulminant course resulting in death course resulting in death rapid and within a few months within a few months III. CNS – – “ “sleeping sickness sleeping sickness” ” with headache, with headache, III. CNS paroxysmal fever, extreme weakness, rapid weight paroxysmal fever, extreme weakness, rapid weight loss, encephalomyelitis, mental deterioration, loss, encephalomyelitis, mental deterioration, coma, and death within 1 year coma, and death within 1 year 18 18
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