Chaga’ ’s s Disease Disease Chaga Terry L Dwelle Dwelle MD MPHTM MD MPHTM 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
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
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 are like microtubules that are associated with future flagellate motility associated 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 There is generally a small zone between the K and ► A A
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 ► May have various shapes from short and fat to long and thin to 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
Epimastigote (old (old crithidia crithidia stage) stage) Epimastigote A K F N Posterior End Anterior End Undulating membrane (UM) ► ► Varies in length (12- -75 microns) 75 microns) Varies in length (12 ► 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 has an undulating membrane where the has an undulating membrane where the Epimastigote promastigote doesn promastigote doesn’ ’t t ► ► The undulating membrane causes the body to undulate The undulating membrane causes the body to undulate
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 vs vs the the Epimastigote Epimastigote with the N with the N The K is posterior to the N posterior to the K posterior to the K ► Binary fission of the Promastigote Promastigote, , Epimastigote Epimastigote and and ► Binary fission of the Trymastigote are the same (K first followed by the A, F, are the same (K first followed by the A, F, Trymastigote the N and then the cell) the N and then the cell) ► ► Metacyclic Tryposmastigote Tryposmastigote is the same as the is the same as the Metacyclic tryposmastigote but is the infectious stage in the vector tryposmastigote but is the infectious stage in the vector
American Trypanosomiasis Trypanosomiasis American From Manson’s Tropical Diseases, pp 1200, Saunder’s 1996.
Trypomastigote of of Trypanosoma Trypanosoma Cruzi Cruzi Trypomastigote F A K Anterior Posterior UM N ► 20 micrometers long 20 micrometers long ► ► Larger Larger kinetoplast kinetoplast than than Trypanosoma Trypanosoma Rhodesiense Rhodesiense ► or Gambiense Gambiense or ► 3 3 zymodeme zymodeme profiles profiles – – all produce human all produce human ► infections infections � Z1 and Z2 � Z1 and Z2 – – arboreal and terrestrial mammalian arboreal and terrestrial mammalian transmission transmission � Z3 � Z3 – – domiciliary parasites domiciliary parasites
Nucleus Large Kinetoplast
Life Cycle Life Cycle Insect Vector Binary Fission of Bug (bite site, Amastigotes and mucous membrane, M. Trypomastigotes Epimastigotes GI) (30 days) Metacyclic Trypomastigote Bug bite Macrophages M. Trypomastigote Other cells (heart, skeletal muscle, (5-12 days) Amastigotes neuroglia, etc) Trypomastigote Blood Stream 4-5 days of binary fission Trypomastigote Amastigotes Pseudocyst Acute ruptures Symptoms 2-3 weeks Trypomastigote
Amastigotes
Transmission Factors Transmission Factors ► Vector exposure ► Vector exposure ► Blood transfusions ► Blood transfusions ► Vertical transmission ► Vertical transmission ► Trans ► Trans- -mammary transmission mammary transmission ► Infected food or meat ► Infected food or meat ► Laboratory accidents ► Laboratory accidents ► Land colonization ► Land colonization ► Quality of human dwellings ► Quality of human dwellings
Vector Vector ► Adult insects can fly. ► Adult insects can fly. ► Feed at night ► Feed at night ► Live in holes, like dark, humid sites ► Live in holes, like dark, humid sites
Before feeding After feeding
Chagas’ ’ Disease Disease Chagas Acute Acute Entry site lesions Entry site lesions Systemic signs and symptoms Systemic signs and symptoms Organ involvement Organ involvement Chronic Chronic Dilation of hollow viscera including the heart Dilation of hollow viscera including the heart
Acute phase Acute phase ► 95% have no acute phase ► 95% have no acute phase ► Children have more symptoms ► Children have more symptoms ► Acute phase is often followed by a life ► Acute phase is often followed by a life- -long long asymptomatic period (70- -90% of those 90% of those asymptomatic period (70 infected) infected) ► Some patients experience a ► Some patients experience a subacute subacute progression of illness that can result in a progression of illness that can result in a rapid demise. rapid demise. ► 10% fatality rate in the acute phase ► 10% fatality rate in the acute phase
Portals of Entry Portals of Entry ► Ocular ► Ocular – – 48% 48% ► Skin ► Skin – – 24% 24% ► Other / ► Other / Inapparent Inapparent – – 28% 28%
Entry site lesions Entry site lesions ► Romana ► Romana’ ’s s sign sign � Unilateral, painless, � Unilateral, painless, erythematous erythematous palpebral palpebral edema edema � Occasional swelling of the entire side of the face � Occasional swelling of the entire side of the face � Preauricular � Preauricular or or submaxillary submaxillary adenopathy adenopathy � Conjunctivitis � Conjunctivitis � Dacroadenitis � Dacroadenitis ► Chagoma Chagoma ► � Erythema � Erythema, , prurritus prurritus, painless infiltration of the dermis , painless infiltration of the dermis � Central desquamation with rare ulceration � Central desquamation with rare ulceration � Exposed parts of a sleeping person � Exposed parts of a sleeping person � Last for weeks � Last for weeks
Organ Involvement Organ Involvement ► Hepatosplenomegaly ► Hepatosplenomegaly ► Lymphadenopathy ► Lymphadenopathy ► Muscles ► Muscles ► GI ► GI ► Pulmonary ► Pulmonary ► Heart ► Heart ► CNS ► CNS – – meningoencephalitis meningoencephalitis ► Bone marrow ► Bone marrow ► Skin ► Skin
Congenital Chagas Chagas’ ’ Disease Disease Congenital ► Low birth weight ► Low birth weight ► Hepatomegaly ► Hepatomegaly ► Meningoencepalitis ► Meningoencepalitis with seizures and with seizures and tremors tremors
Chronic Chagas Chagas Disease Disease Chronic ► ► Often seen at 30- Often seen at 30 -40 years old 40 years old ► Occurs in 10- -30% of those infected 30% of those infected ► Occurs in 10 ► ► Chronic myocarditis myocarditis is most common is most common Chronic � Diffuse � Diffuse multifocal multifocal myocarditis myocarditis with edema and fibrosis with edema and fibrosis � Increased thrombosis seen in the heart wall � Increased thrombosis seen in the heart wall � Apical � Apical aneuryms aneuryms occasionally seen occasionally seen st manifestation (RBBB, PVC � EKG is the 1 � EKG is the 1 st manifestation (RBBB, PVC’ ’s) s) � Sudden death is common � Sudden death is common � May present with CHF, embolism, ruptured aneurysm, vent. � May present with CHF, embolism, ruptured aneurysm, vent. fibrillation fibrillation ► ► Can see dilation of other hollow viscera Can see dilation of other hollow viscera � Esophagus � Esophagus � Colon with � Colon with megacolon megacolon � Ureter � Ureter
Parasitized Aneurysmal dilatation Giant Cell Parasites
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