19 Blood Flagellates Flashcards
Leishmania causative agents
L donovani, L major, L braziliensis
Resrvoir hosts: dog (L infatum) humans (L donovani)
Life cycle: transmit promastigotes by sandfly bites to human -> promastigotes are phagocytosed by MACROPHAGE -> promastigotes turn into amastigoes and do binary fission -> macrophages burst -> amastigotes infect other macrophage -> sandfly bite human and get infected -> amastigotes migrate from midgut to proboscis -> amastigote turn into proamastigote
Leishmania categories and symptoms
Cutaneous* leishmaniasis (L major, tropica, infantum)
baghdad ulcer/delhi boil/bouton d’orient (erythematous papule)
least severe form
volcano sign (papule -> violaceous ulcer)
Mucocutaneous (L braziliensis)
nasal and oral cavities
skin ulcer -> chiclero ulcer
espundia/breda’ s disease (sponge like)
Diffuse cutaneous (L aethiopica L mexicana)
disseminated and chronic lesions
lepromatous leprosy
Visceral* (L donovani/chagasi)
most fatal
affect GI tissues (liver and spleen)
double quotidian fever
hepatomegaly (early stages, fighting infection)
splenomegaly (late stages, splenic destruction)
monocytosis (propagation, downregulation of other immune cells = anemia)
Post-kala azar dermal L: cutaneous eruption -> hypopigmented macular, maculopapular, nodular rash; reservoir for parasites
Leishmania pathogenesis
Oligoparasitic (few parasites)
mucosal leishmaniasis
stronger immune response
few amastigotes and mononuclear cells predominate
cell mediated immunity: IL2 and IFNy (TH1 and NK cells), IL12 -> TH1, ROS, granuloma formation
Polyparasitic end (greater burden) diffuse cutaneous L weak immune response parasitized macrophages no IL2 or IFNy, no TH1, yes TH2 -> suppress macrophage activity
Leishmania diagnosis
Microscope: see amastigotes; aspirates from spleen/bone marrow/lymph nodes; ot for field setting
Freeze-dried DAT: detect antibodies -> coagulation of blood
Leishmanin (montenegro) skin test: detects exposure, delayed hypersensitivity reaction; for CL and MCL
Leishmania treatment, prevention, control
Leishmanization: intentional biting (butt) -> partial immunity; CL early in life
Antimony drugs: meglumine antimonate, sodium stibogluconate
Liposomal amphotericin B (antifungal)
Miltefosine for VL
Paromomycin topical for CL, second line for VL
Vector control: insect repellants, insecticides, ITNs
reservoir control: poisoned baits, dogs
VL and AIDS
HIV predisposes to VL, VL accelerates HIV
Both affect monocytes and macrophages
polyclonal B cell activation
enhances TH2 activity (dec CD8 cytotoxic t cell response)
dec TH1 cells
1 deactivation of macrophage functions and TH1 cells
2 inhibition of ribosome lysozyme fusion
3 enhancement of some TH2 cell functions
Trypanosoma causative agent
T brucei gambiense (W and Central Africa)
T brucei rhodesiense (E and S Africa)
Life cycle: transmit metacyclic trypomastigotes by tsetse fly (Glossina) bite -> transform to bloodstream trypomastigotes -> multiply in bloodstream (binary fission) -> trypomastigotes in acute phase (detectable) -> flies bite human -> transform to procyclic trypomastigotes in fly’s gut -> transform to epimastigotes -> migrate to salivary glands -> transform to metacyclic trypomastigotes
Trypanosoma phases and symptoms
Tb gambiense = chronic and fatal
Tb rhodesiense = acute, fast, and fatal
Initial phase: Chancre formation
eschar = painful, resolves in 2-3 w
Early phase: hemolymphatic phase parasite multiplies in blood/CSF/lymph systemic distribution via bloodstream immunogenic variante surface glycoprotein winterbottom sign, splenomegaly, anemia
Late phase: meningoencephalitic phase
gambian = 3-10 mo, rhodesian = few weeks
kerandel’s sign: pathognomic feature, hyperesthesia, demyelination of neurons of PNS, coma
Trypanosoma pathophysio
immune-mediated hypersensitivity reaction
inflammatory mediators acting on RBC, cardiac tissue, brain tissue
Acute hemorrhagic leukoencephalopathy
breaks down CNS integrity = blood leakage
neuro symptoms: important is GCS <12 = late phase
Trypanosoma diagnosis
Microscopy: curvy and highly motile trypomastigotes, early phase (chancre fluid, blood, LN), late phase (CSF)
Card Agglutination test for Trypanosomes: screening for TB gambiense
Trypanosoma treatment, prevention, control
Hemolymphatic phase: pentamidine (early stage Tbg), suramin (early stage Tbr)
Meningoencephalitic stage: melarsoprol (late stage for both, can cause arsenic encephalopathy, Jarisch-Herxheimer reaction), nitrofurazone, eflornithine (first line for Tbg that don’t respond to melarsoprol)
Surveillance
Vector control
Chagas disease causative agent
South american trypanosomiasis
Trypanosoma cruzi (stercoraria)
obligate, intracellular, protozoan
infect myocytes and cells of reticuloendothelial system
vector: reduviid bugs/triatomine “kissing” bug
reservoir host: zoonotic mammalian animals
transmission: blood feeding, transfusion, congenital, consumption of contaminated blood
bite -> feces are near the bite wound -> enter through wound/intact mucosal membranes (conjunctiva) -> invade inoculated cells and differentiate into intracellular amastigotes -> amastigotes do binary fission -> differentiate into trypomastigotes -> become bloodstream trypomastigotes -> infect other tissues and become amastigotes -> vector bites human -> transforms into epimastigotes in vector’s midgut
Chagas disease phases and symptoms
Acute phase: focal/diffuse inflammation affecting myocardium
chagoma, romana’s sign (unilateral painless swollen palpebrae, conjunctivitis)
Intermediate/latent phase: asymptomatic, serologically positive for infection
Chronic phase: parasites proliferate in pt, fibrotic reactions
heart = cardiomegaly, cardiomyopathy (RV, right sided heart failure), acute chagas myocarditis
GI tract = megacolon, megaesophagus
brain
Chagas disease pathophysio
theory 1: infection-induced autoimmune disease, cross-reaction
theory 2: parasite persistence -> chronic infection -> chronic inflammation
minimal rejection unit: infection in cardiac cell -> inflammation of surrounding cells -> chronic fibrosis (functional loss) -> neuritis and neuronal loss (signal loss)
Chagas disease diagnosis
Direct visualization: blood smear, CSF, lymph fluids; useful for acute phase
Indirect test: ELISA, hemoculture, xenodiagnosis
Imaging: abdominal x-ray (megacolon), chest x-ray (cardiomegaly), esophageal imaging, ECG (cardiomyopathy, acute phase low voltage QRS complex, chronic phase ventricular premature beats, BBB, t-wave inversion, low-voltage QRS)
Biopsy
