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TM: American Trypanosomiasis (Chagas disease) (i) (Dx (ECG (dilated CM…
TM: American Trypanosomiasis (Chagas disease) (i)
Intro
1907-1909: Carlos Chagas accidently discovers the trypanosome, named after his mentor Oswaldo Cruzi
endemic in 21 countries (not Brazil), 100 million @ risk, 15000 deaths/yr
large economic loss in S America, expensive to tx
transmission is concentrated in areas with domestic vector infestation
shows strong spatial clustering
because infection is lifelong the prevalence reflects human migration patterns too
Trypanosoma cruzi
haemoflagellate protozoa (parasitic in blood)
intracellular rep (HAT replicates in blood)
has nucleus + flagella
disease of poverty
Transmission
reduviid bug (kissing bug)
inoculation through direct bite or through mucosal surface
as bug bites you @ night it defaecates next to bite, then you scratch the faeces into the bite
bite causes irradiation + local pruritus but no pain
bug faeces can fall from roof
the bugs thrive in thatched roofs + cracked mud walls
insect of order hemiptera
9 genera
1-3cm in length
nocturnal
feed on human/animal blood
blood transfusions
5% of S American donors sero+ve
BM/organ transplant
lab exposure
transplacental
oral
March 2005 in Brazil
31 confirmed cases, 5 deaths, 64 suspected cases
sugar can juice: garapa (insects inside when crushed)
high dose of trypanosomes (more than bug bite) - a/w more severe acute infection
over 100 mammals are reservoir hosts - rats, dogs, sloths, bats, cats, opossums, armadillos
Life cycle
vector bites human + defaecates
metacyclic trypomastigotes (active infective agents) rubbed into eye/bite
trypomastigotes enter cells + reproduce as amastigotes
host cells die, amastigotes released - some infect new cells (RES, myenteric plexus, cardiac muscle, CNS), some transform to trypomastigotes + remain in bloodstream
vector ingests amastigotes/trypanomastigotes during a blood meal
parasite reproduces asexually in vector's gut, then metacycic trypomastigotes move to rectum to be defaecated out again
Pathogenesis of myocarditis in acute infection
parasites in cardiac muscle cells cause a marked inflamm cellular infiltrate (esp around cardiac cells that have ruptured + released the parasites)
involvement of epicardium: pericardial effusions
involvement of endocardium: thrombus formation
immune lysis by Ig + cell-mediated immunity directed against antigens released from T cruzi-infected cells which become adsorbed onto the surface of infected + non-infected host cells
Dx
peripheral blood (trypomastigotes in blood film if acute)
xenodiagnosis (examining vector) used historically
amastigotes in biopsy specimens
cultue in NNN (Novy-MacNeal-Nicolle) medium + mouse sub inoculation
immunofluorescence antibody assay (IFA)
PCR used increasingly
serology EIA/ELISA
antibody +ve for life after 30 days hence not good for acute infection dx
ECG
dilated CM with increased end-dias + end-sys vols, reduced EF, enlargement of left atrium + right ventricle
dias filling of left ventricle frequently abnormal
advanced cases often show left ventricular post wall hyperkinesis + relatively preserved IV septal motion
apical aneurysm often seen
Imaging
perfusion scanning with thallium-201
may show fixed defects (corresponding to areas of fibrosis) + evidence of reversible ischaemia
MRI with gadolinium
left ventricular cineangiography in advanced cases
dilated hyperkinetic left ventricle with 1 large or several apical aneurysms containing intracavitary thrombus
often evidence of mitral regurg
coronary angiography usually normal (although abnormalities of the coronary microcirculation have been suggested as a case of the clinical manifestations of chagas)
Tx indications
acute phase
pre-transplant
reactivation in immunocompromised e.g. HIV, chemo
acidental exposure
latent phase - no end organ damage
risk vs benefit
recent evidence supports txing majority of patients with chronic latent infection (indeterminate form) - could prevent progression to determinate form
Prevention
insecticides (resistance reported)
mosquito nets
changing house structure (e.g. iron roofs)
screening blood/organ donors + individuals from @ risk countries
no vaccine available to date