leishmania - | department of zoology at ubc
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Leishmania
Obligate intracellular parasites ofvertebrates; intestinal parasites of sandfly(Phlebotominae) vectors.
Large number of species differing inserotypes, disease consequences, andepizootiology, infect man in Neotropics,Eurasia and Africa (Table 5.1).
Herwaldt, B.L. 1999.
Leishmania. The Lancet
354: 1191 -- 1199.
The Diseases
• Cutaneous: chronic skin sore develops atsite of vector bite.
• Mucocutaneous: infection involves mucoidtissue of face and throat; often leads tomarked deformation of features.
• Visceral: involvement of liver, spleen, andother viscera; often fatal.
• Amastigotes transform intopromastigotes in insect.
• Promastigotes (notamastigotes) have LPG andGP63 on surface. LPGextended in metacyclics.Both molecules protect againstenzymes in insect gut andmodulate macrophagebehaviour in vertebrate.
LPG
Sheds complementelements (c5--c9)protecting againstcomplement attack.
Scavenges O2 radicals
Inhibits protein Kinase
Suppresses NOproduction
Inhibits complement lysis
Cleaves C3b to C3biencouragingphagocytosis with CR3receptor: inhibits O2burst.
Proteases attack hostenzymes.
GP63
• After entry, metacyclic transforms intoamastigotes; LPG, GP63 downregulated,surface coat changed.
• Amastigote must have different mechanismof entry into macrophage.
Pathogenesis and diseaseoutcome
• Depends on Th1/Th2 balance: Th1 stimulation,leading to cytotoxic response (through secretion ofgamma IFN-γ and IL2) is critical for protection.
• L. donovani infected macrophages downregulateexpression of MHC-II and IFN-γ receptors.Tyrosine kinases associated with JAK receptor lessactive; STAT cascade reduced.
Treatment and control
• Pentavalent antimony compounds (availablesince 1950). Although side effects common,they are reversible.
• Amphotericin B used
where antimony fails.
But high kidney
toxicity.
Epidemiology
• Several speciesinvolved: differ inserological, pathologicaland epidemiologicalcharacteristics.
• Some have wild, othersdomesticatedreservoirs.
• Find infections andtreat; vector control.