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.

Sandflies• Poor flyers; tend to

remain near breedingsites.

• Bites almostexclusively at night(but Lutzomyiawellcomei (transmitsL. braziliensis) anexception).

• Larvae needmicroclimate withhigh humidity tosurvive. So removeaccumulatingvegetation.

Phlebotomus papatasi