symptomssuchasnausea,vomiting,anddiarrhea.Atlowerconcentrations,
TNFacancontributetothekillingoftheintracellularparasites.Variousother
cytokines(seeabove)eithersynergizewithTNFaorinducedifferentreac-
tions.
&Anemia.Animportantfactorinmalarialpathogenesis,especiallyinma-
lariatropica,isanemia,causedbydestructionofRBCsinschizogony,in-
creasedeliminationofbothinfectedandnoninfectedRBCsinthespleen,in-
hibitionoferythropoiesisbyTNFa,andotherfactors.
&Cytoadherenceandrosetteformation.RBCsinfectedwithmaturingP.
falciparumschizontsadheretotheendotheliumofbloodvesselsinvarious
organs,especiallyinpostcapillaryvenules.Thisphenomenonisduetoanin-
teractionbetweenstrain-specificligandsoftheparasitewithhostreceptors.
DuringthedevelopmentofP.falciparumfromtheringformtothematuring
schizont,buttonlikeprotrusionsoftheerythrocyticmembranedevelop,un-
derwhichhigh-molecular(20 0 – 300 kDa)proteinsareenriched,thenpre-
sentedatthecellsurface.Theseso-calledP.falciparumerythrocytemem-
braneproteins(PfEMP)bindtoavarietyofendothelialreceptors,forinstance
totheintercellularadhesionmolecule(ICAM),thrombospondin,E-selectin
(ELAM),andtheCD36molecule.ICAM- 1 andELAM-1arethoughttobe
mainlyresponsibleforcytoadherenceinthebrain.Thesesubstancesarepro-
ducedinsignificantamountsthereandareinduciblebyTNFaandothercy-
tokines.OutsideofthebrainthereceptorCD36isapparentlythemostim-
portantrecognitionprotein.ThePfEMPantigens,codedforbyabout 150
genes,arevariableandplayaroleinparasiteimmunoevasion.Theadvantage
ofcytoadherencefortheplasmodiaisthatpartoftheirpopulationthus
avoidseliminationinthespleen.Forthehost,however,cytoadherencehas
pathologicalconsequences:ithinderslocalmicrocirculationaswellasgas
andsubstanceexchangeprocesses,theresultinganemiaexacerbatestissue
hypoxiaand,finally,itcausescellandorgandamagewithgravesequelaein
thebraininparticular.RosetteformationreferstoclumpingofRBCsinfected
byP.falciparumwithothernoninfectedonescausedbymechanismssimilar
tocytoadherence.
&Otherprocesses(aselection).DuetothedestructionofRBCsandpara-
sitesandresultingproductionofTNFa,phagocytosingcellsofthereticuloen-
dothelialsystemareactivated.Signsofthisincludesplenicswellinginthe
courseoftheinfectionandincreasedeliminationoferythrocytesinthe
spleen(seeanemia).Renaldamageinacutemalariatropicaiscausedby
capillarycytoadherenceandtubularnecrosis.Inmalariaquartana,such
damageisduetodepositionofimmunecomplexesintherenalcapillaries.
&Pathologicalchanges.Suchchangesareknownfromcasesofmalariatro-
picainparticular.BraincapillariesarecloggedwithinfectedRBCs(thepig-Plasmodium 5299Kayser, Medical Microbiology © 2005 Thieme