Medical Microbiology

&Malignanttertianmalaria(malariatropica),causedbyP.falciparum:

Incubationperiod: sevento 15 daysorlonger.

Parasitemia: oftenatveryhighlevel,upto 20 %ormore!

Course: initialsymptomsoftenmorepronouncedthanin

othertypes.Rapid,severecourseinnonimmuneper-

sons.Highlethalityrateifuntreated(50– 60 %in

personsfromcentralEurope).

Aftershortinitialphasefeverhigh,continuousor

with< 48 hourrhythm.Ifuntreated,diseaselasts

twotothreeweeks.

Recurrence: recrudescenceisrare,usuallywithinoneyear.

Specialcharacteristics: severecomplicationsarepossible,especiallycere-

bralmalaria(e.g.,withconvulsions,disturbedvision

andcoordination,alteredstatesofconsciousness,

coma);severenormocyticanemia;pulmonaryedema

andrespiratoryinsufficiency;renalinsufficiency;

gastrointestinaldisturbances;circulatorycollapse;

hypoglycemia;liquid/electrolyteunbalance,spon-

taneous hemorrhaging; disseminated intravasal

coagulation;hyperpyrexia(39.5– 428 C);hemoglobi-

nuria(“blackwaterfever”);hyperparasitemia.

&Mixedinfections

MixedinfectionswithtwoPlasmodiumspeciesareobservedinabout 3 – 4 %of

allcasesandmayalterthecourseofthedisease.

Pathogenesisandpathology.Theclinicalmanifestationsofmalariaare

causedbytheerythrocyticstages(“bloodstages”)oftheplasmodiaandre-

flectmultifactorialpathogenicprocessaffectingmanydifferentorgans.Only

anoutlineoftheseprocessescanbedrawnhere,especiallywithregardto

falciparum(tropical)malaria.

&Theroleofcytokines.Asaresultoferythrocyticschizogonyandtheat-

tendantruptureoferythrocytes(redbloodcells=RBCs),malarialantigens

(phospholipidsandglycolipids)arereleasedthatstimulatemacrophages

andmonocytestoproducetumornecrosisfactoralpha(TNFa)andothercy-

tokines(IL-1,IL-6,IL-8,etc.).Alsoassociatedwiththisprocessareboutsof

fever,towhichhemozoinpresumablycontributesaswell.Cytokineproduc-

tionisalsoinitiatedbyIFNcproducedintheimmunologicalTH1response.

TNFaplaysaspecialroleinpathogenicity,sincetheconcentrationofthiscy-

tokineinthebloodcorrelateswiththeseverityofaP.falciparuminfection.

Thissubstancealso,athigherconcentrations,inducesfever,inhibitserythro-

poiesis,stimulates erythrophagocytosis,andcausesvariousnonspecific

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Kayser, Medical Microbiology © 2005 Thieme