malaria

Plasmodium Life Cycle

Mark F. Wiser
http://www.tulane.edu/~wiser/malaria/

MALARIA

40% of the world’s population lives in endemic areas3-500 million clinical cases per year1.5-2.7 million deaths (90% Africa)increasing problem (re-emerging disease)resurgence in some areasdrug resistance ( mortality) P. falciparum P. vivax P. malariae P. ovale
causative agent = Plasmodium species protozoan parasite member of Apicomplexa 4 species infecting humans transmitted by anopholine mosquitoes

Life Cycle

sporozoites injected during mosquito feeding invade liver cells exoerythrocytic schizogony (merozoites) merozoites invade RBCs repeated erythrocytic schizogony cycles gametocytes infective for mosquito fusion of gametes in gut sporogony on gut wall in hemocoel sporozoites invade salivary glands

Anopheles

Transmission
sporozoites injected with saliva enter circulation trapped by liver (receptor-ligand)



Exoerythrocytic Schizogony
hepatocyte invasion asexual replication 6-15 days 1000-10,000 merozoites no overt pathology

Hyponozoite Forms

some EE forms exhibit delayed replication (ie, dormant) merozoites produced months after initial infection only P. vivax and P. ovale
relapse = hypnozoite recrudescence = subpatentt

Erythrocytic Stage

intracellular parasite undergoes trophic phaseyoung trophozoite called ‘ring form’ingests host hemoglobincytostomefood vacuolehemozoin (malarial pigment)

Erythrocytic Schizogony

nuclear division = begin schizont stage 6-40 nuclei budding merozoites = segmenter erythrocyte rupture releases merozoites blood stage results in disease symptoms

Clinical Features

characterized by acute febrile attacks (malaria paroxysms) periodic episodes of fever alternating with symptom-free periods manifestations and severity depend on species and host status immunity, general health, nutritional state, genetics recrudescences and relapses can occur over months or years can develop severe complications (especially P. falciparum)


paroxysms associated with synchrony of merozoite release between paroxysms temper-ature is normal and patient feels well falciparum may not exhibit classic paroxysms (continuous fever)
Malaria Paroxysm
tertian malaria quartan malaria

gametocytes

erythrocytic schizogony 48 hr in Pf, Pv, Po 72 hr in Pm

Gametocytogenesis

alternative to asexual replicationinduction factors not knowndrug treatment  #'simmune response  #'sring  gametocytePf : ~10 daysothers: ~same as schizogonysexual dimorphismmicrogametocytesmacrogametocytesno pathologyinfective stage for mosquito

Gametogenesis

occurs in mosquito gut‘exflagellation’ most obvious3X nuclear replication8 microgametes formedexposure to air induces temperature (2-3oC) pH (8-8.3)result of  pCO2 gametoctye activating factor in mosquitoxanthurenic acid

Sporogony

occurs in mosquito (9-21 d)fusion of micro- and macrogametes zygote  ookinete (~24 hr)ookinete transverses gut epithelium ('trans-invasion')

Sporogony

ookinete  oocystbetween epithelium and basal laminaasexual replication  sporozoitessporozoites released

Sporogony

sporozoites migrate through hemocoel sporozoites 'invade' salivary glands



Invasive Stages Merozoite erythrocytes Sporozoite salivary glands hepatocytes Ookinete epithelium

P.vivax ring stage

schizont vivax-ovale

P.ovale troph.

P.ovale schizont

Gametocyte

p.Malariae ring stage

Malariae schizont

pPpPP


P.falciparum

P.falciparum