Plasmodium Life Cycle

Plasmodium Life Cycle
Mark F. Wiser
http://www.tulane.edu/~wiser/malaria/
MALARIA
40% of the world’s population lives in endemic areas
3-500 million clinical cases per year
1.5-2.7 million deaths (90% Africa)
increasing problem (re-emerging disease)
resurgence in some areas
drug 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 phase
young trophozoite called ‘ring form’
ingests host hemoglobin
cytostome
food vacuole
hemozoin (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 replication
induction factors not known
drug treatment  #`s
immune response  #`s
ring  gametocyte
Pf : ~10 days
others: ~same as schizogony
sexual dimorphism
microgametocytes
macrogametocytes
no pathology
infective stage for mosquito
Gametogenesis
occurs in mosquito gut
‘exflagellation’ most obvious
3X nuclear replication
8 microgametes formed
exposure to air induces
 temperature (2-3oC)
 pH (8-8.3)
result of  pCO2
gametoctye activating factor in mosquito
xanthurenic 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  oocyst
between epithelium and basal lamina
asexual replication  sporozoites
sporozoites released
Sporogony
sporozoites migrate through hemocoel
sporozoites `invade` salivary glands
Invasive Stages

Merozoite
erythrocytes
Sporozoite
salivary glands
hepatocytes
Ookinete
epithelium