The lifecycle of the malaria parasite
1
Targeting vivax
P. vivax is one of two
forms of relapsing malaria to infect
humans, and is the most prevalent species in Southeast Asia and South America.
It has the ability to become dormant in the
liver (“hypnozoite”) and can be reactivated after
months or even years leading to an attack of
blood stage malaria despite the absence of a
mosquito bite. MMV is actively looking for new
molecules that will provide complete cure of
patients infected with dormant liver stage
vivax malaria, in addition to the blood
stage infections – a so-called
“radical cure”.
TRANSMISSION
TO MAN
TRANSMISSION
TO MAN
LIVER
Sporozoite
Nucleus
Hypnozoite
vivax dorm
P.
a
9-1
2
S
1h
5.4 days
Infected
Hepatocyte
Schizont
15
m
dg
Mi
Merozoites
ut
(Exflagellation)
1
12-3
6h
•••
Microe
gametocyte
stage
M
O
S
Q
UITO STAGE •••
•
<•••••••••••••••••••••
Diploid
Zygote
ys
a
d
E
X
GE
U
A
L
S TA ins
iv a
r
yg
land
Ookinete
15-30m
ins
VER STAGE
N LI
MA
HU
Sa
l
Oocysts
nt
Sporozoites
3
Macrogametocyte
HU
MAN
9 days
L
BLO O D CE
L
AG
ST
E
Erythrocyte
The timings are for Plasmodium falciparum only
pto
ca
Blocking
transmission
Blocking the transmission of the
parasite from patient to patient is key
if malaria eradication is to be realized.
In the blood of an infected patient a minority
of parasites form gametocytes – the sexual form
of the parasite. It is these gametocytes, taken up in
the mosquito’s blood meal, that infect the mosquito
and thus continue the parasite’s lifecycle. MMV is
working to identify compounds that will target and
destroy these blood stage sexual forms (gametes)
to block transmission from man to mosquito
as well as vector stages (ookinetes and
oocysts) thereby blocking transmission
from the mosquito back
to man.
ls
3
8h
ym
43
-4
Ring
ms
2
G
Gametocytes
Trophozoite
Schizont
i
ni
TRANSMISSION
TO MOSQUITO
d
C y cle le a
ing
to
cl
Targeting
the blood stage
The majority of available
antimalarials target the blood stage in
the parasite lifecycle, since this leads to the
clinical symptoms of malaria. Current treatment
requires a 3-day administration once or twice
daily. Ideally, a drug is needed that requires just
a single oral administration, thereby improving
compliance and allowing the healthcare worker
to directly observe treatment. This is especially
important when treatment follow-up is difficult,
as is the case in many malaria-endemic
countries. MMV is currently trialing
a candidate for a single-dose
cure.
2
© MMV 2010.07
Defeating Malaria Together
www.mmv.org