Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Din Syafruddin
Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makassar 90245
Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta 10430, Indonesia
Presented on Annual Meeting of PDGKI, Makassar 25 April 2015
Introduction
Efforts against malaria has yielded dramatic progress over
the last 10-15 years. The scale up of malaria control
intervention between 2001-2012 resulted in an estimated 3.3
million lives saved (WHO, 2014).
Malaria-control and management strategies include
chemotherapy for patients, indoor residual spraying (IRS),
and long-lasting insecticide treated nets (LLINs) to reduce
mosquito populations
The spread of parasite and anopheline vector resistance and
lack of a efficacious malaria vaccine renew emphasis on
development of innovative preventive tools
cinchona alkaloids
4-aminoquinolines
amodiaquine
8-aminoquinolines
tafenoquine
4-quinoline methanols
9-phenanthrene methanols
antifolic drugs
proguanil
sulpha drugs
quinine
chloroquine,
primaquine,
mefloquine
halofantrine
pyrimethamine,
a) sulphones;
dapsone
b) sulphonamides;
sulphadoxine, sulfalene
sesquiterpene lactones
a) artemisinin,
Quinine
Chloroquine
Proguanil
Sulphadoxinepyrimethamine
Mefloquine
Atovaquone
Artemisinin
First Report
of Resistance
1632
1945
1948
1967
1910
1957
1949
1967
278
12
1
0
1977
1996
2000
1982
1996
2009
5
0
9
Difference
(years)
EIJKMAN INSTITUTE
Extrachromosomal genomes
in the malarial parasites
CO I
CO III
6kb
Cytb
WLC
Q I VP
Cytoplasmic
E
W
G
T
Q
H
I
I
V
YS
G
L
Y
Y
Y
F
A
Y
R
T
Y
L
G131, N245, F264 Mucidin
T
N 250
S
FP
E
Y
V
V
A
M
L
I
I141, T142 Stigmatellin
M
V
S
W
Q
KL
Y268N
TPD
E
S
I
F123, G131, G137, Myxothiazol
T
I
A
P
G M133I G
I
Y268C
N
K
S
P
W
M133, L144, I258, F267,
W
50 Y
D
R
C
P
P V284FS
R
D
F
F
Y268, L271, K272, P275,
Q
H
K
P
R
S
L
I
F
G280, L283, V284
S
F
N
A
V
V
Y
I
QL
L I P
L V
GA
HM
C
Y I G H L F
L
L
Y
V
F G
Atovaquone
G
G
A
I
GV F
T
I
AF T
GT
R FL
V I I
L FP S I Q
LQ I
LW L
A LS
A
V
F
A
F
N27, G33, L217 Antimycin AI F
I L
I
I I L
L SLQ
AV L
Y S
F VL F
L
F
L
FA I
FF S
I C V F
T Y
L
C
F
I I LG
I14, L215 Diuron
M F
L
F
LI I
L I G
L F
GS
HL
L
W
L
I
H F I
G
F
NN
I
A
I
IS
LS
I
F
Y
W
F
L
L
G
N
E
R
P
S
V
Q
Q
L
LW
F
H
K
G
F
N
N
R
P
S
I
L
V
N
L
N
L
K
Y
L
D
H
N
KT
P
E
L
Y
L
300
S
H YD
R
Y
C
T
S
2
SYL
G
A
P
T
Y
M
L
1
S
I
T
L
Y
N
S
0
N
I
N
F
N
Y
I
S
Q
0
V
L HT K V L N I S N
P
P
Q
F KM
A
LG
I
N
2
YD T A LK I P F Y
0
0
A
L
V
G I L
L
W V N GI
Y T T S PS
S
Qi
1.
2.
3.
Qo
NH
Qi
Matrix
COO
Available Insecticides
I. Sodium channel modulators
1. Pyrethroids: permethrin
2. Pyrethrin: pyrethrin
3. DDT
II. GABA-gated chloride channel inhibitors
1. Cyclodione organochlorine: Chlordane, endosulfan,
gammaHCH
2. Phenylfirazole (Fiproles): Ethiprole, Fipronil
III. Acetyl choline esterase inhibitors:
1. Carbamates: Aldiocarb, bendiocarb etc
2. Triazemates
3. Organophosphate: Acephate, temephos, malathion
North Molluca
Molluca
North Sumatera
Central Java (Purworejo)
Lampung
Bangka Belitung
East Nusa Tenggara (Sumba)
Species
An punctulatus
An punctulatus
An. farauti
An vagus
An sundaicus
An vagus
An aconitus
An barbirostris
An balabacensis
An vagus
An sundaicus
An. barbirostris
An kochi
An sundaicus
An letifer
An vagus
An sundaicus
An subpictus
An tesselatus
An minimus
An flavirostris
An indefinitus
An kochi
An maculatus
(n)
= 97
3
3
5
2
2
1
7
7
5
6
23
1
1
6
2
3
2
9
1
1
2
3
1
1
GCA
WT
3(100%)
3(100%)
4(80%)
2(100%)
2(100%)
0
5(71%)
6(86%)
5(100%)
4(67%)
22(96%)
0
0
6(100%)
2(100%)
3(100%)
2(100%)
9(100%)
1(100%)
1(100%)
2(100%)
3(100%)
1(100%)
1(100%)
(%)
(TCA)
RT
0
0
0
0
0
1(100%)
2(29%)
1(14%)
0
2(33%)
1(4%)
1(100%)
1(100%)
0
0
0
0
0
0
0
0
0
0
0
(GGA)
RT
0
0
1(20%)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
(%)
Study Sites
G119
wild type
119S
Resistance Type
Lampung
100
Purworejo
100
North Molluca
100
Bangka Belitung
100
IRRITANCY
TOXICITY
REPELLENCY
Wainyapu
Umbungedo
All villages
Cluster 1
(W1)
Cluster 2
(W2)
Cluster 3
(U1)
Cluster 4
(U2)
Cluster
1+4
Cluster
2+3
90%
Active+
10%
placebo
10% Active+
90% placebo
10% Active+
90% placebo
90% Active+
10%placebo
Active
clusters
Placebo
clusters
Household
108
114
115
108
216
Active:placebo
(98:10)
(11:103)
(12:103)
(98:10)
(196:20)
229
(23:206)
Population
368
523
596
633
1001
1119
Samples
42
44
43
41
83
87
Malaria
incident
26
40
21
31
61
652
602
866
888
1540
1468
0.040
0.066
0.024
0.006
0.020
0.042
Incidence density
Person-week
Incidence
rate
0.484 (0.3140.746)
Wainyapu
Umbungedo
All villages
Cluster 1
(W1)
Cluster 2
(W2)
Cluster 3
(U1)
Cluster 4
(U2)
Cluster
1+4
Cluster
2+3
90%
Active+
10%
placebo
10% Active+
90% placebo
10% Active+
90% placebo
90% Active+
10%placebo
Active
clusters
Placebo
clusters
0.619
0.909
0.488
0.122
0.373
0.701
Cumulative
incidence
Proportion
of
Incidence
0.533 (0.390
0.727)
Un-adjusted
2
2.356 (p = 0.124)
70
3.5
60
50
2.5
40
30
20
10
0.5
Week
Indoor - A.I
1.5
Indoor - Placebo
Week
Indoor - A.I
Indoor - Placebo
Study team
1. Eijkman Institute for Molecular
Biology, Jakarta, Indonesia
Din Syafruddin*
Krisin Chand
Puji BS Asih
Christian Nixon
Christina Nixon
2. Eijkman-Oxford Clinical Research
Unit, Jakarta, Indonesia
Kevin Baird
Siti Nurlaela
3. University Hasanuddin, Makassar,
Indonesia
Din Syafruddin*
Isra Wahid
Hasanuddin
Joko Hendarto
Dian Sidik
Thank you