Cured (%)
100
Mefloquine +
artesunate
80
Mefloquine25
60
Mefloquine15
40
Year
AFRICA
ASIA
SOUTH
AMERICA
Updated
15 Jan.
2006
Countries
Drug
Line
AS + AQ
1st
Angola, Benin, Burkina Faso, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya
Mali, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia
AL
1st
AL
2nd
AS + SP
1st
Cambodia, Thailand
AS + MQ
1st
AL
1st
Indonesia
AS + AQ
1st
AS + SP
1st
Viet Nam
DP
1st
AS + SP
2nd
Philippines, Iran
AL
2nd
Ecuador, Peru
AS + SP
1st
AS + MQ
1st
AL
1st
AFRICA
Updated
15 Jan.
2006
Countries
Drug
Line
Burundi, Cameroon, Cte d'Ivoire, DRC, Eq.Guinea, Gabon, Ghana, Guinea, Liberia,
Madagascar, Senegal, ST&P, Sierra Leone, Sudan (S), Zanzibar
AS + AQ
1st
Angola, Benin, Burkina Faso, Comoros, Ethiopia, Gambia, Guinea Bissau, Kenya
Mali, Namibia, Niger, Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia
AL
1st
AL
2nd
AS + SP
1st
Cambodia, Thailand
AS + MQ
1st
AL
1st
Indonesia
AS + AQ
1st
AS + SP
1st
Viet Nam
DP
1st
AS + SP
2nd
Philippines, Iran
AL
2nd
29% deploying
ASIA
60% deploying
SOUTH
AMERICA
Ecuador, Peru
AS + SP
1st
AS + MQ
1st
71% deploying
AL
1st
Which combination
therapies ?
WHO Technical Consultation on Antimalarial
Combination Therapy April 2001
Based on available safety and efficacy data the
following therapeutic options, currently available,
have the potential for deployment (in priority order)
regardless of cost:
artemether-lumefantrine
artesunate (3 days) + amodiaquine
artesunate (3 days) + SP where SP is still effective
amodiaquine + SP where amodiaquine and SP are
still efficacious
artesunate (3 days) + mefloquine in areas of low
transmission
THERAPEUTIC OPTIONS
NOT RECOMMENDED BY WHO
WITH OBJECTIVE OF DELAYING RESITANCE
Malaria diagnosis
Parasitological confirmation
(microscopy or RDT) before treatment
Exceptions:
children under 5 years of age, from areas
of high transmission where treatment is
based on clinical diagnosis
suspected severe malaria where
parasitological confirmation is not
immediately possible
Changing
antimalarial treatment policy
Treatment failure of >10% (as assessed
through monitoring of therapeutic efficacy
at 28 days)
New treatment an average cure rate
of > 95% as assessed in clinical trials
1930s
1940s
1950s
1960s
Artemisinin
Artesunate
Artemether
Mefloquine
Pyronaridine
Halofantrine
Artemether-lumefantrine
Atovaquone-proguanil
1970s
1980s
1990s
Treatment of uncomplicated
falciparum malaria
Artemisinin-based combination therapies
(ACT) are the treatments recommended
for all cases of uncomplicated falciparum
malaria including:
in infants,
in people living with HIV/AIDS
for home-based management of malaria
pregnant women in the 2nd and 3rd
trimesters
Exception:
1st trimester of pregnancy
Treatment of uncomplicated
falciparum malaria
The following ACTs are presently
recommended:
artemether-lumefantrine
artesunate + amodiaquine
artesunate + mefloquine
artesunate + sulfadoxine-pyrimethamine
Efficacy of ACTs depend on the efficacy
of the partner medicine
The artemisinin derivatives
(oral formulations) and partner
medicines of ACTs are not
recommended as monotherapy
Treatment of uncomplicated
falciparum malaria
Second-line treatment:
alternative ACT
quinine + tetracycline
or doxycycline
or clindamycin
Treatment of severe
falciparum malaria
Any of the following antimalarial medicines
are recommended
Artesunate i.v. or i.m
artemether i.m.
quinine (i.v. infusion or i.m. injection).
Full course of ACT or quinine + clindamycin
or doxycycline when patient can tolerate
oral treatment
4 months
5 years
6 11 years
12 14
years
> 14 years
Weight
group
5 14 kg
15 -24 kg
25 34 kg
>34 kg
Blister
color
Yellow
(Day 1)
(Day 2)
(Day 3)
1 tb R,
1 tb R,
1 tb R,
1 tb Z
1 tb Z
1 tb Z
2 tb R,
2 tb R,
2 tb R,
2 tb Z
2 tb Z
2 tb Z
3 tb R,
3 tb R,
3 tb R,
3 tb Z
3 tb Z
3 tb Z
4 tb R,
4 tb R,
4 tb R,
4 tb Z
4 tb Z
4 tb Z
Blue
Orange
Green
Artesunate+Amodiaquine
Amodiaquine
A tablet contains:
153.1mg of base as Chlorohydrate or
200mg of base as Hydrochloride
Artesunate
A tablet contains:
50mg of Sodium Artesunate
Dosing Schedule
The total recommended treatment is as follow:
4mg/kg body weight of Artesunate
10mg/kg body weight of Amodiaquine
Both must be given once a day, at the same time, for three days
Artesunate+Amodiaquine
Age
Amodiaquine
Day 1
Day 2
Day 3
Day 1
Day 2
Day 3
5 mnt
11 mnts
25 mg
25 mg
25 mg
76 mg
76 mg
76 mg
16
years
50 mg
50 mg
50 mg
153 mg
153 mg
153 mg
7 13
years
100 mg
100 mg
100 mg
306 mg
306 mg
306 mg
Over 13
years
200 mg
200 mg
200 mg
612 mg
612 mg
612 mg
MECHANISM OF ACTION
Exerts antimalarial activity by iron-mediated cleavage
of the peroxide bridge and generation of an organic
free radical.
The interaction of artemisinin with haem in the parasite
may turn out to be essential.
Haem bound iron (but also free iron) may serve as a
catalyst.
The artemisinin radical binds subsequently to
membrane proteins, and alkylation reactions
eventually cause destruction of the parasite.
(Vries et al, Drugs, 1996
ANTIMALARIAL EFFICACY
Chemoprophylaxis
Sickle Cell Anaemia
Daily Proguanil
Age Group
* Weight
group (Kg)
PRIMAQUINE
(15 mg base)
0.5 mg/kg bw
Start
concurrently
with CQ and
give daily for
14 days
Day 1
Day 2
Day 3
4 months up
to 12 months
4 - <10
13 months up
to 5 years
10 - <19
6 - 7 years
19 - < 24
8 - 11 years
24 - <35
12 - 14 years
35 - < 50
15 +
50 or more
Quinine
Loading dose:
Quinine dihydrochloride 20 mg salt/ kg bw
diluted in 10 ml/kg bw of 5% dextrose or
dextrose saline administered by IV infusion
over a period of four hours for both adult and
children. In severe Childhood falciparum
malaria, if patient received quinine or quinidine
or mefloquine in 48 hrs before arrival, give 10
mg/kg over 2 hours.
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