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Table 1.

Currently Available Antimalarial Drugs

Arylaminoalcohols
4-aminoquinolones:
Chloroquine
Amodiaquine
Amopyraquine
Structurally Related Compounds
Pyronaridine
Piperaquine
Quinine
Quinidine
Mefloquine
Halofantrine
Lumefrantrine
(Benflumetol)
8-aminoquinolones
Primaquine
Tafenoquine (Etaquine)
Dihydrofolate reductase inhibitors
Pyrimethamine
Proguanil
Chlorproguanil
Pyrimethamine-
sulfadoxine
Chlorproguanil-dapsone
Artemisinin and deriatives
Artemisinin
Artemether
Artesunate
Artemotil
Dihydroartemisinin
Hydroxynaphthaquinones
Atovaquone
Atovaquone-proguanil
Antibiotics with antimalarial activity
Sulfonamides
Tetracyclines
Chloramphenicol
Fluoroquinolones (weak)
Rifamycins (weak)
Macrolides
Clindamycin
Lincomycin
Drugs in italics are either still investigational, or are not widely available
Table 2. Dosing Schedule for Artesunate plus Amodiaquine

Dose in mg (no. of tablets)


Artesunate Amodiaquine (base)
Day 1 Day 2 Day 3 Day 1 Day 2 Day 3

Age
511 months 25 () 25 25 76 () 76 76
16 years 50 (1) 50 50 153 (1) 153 153
713 years 100 (2) 100 100 306 (2) 306 306
>13 years 200 (4) 200 200 612 (4) 612 612

Table 3. Dosing Schedule for Artesunate plus Sulfadoxine-Pyrimethamine

Dose in mg (no. of tablets)


Artesunate Sulfadoxine-pyrimethamine
Age
Day 1 Day 2 Day 3 Day 1 Day 2 Day 3
511 months 25 () 25 25 250/12.5 ()
16 years 50 (1) 50 50 500/25 (1)
713 years 100 (2) 100 100 1000/50 (2)
>13 years 200 (4) 200 200 1500/75 (3)

Table 4. Dosing Schedule for Artemether-Lumefantrine


No. of tablets recommended

Body weight in kg at approximate timing of dosinga


(age in years) 0h 8h 24 h 36 h 48 h 60 h
514 (<3) 1 1 1 1 1 1
1524 (39) 2 2 2 2 2 2
2534 (914) 3 3 3 3 3 3
>34 (>14) 4 4 4 4 4 4
a
Co-Artem: 1 Tablet contains 20mg Artemether and 120mg Lumefantrine. The drug should be
taken with food or milk as. Bioavailability is significantly enhanced with coadministartion of fat,
each dosage should be taken with milk or fatty snack.

Table 5. Dosing Schedule for Artesunate plus Mefloquine*

Dose in mg (no. of tablets)


Artesunate Mefloquine (base)
Age
Day 1 Day 2 Day 3 Day 1 Day 2 Day 3
511 months 25 () 25 25 125 ()
16 years 50 (1) 50 50 250 (1)
713 years 100 (2) 100 100 500 (2) 250 (1)
>13 years 200 (4) 200 200 1000 (4) 500 (2)
*alternatively the total dose of mefloquine may be split into three, with one third of the dose being taken
on days 1, 2 and 3.

Table 6. Recommendations on the Treatment of Falciparum Malaria in Non-immune


Travellers

For travelers returning to non-endemic countries:1

1. Artemether-lumefantrine (1.5 mg/12 mg/kg twice daily for 3 days)


2. Atovaquone-proguanil (1 g/400 mg once daily for 3 days)
3. Quinine (10 mg salt/kg 8-hourly) plus Doxycycline2 (3.5 mg/kg once daily) or
Clindamycin (10 mg/kg 12-hourly); all drugs to be given for 7 days.

For severe malaria:

Antimalarial treatment of severe malaria in travelers is the same as the general recommendation
(table 7)

Travellers with severe malaria should be managed in an intensive care unit

Haemofiltration or haemodialysis should be started early in acute renal failure or severe


metabolic acidosis

Positive pressure ventilation should be started in case of respiratory distress and coma with
breathing
abnormalities

1
Halofantrine is not recommended as first-line treatment for uncomplicated malaria because of
cardiotoxicity.

2
Doxycycline should not be used in children under 8 years of age and in pregnancy.

Table 7. Antimalarial Treatment of Severe Malaria

Artesunate1 2.4 mg/kg i.v. or i.m. on admission, at 12, 24 hours, then daily.
Artesunic acid (60mg) is dissolved in 1ml of 5% sodium
bicarbonate and further diluted into 5ml with 5% dextrose or
normal saline for intravenous injection (given as a bolus over 2
min). 1 ampoule=60mg

Artemether 3.2 mg/kg i.m. on admission followed by 1.6 mg/kg daily. NOT
for i.v. administration. 1 ampoule = 80mg. Injections to the
anterior thigh.

Quinine 20mg /kg of dihydrochloride salt by intravenous infusion over 4


hrs followed by 10 mg/kg infused over 2 - 8 hrs every 8 hours.
If intravenous route not possible then give by intramuscular
injection to the anterior thigh. The first dose should be divided;
10mg salt/kg to each thigh. Quinine should be diluted, inject no
more than 180mg/ml.

Quinidine 10 mg base/kg infused at constant rate over 1-2 hr followed by


0.02 mg/kg/min as constant infusion, with electrocardiographic
monitoring.
1
Parenteral artesunate is the drug of choice for the treatment of severe malaria in adults. For children
in high transmission areas there is as yet insufficient evidence to recommend any of the above
antimalarial medicines over another.

Table 8. Treatment of Uncomplicated Vivax and Ovale Malaria.

Chloroquine 25 mg base/kg bw divided over 3 days, combined with primaquine 0.25 mg


base/kg bw, taken with food once daily for 14 days is the treatment of choice for
chloroquine-sensitive infections. In Oceania and South-East Asia the dose of primaquine
should be 0.5 mg/kg bw.
Amodiaquine (30 mg base/kg bw divided over 3 days as 10mg/kg bw single daily doses)
combined with primaquine should be given for chloroquine-resistant vivax malaria.

In moderate G6PD deficiency, primaquine 0.75 mg base/kg bw should be given once a


week for 8 weeks. In severe G6PD deficiency, primaquine should not be given.

Where ACT has been adopted as the first-line treatment for P. falciparum malaria, it may
also be used for P. vivax malaria in combination with primaquine for radical cure.
Artesunate plus sulfadoxine-pyrimethamine is the exception as it will not be effective
against P. vivax in many places.

Table 9. Treatment of Malaria in Pregnancy

Falciparum Malaria in Pregnancy


Treatment Transmission
Trimester Current Treatment regimens
group region

Uncomplicated Chloroquine- As this is only valid for a very limited number of


malaria sensitive regions in the world, we do not advise the use of
this drug during pregnancy, unless reliable
P. falciparum information on drug resistance is available.
Treat as for Chloroquine-resistant or
unknown resistance (see below)
Parasitemia
<4% and no
signs of severity

Chloroquine- Supervised Oral Quinine plus Clindamycin


resistant or
unknown 1st Quinine sulfate: 10 mg salt/kg/dose 8 hourly
resistance for 7 days plus Clindamycin: 10 mg/kg
12-hourly for 7 days

2nd & 3rd 1. Supervised Oral Artemisinin Combination


Therapy1

ACT should be known to be effective in the


region.

For dosages see Tables 2, 3, 4

Since mefloquine has been associated with


stillbirth, it should only be used if no safer
alternative is available.

2. Supervised Oral Artesunate plus


Clindamycin1

Artesunate 2 mg/kg once daily for 7 days plus


Clindamycin 10 mg/kg 12-hourly p.os full 7
days

3. Supervised Oral Quinine plus Clindamycin

Quinine sulfate: 10 mg salt/kg/dose 8 hourly


for 7 days plus Clindamycin: 10 mg/kg 12-
hourly for 7 days
4. Supervised Artesunate-Atovaquone-
Proguanil (AAP)1,2

can be used in case of recrudescence2

3 day oral regimen: Artesunate 4 mg/kg/day,


Atovaquone 20 mg/kg/day and Proguanil 8
mg/kg/day

Severe Malaria 1. Artesunate i.v. initial dose 2.4mg/kg, then


2.4mg/kg at 12h and 24h after admission, then
P. falciparum once daily until patient can tolerate oral
medication. Total course 7 days.

If artesunate is not available;


One or more
criteria for
severity!
2a. Artemether i.m. initial dose 3.2mg/kg i.m.
(see Table 13) anterior thigh day 1, then 1.6mg/kg i.m. once
All
daily from day 2-7, or until patient can tolerate
oral artesunate3

or

2b. Quinine i.v. loading dose 20mg/kg i.v. over


4h on admission, then 10mg/kg i.v. over 2 to 4h,
8-hourly for a total of 7 days, or until patient can
tolerate oral medication.

1 oral Artesunate 1 Tablet contains 50mg, a suspension is made by dissolving 1 tablet in 5ml of
water, 1ml equals 10mg, using a syringe
2
Malarone (AQ/PG) - one tablet contains 250 mg Atovaquone and 100 mg Proguanil. Give
Atovaquone-Proguanil with food. If patient vomits within 30 minutes of taking a dose, then
repeat the whole dose. If vomiting occurs after 3060mins of taking a dose, repeat half the
dosage.
3
to prevent recrudesence follow-on treatment should be given, when the patient is able to take
oral medication. Follow-on treatment can be a full course of the ACT of choice in the region (see
text).

Malaria in Pregnancy, other than Falciparum

Uncompl. Chloroquine- All Oral Chloroquine; initial dose 10 mg base/kg


malaria sensitive then10 mg base/kg after 24 hours, followed by 5 mg
base/kg after 48 hours (total dose 25 mg/kg).
P. vivax (P. vivax and
P. ovale) (for radical treatment see below)

No studies available but we would consider:

Chloroquine-
resistant or
unknown 1st Quinine sulphate: 10 mg salt / kg every 8h for 7
resistance days

2nd and Artesunate amodiaquine or other ACT available


3rd in the region (see treatment of uncomplicated
falciparum malaria during pregnancy)

Uncompl. Chloroquine- Chloroquine (dosage see above)


malaria sensitive

P. ovale

Uncompl. All regions Chloroquine (dosage see above)


malaria

P. malariae

Radical Primaquine is contraindicated during pregnancy. It is used for eradication of


treatment of hypnozoites, dormant in the liver to prevent relapses, in P. vivax and P. ovale
hypnozoites infections. During pregnancy radical treatment of hypnozoites is not possible.
Pregnant patients with P. vivax and P. ovale infections should be maintained
P. vivax & on chloroquine prophylaxis for the duration of their pregnancy. The
ovale chemoprophylactic dose for chloroquine sulphate is 300 mg base (=500 mg
salt) orally once per week. Radical treatment with primaquine can then be
startyed a few months after delivery.

After delivery; because primaquine can cause hemolytic anemia in persons


with G6PD deficiency, patients must be screened for G6PD deficiency prior to
starting treatment with primaquine. For persons with borderline G6PD
deficiency or as an alternate to the above regimen, primaquine may be given
45mg orally one time per week for 8 weeks; consultation with an expert in
infectious disease and/or tropical medicine is advised if this alternative
regimen is considered in G6PD-deficient persons.

Table 10. Management of Falciparum Malaria in Neonates

Falciparum Malaria in Neonates1

1. Artesunate i.v. initial dose 2.4mg/kg at T0h and T12h


on day 1, then continue with 2.4mg/kg once daily for a full
All cases All regions 7-day course..
should initially
be considered
as severe
malaria 2. Artemether i.m. initial dose 3.2mg/kg i.m. in anterior
thigh, and then 1.6mg/kg i.m. once daily from day 2-7, or
P. falciparum until neonate can tolerate oral artesunate.

3. i.v. Quinine (in 10% Dextrose); loading dose 20mg


(base)/kg i.v. over 4h on day 1, then 10mg/kg i.v. over 2 to
4 hours every 8h, for a full 7 day course.
1
a full course of i.v. treatment is recommended.

Table 11. Recent WHO Definitions of Treatment Failure

ETF Early treatment failure; one or more of the following

A) Development of danger signs or severe malaria on Day 1, Day 2 or Day 3, in


the presence of parasitaemia;

B) Parasite count on day 2 higher than day 0 irrespective of temperature

C) Axillary temperature 37.5oC on Day 3 in the presence of parasitaemia; For


areas of low to moderate transmission that there must be a measured increase in
axillary temperature on day 3.

D) Parasitaemia on Day 3 25% of count on Day 0


LTF Late treatment failure, one of the following

A) Development of danger signs or severe malaria in the presence of parasitaemia


on any day from Day 4 to Day 14, without previously meeting any of the criteria
of early treatment failure;

B) In areas of intense transmission; axillary temperature 37.5oC in the presence


of parasitaemia on any day from day 4 to day 14, without previously meeting
any of the criteria of early treatment failure.

In areas of low to moderate transmission; presence of parasitaemia on any day


from day 4 to day 28, and a measured axillary temperature > 37.5oC , without
previously meeting any of the criteria of early treatment failure. If history of fever,
rather than measured fever was accepted as an entry criterion for the study, then
parasitaemia with history of fever suffices for LTF.
LPF Late Parasitological Failure, in high transmission settings, defined as presence
of parasitaemia on day 14, and a measured axillary temperature <37.5oC without
previously meeting any of the criteria of early or late treatment failure. In low to
moderate transmission settings the definition is the same, except that parasitaemia
at any time from Day 7 to Day 28 qualifies.
ACR Adequate clinical response; one of the following during the follow-up period
from day 4 to 14

A) Absence of parasitaemia on day 14 irrespective of axillary temperature,


without previously meeting any of the criteria of early or late treatment failure;

B) Axillary temperature < 37.5oC irrespective of the presence of parasitaemia,


without previously meeting any of the criteria of early or late treatment failure.
ACPR Adequate clinical and parasitological response.
In a high transmission setting this is defined as above (A), but in low to moderate
transmission settings the assessment is made on day 28.