Treatment of

Malaria
-By Dr Mahnoor, MU-1 HO.
 Treatment of Malaria

Treatment should be guided by the following four main factors:

• Infecting Plasmodium species;
• Clinical status of the patient;
• Expected drug susceptibility of the infecting parasite as determined by the
geographic area where the infection was acquired; and
• Previous use of antimalarials, including those taken for malaria
chemoprophylaxis.
Treatment of Malaria

A. Non-Falciparum Malaria

B. Uncomplicated Falciparum Malaria

C. Severe Malaria
 (A) Non-falciparum Malaria

• First Line Drug Chloroquine

• Due to increasing resistance of P vivax to chloroquine

Artemisinin-based Combination Therapies (ACTs)

Or other First-line Regimes for P falciparum infections can be used.

For P vivax and P ovale Chloroquine + Primaquine or Tafenoquine

 (B) Uncomplicated Falciparum
Malaria
P Falciparum is resistant to chloroquine and sulfadoxine-pyrimethamine in most
areas

ACTs (Artemisinin-based combination therapies) are first line therapies

 WHO recommendations for the treatment of
Uncomplicated Falciparum Malaria .
01 02 03
Artemether- Artesunate- Artesunate-
lumefantrine amodiaquine mefloquine
(Coartem, Riamet) (ASAQ)

04 05 06
Artesunate- Dihydroartimisi
Artesunate-
sulfadoxine- nin-
pyronaridine
pyrimethamin piperaquine
e
-WHO recommends six ACTs to treat falciparum malaria
 Severe Malaria

Intravenous Artesunate is the standard of care for severe malaria

• If artesunate cannot be obtained promptly, severe malaria should be treated with

 Intravenous Quinine or
 Intravenous Quinidine or
 An Oral agent until Intravenous Artesunate is Available.
 In endemic regions, if parenteral therapy is not available, intrarectal administration
of artemether or artesunate is also effective.
 Severe Malaria
• Patients receiving intravenous quinine or quinidine should receive continues
cardiac monitoring
• If QTc prolongation exceeds 25% of baseline, the infusion rate should be
reduced
 Severe Malaria
-Blood Glucose should be monitored every 4-6 hours, and 5-10% dextrose may be
co-administered to decrease the likelihood of hypoglycemia.

-Appropriate care of severe Malaria includes maintenance of fluids and

electrolytes
-Respiratory and hemodynamic support
-And consideration of blood transfusions, anticonvulsants, antibiotics for bacterial
infections, and hemofiltration or hemodialysis.
-Exchange transfusion is sometimes used for those with high parasitemia (greater
than 5-10%), but beneficial effects have not clearly been demonstrated.
 Treatment of Malaria
Chloroquine-sensitive Drug Therapy Alternative Drugs

Plasmodium falciparum Chloroquine phosphate,

And Plasmodium 1 g at 0 hours, then 0.5 g
malariae infections at 6, 24 and 48 hours
or-
Chloroquine phosphate, 1
g at 0 hours and 24 hours
then 0.5 g at 48 hours

Plasmodium Vivax and Chloroquine (as above), If suspected resistance

Plasmodium ovale then (if G6PD normal) then therapies listed for
infections primaquine, 30-mg base uncomplicated
daily for 14 days or chloroquine-resistant
tafenoquine 300mg once Falciparum plus
primaquine
 Treatment of Malaria
Chloroquine- Drug Therapy Alternative Drugs
Resistant
Uncomplicated Co-Artem ( artemether 20mg, lumefantrine Mefloquine, 15mg/kg or 750
infections with 120 mg) four tablets twice daily for 3 days mg once
chloroquine-resistant (or artemether 80 mg, lumefantrine 480 mg then 500 mg in 6-8 hours.
P.Falciparum 1 tablet twice daily for 3 days) Or
Or Dihydroartemisinin-
Malarone, four tablets (total of 1 g of piperaquine
atovaquone, 400 mg of proguanil) daily for 3 ( dihydroartemisinin 40 mg,
days piperaquine 320mg), 4 tablets
Or daily for 3 days
Quinine Sulfate, 650 mg three times daily Or
for 3-7 days. ASAQ(artesunate 100 mg,
Plus one of the following( when quinine amodiaquine 270 mg), two
given for < 7 days) tablets daily for 3 days.
Doxycycline, 100 mg twice daily for 7 days
Or ‘
Clindamycin, 600 mg twice daily for 7 days.
 Treatment of Malaria
Drug Therapy Alternative Drugs
Severe or complicated Inj. Artesunate Quinidine gluconate 10mg/kg intravenously over
infections with 2.4mg/kg intravenously 1-2 hours, then 0.02 mg/kg intravenously per
P.falciparum every 12 hours for 1 minute
day, then daily Or
(i.e; at 0 hours, 12 Quinidine gluconate 15mg/kg intravenously over
hours, and 24 hours, 4 hours, then 7.5 mg/kg intravenously over 4
and thereafter, hours every 8 hours.
administered once
daily until the patient is Or
able to tolerate oral Quinine dihydrochloride, 20mg/kg intravenously
antimalarial therapy) over 4 hours then 10mg/kg intravenously every 8
hours.
Or
Artemether, 3.2 mg/kg intramuscularly, then 1.6
mg/kg/day intramusculary.
Avoid loading doses of Quinine and Quinidine in persons who have received quinine, quinidine or mefloquine in
the prior 24 hours.
 Major Antimalarial Drugs

Chloroquine 4-aminoquinoline Treatment and

chemoprophylaxis of
infection with sensitive
parasites.
Amodiaquine 4-aminoquinoline Treatment of
Plasmodium
Falciparum, optimally
in fixed combination
with Artesunate
Piperaquine 4-aminoquinoline Treatment of
Plasmodium
Falciparum in fixed
combination with
dihydroartemisinin.
 Major Antimalarial Drugs

Quinine Quinoline Methanol Oral and intravenous

(for severe infections)
treatment of P
Falciparum
Quinidine Quinoline Methanol Intravenous therapy
of severe infections
with plasmodium
falciparum
Mefloquine Quinoline Methanol Chemoprophylaxis and
treatment of infections
with plasmodium
Falciparum
 Major Antimalarial Drugs

Primaquine, 8-Aminoqunioline Radical cure and

tafenoquine terminal prophylaxis of
infections with
Plasmodium vivax and
Plasmodium ovale
Alternative for malaria
Chemoporphylaxis.
 Major Antimalarial Drugs

Sulfadoxine- Folate-antagonist Treatment of

Pyrimethamine combination P.falciparum, optimally
(Fansidar) in combination with
artesunate;
intermittent preventive
therapy
Atovaquone-Proguanil Quinone-folate Treatment and
(Malarone) Antagonist chemoprophylaxis of
Combination P.falciparum infection
 Major Antimalarial Drugs

Doxycycline Tetracycline Treatment (with

quinine) of infections
with P Falciparum;
Chemoprophylaxis
 Major Antimalarial Drugs

Halofantrine Phenanthrene Treatment of infections

methanol with some
Chloroquine-resistant
P Falciparum
Lumefantrine Amyl Alcohol Treatment of P
Falciparum Malaria in
fixed combination with
artemether (Coartem)
 Major Antimalarial Drugs

Pyronaridine Benzonaphythridine Treatment of P

falciparum malaria in
fixed combination
artesunate
 Major Antimalarial Drugs

Artemisinin Sesquiterpene lactone Treatment of

(artesunate, endoperoxides Plasmodium
artemether, Falciparum in oral
dihydroartemisinin) combination regimes
for uncomplicated
disease and
parenterally for
severe Malaria.
 Antimalarial Drugs
1. Chloroquine—
• Chloroquine is the drug of choice for the treatment of non-
falciparum and sensitive falciparum malaria.
• It rapidly terminates fever (in 24–48 hours) and clears parasitemia (in
48–72 hours) caused by sensitive parasites.
• Chloroquine is also the preferred chemoprophylactic agent in malarious
regions without resistant falciparum malaria.
• Chloroquine is usually well tolerated, even with prolonged use.
• Pruritus is common, primarily in Africans.
• Nausea, vomiting, abdominal pain, headache, anorexia, malaise,
blurring of vision, and urticaria are uncommon.
• Dosing after meals may reduce some adverse events.
 Antimalarial Drugs
1. Chloroquine—
 Contraindications & Cautions:
-Chloroquine is contraindicated in patients with psoriasis or porphyria,
in whom it may precipitate acute attacks of these diseases.
-Chloroquine is considered safe in pregnancy and for young children
 RESOCHIN (250 mg)

4 tablets stat
Then 2 tablets after 6 hours
then 2 tab at 24 hours and 2 tablets at 48
hours. Chloroquine phosphate, 1 g at 0 hours,
then 0.5 g at 6, 24 and 48 hours
or-
Chloroquine phosphate, 1 g at 0 hours
and 24 hours then 0.5 g at 48 hours
 Antimalarial Drugs
2. Amodiaquine, Piperaquine and Pyronaridine:
—Amodiaquine
• Use of amodiaquine decreased after recognition of rare but serious side
effects, notably agranulocytosis, aplastic anemia, and hepatotoxicity.
However, serious side effects are rare with short-term use, and artesunate-
amodiaquine is one of the standard ACTs recommended to treat falciparum
malaria.

-Piperaquine coformulated with dihydroartemisinin in an ACT.

• Piperaquine appears to be well tolerated and in combination with
dihydroartemisinin, offers a highly efficacious therapy for
falciparum and vivax malaria.
DIPHOS (40/320)
Dihydroartemisinin
(40 mg) and
Piperaquine Phosphate (320mg)

-4 tablets daily for 3 days

 Antimalarial Drugs
2. Amodiaquine, Piperaquine and Pyronaridine:

Pyronaridine
• The combination of artesunate plus pyronaridine has shown excellent
efficacy against falciparum and vivax malaria and has been well tolerated,
although elevated transaminases can be seen.
 Antimalarial Drugs
3-Mefloquine is effective against many chloroquine-resistant strains of P
falciparum and against other malarial species.
• It is used in combination with artesunate for falciparum malaria.
• Mefloquine is recommended by the CDC for chemoprophylaxis in all malarious areas
except those with no chloroquine resistance (where chloroquine is preferred) and some rural
areas of Southeast Asia with a high prevalence of mefloquine resistance.
• Adverse effects with weekly dosing of mefloquine for chemoprophylaxis
include nausea, vomiting, dizziness, sleep and behavioral disturbances,
epigastric pain, diarrhea, abdominal pain, headache, rash and, uncommonly,
seizures and psychosis.
 Antimalarial Drugs
3-Mefloquine
• There is an FDA black box warning about neuropsychiatric toxicity,
possibly including rare, irreversible effects.
• Mefloquine should be avoided in persons with histories of psychiatric
disease or seizures
• Adverse effects are more common (up to 50% of treatments) with the higher
dosages of mefloquine required for treatment. These effects may be lessened
by splitting administration into two doses separated by 6–8 hours.
• Serious neuropsychiatric toxicities (depression, confusion, acute psychosis, or
seizures) have been reported in less than 1 in 1000 treatments, but some
authorities believe that these are more common.
 Antimalarial Drugs
3-Mefloquine
• Mefloquine can also alter cardiac conduction, and so it should not be co-
administered with quinine, quinidine, or halofantrine, and caution is
required if these drugs are used to treat malaria after mefloquine
chemoprophylaxis.

• Mefloquine is generally considered safe in young children and pregnant

women.
 Antimalarial Drugs

4. Quinine and Quinidine—

• Quinine and quinidine are effective treatments for severe falciparum
malaria, although intravenous artesunate is the standard of care.
• The drugs can be administered in divided doses or by continuous intravenous
infusion;
• Treatment should begin with a loading dose to rapidly achieve effective
plasma concentrations.
• Intravenous quinine and quinidine should be administered with cardiac
monitoring because of their cardiac toxicity.
• Therapy should be changed to an oral agent as soon as the patient has
improved and can tolerate oral medications.
 Antimalarial Drugs

4. Quinine and Quinidine—

• poor tolerance may limit compliance.
• Quinine is commonly used with a second drug (most often doxycycline) to
shorten the duration of use (to 3 days) and to limit toxicity.
• Therapeutic dosages of quinine and quinidine commonly cause tinnitus,
headache, nausea, dizziness, flushing, and visual disturbances.
• Hematologic abnormalities include hemolysis (especially with G6PD
deficiency), leukopenia, agranulocytosis, and thrombocytopenia .
 Antimalarial Drugs

4. Quinine and Quinidine—

• Therapeutic doses may cause hypoglycemia through stimulation of insulin
release; this is a particular problem in severe infections and in pregnant
patients, who have increased sensitivity to insulin.
• Quinine can stimulate uterine contractions, especially in the third trimester.
However, this effect is mild, and quinine and quinidine remain drugs of choice
for severe falciparum malaria even during pregnancy.
• Intravenous infusions of the drugs may cause thrombophlebitis
• Overly rapid infusions can cause severe hypotension.
• ECG abnormalities (QT prolongation) are fairly common, but dangerous
arrhythmias are uncommon when the drugs are administered appropriately.
• Quinine should not be given concurrently with mefloquine and should be used
with caution in a patient who has previously received mefloquine.
 Antimalarial Drugs
• 5. Primaquine and tafenoquine—
• Primaquine phosphate is the drug of choice for the eradication of dormant
liver forms of P vivax and P ovale.
• Primaquine also acts against erythrocytic stage parasites, although this
activity is too weak for the treatment of active disease, and against
gametocytes.
• Primaquine can also be used for chemoprophylaxis to prevent P falciparum
and P vivax infection in persons with normal levels of G6PD.
 Antimalarial Drugs
• 5. Primaquine and tafenoquine—
• Primaquine in recommended doses is generally well tolerated.
• It infrequently causes nausea, epigastric pain abdominal cramps, and
headache, especially when taken on an empty stomach.
• Rare adverse effects include leukopenia, agranulocytosis, leukocytosis, and
cardiac arrhythmias.
• Standard doses of primaquine may cause hemolysis or
methemoglobinemia (manifested by cyanosis), especially in persons with
G6PD deficiency or other hereditary metabolic defects.
• Patients should be tested for G6PD deficiency before primaquine is
prescribed.
• Primaquine should be discontinued if there is evidence of hemolysis or
anemia and
• should be avoided in pregnancy
 Primaquine
primaquine, 30-mg base daily
for 14 days
 Antimalarial Drugs
• 5. Primaquine and tafenoquine—
• Tafenoquine, has a much longer half-life than primaquine.
• These two medications share the risk of hemolysis with G6PD deficiency
and probably other toxicities;
• tafenoquine should not be used during pregnancy or in those with G6PD
deficiency.
• Tafenoquine is FDA-approved for patients at least 16 years of age for two
indications, but with different formulations, marketed by different companies.
• To eliminate hepatic stages of P vivax, a single dose (Krintafel, two 150-mg
tablets once daily) is taken with food soon after initiation of primary therapy
(with chloroquine or other agents).
• For malaria chemoprophylaxis, the drug ( Arakoda, two 100-mg tablets) is
taken once daily for 3 days and then weekly until 1 week after the last
exposure.
 G6PD & Primaquine
● Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathological
disease in humans. This disease is described as a widespread, heritable, X-chromosome linked
abnormality
●  G6PD enzyme was demonstrated to play an active role in survival of erythrocytes.
● It is known that in the pentose phosphate pathway of erythrocytes, glucose-6 phosphate
dehydrogenase (G6PD) enzyme provides the production of NADPH and GSH (reduced
Glutathione)
● GSH, produced by pentose phosphate pathway can react with H 2O2 and reduce it to H2O.
This prevents the generation of oxidative stress within red blood cells;
● oxidative stress can be induced in erythrocytes whose G6PD enzymes are deficient. In this
situation, GSH is not produced and H2O2 is not reduced to H2O, leading to oxidative stress and
hemolysis. 
● When primaquine is administered to individuals with G6PD deficiency, its metabolites lead to
more severe hemolysis by inducing oxyhemoglobin generation, GSH depletion and stimulation of
the hexose monophosphate pathway.
 G6PD & Primaquine
Oxidative Drugs
Primaquine
Sulfonamide
Chloroquine
Chloramphenicol
Quinine
Nitrofurantoin
Nalidixic acid
Isoniazid
 Antimalarial Drugs

• 6. Inhibitors of folate synthesis—Inhibitors of two parasite

enzymes involved in folate metabolism, dihydrofolate reductase (DHFR)
and dihydropteroate synthase (DHPS), are used, generally in combination
regimens, for the treatment and prevention of malaria.
• Fansidar is a fixed combination of sulfadoxine (500 mg) and
pyrimethamine (25 mg).
• Advantages of sulfadoxine-pyrimethamine include ease of administration (a
single oral dose) and low cost. However, resistance is a major problem.
• Sulfadoxine-pyrimethamine plus artesunate has shown efficacy for
malaria treatment in some areas but is best replaced by more effective
ACTs.

• Another antifolate combination, trimethoprim sulfamethoxazole (TMP-

SMZ), is widely used to prevent coinfections in patients infected with HIV.
 Antimalarial Drugs
7. Artemisinins—Artemisinin (qinghaosu) is a
sesquiterpene lactone endoperoxide, the active
component of an herbal medicine that has been
used for various indications in China for over
2000 years. Analogs have been synthesized to
increase solubility and improve antimalarial
efficacy.
• The most important of these analogs are
artesunate, artemether, and
dihydroartemisinin.
• WHO encourages availability of oral
artemisinins only in coformulated combination
regimens.
 WHO recommendations for the treatment of
Uncomplicated Falciparum Malaria .
01 02 03
Artemether- Artesunate- Artesunate-
lumefantrine amodiaquine mefloquine
(Coartem, Riamet) (ASAQ)

04 05 06
Artesunate- Artesunate- Dihydroartimisi
pyronaridine sulfadoxine- nin-
pyrimethamin piperaquine
e
 Antimalarial
7. Artemisinins—
Drugs
• Artemisinins are very well tolerated.
• The most commonly reported adverse effects have been
nausea, vomiting, and diarrhea, which may often be due to
acute malaria, rather than drug toxicity.
• Hemolysis may occur weeks after therapy with intravenous
artesunate.
• Artemisinins are teratogenic in animals, but with good
safety seen in humans, and
• WHO recommends ACTs (Artemisinin based combination
regime) to treat uncomplicated malaria and intravenous
artesunate to treat complicated malaria during all
trimesters of pregnancy.
 Inj. GEN-M (120mg)
at 0 hours, 12 hours, and 24 hours,
and thereafter, administered
once daily until the patient is
able to tolerate oral antimalarial
therapy

Inj. Artesunate 2.4mg/kg

intravenously every 12 hours for 1
day, then daily
(i.e; at 0 hours, 12 hours, and 24 hours,
and thereafter, administered once daily
until the patient is able to tolerate oral
antimalarial therapy)
 Antimalarial Drugs
• 8. Atovaquone plus proguanil
• Malarone, a fixed combination of atovaquone(250 mg) and the
antifolate proguanil (100 mg), is highly effective for both the
treatment and chemoprophylaxis of falciparum malaria,
• It also appears to be active against other species of malaria
parasites.
• Unlike, most other antimalarials, Malarone provides activity
against both erythrocytic and hepatic stage parasites.
• . Malarone is generally well tolerated.
• Adverse effects include abdominal pain, nausea, vomiting,
diarrhea, headache, and rash, and these are more common with the
higher dose required for treatment.
• Reversible elevations in liver enzymes have been reported.
• The safety of atovaquone in pregnancy is unknown
 Antimalarial Drugs
9.Lumefantrine—Lumefantrine, an aryl alcohol related to halofantrine, is available
only as a fixed-dose combination with artemether (Coartem or Riamet).
• Co-artem is highly effective for the treatment of falciparum malaria.
• Co-artem is the first-line therapy for malaria in many malarious
countries.
• Coartem is well tolerated;
• side effects include headache, dizziness, loss of appetite, gastrointestinal
symptoms, and palpitations.
• Importantly, Co-artem does not generally cause QT prolongation or the
serious cardiac toxicity seen with halofantrine
GEN-M (80/480)
1 tab.
Twice daily
For 3 days

Co-Artem ( artemether 20mg,

lumefantrine 120 mg) four tablets
twice daily for 3 days
or
 Artemether 80 mg, lumefantrine 480
mg 1 tablet twice daily for 3 days)
 Antimalarial Drugs
10. Antibiotics—
• Doxycycline is commonly used in the treatment of falciparum malaria in
conjunction with quinidine or quinine, allowing a shorter and better-tolerated
course of those drugs.
• Doxycycline is also a standard chemoprophylactic drug, especially for use in areas of
Southeast Asia with high rates of resistance to other antimalarials, including mefloquine .
• Doxycycline side effects include gastrointestinal symptoms, candidal vaginitis,
and photosensitivity.
• Clindamycin can be used in conjunction with quinine or quinidine in those for
whom doxycycline is not recommended, such as children and pregnant
women
• The most common toxicities with clindamycin are gastrointestinal
Thank You