Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

severe disease (or unable to take oral medication initially): all Plasmodium species

1st line – parenteral antimalarial regimen

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
nonpregnant
1st line – 

parenteral antimalarial regimen

Severe malaria is almost always caused by falciparum infection. However, severe nonfalciparum infection is also possible. Patients are classified as having severe malaria if they meet certain criteria.[49][104] See the Criteria section for more information. Treatment of severe malaria is the same, regardless of species.[104]

Patients with severe disease should be treated aggressively with parenteral antimalarial therapy.[38] Parenteral therapy may also be used for those patients who cannot tolerate oral therapy. Delays in antimalarial therapy may increase morbidity and mortality.[39]

Parenteral artesunate is the recommended first-line treatment.[49][104]​​​ It should be given until the patient is able to take oral treatment (but for at least 24 hours) and parasitemia has fallen to <1% (usually a minimum of 3 doses is suggested), followed by a suitable oral regimen.[49][104]​​ If parenteral artesunate is not readily available, oral antimalarials may be given while obtaining the drug.[104]

Intravenous artesunate is the recommended first-line treatment in the US as the previous first-line treatment, intravenous quinidine, has now been discontinued. Intravenous artesunate is approved by the Food and Drug Administration and is commercially available.[129] CDC: how to acquire IV artesunate in the United States Opens in new window

The World Health Organization (WHO) recommends intramuscular artemether if parenteral artesunate is not available.[49] A Cochrane review found that artemether is more effective than quinine in children and adults with severe malaria, and is inferior to artesunate in adults. This review therefore supports current WHO recommendations.[131]

In areas where parenteral artesunate is not available, the WHO recommend considering a single dose of rectal artesunate in children ages <6 years for prereferral treatment, but the child should be referred immediately to an appropriate facility for further care. Rectal artesunate is not recommended in older children and adults.[130]​​

Primary options

artesunate: children and adults: consult specialist for guidance on dose

Secondary options

artemether: children and adults: consult specialist for guidance on dose

Plus – switch to oral antimalarial regimen

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
nonpregnant
Plus – 

switch to oral antimalarial regimen

Treatment recommended for ALL patients in selected patient group

Following initial parenteral treatment, it is essential to continue and complete treatment with an effective oral antimalarial regimen, once the patient is able to tolerate oral therapy.[49][104]​​​ Follow-on treatment can be started 4-24 hours after the last dose of artesunate.[104]

Examples of suitable oral regimens are outlined below.[49][104]​​​ Other drug regimens may be recommended; consult your local guidelines for recommended regimens. Mefloquine is generally not recommended for follow-on treatment of severe malaria due to the increased risk of post-malaria neurologic syndrome.

Treatment courses, where given, are the total treatment course for intravenous and oral therapy combined.

Primary options

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

OR

atovaquone/proguanil: children 5-8 kg: (62.5/25 mg tablet) 2 tablets orally once daily for 3 days; children 9-10 kg: (62.5/25 mg tablet) 3 tablets orally once daily for 3 days; children 11-20 kg: (250/100 mg tablet) 1 tablet orally once daily for 3 days; children 21-30 kg: (250/100 mg tablet) 2 tablets orally once daily for 3 days; children 31-40 kg: (250/100 mg tablet) 3 tablets orally once daily for 3 days; children >40 kg and adults: (250/100 mg tablet) 4 tablets orally once daily for 3 days

OR

quinine sulfate: children 8.3 mg base/kg orally three times daily for 7 days; adults: 542 mg base orally three times daily for 7 days

-- AND --

clindamycin: children and adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

or

doxycycline: children ≥8 years of age: 2.2 mg/kg orally twice daily; adults: 100 mg orally twice daily for 7 days

Plus – primaquine (in low-transmission areas)

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
nonpregnant
Plus – 

primaquine (in low-transmission areas)

Treatment recommended for ALL patients in selected patient group

In low-transmission areas, the World Health Organization recommends giving a single low dose of primaquine with artemisinin-based combination therapy (ACT) to reduce transmission, to all patients with parasitologically confirmed P falciparum malaria except for infants ages <1 month and women breast-feeding infants ages <1 month.[49]

Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is not required in these patients.[49] One study found that a single low dose of primaquine, when used as a gametocytocide, was unlikely to cause serious toxicity, even in patients with G6PD deficiency.[127] One Cochrane review found that a single low dose of primaquine (added to ACT) is as effective as higher doses and reduces the infectiousness of people to mosquitoes at days 3-4 and 8. [ Cochrane Clinical Answers logo ] There was no evidence of increased hemolysis at this dose; however, it should be noted that very few patients with G6PD deficiency were included in the trials. It is unclear whether this would reduce malaria transmission in communities.[128]

Primary options

primaquine phosphate: children and adults: 0.25 mg base/kg orally as a single dose

Plus – supportive care ± intensive care

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
nonpregnant
Plus – 

supportive care ± intensive care

Treatment recommended for ALL patients in selected patient group

Supportive therapy is vital and is aimed at correcting complications. It includes careful fluid management, often with renal support; airway protection; control of seizures; and transfusion of blood products. Fluid bolus in children can increase mortality and should be avoided.[156] Hypoglycemia may be worsened by quinine-induced hyperinsulinemia, so should be monitored closely.

Severe malaria is a medical emergency. Consider admission to an intensive care unit. Patients with hyperparasitemia, jaundice, anemia, and renal impairment do not necessarily require intensive care; however, such features are often associated with other complications. Some patients may be able to be managed on an experienced floor or high dependency unit. The decision to admit to intensive care should be discussed with an infectious diseases specialist.

1st line – parenteral antimalarial regimen

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
pregnant
1st line – 

parenteral antimalarial regimen

Treatment of malaria in pregnancy must be managed together with an infectious diseases specialist.

Severe malaria is almost always caused by falciparum infection. However, severe nonfalciparum infection is also possible. Patients are classified as having severe malaria if they meet certain criteria.[49][104]​​ See the Criteria section for more information. Treatment of severe malaria is the same, regardless of species.[104]​​

Patients with severe disease should be treated aggressively with parenteral antimalarial therapy.[38]​ Parenteral therapy may also be used for those patients who cannot tolerate oral therapy.

Parenteral artesunate is the treatment of choice for severe malaria in all trimesters of pregnancy.[49][104] World Health Organization, Communicable Diseases Cluster. Severe falciparum​ It should be given until the patient is able to take oral treatment (but for at least 24 hours) and parasitemia has fallen to <1% (usually a minimum of 3 doses is suggested), followed by a suitable oral regimen.[49][104]​ If parenteral artesunate is not readily available, oral antimalarials may be given while obtaining the drug.[104]

Intravenous artesunate is the recommended first-line treatment in the US in all trimesters of pregnancy as the previous first-line treatment, intravenous quinidine, has now been discontinued. Intravenous artesunate is approved by the Food and Drug Administration and is commercially available.[104]​​[129] CDC: how to acquire IV artesunate in the United States Opens in new window

The World Health Organization recommends intramuscular artemether if parenteral artesunate is not available.[49]

Primary options

artesunate: adults: consult specialist for guidance on dose

Secondary options

artemether: adults: consult specialist for guidance on dose

Plus – switch to oral antimalarial regimen

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
pregnant
Plus – 

switch to oral antimalarial regimen

Treatment recommended for ALL patients in selected patient group

Following initial parenteral treatment, it is essential to continue and complete treatment with an effective oral antimalarial regimen, once the patient is able to tolerate oral therapy.[49][104]​​​

Examples of suitable oral regimens are outlined below.[49][104]​​​ Other drug regimens may be recommended; consult your local guidelines for recommended regimens.

Blood glucose levels should be monitored regularly due to associated recurrent hypoglycemia with quinine therapy.

Treatment courses, when given, are the total treatment course for intravenous and oral therapy combined.

Primary options

quinine sulfate: adults: 542 mg base orally three times daily for 7 days

and

clindamycin: adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

OR

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

Plus – supportive + intensive care

Back
ACUTE
|
severe disease (or unable to take oral medication initially): all Plasmodium species
|
pregnant
Plus – 

supportive + intensive care

Treatment recommended for ALL patients in selected patient group

Pregnant patients with severe disease should be treated aggressively with parenteral antimalarial therapy and transferred to the intensive care unit for intensive monitoring and support.[38] Delays in antimalarial therapy may increase morbidity and mortality.[39]

Supportive therapy is vital and is aimed at correcting complications. It includes careful fluid management, often with renal support; airway protection; control of seizures; and transfusion of blood products. Hypoglycemia may be worsened by quinine-induced hyperinsulinemia, so should be monitored closely.

Plasmodium falciparum (or unknown species): uncomplicated disease

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium falciparum (or unknown species): uncomplicated disease
|
infection originating in chloroquine-sensitive region: nonpregnant
1st line – 

oral antimalarial regimen

Infections acquired in these regions may be assumed to be chloroquine-sensitive. Although chloroquine resistance is widespread in most regions of the world, there have been no reports of clinically significant chloroquine resistance in infections acquired in parts of Central America (west of Panama Canal), Haiti and the Dominican Republic, and some parts of the Middle East. If the species cannot be identified, the patient should be treated as for P falciparum infection.[104]

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine.​ Drug options for chloroquine-resistant P falciparum may also be used if these drugs are not available.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option. Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations.[49]​ However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Most authorities recommend that travelers with P falciparum malaria should be hospitalized for treatment. Several observational studies conducted in centers with a special interest suggested that falciparum malaria can be managed on an outpatient basis, though specific criteria for safe outpatient management in a nonexpert setting are unclear.[114][115][116][117] Where outpatient management is planned, daily review with slide microscopy has been suggested.[113]

Primary options

chloroquine phosphate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

Secondary options

hydroxychloroquine sulfate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

OR

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

Consider – primaquine (in low-transmission areas)

Back
ACUTE
|
Plasmodium falciparum (or unknown species): uncomplicated disease
|
infection originating in chloroquine-sensitive region: nonpregnant
Consider – 

primaquine (in low-transmission areas)

Treatment recommended for SOME patients in selected patient group

In low-transmission areas, the World Health Organization recommends giving a single low dose of primaquine with artemisinin-based combination therapy (ACT) to reduce transmission, to all patients with parasitologically confirmed P falciparum malaria except for infants ages <1 month and women breastfeeding infants ages <1 month.[49]

Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is not required in these patients.[49] One study found that a single low dose of primaquine, when used as a gametocytocide, was unlikely to cause serious toxicity even in patients with G6PD deficiency.[127]​ One Cochrane review found that a single low dose of primaquine (added to ACT) is as effective as higher doses and reduces the infectiousness of people to mosquitoes at days 3-4 and 8. [ Cochrane Clinical Answers logo ] There was no evidence of increased hemolysis at this dose; however, it should be noted that very few patients with G6PD deficiency were included in the trials. It is unclear whether this would reduce malaria transmission in communities.[128]

Primary options

primaquine phosphate: children and adults: 0.25 mg base/kg orally as a single dose

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium falciparum (or unknown species): uncomplicated disease
|
infection originating in chloroquine-resistant region (or unknown resistance): nonpregnant
1st line – 

oral antimalarial regimen

Chloroquine resistance is widespread in most regions of the world (except Central America west of Panama Canal, Haiti and the Dominican Republic, and some parts of the Middle East).

The Centers for Disease Control and Prevention recommends artemether/lumefantrine (preferred) or atovaquone/proguanil. Alternatively, quinine plus doxycycline or tetracycline or clindamycin may also be used. Doxycycline or tetracycline are preferred to clindamycin, due to the availability of more data. However, use of doxycycline or tetracycline should be avoided in children ages under 8 years. Quinine should be given for 3 days, except for infections acquired in Southeast Asia where 7 days of treatment is required. Mefloquine is recommended if no other options are available due to an increased rate of adverse effects and concerns about longer-lasting or permanent neuropsychiatric complications.[104][118]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization recommends artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option.[49] [ Cochrane Clinical Answers logo ] Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations. However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Most authorities recommend that travelers with P falciparum malaria should be hospitalized for treatment. Several observational studies conducted in centers with a special interest suggested that falciparum malaria can be managed on an outpatient basis, though specific criteria for safe outpatient management in a nonexpert setting are unclear.[114][115][116][117] Where outpatient management is planned, daily review with slide microscopy has been suggested.[113]

Primary options

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

Secondary options

atovaquone/proguanil: children 5-8 kg: (62.5/25 mg tablet) 2 tablets orally once daily for 3 days; children 9-10 kg: (62.5/25 mg tablet) 3 tablets orally once daily for 3 days; children 11-20 kg: (250/100 mg tablet) 1 tablet orally once daily for 3 days; children 21-30 kg: (250/100 mg tablet) 2 tablets orally once daily for 3 days; children 31-40 kg: (250/100 mg tablet) 3 tablets orally once daily for 3 days; children >40 kg and adults: (250/100 mg tablet) 4 tablets orally once daily for 3 days

OR

quinine sulfate: children: 8.3 mg base/kg orally every 8 hours for 3 or 7 days depending on location; adults: 542 mg base orally every 8 hours for 3 or 7 days depending on location

-- AND --

doxycycline: children ≥8 years of age: 2.2 mg/kg orally twice daily for 7 days; adults: 100 mg orally twice daily for 7 days

or

tetracycline: children ≥8 years of age: 25 mg/kg/day orally given in 4 divided doses for 7 days; adults: 250 mg orally four times daily for 7 days

or

clindamycin: children and adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

Tertiary options

mefloquine hydrochloride: children and adults: consult specialist for guidance on dose

Consider – primaquine (in low-transmission areas)

Back
ACUTE
|
Plasmodium falciparum (or unknown species): uncomplicated disease
|
infection originating in chloroquine-resistant region (or unknown resistance): nonpregnant
Consider – 

primaquine (in low-transmission areas)

Treatment recommended for SOME patients in selected patient group

In low-transmission areas, the World Health Organization recommends giving a single low dose of primaquine with artemisinin-based combination therapy (ACT) to reduce transmission, to all patients with parasitologically confirmed P falciparum malaria except for infants ages <1 month and women breastfeeding infants ages <1 month.[49]

Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is not required in these patients.[49] One study found that a single low dose of primaquine, when used as a gametocytocide, was unlikely to cause serious toxicity even in patients with G6PD deficiency.[127] One Cochrane review found that a single low dose of primaquine (added to ACT) is as effective as higher doses and reduces the infectiousness of people to mosquitoes at days 3-4 and 8. [ Cochrane Clinical Answers logo ] There was no evidence of increased hemolysis at this dose; however, it should be noted that very few patients with G6PD deficiency were included in the trials. It is unclear whether this would reduce malaria transmission in communities.[128]

Primary options

primaquine phosphate: children and adults: 0.25 mg base/kg orally as a single dose

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium falciparum (or unknown species): uncomplicated disease
|
pregnant
1st line – 

oral antimalarial regimen

Treatment of malaria in pregnancy must be managed together with an infectious diseases specialist.

The Centers for Disease Control and Prevention recommends artemether/lumefantrine, quinine plus clindamycin, or mefloquine (if no other options due to concerns about longer-lasting or permanent neuropsychiatric complications) in all trimesters of pregnancy in chloroquine-resistant regions. Quinine should be given for 3 days, except for infections acquired in Southeast Asia where 7 days of treatment is required. Chloroquine or hydroxychloroquine (or one of the options for chloroquine-resistant regions if these drugs are not available) are recommended in all trimesters of pregnancy in chloroquine-sensitive regions.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in all trimesters of pregnancy.[49]​ Consult your local guidelines for more information.

Low-certainty evidence suggests that ACT may be used to treat uncomplicated falciparum malaria in the first trimester of pregnancy. The World Health Organization (WHO) strongly recommends artemether/lumefantrine. There is insufficient evidence to make a recommendation for the routine use of other ACT in the first trimester. However, artesunate plus mefloquine, dihydroartemisinin plus piperaquine, or artesunate plus amodiaquine (if available) may be considered if artemether/lumefantrine is not recommended, or it is not available. There are no data on artesunate plus pyronaridine. ACT containing sulfadoxine/pyrimethamine is contraindicated in the first trimester.[49][145]

Current evidence suggests that ACT may also be used safely in the second and third trimesters of pregnancy.[49][146][147][148][149]​​

Experience with artemisinin-derivatives in the second and third trimesters is reassuring, with no adverse effects reported in mothers or babies.[150][151][152][153]

Blood glucose levels should be monitored regularly due to associated recurrent hypoglycemia with quinine therapy.

Primary options

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

OR

quinine sulfate: adults: 542 mg base orally every 8 hours for 3 or 7 days depending on location

and

clindamycin: adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

OR

chloroquine phosphate: adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

OR

hydroxychloroquine sulfate: adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

Secondary options

mefloquine hydrochloride: adults: consult specialist for guidance on dose

Plasmodium ovale: uncomplicated disease

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium ovale: uncomplicated disease
|
nonpregnant
1st line – 

oral antimalarial regimen

P ovale infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends either chloroquine or artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option. Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations.[49]​ However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Primary options

chloroquine phosphate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

Secondary options

hydroxychloroquine sulfate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

OR

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

Plus – antirelapse treatment (primaquine or tafenoquine)

Back
ACUTE
|
Plasmodium ovale: uncomplicated disease
|
nonpregnant
Plus – 

antirelapse treatment (primaquine or tafenoquine)

Treatment recommended for ALL patients in selected patient group

Treatment for the acute phase of P ovale malaria should be followed by antirelapse therapy to eliminate the hypnozoite stages that are dormant within the liver. Treatment options include primaquine or tafenoquine. Tafenoquine has a longer half-life and duration of action compared with primaquine and has the advantage of single-dose administration.[49][104]

Primaquine is recommended in all children and nonpregnant adults, except for infants ages <1 month, women breastfeeding infants ages <1 month, and people with G6PD deficiency.[49][104]​ Primaquine may be used in combination with any of the drugs recommended for the treatment of the acute phase of infection.[49][104]​ The hypnozoiticidal activity of primaquine is predominantly a function of the total dose administered. One Cochrane review found no difference in efficacy between the higher dose 7-day course and the standard dose 14-day course in G6PD-normal patients.[134]​ A higher total dose is recommended in Africa, South-East Asia, and Oceania; whereas, a lower total dose may be used in areas on the Indian subcontinent and the Americas.[49] The most common adverse effect is gastrointestinal upset, which can be minimized if taken with food. Determination of G6PD status using a suitable test is required to guide the safe administration of primaquine.[49][104]

Tafenoquine is recommended as an alternative to primaquine. While the Centers for Disease Control and Prevention (CDC) recommends use for P ovale malaria, the World Health Organization (WHO) currently only recommends use in patients with P vivax malaria in South America.[49][104]​​ Tafenoquine is only recommended for use in patients who are receiving treatment with chloroquine (or hydroxychloroquine) for the treatment of the acute phase of infection. It is not recommended for patients who are receiving artemisinin-based combination therapy (ACT).[49][104]​​ The CDC recommends use in adolescents ages ≥16 years and nonpregnant adults, while the WHO recommends use in children ages ≥2 years.[49][104]​​ Tafenoquine is not approved for use in Europe as yet. Tafenoquine has been associated with methemoglobinemia, psychiatric adverse effects, and hypersensitivity reactions. Due to its long half-life, adverse effects may be delayed in onset and/or duration. It should not be used in patients with a history of a psychotic disorder. Quantitative or semiquantitative determination of G6PD activity is required before administration of tafenoquine.[49][104]

Patients in whom primaquine or tafenoquine are contraindicated should continue on weekly chloroquine prophylaxis for one year from the acute infection.[104]

Primary options

primaquine phosphate: children: 0.5 mg base/kg orally once daily for 14 days, maximum 30 mg/day; adults: 30 mg base orally once daily for 14 days

More

Secondary options

tafenoquine: adolescents ≥16 years of age and adults: 300 mg orally as a single dose

More

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium ovale: uncomplicated disease
|
pregnant
1st line – 

oral antimalarial regimen

P ovale infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine in all trimesters.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in all trimesters of pregnancy.[49] Artemether/lumefantrine is a commonly used option. Consult your local guidelines for more information.

Patients should be maintained on chloroquine prophylaxis once weekly until after delivery.[104]

Antirelapse treatment with either primaquine or tafenoquine is contraindicated in pregnancy and breastfeeding.[49][104]

Primary options

chloroquine phosphate: adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours, and once weekly for duration of pregnancy thereafter

OR

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

Secondary options

hydroxychloroquine sulfate: adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

Plasmodium vivax: uncomplicated disease

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-sensitive region: nonpregnant
1st line – 

oral antimalarial regimen

P vivax infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine. Drug options for chloroquine-resistant P vivax may also be used if these drugs are not available.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends either chloroquine or artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option. Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations.[49]​ However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Primary options

chloroquine phosphate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

More

Secondary options

hydroxychloroquine sulfate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

OR

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

Plus – antirelapse treatment (primaquine or tafenoquine)

Back
ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-sensitive region: nonpregnant
Plus – 

antirelapse treatment (primaquine or tafenoquine)

Treatment recommended for ALL patients in selected patient group

Treatment for the acute phase of P vivax malaria should be followed by antirelapse therapy to eliminate the hypnozoite stages that are dormant within the liver. Treatment options include primaquine or tafenoquine. Tafenoquine has a longer half-life and duration of action compared with primaquine and has the advantage of single-dose administration.[49][104]

Primaquine is recommended in all children and nonpregnant adults, except for infants ages <1 month, women breastfeeding infants ages <1 month, and people with G6PD deficiency.[49][104]​ Primaquine may be used in combination with any of the drugs recommended for the treatment of the acute phase of infection.[49][104]​ The hypnozoiticidal activity of primaquine is predominantly a function of the total dose administered. One Cochrane review found no difference in efficacy between the higher dose 7-day course and the standard dose 14-day course in G6PD-normal patients.[134]​ A higher total dose is recommended in Africa, South-East Asia, and Oceania; whereas, a lower total dose may be used in areas on the Indian subcontinent and the Americas.[49]​ The most common adverse effect is gastrointestinal upset, which can be minimized if taken with food. Determination of G6PD status using a suitable test is required to guide the safe administration of primaquine.[49][104]

Tafenoquine is recommended as an alternative to primaquine. While the CDC recommends use for P ovale malaria, the WHO currently only recommends use in patients with P vivax malaria in South America.[49][104]​​ Tafenoquine is only recommended for use in patients who are receiving treatment with chloroquine (or hydroxychloroquine) for the treatment of the acute phase of infection. It is not recommended for patients who are receiving ACT.[49][104]​​ The CDC recommends use in adolescents ages ≥16 years and nonpregnant adults, while the WHO recommends use in children ages ≥2 years.[49][104]​​ Tafenoquine is not approved for use in Europe as yet. Tafenoquine has been associated with methemoglobinemia, psychiatric adverse effects, and hypersensitivity reactions. Due to its long half-life, adverse effects may be delayed in onset and/or duration. It should not be used in patients with a history of a psychotic disorder. Quantitative or semiquantitative determination of G6PD activity is required before administration of tafenoquine.[49][104]

One Cochrane review found moderate-certainty evidence that a single dose of tafenoquine prevents relapse of P vivax malaria in adults compared with no antihypnozoite treatment, and that there is probably little or no difference between tafenoquine and primaquine in preventing relapses.[137]

Patients in whom primaquine or tafenoquine are contraindicated should continue on weekly chloroquine prophylaxis for one year from the acute infection.[104]

Primary options

primaquine phosphate: children: 0.5 mg base/kg orally once daily for 14 days, maximum 30 mg/day; adults: 30 mg base orally once daily for 14 days

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Secondary options

tafenoquine: adolescents ≥16 years of age and adults: 300 mg orally as a single dose

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1st line – oral antimalarial regimen

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ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-sensitive region: pregnant
1st line – 

oral antimalarial regimen

P vivax infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine in all trimesters (or one of the options for chloroquine-resistant regions if these drugs are not available).[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in all trimesters of pregnancy.[49]​ Artemether/lumefantrine is a commonly used option. Consult your local guidelines for more information.

Patients should be maintained on chloroquine prophylaxis once weekly until after delivery.[104]

Antirelapse treatment with either primaquine or tafenoquine is contraindicated in pregnancy and breastfeeding.[49][104]

Primary options

chloroquine phosphate: adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours, and once weekly for duration of pregnancy thereafter

OR

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

Secondary options

hydroxychloroquine sulfate: adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-resistant region: nonpregnant
1st line – 

oral antimalarial regimen

P vivax infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

Treatment (or prophylactic) failure with chloroquine for Plasmodium vivax malaria has been observed in at least 24 countries, particularly in Indonesia and Papua New Guinea.[133]

The Centers for Disease Control and Prevention recommends artemether/lumefantrine (preferred) or atovaquone/proguanil. Alternatively, quinine plus doxycycline or tetracycline or clindamycin may also be used. Doxycycline or tetracycline are preferred to clindamycin, due to the availability of more data. However, use of doxycycline or tetracycline should be avoided in children ages under 8 years. Mefloquine is recommended if no other options are available due to an increased rate of adverse effects and concerns about longer-lasting or permanent neuropsychiatric complications.[104][118]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization recommends artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option.[49]​ Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations. However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Primary options

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

Secondary options

atovaquone/proguanil: children 5-8 kg: (62.5/25 mg tablet) 2 tablets orally once daily for 3 days; children 9-10 kg: (62.5/25 mg tablet) 3 tablets orally once daily for 3 days; children 11-20 kg: (250/100 mg tablet) 1 tablet orally once daily for 3 days; children 21-30 kg: (250/100 mg tablet) 2 tablets orally once daily for 3 days; children 31-40 kg: (250/100 mg tablet) 3 tablets orally once daily for 3 days; children >40 kg and adults: (250/100 mg tablet) 4 tablets orally once daily for 3 days

OR

quinine sulfate: children: 8.3 mg base/kg orally every 8 hours for 3 days; adults: 542 mg base orally every 8 hours for 3 days

-- AND --

doxycycline: children ≥8 years of age: 2.2 mg/kg orally twice daily for 7 days; adults: 100 mg orally twice daily for 7 days

or

tetracycline: children ≥8 years of age: 25 mg/kg/day orally given in 4 divided doses for 7 days; adults: 250 mg orally four times daily for 7 days

or

clindamycin: children and adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

Tertiary options

mefloquine hydrochloride: children and adults: consult specialist for guidance on dose

Plus – antirelapse treatment (primaquine)

Back
ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-resistant region: nonpregnant
Plus – 

antirelapse treatment (primaquine)

Treatment recommended for ALL patients in selected patient group

Treatment for the acute phase of P vivax malaria should be followed by antirelapse therapy to eliminate the hypnozoite stages that are dormant within the liver. Primaquine is the recommended option in these patients because tafenoquine is not recommended in patients receiving ACT for the treatment of the acute phase of infection. Primaquine may be used in combination with any of the drugs recommended for the acute phase.[49][104]

Primaquine is recommended in all children and nonpregnant adults, except for infants ages <1 month, women breastfeeding infants ages <1 month, and people with G6PD deficiency.[49][104]

The hypnozoiticidal activity of primaquine is predominantly a function of the total dose administered. One Cochrane review found no difference in efficacy between the higher dose 7-day course and the standard dose 14-day course in G6PD-normal patients.[134]

A higher total dose is recommended in Africa, South-East Asia, and Oceania; whereas, a lower total dose may be used in areas on the Indian subcontinent and the Americas.[49]

The most common adverse effect is gastrointestinal upset, which can be minimized if taken with food.

Determination of G6PD status using a suitable test is required to guide the safe administration of primaquine.[49][104]

Primary options

primaquine phosphate: children: 0.5 mg base/kg orally once daily for 14 days, maximum 30 mg/day; adults: 30 mg base orally once daily for 14 days

More

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium vivax: uncomplicated disease
|
infection originating in chloroquine-resistant region: pregnant
1st line – 

oral antimalarial regimen

P vivax infection is rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

Treatment (or prophylactic) failure with chloroquine for Plasmodium vivax malaria has been observed in at least 24 countries, particularly in Indonesia and Papua New Guinea.[133]

The Centers for Disease Control and Prevention recommends artemether/lumefantrine, quinine plus clindamycin, or mefloquine (if no other options due to concerns about longer-lasting or permanent neuropsychiatric complications) in all trimesters of pregnancy in chloroquine-resistant regions. Quinine should be given for 3 days, except for infections acquired in Southeast Asia where 7 days of treatment is required.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in all trimesters of pregnancy.[49] Artemether/lumefantrine is a commonly used option. Consult your local guidelines for more information.

Blood glucose levels should be monitored regularly due to associated recurrent hypoglycemia with quinine therapy.

Antirelapse treatment with either primaquine or tafenoquine is contraindicated in pregnancy and breastfeeding.[49][104]

Primary options

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

OR

quinine sulfate: adults: 542 mg base orally three times daily for 3 or 7 days depending on location

and

clindamycin: adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

Secondary options

mefloquine hydrochloride: adults: consult specialist for guidance on dose

Plasmodium malariae or Plasmodium knowlesi: uncomplicated disease

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium malariae or Plasmodium knowlesi: uncomplicated disease
|
nonpregnant
1st line – 

oral antimalarial regimen

P malariae and P knowlesi infections are rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present or parasite density is high ( P knowlesi).

P knowlesi, which is found in parts of Southeast Asia, replicates every 24 hours. Therefore, rapid diagnosis and prompt treatment of infection is essential.[132]​ Hospitalization should be considered to monitor for clinical response and parasitemia due to the risk of complications.[104]

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine. Alternative options include artemether/lumefantrine, atovaquone/proguanil, or quinine plus doxycycline or tetracycline or clindamycin. Doxycycline or tetracycline are preferred to clindamycin, due to the availability of more data. However, use of doxycycline or tetracycline should be avoided in children ages under 8 years. Mefloquine is recommended if no other options are available due to an increased rate of adverse effects and concerns about longer-lasting or permanent neuropsychiatric complications.[104][118]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization recommends either chloroquine or artemisinin-based combination therapy (ACT) in these patients. Artemether/lumefantrine is a commonly used option.[49]​ Other ACT regimens (e.g., dihydroartemisinin plus piperaquine, artesunate plus mefloquine, artesunate plus amodiaquine, artesunate plus sulfadoxine/pyrimethamine, and artesunate plus pyronaridine) may be available in some geographic locations. However, in many countries these drugs are not licensed or available. Consult your local guidelines for more information.

Primary options

chloroquine phosphate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

Secondary options

hydroxychloroquine sulfate: children: 10 mg base/kg orally as a single dose initially, followed by 5 mg base/kg at 6, 24, and 48 hours, total dose 25 mg base/kg; adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

OR

artemether/lumefantrine: children and adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses; children 5-15 kg: 1 tablet per dose; children 15-24 kg: 2 tablets per dose; children 25-34 kg: 3 tablets per dose; children ≥35 kg and adults: 4 tablets per dose

OR

atovaquone/proguanil: children 5-8 kg: (62.5/25 mg tablet) 2 tablets orally once daily for 3 days; children 9-10 kg: (62.5/25 mg tablet) 3 tablets orally once daily for 3 days; children 11-20 kg: (250/100 mg tablet) 1 tablet orally once daily for 3 days; children 21-30 kg: (250/100 mg tablet) 2 tablets orally once daily for 3 days; children 31-40 kg: (250/100 mg tablet) 3 tablets orally once daily for 3 days; children >40 kg and adults: (250/100 mg tablet) 4 tablets orally once daily for 3 days

OR

quinine sulfate: children: 8.3 mg base/kg orally every 8 hours for 3 days; adults: 542 mg base orally every 8 hours for 3 days

-- AND --

doxycycline: children ≥8 years of age: 2.2 mg/kg orally twice daily for 7 days; adults: 100 mg orally twice daily for 7 days

or

tetracycline: children ≥8 years of age: 25 mg/kg/day orally given in 4 divided doses for 7 days; adults: 250 mg orally four times daily for 7 days

or

clindamycin: children and adults: 20 mg base/kg/day orally given in 3 divided doses for 7 days

1st line – oral antimalarial regimen

Back
ACUTE
|
Plasmodium malariae or Plasmodium knowlesi: uncomplicated disease
|
pregnant
1st line – 

oral antimalarial regimen

P malariae and P knowlesi infections are rarely life-threatening and can usually be managed on an outpatient basis unless comorbidities are present.

P knowlesi, which is found in parts of Southeast Asia, replicates every 24 hours. Therefore, rapid diagnosis and prompt treatment of infection is essential.[132]​ Hospitalization should be considered to monitor for clinical response and parasitemia due to the risk of complications.[104]

The Centers for Disease Control and Prevention (CDC) recommends treatment with chloroquine (preferred) or hydroxychloroquine in all trimesters.[104]

International guidelines may recommend different antimalarial regimens. For example, the World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) in all trimesters of pregnancy.[49] Artemether/lumefantrine is a commonly used option. Consult your local guidelines for more information.

Primary options

chloroquine phosphate: adults: 600 mg base orally as a single dose initially, followed by 300 mg base at 6, 24, and 48 hours

OR

artemether/lumefantrine: adults: (20/120 mg tablet) 1 dose initially followed by another dose at 8 hours then 1 dose twice daily for 2 days, total 6 doses (1 dose = 4 tablets in adults)

Secondary options

hydroxychloroquine sulfate: adults: 620 mg base orally as a single dose, followed by 310 mg base at 6, 24, and 48 hours

ONGOING

Plasmodium falciparum: recurrent infection

1st line – consult specialist and retreatment

Back
ONGOING
|
Plasmodium falciparum: recurrent infection
1st line – 

consult specialist and retreatment

A specialist should be consulted for guidance on treating these patients.

Recurrence of Plasmodium falciparum malaria can occur from either treatment failure or reinfection. Treatment failure may be due to drug resistance or inadequate treatment exposure (e.g., vomiting dose, suboptimal dose, poor adherence).

Treatment failure should be confirmed parasitologically, with microscopy or lactate dehydrogenase (LDH)-based rapid diagnostic tests, if possible.[49]

Recurrence of fever and parasitemia within 28 days of treatment is usually due to treatment failure, and an alternative artemisinin-based combination therapy (ACT) that is known to be effective in the region is recommended.[49]

Recurrence after 28 days may be due to either treatment failure or new infection, and a first-line ACT is recommended. However, reuse of mefloquine within 60 days of the first treatment is associated with an increased risk of neuropsychiatric events, and a regimen that does not contain mefloquine should be used.[49]

Retreatment with the same ACT showed similar efficacy to an alternative ACT or quinine plus clindamycin in a phase III randomized controlled trial.[154]

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