Drugs against malaria act at different stages of the parasite life cycle (Fig1.). Blood schizontocidal drugs (suppressive or clinical) attack parasite in erythrocyte, preventing or ending clinical attack. Gametocytocidal drugs destroy sexual forms in human, decreasing transmission. Tissue schizonticidal drugs (causal, true) act on early stages of parasite development in liver, before the release of merozoites into blood. Hypnozoitocidal drugs kill dormant hypnozoites in liver, preventing relapses of infection. Finally, sporontocidal drugs inhibit development of oocysts in mosquito, decreasing malaria transmission.
The choice of malaria treatment is first of all influenced by what type of species cause the

Fig1. Action of antimalarials

infection. Some species rarely have chloroquine resistance (e.g. P.vivax) or they have a hypnozoite stage that is only eradicated by primaquine or tafenoquine. The parasite sensitivity is a very important factor to consider. It is well known today that P.falciparum has evolved multi-drug resistance in many parts of the world. Another factor, that may influence the drug choice, is the host's degree of immunity. Some classes of drug are acceptable for the treatment of "semi-immune" patients, but "unacceptable" for non-immunes. Finally, risk-benefit analysis of drug adverse effects and treatment potentials should be always made prior to any therapy initiation

Major Drugs to Treat Malaria
» Chloroquine (Aralen ®, Dawaquine ®)
» Amodiaquine (Camoquine ®)
» Quinine and Quinidine
» Sulfa combinations (Fansidar ®, Metakelfin ®)
» Mefloquine (Lariam ®)
» Halofantrine (Halfan ®)
» Atovaquone-proguanil (Malarone ®)
» Atemisinin derivatives (Paluther ®)

Treatment of benign non-falciparum malaria
Chloroquine is usually a drug of choice for the treatment and prophylaxis of P.vivax, P.ovale and P.malariae. Chloroquine resistant P.falciparum is extensively spread throughout the world. Therefore, the use of chloroquine against falciparum malaria is only limited to sensitive P.falciparum strains.
Chloroquine acts against the asexual intra-erythrocytic forms of the parasite. It is also gametocytocidal against P.vivax and immature gametocytes of P.falciparum. It is safe for children and in pregnancy. Chloroquine is generally well tolerated in its usual 3-day course. However, the side effects may sometimes include dysphagia, nausea, dizziness, headache, blurred vision and pruritus. Pruritus is more common in dark-skinned people, and if happens, anti-histamines can be offered to the patient and generally the use of chloroquine should be continued.
Detailed dosage and the schedule of chloroquine use are summarized in tables (links to Tables1-2). If symptoms of malaria persist at the end of the chloroquine treatment it could mean that there was an additional (mixed) infection with chloroquine resistant strain of the parasite (e.g. P.falciparum or rarely P.vivax). Chloroquine resistant P.vivax has been recently documented in some parts of Southeast Asia (e.g. India, Indonesia, Papua New Guinea, Burma) and Latin America (e.g. Guyana).
Mefloquine is an effective drug to use in chloroquine-resistant cases (or when chloroquine is not available). It also acts on asexual intra-erythrocytic forms. Mefloquine is an effective prophylaxic agent against chloroquine-resistant P.falciparum. Unlike the prophylactic dose (link to Prophylaxis table), treatment dose is less well tolerated (link to Table2). Side effects (5-50%) may include neuropsychiatric reactions, dizziness, cardiac dysrythmias, GI symptoms (vomiting, nausea etc.).
Quinine is another alternative in managing a chloroquine-resistant case (link to the treatment schedule, Table2.). Quinine may be combined with tetracyclines or clindamycin to reduce the course of treatment. Tetracyclines are contraindicated in children < 8 years old and pregnant women.
Importantly, tetracyclines alone should never be used for treatment, only in combination with other major antimalarials. Clindamycin may be used successfully for treatment in combination with quinine, especially for pregnant women and young children, although Mefloquine and Sulfadoxine/Pyremethamine are more effective in these groups.
Primaquine (see also Tafenoquine) is necessary to administer (see dose & schedule [link to Table2.]) for radical cure of P.vivax and P.ovale, because it acts against hypnozoites of P.vivax and P.ovale. However, it is also active against exo-erythrocytic schizonts and gametocytes. Primaquine can cause hemolysis in G6PD-deficient patients. In case of mild G6PD-deficiency, primaquine can be used weekly, instead of daily. Primaquine is contraindicated in pregnant and lactating women (see Malaria in Pregnancy).
There is no need for primaquine use in congenital and transfusion-induced malaria cases, because there is no hepatic cycle.
Tafenoquine is a new drug developed by US army. It is a derivative of primaquine, thus very similar to it in many ways. However, it is much more active than primaquine (7 fold) in animal studies.
High fever, headache and other inflammatory symptoms can be successfully controlled by Paracetomol, which is the safest antipyretic. Aspirin should be avoided in children because of its association with Raye's syndrome.
Iron and Folic acid supplementation can be used to manage anemia. Oral rehydration with Glucose is also important to compensate for dehydration and fasting.

Treatment of uncomplicated falciparum malaria
If the infection was acquired in the area proven to be chloroquine-sensitive (e.g. parts of Middle East, Haiti, Dominican Republic, Central America), then patient can be simply managed with chloroquine.
On the other hand if the infection was acquired in the chloroquine-resistant area (which is very often the case nowadays), at least the following drugs and combinations can be used:

  • Quinine + Tetracycline
  • Quinine + Doxycycline
  • Quinine + Pyremethamine/Sulfadoxine
  • Mefloquine
  • Malarone
  • Artemisinins (Artesunate, Artemether)
More details about the dosage and schedule can be found in our reference table (link to the treatment Table2.).
Below we will summarize the rationale for using any major anti-malarial in treating falciparum infection.
Quinine is a drug of choice for non-immune patients in most areas where multidrug-resistant strains of P.falciparum are prevalent. It acts against intra-erythrocytic forms and gametocytes. Quinine is available in both oral and parenteral forms. Oral form is used to treat uncomplicated and chloroquine-resistant falciparum malaria, while parentaral treatment is indicated in severe malaria. Quinine is safe in pregnancy and for children. It has a disadvantage of causing side effects when used for up to a week. The major adverse effect is 'cinchonism'. It comprises of tinnitus, deafness, headache, nausea and visual disturbance. 'Cinchonism' affects the majority of conscious patients and normally it does not warrant dose reduction. In order to reduce the side effects, quinine treatment shortening may be achieved through its combination with sulfa drugs (Fansidar , Metakelfin ).
Fancidar acts on asexual intracellular stages. It is used in combination with short course of quinine in treatment of uncomplicated multi-resistant falciparum malaria. Fansidar and Metakelfin are contraindicated in sulfa-allergic patients.
Mefloquine (Lariam ®) is highly effective against P.falciparum throughout the world except the South-East Asia (resistance)! If the patient comes from those resistant areas, the combination of Mefloquine with Artesunate can be used. In general, treatment dose (link to Table2) of Mefloquine is less well tolerated compared to the prophylactic dose. Side effects may include neuropsychiatric reactions, dizziness, cardiac dysrythmias, GI symptoms (vomiting, nausea etc.). Safety of Mefloquine in pregnancy and during lactation is controversial.
Malarone (Atovaquone + Proguanil) has proved very effective against uncomplicated multidrug-resistant falciparum malaria (link to Table2). Usually, malarone is well tolerated. However, it is an expensive drug.
Artemisinins is a relatively novel class of anti-malarial drugs. They are all derived from Chinese herb qinghaosu. Artemisinins act on earlier parasite developmental stages compared to chloroquine and quinine. They provide rapid parasite clearance. No resistance has been reported to date. The combinations of artemisinins with other anti-malarials seem very promising (e.g. Artesunate + Mefloquine, Artemether + Lumefantrine etc.).
Riamet ® (Co-artemether) is a recently marketed combination of Artemether (20 mg) and Lumefantrine (120 mg). The six-dose regimen (link to Table2.) proved very effective against multidrug-resistant P.falciparum. Artemether + Lumefantrine combination is as effective as Artesunate + Mefloquine. Moreover, it is better tolerated than regimens containing mefloquine + no neurotoxicity and cardiotoxicity.

Treatment of severe complicated malaria
This section will summarize currently available antimalarial drugs used for parenteral treatment in severe malaria (see Table3. [link]). More detailed information on complex management of a complicated malaria case in the Intensive Care Unit (ICU) is available throughout the following links: Management of Severe Malaria (WHO) http://mosquito.who.int/docs/hbsm.pdf and Malaria in ICU: http://www.anaesthetist.com/icu/infect/proto.htm
The basic principles of management of severe falciparum malaria are covered below.

  • Severe malaria caused by P.falciparum has a poor prognosis if treatment is not started immediately.
  • All suspected cases should undergo rapid clinical assessment.
  • Blood should be withdrawn for lab analysis.
  • Weight of the patient and blood sugar should be checked as soon as possible.
  • Appropriate parenteral antimalarial therapy should be initiated.
  • Chosen drug regimen has to account for the local drug resistance pattern (if available).
  • Drug dosage must be calculated according to the patient's body weight (see Table3. [link]).
  • The antimalarial drug should be given parenterally whenever possible to insure the therapeutic blood level.
  • Therapeutic response should be monitored frequently by:
    • Repeated clinical assessment
    • Examination of blood films
    • Measurement of glucose level, temperature, pulse and blood pressure
  • Switch to oral drugs should be done whenever patient is able to swallow and retain tablets
  • Artemisinins are as effective as quinine. They provide even faster parasitemia clearance.
  • Patient should be transferred to the highest available level of the medical care
  • Hypoglycemia should be avoided, electrolyte derangement should be corrected and all vital functions have to be ensured
  • Patient should be nursed appropriately (e.g. airways cleaned, frequently turned etc.)
  • Harmful use of corticosteroids, heparin etc. should be avoided
Table1. Dosage schedule for Chloroquine treatment (WHO)
    Number of tablets
Weight (kg) Age (years) Tablets, 100 mg of base Tablets, 150 mg of base
Day1 Day2 Day3 Day4 Day5 Day6
5-6 < 4 months 0.5 0.5 0.5 0.5 0.25 0.25
7-10 4-11 months 1 1 0.5 0.5 0.5 0.5
11-14 1-2 1.5 1.5 0.5 1 1 0.5
15-18 3-4 2 2 0.5 1 1 1
19-24 5-7 2.5 2.5 1 1.5 1.5 1
25-35 8-10 3.5 3.5 2 2.5 2.5 1
36-50 11-13 5 5 2.5 3 3 2
50+ 14+ 6 6 3 4 4 2

Table2. Treatment of uncomplicated malaria
Chloroquine-sensitive P.vivax & P. falciparum ADULT DOSAGE PEDIATRIC DOSAGE COMMENTS
Chloroquine (oral) 600 mg base (1000 mg phosphate salt), followed by 300 mg base (500 mg salt) 6 hours later, then 300 mg base x 2 days 10 mg base (max 600 mg base) orally, followed by 5 mg/kg 6 hours later, then 5 mg/kg base x 2 days See Table2. for the schedule!
Chloroquine-resistant P.vivax ADULT DOSAGE PEDIATRIC DOSAGE  
Mefloquine (Lariam ®, oral) 1,250 mg (split dose: 750 mg + 500 mg 8-12 hrs after) x 1day 25 mg/kg (split dose 15 mg/kg + 10 mg/kg 6 hrs after); < 45 kg NOT to be taken by aircraft pilots or drivers of public transport
Quinine sulfate + Doxycycline (oral) 650 mg every 8 hr x 3-7 days plus Doxycycline 100 mg bid x 7 days 25 mg/kg/day in 3 divided doses x 3-7 days plus Doxycycline 2 mg/kg/day up to 100 mg x 7 days Doxycycline: NOT for children < 8 years old and in pregnancy
Prevention of P. vivax relapse ADULT DOSAGE PEDIATRIC DOSAGE  
Primaquine (oral) 15 mg base (26.3 mg phosphate salt) daily x 14days 0.3 mg base (0.5 mg salt) per kg/day x 14 days NOT in pregnant or lactating women or in G6PD-deficiency
Chloroquine-resistant P. falciparum ADULT DOSAGE PEDIATRIC DOSAGE  
Quinine sulfate (oral) 600 mg every 8 hrs x 7 days 10 mg//kg/every 8 hrs x 7 days Very bitter, may causes cinchonism
* Tetracycline (oral) 250 mg every 6 hrs x 7 days NOT for children or pregnant women
* Doxycycline (oral) 100 mg daily 7 days NOT for children < 8 years old CAUTION: contraceptive pills may become less effective!
* Fancidar ® (Pyrimethamine 25mg + Sulphadoxine 500mg) oral 2-3 tablets on day 2, one dose 6 week - 1 year - ? tablet on day 2
1-3 years - ? tablet on day 2
4-8 years - 1 tablet on day 2
9-14 years - 2 tablets on day 2
CAUTION: if patient has allergy to sulfa drugs!
Mefloquine (Lariam ®, oral) 1,250 mg (split dose: 750 mg + 500 mg 6-8 hrs apart) x 1 day 25 mg/kg (split dose 15 mg/kg + 10 mg/kg 6 hrs apart); in a child < 45 kg Vivid dreams (nightmares), nausea, vomiting, dysphoria, weakness
Malarone ® (Atovaquone 250mg + Proguanil 100mg) oral 4 tabs once daily x 3 days 11-20 kg: 1 tab once daily x 3 days
21-30 kg: 2 tabs once daily x 3 days
31-40 kg: 3 tabs once daily x 3 days
Riamet ® (Artemether 20mg + Lumefantrine 120mg) 4 tabs twice a day x 3 days < 15 kg: 1 tab twice daily x 3 days
15 - < 25 kg: 2 tabs twice daily x 3 days
25 - < 35 kg: 3 tabs twice daily x 3 days
* Given together with Quinine

Table3. Treatment of severe chloroquine-resistant falciparum malaria (antimalarials)
Quinine (IV) 20mg salt/kg (loading dose) diluted in 10 mL/kg isotonic fluid by IV infusion over 4 hrs then, 8 hrs after the start of the loading dose, 10 mg salt/kg over 4 hrs every 8 hrs until patient can swallow. The 7-day course of quinine tablets should be completed (10mg salt/kg every 8-12 hrs) 20mg salt/kg (loading dose) diluted in 10 mL/kg isotonic fluid by IV infusion over 2 hrs then, 12 hrs after the start of the loading dose, 10 mg salt/kg over 2 hrs every 12 hrs until patient can swallow. The 7-day course of quinine tablets should be completed (10mg salt/kg every 8-12 hrs)
Artesunate (IV) 2.4 mg/kg (loading dose) IV on day 1 followed by 1.2 mg/kg daily for at least 3 days until the patient can swallow Same as in adults (weight adjustment)
Intramuscular IM injection (IV is not available) ADULT DOSAGE PEDIATRIC DOSAGE
Quinine (IM) 20 mg salt/kg diluted to 60-100 mg/mL (loading dose) IM (anterolateral thigh, divided half into each leg), then 10 mg salt/kg every 8 hrs until patient can swallow Same as in adults (weight adjustment)
Artemether (IM) 3.2 mg/kg (loading dose) IM on day 1 followed by 1.6 mg/kg daily for at least 3 days until the patient can swallow Same as in adults (weight adjustment). The use of 1 mL tuberculin syringe is advisable because of the small injection volume
Rectal (suppositories)
(IV/IM are not available)
Suppositories of artemisinin 40 mg/kg loading dose intrarectally, followed by 20 mg/kg at 4, 24, 48 and 72 hrs followed by oral drug Same as in adults (weight adjustment)
Suppositories of artesunate One 200 mg suppository intrarectally at 0, 4, 8, 12, 24, 36, 48 and 60 hrs followed by an oral antimalarial drug  


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