Treating uncomplicated malaria

Patients diagnosed with uncomplicated malaria can be effectively treated with oral antimalarials. In this video, from our Malaria Mini: The Basics course, we look at how each treatment works, which drugs should be used for specific malaria strains, and the critical step you need to take to avoid a patient relapse.

Many clinicians lack the experience and relevant caseload that is necessary to master the treatment of malaria. This course will teach you how to confidently tackle this disease in your clinical practice. You’ll learn about the parasite’s life cycle and epidemiology, how to take a proper travel history, how to prevent, diagnose, and treat infections, and when to refer your patient to an expert in time to save a life!

Uncomplicated malaria

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Now that we know how malaria develops and how to recognize the symptoms, how do we treat this disease? Patients diagnosed with malaria are generally categorized as having either uncomplicated, or severe malaria. Patients diagnosed with uncomplicated malaria can be effectively treated with oral anti-malarials. 

Confirming malaria before treatment

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It is preferable that treatment for malaria not be initiated until the diagnosis has been established by laboratory testing. Presumptive treatment, without the benefit of prior laboratory confirmation, should be reserved for extreme circumstances, such as strong clinical suspicion, or severe disease in a setting where prompt laboratory diagnosis is not available.

Chloroquine treatment for uncomplicated malaria

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The treatment of uncomplicated malaria generally caused by Plasmodium vivax, Plasmodium ovale, or Plasmodium knowlesi usually involves the drug chloroquine. So, how does chloroquine work? Remember earlier in the course when we discussed what the parasite is doing once it invades a red blood cell, the parasite takes in hemoglobin by pinocytosis and breaks it down into amino acids that it can use.

How chloroquine works in malaria

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Remember, the parasite has heme polymerase, which detoxifies heme and hematin to turn it into hemozoin, which it can use. And heme polymerase is the target of a family of drugs known as 8-aminoquinolines, the most common of which is chloroquine. These drugs work by blocking the parasite heme polymerase, which makes heme and hematin toxic to the parasite, which leads to its death.

Dormant liver forms in Plasmodium vivax and ovale

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With Plasmodium ovale and Plasmodium vivax, a small number of parasites remain dormant inside liver cells. We refer to these as hypnozoites, and they are found in virtually all patients with these two types. Therefore, in these two types, even if you treat and kill the active malaria in the red cells, you may not be able to kill this dormant form. This means the patient could have a relapse of vivax and ovale if you don't also target the dormant hypnozoites in the liver.

Preventing Plasmodium vivax and ovale relapse

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So you treat uncomplicated Plasmodium vivax and Plasmodium ovale malaria with chloroquine to target the active malaria. And then you come back after treatment with primaquine. This agent penetrates into the liver cell and kills the hypnozoites.

Primaquine and G6PD deficiency risk

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So you use chloroquine plus primaquine to prevent relapse of these two types of malaria. Now, a caution about primaquine. Primaquine can cause massive hemolysis if given to patients who have G6PD deficiency. So if you're treating persons of African descent and a few others, you would test them for the presence of G6PD deficiency before giving them primaquine. 

Treating malaria in pregnancy: avoiding primaquine

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Primaquine should also be avoided in pregnant women because it has been shown to cause developmental abnormalities in the babies. In addition, if the fetus is G6PD deficient, massive hemolysis can occur, which can be fatal. So primaquine is contraindicated in pregnancy. Instead, you would generally treat with chloroquine first, then wait until after delivery and treat the mother and baby with primaquine. 

Chloroquine for chloroquine-sensitive falciparum malaria

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So what about falciparum malaria? Milder cases of falciparum malaria may occur in individuals who were previously infected and that have antibodies to the disease. For uncomplicated Plasmodium falciparum infections, acquired in areas without chloroquine resistant strains, which includes Central America, west of the Panama Canal, Haiti, and the Dominican Republic, patients can also be treated with oral chloroquine. 

Artemether-lumefantrine for chloroquine-resistant falciparum malaria

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For uncomplicated Plasmodium falciparum infections acquired in areas with chloroquine resistance, four treatment options are available. Artemether-lumefantrine is the preferred option, if readily available. Artemether is related to artesunate, which works by disrupting the mitochondrial membrane and the energy production of the mitochondria, causing the parasite to die. Lumefantrine’s precise mechanism of action is unknown, but available data suggests that it inhibits nucleic acid and protein synthesis. 

Atovaquone-proguanil for falciparum malaria

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The second option is a combination of atovaquone, which is a structural analogue of Coenzyme Q found in the mitochondria electron transport system, and the sulfa analog proguanil, which inhibits the synthesis of folic acid in the parasite.

Quinine plus doxycycline for falciparum malaria

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The third option is quinine sulfate plus doxycycline, tetracycline, or clindamycin. Quinine is one of the eight aminoquinolines which blocks heme polymerase. Doxycycline, tetracycline, and clindamycin all inhibit protein synthesis in the parasite. Either of the tetracyclines are preferred to clindamycin because there are more efficacy data available.

Mefloquine for falciparum malaria

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The fourth option is mefloquine. Mefloquine acts as a blood schizonticide. However, its exact mechanism of action is not known. Mefloquine is generally reserved for cases where the other options cannot be used, because when used in therapeutic doses, in contrast to preventive doses, rare severe neuropsychiatric reactions can occur.