General Approach to Treatment

Overview

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

Once the diagnosis of malaria has been made, appropriate antimalarial treatment must be initiated immediately. The Malaria Treatment Tables can be used as a guide for treatment of malaria in the United States. The drug or drug combination recommended for each specific situation is listed, as well as the adult and pediatric doses. It is important to note that the base/salt conversions for antimalarials are a recurrent source of confusion and can contribute to treatment errors. In the treatment table, where appropriate, the antimalarial dose is expressed in base with the salt equivalency noted in parentheses.

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.

Infecting Plasmodium species

Determination of the infecting Plasmodium species for treatment purposes is important for four main reasons. Firstly, Plasmodium falciparum and P. knowlesi infections can cause rapidly progressive severe illness or death, while the other species, P. vivax, P. ovale, and P. malariae, are less likely to cause severe disease. Secondly, P. vivax and P. ovale infections also require treatment for the hypnozoites, which remain dormant in the liver and can cause relapsing episodes. Thirdly, P. falciparum and P. vivax species have different drug resistance patterns in different geographic regions of the world. Finally, for P. falciparum and P. knowlesi infections, the urgent initiation of appropriate therapy is especially critical.

Clinical status of the patient

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 antimalarials. However, patients who have one or more of the following clinical criteria—impaired consciousness/coma, severe anemia (hemoglobin <7 g/dL), acute kidney injury, acute respiratory distress syndrome, circulatory collapse/shock, disseminated intravascular coagulation, acidosis, jaundice (along with at least one other sign of severe malaria)—and/or percent parasitemia of ≥5% are considered to have manifestations of severe disease and should be treated aggressively with intravenous antimalarial therapy.

Drug susceptibility of the infecting species

Knowledge of the geographic area where the infection was acquired provides information on the likelihood of drug resistance of the infecting parasite and enables the treating clinician to choose an appropriate drug or drug combination. Information on malaria risk and parasite resistance can be found in the malaria chapter in CDC's Yellow Book website. If the diagnosis of malaria is suspected and cannot be confirmed or if the diagnosis of malaria is confirmed but species determination is not possible, antimalarial treatment effective against chloroquine-resistant P. falciparum must be initiated immediately and revisited once confirmatory results become available.

Previous use of antimalarials

It is important to consider if malaria occurred while an individual was taking a drug for malaria chemoprophylaxis. In this case, the treatment regimen should not include the drug or drug combination used for prophylaxis unless no other options are available.

After initiation of treatment, the patient's clinical and parasitological status should be monitored. In infections with P. falciparum, P. knowlesi, or suspected chloroquine-resistant P. vivax, blood smears should be repeated every 12–24 hours to monitor parasitological response to treatment, i.e., decrease in parasite density. It is recommended to document a negative malaria smear after treatment, but this could be done as an outpatient depending on clinical and parasitological response and the judgement of the treating clinician. Note that gametocytes, the sexual stage of the parasite, are not targeted by most antimalarials and should not be counted in assessing parasite density.