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Part 2: Treatment: General Approach § Treatment: Uncomplicated Malaria

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Treatment: General Approach | Treatment: Uncomplicated Malaria | References

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For download: Treatment Guidelines Table
Treatment summary in tabular form (Updated March 6, 2007)
Download PDF version formatted for print (71 KB/3 pages)

Treatment: General Approach

Treatment for malaria should not be initiated until the diagnosis has been confirmed by laboratory investigations. "Presumptive treatment" without the benefit of laboratory confirmation should be reserved for extreme circumstances (strong clinical suspicion, severe disease, impossibility of obtaining prompt laboratory confirmation).

Once the diagnosis of malaria has been confirmed, appropriate antimalarial treatment must be initiated immediately. Treatment should be guided by three main factors: the infecting Plasmodium species, the clinical status of the patient, and the drug susceptibility of the infecting parasites as determined by the geographic area where the infection was acquired.

Determination of the infecting Plasmodium species for treatment purposes is important for three main reasons:

• P. falciparum infections can cause rapidly progressive severe illness or death while the non-falciparum ( P. vivax, P. ovale, or P. malariae) species rarely cause severe manifestations;
• P. vivax and P. ovale infections require treatment for the hypnozoite forms that remain dormant in the liver and can cause a relapsing infection;
• and P. falciparum and P. vivax species have different drug resistance patterns in differing geographic regions. For P. falciparum infections, the urgent initiation of appropriate therapy is especially critical.

The second factor affecting treatment is the 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 normocytic anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, circulatory shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia of > 5%) are considered to have manifestations of more severe disease and should be treated aggressively with parenteral antimalarial therapy.¹⁵

Finally, 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 and treatment course. 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 P. falciparum must be initiated immediately.

Malaria is a nationally notifiable disease and all cases should be reported to your state health department, which are forwarded onto the CDC. CDC clinicians are on-call 24 hours to provide advice to clinicians on the diagnosis and treatment of malaria and can be reached through the Malaria Hotline 770-488-7788 Monday – Friday, 8:00 am to 4:30 pm. Off-hours, weekends, and federal holidays, call 770-488-7100 and ask to have the malaria clinician on-call to be paged.

The three-page Treatment Guidelines table ( Download PDF version formatted for print (67 KB/3 pages)) can be used as a guide for treatment of malaria in the United States. The drug or drug combinations recommended for treatment are listed in bold on the first line of each box in the adult and pediatric “drug and dose” columns. Each drug and its recommended dose are then listed individually on the lines below in the same box. It is important to note that the base/salt conversions for antimalarials are a continual source of confusion and can contribute to treatment errors. In this treatment table (where appropriate), the antimalarial dose is expressed in base with the salt equivalency noted in parenthesis.

After initiation of treatment, the patient's clinical and parasitologic status should be monitored. In infections with P. falciparum or suspected chloroquine-resistant P. vivax, blood smears should be made to confirm adequate parasitologic response to treatment (decrease in parasite density followed by clearance).

Treatment: Uncomplicated Malaria

P. falciparum or Species Not Identified

For P. falciparum infections acquired in areas without chloroquine-resistant strains, which include Central America west of the Panama Canal, Haiti, the Dominican Republic, and most of the Middle East, patients should be treated with oral chloroquine. A chloroquine dose of 600 mg base (= 1,000 mg salt) should be given initially, followed by 300 mg base (= 500 mg salt) at 6, 24, and 48 hours after the initial dose for a total chloroquine dose of 1,500 mg base (=2,500 mg salt). As a 2nd line alternative for treatment, a hydroxychloroquine dose of 620 mg base (=800 mg salt) po can be given immediately, followed by 310 mg base (=400 mg salt) po at 6, 24, and 48 hours after the initial does for a total hydroxychloroquine dose of 1,550 mg base (=2,000 mg salt).

For P. falciparum infections acquired in areas with chloroquine-resistant strains, three treatment options are available. The first two treatment options are quinine sulfate plus doxycycline, tetracycline, or clindamycin; or atovaquone-proguanil (Malarone). Both of these options are very efficacious. For the quinine sulfate combination options, quinine sulfate plus either doxycycline or tetracycline is generally preferred to quinine sulfate plus clindamycin because there are more data on the efficacy of quinine plus doxycycline or tetracycline. Quinine treatment should continue for 7 days for infections acquired in Southeast Asia and for 3 days for infections acquired in Africa or South America. The third option, mefloquine, is associated with a higher rate of severe neuropsychiatric reactions when used at treatment doses. We recommend this third option only when the quinine sulfate combination or atovaquone-proguanil options cannot be used.

For pediatric patients, the treatment options are the same as for adults except the drug dose is adjusted by patient weight. The pediatric dose should never exceed the recommended adult dose. For children less than eight years old, doxycycline and tetracycline are generally not indicated; therefore, quinine (given alone for a full 7 days regardless of where the infection was acquired or given in combination with clindamycin as recommended above) and atovaquone-proguanil are recommended treatment options for chloroquine-resistant P. falciparum infections; mefloquine can be considered if these options are not available. In rare instances, doxycycline or tetracycline can be used in combination with quinine in children less than eight years old if other treatment options are not available or are not tolerated, and the benefit of adding doxycycline or tetracycline is judged to outweigh the risk.

If infections initially attributed to “species not identified” are subsequently diagnosed as being due to P. vivax or P. ovale, additional treatment with primaquine should be administered (see P. vivax and P. ovale, below).

P. malariae

There has been no widespread evidence of chloroquine resistance in P. malariae species; therefore, chloroquine remains the drug of choice for all P. malariae infections. As a 2nd line alternative for treatment, hydroxychloroquine may be given instead.

P. vivax and P. ovale

Chloroquine (hydroxychloroquine as 2nd line alternative for treatment) remains the treatment of choice for all P. vivax and P. ovale infections except for P. vivax infections acquired in Papua New Guinea or Indonesia. Reports have confirmed a high prevalence of chloroquine-resistant P. vivax in these two specific areas. Rare case reports of chloroquine-resistant P. vivax have also been documented in Burma (Myanmar), India, and South America. Persons acquiring P. vivax infections from regions other than Papua New Guinea or Indonesia should initially be treated with chloroquine. If the patient does not respond to chloroquine, treatment should be changed to one of the two regimens recommended for chloroquine-resistant P. vivax infections, and your state health department and the CDC should be notified (CDC Malaria Hotline: (770) 488-7788 Monday-Friday 8am to 4:30pm EST; (770) 488-7100 after hours, weekends and holidays). Persons acquiring P. vivax infections in Papua New Guinea or Indonesia should initially be treated with a regimen recommended for chloroquine-resistant P. vivax infections. The two treatment regimens for chloroquine-resistant P. vivax infections are quinine sulfate plus doxycycline or tetracycline, or mefloquine. These two treatment options are equally recommended. There are no adequate, well-controlled studies to support the use of atovaquone-proguanil to treat chloroquine-resistant P. vivax infections.

In addition to requiring blood stage treatment, infections with P. vivax and P. ovale can relapse due to hypnozoites that remain dormant in the liver. To eradicate the hypnozoites, patients should be treated with a 14-day course of primaquine phosphate. CDC has recently changed its recommendations for treating hypnozoites by increasing the recommended primaquine phosphate dose to 30 mg (base) by mouth daily for 14 days. Because primaquine can cause hemolytic anemia in persons with glucose-6-phosphate-dehydrogenase (G6PD) deficiency, persons must be screened for G6PD deficiency prior to starting primaquine treatment. For persons with borderline G6PD deficiency or as an alternate to the above regimen, primaquine may be given at the dose of 45 mg (base) orally one time per week for 8 weeks ; consultation with an expert in infectious disease and/or tropical medicine is advised if this alternative regimen is considered in G6PD-deficient persons. Primaquine must not be used during pregnancy.

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