What to know
- Initiate antimalarial treatment immediately upon laboratory diagnosis.
- For most cases of uncomplicated malaria, artemether-lumefantrine (Coartem®) is the preferred treatment; administer with fatty foods or drink.
- As of 2026, extend the duration of artemether-lumefantrine to a 5-day regimen for uncomplicated Plasmodium falciparum infections.
- Patients with P. falciparum, Plasmodium knowlesi, or malaria of unknown species should be hospitalized initially due to the potential for rapid, severe disease progression and monitored with daily blood smears.
- To prevent future relapses, infections caused by Plasmodium vivax and Plasmodium ovale require anti-relapse treatment in addition to acute blood-stage treatment.
Clinical resources
CDC Malaria Hotline
Healthcare providers can call the CDC Malaria Hotline for clinical consultation about malaria diagnosis and treatment:
- Monday – Friday, 9 a.m. 5 p.m. EST: (770) 488-7788
- After hours, weekends, and federal holidays: (770) 488-7100
Reference Algorithm for Diagnosis and Management of Malaria for a summary of the recommended steps to evaluate, diagnose, and treat malaria patients.
Use Malaria Treatment Tables for drug recommendations, as well as adult and pediatric dosing.
General approaches to treatment
Patients diagnosed with malaria without any manifestations of severe disease (clinical criteria and/or parasitemia ≥5%) can be effectively treated with oral antimalarials for uncomplicated malaria if tolerated. If they are unable to tolerate oral medications, intravenous artesunate should be used. See treatment of severe malaria.
Malaria treatment ideally should not be initiated until diagnosis has been confirmed by laboratory testing, such as microscopic examination of thick and thin blood smear, antigen-based rapid diagnostic test, or nucleic acid amplification test. Diagnostic testing for malaria should be done urgently and without delay, with turnaround times of a few hours and should not be sent out to laboratories that take days to return results. Results are necessary to inform treatment and guide clinical management decisions.
Treatment prior to laboratory testing may impact the ability to subsequently confirm the diagnosis and could delay identification of other causes of illness. However, uncomplicated malaria can quickly progress to severe malaria, especially if treatment is delayed. If malaria is strongly suspected clinically—such as in febrile patients with recent travel to a malaria-endemic area and findings of hemolysis or thrombocytopenia—and reliable laboratory diagnosis will be delayed beyond a few hours, presumptive treatment for P. falciparum malaria can be started in a facility able to appropriately manage malaria while awaiting diagnostic test results (not to exceed 24 hours) or arranging urgent referral of the patient.
Choosing a treatment regimen
Treatment should be guided by the clinical status of the patient, infecting Plasmodium species, and the expected drug susceptibility of the infecting parasite, which is informed by the geographic area where the infection was acquired. The treatment regimen should not include the drug or drug combination that the patient used for prophylaxis unless no better options are available.
In most cases of uncomplicated malaria, artemether-lumefantrine can be used as the first-line regimen. If the preferred treatment is not readily available, patients may begin taking whichever effective regimen is immediately accessible. Once a treatment regimen is started and well tolerated, there is generally no need to switch regimens even if a preferred regimen becomes available—except in the rare situations where quinine was started—due to potential side effects. If switching to an alternative regimen, provide a complete treatment course.
If there is any uncertainty about the infecting species, one should assume Plasmodium falciparum may be present. Plasmodium malariae, P. knowlesi, and P. falciparum can be challenging to distinguish by microscopic examination of a blood smear. Mixed species infections are possible and are difficult to confirm without molecular testing. PCR testing or blood smear review by an experienced pathologist or a reference laboratory should be done for species confirmation.
Identifying the infecting Plasmodium species is important to guide treatment for three main reasons:
- Infections caused by P. falciparum and P. knowlesi can lead to rapidly progressive severe illness or death. Urgent initiation of recommended therapy is critical. Although severe disease is possible, it is less likely with infections caused by the other species—P. vivax, P. ovale, and P. malariae.
- Plasmodium vivax and P. ovale infections require treatment for hypnozoites, which can remain dormant in the liver and cause relapsing episodes.
- The different species exhibit different drug resistance patterns across various geographic regions.1
Plasmodium falciparum or species unknown
Due to the risk of progression to severe disease in patients with P. falciparum infection, hospitalization is recommended. P. falciparum is resistant to chloroquine in most parts of the world. Mefloquine-resistant P. falciparum has been reported in certain parts of Southeast Asia. Artemisinin partial resistance, characterized by delayed clearance of P. falciparum after treatment, has been confirmed in certain areas in Southeast Asia and an increasing number of countries in Africa. Additionally, late treatment failures (recrudescence) have been reported 2–8 weeks following initial three-day treatment courses of artemether-lumefantrine in endemic areas as well as in travelers.2 Although with emerging resistance the rate of parasite reduction and clearance may be slower and late treatment failures can occur, IV artesunate and oral artemisinin-based combination therapies (ACTs) are generally still effective and remain the first-line treatment in the United States and globally.3 Patients with higher parasitemia (>2%), body weight ≥65 kg, who are pregnant, non-immune, or who have acquired malaria in areas with decreasing susceptibility to either artemisinin or lumefantrine, may be at higher risk for treatment failures.
When treating patients diagnosed with P. falciparum in the United States using artemether-lumefantrine, healthcare providers should administer an extended five-day course (twice a day for 5 days for a total of 10 doses) for all patients, regardless of the country of acquisition or other patient factors. The extended regimen of artemether-lumefantrine has been demonstrated to be safe and well-tolerated in clinical studies and should decrease the risk of treatment failures by increasing the exposure of the parasite to both the artemisinin component and lumefantrine.
Four treatment options for uncomplicated P. falciparum infections acquired in areas with chloroquine resistance (or if species is unknown at time of diagnosis) are listed in order of preference.4 See Malaria Treatment Table 1 for adult and pediatric dosing recommendations.
- Artemether-lumefantrine (Coartem®): The preferred treatment is an extended 5-day (10-dose) course of artemether-lumefantrine, the only ACT currently available in the United States. ACTs are the preferred treatment for uncomplicated P. falciparum globally because of the artemisinin component's ability to rapidly reduce the parasite load. Treatment failures, especially late failures, have occurred with a standard 3-day (6-dose) course.2 To maximize absorption and minimize treatment failure, artemether-lumefantrine should be taken with fatty food or a milky drink.
- Atovaquone-proguanil (Malarone™): The second line treatment option is atovaquone-proguanil (Malarone™) because it is generally better tolerated than other options below. Treatment failures, especially early failures, can occur, and parasite clearance times are generally longer compared to artemether-lumefantrine.2 To maximize absorption, atovaquone-proguanil should be taken with fatty food or a milky drink.
- Quinine sulfate plus doxycycline: If neither artemether-lumefantrine or atovaquone-proguanil are available, a third option is quinine sulfate combined with doxycycline/ tetracycline (or clindamycin). This regimen may not be as well tolerated.5
- Mefloquine: The fourth option, mefloquine, is associated with rare but potentially severe neuropsychiatric reactions and should only be considered when no other options are available. Mefloquine is contraindicated in those with a history of seizures or psychiatric disorders. Additionally, mefloquine as monotherapy is not recommended for infections acquired in certain parts of Southeast Asia due to drug resistance.
In addition, uncomplicated P. falciparum infections acquired in chloroquine-sensitive areas (Central America west of the Panama Canal, Haiti, and the Dominican Republic) can be treated with either oral chloroquine or hydroxychloroquine.
For infections initially classified as "species not identified" that are later diagnosed as being due to P. vivax or P. ovale, additional treatment with primaquine or tafenoquine should be administered (see P. vivax and P. ovale section).
Plasmodium vivax and Plasmodium ovale
For patients with confirmed P. ovale mono-infections or P. vivax mono-infections acquired from areas outside Papua New Guinea or Indonesia, treatment with chloroquine (or hydroxychloroquine) is recommended.3 Chloroquine (or hydroxychloroquine) is safe for use in pregnant women and all pediatric patients.3 There is high prevalence of chloroquine-resistant P. vivax in Papua New Guinea or Indonesia. Sporadic reports of chloroquine-resistant P. vivax have also been documented elsewhere (e.g., Burma [Myanmar], Cambodia, India, and Central and South America). There is currently no evidence of widespread resistance among P. ovale parasites.
If chloroquine (or hydroxychloroquine) is not available, or if the infection is acquired in Papua New Guinea or Indonesia, a regimen recommended for chloroquine-resistant infections should be used. Preferred options include artemether-lumefantrine or atovaquone-proguanil; an additional option is quinine sulfate plus doxycycline/ tetracycline (or clindamycin); or, if no other alternatives are available, mefloquine. See Malaria Treatment Table 2 for adult and pediatric dosing recommendations.
P. vivax and P. ovale infections, unlike the other species, can result in relapses month to years after initial infection due to the presence of hypnozoites (dormant liver-stage forms of the malaria parasite). In addition to treatment for the blood stage parasites during the acute phase of malaria illness, to reduce the risk of relapse, patients with P. vivax or P. ovale infections should also be treated with either primaquine phosphate or tafenoquine, which target liver-stage hypnozoites.
Both tafenoquine and primaquine can cause hemolytic anemia in people with glucose-6-phosphate-dehydrogenase (G6PD) deficiency, and quantitative G6PD testing should occur prior to starting treatment with these drugs. Since G6PD quantitative testing can vary greatly across different laboratories and assays, clinicians should follow reference ranges provided by each laboratory.
Primaquine phosphate can be used in combination with or following any of the drug options for treatment of the acute phase of infection. CDC recommends a daily dose of 30 mg (base) of primaquine phosphate by mouth for 14 days for adults. For patients weighing ≥70 kg, the total dose of primaquine should be adjusted to 6 mg/kg, divided into daily doses of 30 mg for the number of days needed to complete the total dose.6 A daily dose of 1.0 mg/kg for 7 days is an alternative regimen recommended by WHO in those with ≥70% G6PD activity.3
Tafenoquine (300mg single dose) should be used only in conjunction with chloroquine and in patients who are at least 16 years old.
For patients with intermediate G6PD deficiency (30–70% G6PD activity), clinicians may consider giving primaquine at 45 mg (base) orally once a week for eight weeks, with close monitoring for signs of hemolysis. Tafenoquine should not be given if G6PD quantitative results are not normal. Primaquine and tafenoquine should not be used during pregnancy (see Alternatives for Pregnant Women). Tafenoquine should not be used in children less than 16 years old. Relapses may still occur despite the administration of primaquine or tafenoquine due to several factors, but particularly in individuals with impaired metabolism of cytochrome P450 2D6 when using primaquine.
Patients who are not able to take primaquine or tafenoquine (e.g., due to G6PD deficiency or pregnancy) should be put on chloroquine prophylaxis (300 mg [base] orally once a week) for an extended period, often one year from the acute infection, as most relapses occur within this timeframe. If the patient has recurrent relapses or acquired P. vivax infection in an area with chloroquine-resistant P. vivax, consult with an expert in infectious disease or malaria, such as the CDC Malaria Hotline, to discuss alternative regimens.
Plasmodium malariae
Plasmodium malariae is difficult to distinguish from P. falciparum and may be indistinguishable from P. knowlesi on a blood smear. If P. malariae mono-infection is confirmed, ideally by PCR, then chloroquine (or hydroxychloroquine) can be used. In addition, any of the regimens listed above for the treatment of chloroquine-resistant P. falciparum may be used for the treatment of P. malariae infections. See Malaria Treatment Table 3 for adult and pediatric dosing recommendations. There is currently no evidence of widespread resistance in P. malariae parasites, though there have been case reports of treatment failures, especially when using a shorter-acting treatment regimen.
Plasmodium knowlesi
Plasmodium knowlesi is a simian malaria, which can also cause illness in humans and is endemic to areas of Southeast Asia. Due to the risk of progression to severe disease among patients with P. knowlesi, it is critical to promptly initiate therapy, and patients should be hospitalized to confirm clinical improvement and a reduction in parasitemia. Plasmodium knowlesi can be confused with P. falciparum or P. malariae on a blood smear. Species confirmation should be done with PCR. If P. knowlesi mono-infection is confirmed, ideally by PCR, then chloroquine (or hydroxychloroquine) can be used. In addition, any of the regimens listed above for the treatment of chloroquine-resistant P. falciparum may be used for the treatment of P. knowlesi infection. There is currently no evidence of widespread resistance in P. knowlesi parasites. See Malaria Treatment Table 3 for adult and pediatric dosing recommendations.
Monitoring treatment response
Patients diagnosed with P. falciparum or P. knowlesi infection, or when the species is unknown at the time of diagnosis, should be hospitalized initially due to the potential for rapid, severe disease progression to ensure medication is tolerated and that the patient is improving.7 Following the initiation of treatment, clinical and parasitological status should be monitored. In hospitalized patients, blood smears should be repeated daily to assess the parasitological response to treatment, i.e., decrease in parasitemia. Ideally, a negative blood smear should be documented before discharge. For patients who were never hospitalized or who are responding well to treatment (e.g., afebrile with declining parasitemia) and are discharged before achieving a negative blood smear, follow-up blood smear(s) should be obtained in an outpatient setting, ideally within one week of completing treatment.
Gametocytes, the sexual stage of the parasite, do not cause symptoms, are not targeted by many antimalarials, and should not be included in calculating parasitemia or in determining parasite clearance/ negativity.
All patients should be counseled to seek care immediately if they experience recurring fever or other concerning symptoms (e.g., signs and symptoms of hemolysis). Although less common than following IV artesunate, post-artesunate delayed hemolysis has been reported in patients receiving oral ACTs.A
Special populations
Treatment for pediatric patients
For pediatric patients, the preferred treatment options are generally the same as for adults, but the drug dose should be adjusted based on the patient's weight. The pediatric dose should never exceed the recommended adult dose.
Artemether-lumefantrine and atovaquone-proguanil should only be used in children ≥5 kg.
Pediatric dosing with quinine may be challenging due to the unavailability of non-capsule formulations. If using a quinine-based regimen for children less than eight years old, combine with clindamycin or doxycycline. Tetracycline is not recommended for children younger than eight years old.
Treatment for pregnant women
See treatment options for pregnant women to find additional considerations for treating patients who are pregnant. See Malaria Treatment Table 4 for specific drug and dosing recommendations.
- Use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.
- WHO Malaria Threats Map, World Health Organization
- Hwang J, Halsey ES, Plucinski MM, Barratt JLN, Gutman JR, Chang MA, Williams S, Mace KE, Lin JT, Rosenthal PJ, Parikh S, Ridpath AD. Extending the duration of artemether-lumefantrine treatment for uncomplicated Plasmodium falciparum malaria: updated US Centers for Disease Control and Prevention guidance based on review of surveillance, consultations, and published data. [Publication pending]
- WHO guidelines for malaria, 13 August 2025. Geneva: World Health Organization; 2025. https://doi.org/10.2471/ B09514. Licence: CC BY-NC-SA 3.0 IGO
- Schultz JS, Mace KE, Tan KR. Return to Travel in the Coronavirus Disease 2019 Pandemic Recovery Period and Implications for Imported Malaria: Reinforcing Prevention, Early Diagnosis, and Appropriate Treatment of Malaria. Clin Infect Dis. 2023 Apr 3;76(7):1161-1163. doi: 10.1093/cid/ciad061. PMID: 36723870; PMCID: PMC10450225
- Looareesuwan S, Vanijanonta S, Viravan C. et al. Randomised trial of mefloquine-tetracycline and quinine-tetracycline for acute uncomplicated falciparum malaria. Acta Trop. 1994;57:47-537942354
- Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg. 2006 Sep;75(3):402-15. PMID: 16968913.
- Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of Malaria in the United States: A Systematic Review. JAMA. 2007;297(20):2264–2277. doi:10.1001/jama.297.20.2264
- Pending treatment failure publication