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Treatment of Malaria: Guidelines For Clinicians (United States)


We encourage clinicians to report all cases of laboratory-confirmed malaria to help CDC’s surveillance efforts. Refer to our information on the Malaria Case Surveillance Report Form (

Evaluation and Diagnosis

Because malaria cases are seen relatively rarely in North America, misdiagnosis by clinicians and laboratorians has been a commonly documented problem in published reports. However, malaria may be a common illness in areas where it is transmitted and therefore the diagnosis of malaria should routinely be considered for any febrile person who has traveled to an area with known malaria transmission in the past several months preceding symptom onset.

Symptoms of malaria are generally non-specific and most commonly consist of fever, malaise, weakness, gastrointestinal complaints (nausea, vomiting, diarrhea), neurologic complaints (dizziness, confusion, disorientation, coma), headache, back pain, myalgia, chills, and/or cough. The diagnosis of malaria should also be considered in any person with fever of unknown origin regardless of travel history.

Patients suspected of having malaria infection should be urgently evaluated. 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, or severe disease, in the setting of no availability of prompt laboratory confirmation, usually by microscopy).

Laboratory diagnosis of malaria can be made through microscopic examination of thick and thin blood smears. Thick blood smears are more sensitive in detecting malaria parasites because the blood is more concentrated allowing for a greater volume of blood to be examined; however, thick smears are more difficult to read. Thin smears aid in parasite species identification and quantification. Blood films need to be read immediately; off-hours, qualified personnel who can perform this function should be on-call. A negative blood smear makes the diagnosis of malaria unlikely. However, because non-immune individuals may be symptomatic at very low parasite densities that initially may be undetectable by blood smear, blood smears should be repeated every 12-24 hours for a total of 3 sets. If all 3 are negative, the diagnosis of malaria has been essentially ruled out.

After malaria parasites are detected on a blood smear, the parasite density should then be estimated. The parasite density can be estimated by looking at a monolayer of red blood cells (RBCs) on the thin smear using the oil immersion objective at 100x. The slide should be examined where the RBCs are more or less touching (approximately 400 RBCs per field). The parasite density can then be estimated from the percentage of infected RBCs, after counting 500 to 2000 RBCs.

In addition to microscopy, other laboratory diagnostic tests are available. Several antigen detection tests (rapid diagnostic tests or RDTs) using a “dipstick” or cassette format exist, but only one is approved for general diagnostic use in the United States. RDTs can more rapidly determine that the patient is infected with malaria, but they cannot confirm the species or the parasitemia. Therefore, microscopy should also be done as soon as possible to confirm RDT results, species, and determine parasitemia. Laboratories that do not provide in-house on-the-spot microscopy services should maintain a stock of malaria RDTs so that they will be able to perform malaria diagnostic testing when urgently needed.

Parasite nucleic acid detection using polymerase chain reaction (PCR) is more sensitive and specific than microscopy but can be performed only in reference laboratories and so results are not often available quickly enough for routine diagnosis. However, PCR is a very useful tool for confirmation of species and detecting of drug resistance mutations. CDC offers malaria drug resistance testing for all malaria diagnosed in the United States free of charge. Serologic tests, also performed in reference laboratories, is not practical for routine diagnosis of acute malaria. Your state health department or the CDC can be contacted for more information on utilizing one of these tests.