Evaluation and Diagnosis

Evaluation and Diagnosis

Malaria is a common cause of febrile illness in areas where it is transmitted; therefore, the diagnosis and management of malaria should routinely be considered for any febrile person who has traveled to an area with malaria in the weeks to months preceding symptom onset. The CDC's Algorithm for Diagnosis and Management of Malaria provides guidance on the recommended steps to adequately assess and treat malaria patients.

Symptoms of malaria are generally non-specific and most commonly consist of fever, headache, malaise, weakness, gastrointestinal distress (nausea, vomiting, diarrhea), neurologic complaints (dizziness, confusion, disorientation, coma), 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 should be urgently evaluated.

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, they are more difficult to read. Thin smears aid in parasite species identification and quantification. Blood smears need to be done and read as soon as possible, within 24 hours of patient presentation; qualified personnel who can perform these tasks should always 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 which may be initially undetectable, blood smears should be repeated every 12–24 hours for a total of three sets before the diagnosis of malaria can be ruled out.

Once malaria parasites are detected on a blood smear, the parasite density should then be estimated. This can be done 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 2,000 RBCs. Gametocytes, the sexual stage of the parasite, are not responsible for clinical symptoms and should not be counted when determining parasite density. More information on diagnostic procedures for malaria can be found on CDC's DPDx website.

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, BinaxNOW™, is approved for diagnostic use in the United States. RDTs can more rapidly determine that the patient has malaria, but they are less sensitive than microscopy and cannot confirm each specific species of the malaria parasite or the parasite density. Therefore, microscopy should also be done as soon as possible to confirm RDT results and determine both species and parasite density. Laboratories that do not provide in-house, on-the-spot microscopy services should maintain a stock of malaria RDTs so they will be able to perform malaria diagnostic testing urgently when needed.

Parasite nucleic acid detection using polymerase chain reaction (PCR) is more sensitive and specific than microscopy but results are often not available quickly enough for routine diagnosis. PCR is a very useful tool for confirmation of species and detection of mutations associated with drug resistance. CDC offers malaria drug-resistance testing for all malaria cases diagnosed in the United States free of charge. Serologic tests are not recommended for diagnosis of acute malaria as they can remain positive for years after infection. Your state health department or CDC can be contacted for more information on utilizing one of these tests.