Evaluation and Diagnosis of Malaria

Clinical resources

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.

Evaluation

Patients suspected of having malaria should be urgently evaluated in a facility that is able to provide immediate diagnosis and treatment. Laboratory test results are needed to determine appropriate patient disposition.

Malaria is a common cause of febrile illness in areas where it is transmitted.1 Consider malaria in the differential diagnosis of any patient who has been in a malaria-endemic area within the past 12 months, regardless of malaria prophylaxis history. Of malaria cases reported to CDC during 2018, 99% of patients with P. falciparum and almost 60% with P. vivax had illness onset within ≤ 90 days of their return to the United States.2 Ninety-four percent of patients with P. vivax had an illness onset within a year. In rare cases, malaria can present more than one year after travel. The diagnosis of malaria should also be considered in any person with fever of unknown origin regardless of travel history as malaria can be transmitted rarely through other mechanisms such as contaminated blood or tissue products, congenital transmission, or local mosquito-borne transmission.

Symptoms of malaria are generally non-specific and commonly consist of:

• Fever/chills
• Headache
• Malaise
• Weakness
• Gastrointestinal distress (abdominal pain, nausea, vomiting, diarrhea)
• Neurologic complaints (dizziness, confusion, disorientation, seizure, coma)
• Body aches and/or
• Cough

Untreated, malaria can progress rapidly to severe complications including kidney failure, pulmonary edema, severe anemia, coma, and death.

Diagnosis

An initial diagnostic test for malaria must be available immediately (i.e., results available within a few hours) and should not be sent out to laboratories that take days or weeks to return results.34 If your facility does not have immediate, onsite malaria testing available, strongly consider transferring the patient for urgent evaluation of malaria.

The diagnosis of malaria requires laboratory testing. Initial laboratory diagnosis of malaria can be made through microscopic examination of thick and thin blood smears. Preliminary review of blood smears concerning for intracellular parasites in a patient with clinical suspicion of malaria is sufficient to initiate treatment. In addition, a malaria antigen-based rapid diagnostic tests (RDTs) or a nucleic acid amplification test (NAAT) (e.g., multiplex PCR platforms should be performed concurrently if faster results are available to enable prompt treatment. Microscopic evaluation of a blood smear must be performed on blood specimens from all individuals with suspected malaria to confirm infection, determine species (if not already available), calculate parasitemia, and monitor response to treatment.

Thick and thin blood smears

Thick blood smears are more sensitive in detecting malaria parasites because the procedure examines a greater volume of blood; however, thick blood smears are more difficult to read. Thin blood smears aid in parasite species identification and quantification.

A negative blood smear read by a qualified microscopist makes the diagnosis of malaria unlikely, and alternative diagnoses should be considered. However, because very low parasite densities may be initially below the limit of detection, blood smears should be repeated every 12–24 hours for a total of three sets before the diagnosis of malaria can be ruled out.5

Once malaria parasites are detected on a blood smear, the parasitemia should be estimated to inform treatment decisions. Note that RBCs which have more than a single parasite are still counted as one infected cell. Gametocytes—the sexual stage of the parasite—are not responsible for clinical symptoms, should not be counted when determining parasitemia, and can be present despite successful treatment. Find more information on microscopic examination of thin and thick blood smears and quantifying parasites.

Rapid diagnostic tests

Several malaria antigen-based detection tests (rapid diagnostic tests, or RDTs) that use a "dipstick" or cassette format are available globally. The FDA has approved one test, BinaxNOW™, for diagnostic use in the United States.A

RDTs can more rapidly determine that a patient has malaria, allowing for immediate treatment initiation. Note the BinaxNOW™ is less sensitive than microscopy, particularly for non-falciparum species. Also, P. falciparum parasites from some areas have histidine rich protein (HRP) 2 and/or 3 deletions which can provide false negative results. Additionally, RDTs may remain positive even weeks after effective treatment.

A negative RDT does not rule out malaria, and RDTs cannot confirm the species of the malaria parasite, determine parasitemia, or monitor responses to treatment and parasite clearance. Therefore, microscopy should always be ordered concurrently to confirm both positive and negative RDT results, determine species, and calculate parasitemia.

Other testing options

Parasite nucleic acid detection from nucleic acid amplification tests (NAATs) such as polymerase chain reaction (PCR) is more sensitive and specific than microscopy and is a useful tool for confirmation of species and detection of mixed infections, but results are often not available quickly enough to guide case management. Some multi-pathogen molecular assays can have more rapid turnaround times than standard PCR methods but may not distinguish all Plasmodium species.

If a patient's specimen has a positive NAAT result, immediate treatment should be initiated. However, a blood smear should still be conducted concurrently to calculate parasitemia, determine species (if not already available), and monitor the response to treatment. A negative validated molecular test makes the diagnosis of malaria unlikely, and sequential blood smears to rule out malaria are generally not necessary. Use of standard PCR testing is encouraged to confirm the species of malaria parasite and detect mixed infections because this may impact anti-relapse treatment considerations. Note PCR tests may remain positive even weeks after effective treatment.

Serologic tests are not recommended for the diagnosis of acute malaria because they may remain positive for months to years after an initial infection.

Disease classification

Patients diagnosed with malaria are categorized as having either uncomplicated or severe malaria. Uncomplicated malaria can quickly progress to severe malaria, especially if treatment is delayed. Severe malaria can rapidly lead to death.

Manifestations of severe malaria include any one of the following:

• Impaired consciousness/ coma

• Prostration

• Seizures

• Severe anemia (hemoglobin <7 g/dL)

• Acute kidney injury/ decreased urine output

• Pulmonary edema or acute respiratory distress syndrome

• Circulatory collapse/ shock

• Acidosis

• Jaundice

• Abnormal bleeding/ disseminated intravascular coagulation

• Hypoglycemia

• Parasite density of ≥5%