Malaria laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

The diagnosis of malaria is confirmed by the identification of the malaria parasite in the patient's blood under microscopy. Laboratory tests may also reveal anemia with decreased hemoglobin, hematocrit, and haptoglobin in addition to either a decreased or increased leukocyte count. Biochemistry may reveal hypoglycemia, elevated LDH, acidosis, and mild hyponatremia due to vomiting and diarrhea. In severe disease, elevated creatinine, proteinuria, and hemoglobinuria may be present secondary to renal failure. Other malaria-specific tests include: the antigen detection test, PCR, and serology test for the presence of antibodies against the plasmodium. Drug resistance tests should also be performed to assess the susceptibility of the microorganism to the antimalarial drugs.

Laboratory Findings

Microscopic Diagnosis

• This technique remains the gold standard for laboratory confirmation of malaria. Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. This is possible because each of the four major parasite species has distinguishing characteristics.

• Prior to examination, the specimen is stained (most often with the Giemsa stain) to give the parasites a distinctive appearance.

• Two types of blood films are traditionally used:

• Thin films - similar to usual blood films and allow species identification since the parasite's appearance is best preserved in this preparation.
• Thick films - allow the microscopist to screen a larger volume of blood, and are about eleven times more sensitive than the thin film, so picking up low levels of infection is easier on the thick film, but the appearance of the parasite is much more distorted and therefore distinguishing between the different species can be much more difficult.

This test has the limitation of depending on the quality of the reagents, of the microscope, and on the experience of the laboratories.

Antigen Detection

• Considered a "Rapid Diagnostic Tests" (RDTs), this test offers a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available.

• Detects the antigens derived from malaria parasites. It most often uses a dipstick or cassette format, and provides results in 2-15 minutes.

• Although they may be used in some settings, before malaria RDTs can be widely adopted, several issues remain to be addressed, including:

• Improving their accuracy
• Lowering their cost
• Ensuring their adequate performance under adverse field conditions

• In 2007, the U.S. Food and Drug Administration (FDA) approved the first RDT for use in the United States. This RDT is approved for use by hospital and commercial laboratories, not by individual clinicians or by patients themselves. It is recommended that all RDTs are followed-up with microscopy to confirm the results and if positive, to quantify the proportion of red blood cells that are infected. The use of this RDT may decrease the amount of time that it takes to determine that a patient is infected with malaria.

Molecular Diagnosis

PCR

• Parasite nucleic acids are detected using polymerase chain reaction (PCR).
• Although this technique may be slightly more sensitive than smear microscopy, it is of limited utility for the diagnosis of acutely ill patients in the standard healthcare setting.
• PCR results are often not available quickly enough to be of value in establishing the diagnosis of malaria infection.
• PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT.
• Levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls.

Serology

• Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA).
• Serology does not detect current infection but rather measures past exposure.

Drug Resistance Tests

• Drug resistance tests must be performed in specialized laboratories to assess the susceptibility to antimalarial compounds of parasites collected from a specific patient.
• Two main laboratory methods are available:

• In vitro tests - The parasites are grown in culture in the presence of increasing concentrations of drugs; the drug concentration that inhibits parasite growth is used as endpoint.
• Molecular characterization - Molecular markers assessed by PCR or gene sequencing also allow the prediction, to some degree, of resistance to some drugs. CDC recommends that all cases of malaria diagnosed in the United States should be evaluated for evidence of drug resistance.

Other Laboratory Tests

Shown below is a table summarizing nonspecific laboratory abnormalities associated with malaria.

Laboratory findings

Test	Findings
Complete blood count	Decreased hemoglobin Decreased hematocrit Microcytosis Decreased haptoglobin
White blood cell count	Elevated or Decreased Leukocyte Count
Biochemistry	Hypoglycemia Elevated creatinine Elevated LDH Possible hyponatremia Acidosis: High lactate; Low bicarbonate
Coagulation	Thrombocytopenia
Urinalysis	Proteinuria Hemoglobinuria

Gallery

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  Magnified 1000x, this Giemsa-stained photomicrograph revealed some of the ultrastructural morphology exhibited by an immature Plasmodium vivax schizont Adapted from Public Health Image Library (PHIL), Centers for Disease Control and Prevention.