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Diagnosis

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Overview | Clinical Diagnosis | Presumptive Treatment | Microscopic Diagnosis | Antigen Detection | Molecular Diagnosis | Serology | Drug Resistance Tests

Little girl with suspected malaria seen at the Moronacocha Health Center, in the outskirts of Iquitos, on the Peruvian Amazon. The clinical suspicion was confirmed when the blood smear (being taken here by a health worker) confirmed the presence of malaria parasites. (Image contributed by Dr. Jaime Chang, USAID/Peru.)

Overview

Malaria must be recognized promptly in order to treat the patient in time and to prevent further spread of infection in the community.

Malaria can be suspected based on the patient's symptoms and the physical findings at examination. However, for a definitive diagnosis to be made, laboratory tests must demonstrate the malaria parasites or their components.

Diagnosis of malaria can be difficult:

• Where malaria is not endemic any more (such as the United States), health care providers are not familiar with the disease. Clinicians seeing a malaria patient may forget to consider malaria among the potential diagnoses and not order the needed diagnostic tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope.
• In some areas, malaria transmission is so intense that a large proportion of the population is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infection. In that situation, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites.
• In many malaria-endemic countries, lack of resources is a major barrier to reliable and timely diagnosis. Health personnel are undertrained, underequipped and underpaid. They often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis and HIV/AIDS.

Clinical Diagnosis

Clinical diagnosis is based on the patient's symptoms and on physical findings at examination.

The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness).

In severe malaria (caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the suspicion index for malaria.

Thus, in most cases the early clinical findings in malaria are not typical and need to be confirmed by a laboratory test.

Microscopic Diagnosis

Blood smear stained with Giemsa, showing a white blood cell (on left side) and several red blood cells, two of which are infected with Plasmodium falciparum (on right side).

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. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian.

more: Diagnosis (Microscopy)

Alternate methods for laboratory diagnosis include:

Antigen Detection

Various test kits are available to detect antigens derived from malaria parasites. Such immunologic ("immunochromatographic") tests most often use a dipstick or cassette format, and provide results in 2-15 minutes. These "Rapid Diagnostic Tests" (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in some clinical settings and programs. However, before malaria RDTs can be widely adopted, several issues remain to be addressed, including improving their accuracy; lowering their cost; and ensuring their adequate performance under adverse field conditions. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs, at http://www.wpro.who.int/rdt/.

On June 13, 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.

more: Diagnosis (Rapid Diagnostic Test)

Molecular Diagnosis

Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).

Related Source: Molecular Diagnosis of Malaria and Babesiosis

Other techniques related to malaria diagnosis are:

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 experience.

more: Serology

Drug Resistance Tests

Drug resistance tests are 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 allow also the prediction, to some degree, of resistance to some drugs; however, the predictive values of these molecular tests are still being evaluated.

more: Drug Resistance