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Although malaria is no longer endemic within the United States, this infection can be life threatening, and laboratory requests for blood smear examination and organism identification should be treated as "STAT" requests. Malaria is usually associated with patients having a history of travel within an area where malaria is endemic, although other routes of infection are well documented.
Endemic vs Non-endemic Area Patients. It is important to recognize that patients from endemic vs non-endemic areas may present with different symptoms. Patients from endemic areas may have had multiple exposures to the parasite, and they tend to have residual antibody present. They may present with typical symptoms (periodic fevers). These patients generally carry a heavier parasite load before becoming symptomatic; thus, the diagnosis may be easier to obtain. Patients from a non-endemic area (immunologically naïve) generally have no previous parasite exposure, have no residual antibody, have a very low parasitemia, and tend to present with very non-specific symptoms. With a low parasite load, diagnosis may be much more difficult. These cases are often missed using hematology automated instruments.
Frequently, for different reasons, organism recovery and subsequent identification may be more difficult than the textbooks imply. It is very important that this fact be recognized, particularly when one is dealing with a possibly fatal infection with P. falciparum or P. knowlesi.
When requests for malarial smears are received in the laboratory, some patient history information should be made available to the laboratorian. This information should include the following:
1. Where has the patient been and what was the date of return to the United States? ("Where do you live?") Airport malaria has been documented from transported infected mosquitos released from within the plane.
2. Has malaria ever been diagnosed in the patient before? If so, what species was identified?
3. What medication (prophylaxis or otherwise) has the patient received, and how often? When was the last dose taken?
4. Has the patient ever received a blood transfusion? Is there a possibility of other needle transmission (drug user)?
5. When was the blood specimen drawn, and was the patient symptomatic at the time? Is there any evidence of a fever periodicity?
Answers to such questions may help eliminate the possibility of infection with P. falciparum or P. knowlesi, those species that are considered the most pathogenic.
Although P. vivax was formerly considered less pathogenic, current information reflects more serious sequelae than previously recognized.
Often the diagnosis of malaria is considered, and a single blood specimen is submitted to the laboratory for examination; however, single films or specimens cannot be relied upon to exclude the diagnosis, especially when partial prophylactic medication or therapy is used. Partial use of antimalarial agents may be responsible for reducing the numbers of organisms within the peripheral blood, thus leading to a blood smear that contains few organisms, which then reflects a low parasitemia when in fact serious disease is present. Patients with a relapse case or an early primary case may also have few organisms in the blood smear.
Although several anticoagulants have been used, EDTA is recommended by most parasitologists for use with malaria parasites. Extended delay before preparing films from blood in anticoagulants can result in atypical morphology and presentation of parasites. If this method is used, for reliable staining of malaria parasites (including retaining normal parasite morphology and characteristic features like Schüffner’s stippling), blood films should be made immediately or within 1 h of collection. If the blood has been standing in the anticoagulant. for more than an hour, parasite morphology may change and appear atypical. This can include exflagellation of Plasmodium gametocytes.
It is recommended that both thick and thin blood films be prepared upon admission of the patient, and at least 200 to 300 oil immersion fields should be examined on the thin film before a negative report is issued. Since one set of negative films will not rule out malaria, additional blood specimens should be examined over a 36-h time frame. Although Giemsa stain is recommended for all parasitic blood work, the organisms can also be seen with use of other blood stains such as Wright's stain. Blood collected with use of EDTA anticoagulant is recommended; however, if the blood remains in the tube for any length of time, true stippling may not be visible within the infected RBCs (P. vivax, as an example). Also, when using anticoagulants, it is important to remember that the proper ratio between blood and anticoagulant is necessary for good organism morphology. Heparin can also be used, but EDTA is preferred. Finger-stick blood is recommended, particularly when the volume of blood required is minimal (no other hematologic procedures have been ordered). The blood should be free-flowing when taken for smear preparation and should not be contaminated with alcohol used to clean the finger prior to the stick. However, many laboratories no longer routinely perform finger sticks; EDTA blood is used.
Accuracy of species diagnosis is essential for good patient management, since identification to the species level may determine which drug or combination of drugs will be indicated. Some patients with P. falciparum infections may not yet have the crescent shaped gametocytes in the blood. Low parasitemias with the delicate ring forms may be missed; consequently, oil immersion examination at x 1,000 is mandatory. The prevalence of Plasmodium gametocytes in asymptomatic individuals has generated increased interest regarding malaria elimination. The proportion of infections carrying gametocytes and gametocyte density should be reported; the identification and treatment of gametocyte reservoirs is an essential component of malaria elimination strategies.
Malaria is one of the few parasitic infections considered to be immediately life threatening, and a patient with the diagnosis of P. falciparum or P. knowlesi malaria should be considered a medical emergency because the disease can be rapidly fatal. Any laboratory providing the expertise to identify malarial parasites should do so on a 24-h basis, 7 days/week.
Patients with malaria may appear for diagnostic blood work when least expected. Laboratory personnel should be aware of the "STAT" nature of such requests and the importance of obtaining some specific patient history information. The typical textbook presentation of the blood smears may not be seen by the technologist. It becomes very important that the smears be examined at length and under oil immersion. The most important thing to remember is that even though a low parasitemia may be present on the blood smears, the patient may still be faced with a serious, life-threatening disease.
Plasmodium vivax (benign tertian malaria)
Plasmodium malariae (quartan malaria)
Plasmodium ovale
Plasmodium knowlesi (simian malaria)(Early stages mimic P. falciparum; later stages mimic P. malariae)
Early stages mimic P. falciparum; later stages mimic P. malariae