Clinical Information

Malaria is a mosquito-transmitted disease caused by apicomplexan parasites in the genus Plasmodium. It is an important cause of morbidity and mortality worldwide, with the World Health Organization (WHO) estimating 219 million cases and 435,000 malaria-related deaths in 2017. Malaria disproportionately affects individuals living in Africa (90% of cases), with individuals living in southeast Asia and the eastern Mediterranean regions next most affected. Malaria is also encountered outside of endemic regions, such as the United States, usually in returning travelers.

Malaria is caused primarily by 4 species of the protozoa Plasmodium: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale. A fifth Plasmodium species, Plasmodium knowlesi, is a simian parasite that may be an important source of human infection in some regions of Southeast Asia. Differentiating P falciparum and P knowlesi from other species is important since both can cause life-threatening infections. In addition, P falciparum is typically resistant to many commonly used antimalarial agents, such as chloroquine.

Microscopy of Giemsa-stained thick and thin blood films is the standard laboratory method for diagnosis and differentiation of malaria parasites. Under optimal conditions, the sensitivity of the thick film microscopy is estimated to be 10 to 30 parasites per microliter of blood. However, microscopic diagnosis requires considerable expertise and may be insensitive or nonspecific when inadequate training and facilities are available. Furthermore, prolonged exposure to EDTA, transportation conditions, and prior use of antimalarial drugs may alter parasite morphology and negatively impact the ability to perform species identification by microscopy. Finally, Babesia parasites have a similar appearance to P falciparum ring forms (early trophozoites) on peripheral blood films, resulting in potential diagnostic confusion.

Polymerase chain reaction (PCR) analysis is an alternative method of malaria diagnosis that allows for sensitive and specific detection of Plasmodium species DNA from peripheral blood. PCR may be more sensitive than conventional microscopy in very low parasitemias and is more specific for species identification. It may be particularly useful when subjective microscopy does not permit certain identification of the species present. Malaria PCR can be used in conjunction with a traditional blood film or Babesia PCR when the clinical or morphologic differential includes both babesiosis and malaria. Examination of the thin film also allows for calculation of percent parasitemia, which can be used to predict prognosis and monitor response to treatment. This test does not include blood smear examination or calculation of parasitemia.