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A diagnosis of malaria should be supported by the identification of the parasites on a thin or thick blood smear. The only rare exception is P falciparum infection, in which all the parasites during the life cycle can be sequestered out of the peripheral blood in late-stage forms. If no alternative diagnosis is found in an at-risk patient with possible cerebral malaria (ie, unrevealing lumbar puncture findings), initiate therapy for presumptive malaria and continue to obtain additional blood smears to confirm the diagnosis. This is not an occult infection.

•Alternative diagnostic methods
◦Alternative diagnostic methods typically are used if the laboratory does not have sufficient expertise in detecting parasites in blood smears.
◦The quantitative buffy coat (QBC) is a technique that is as sensitive as thick smears. Because results cannot be used to speciate Plasmodium, a thin smear must be examined.
◦Monoclonal antibody to histidine-rich protein-2 (ParaSight-F, immunochromatographic test [ICT]) appears to be very sensitive and specific.
◦A rapid dipstick test that detects LDH of the parasite (eg, OptiMal) can also be used to distinguish P falciparum from the other species. This is particularly useful if laboratory expertise in differentiating the species is lacking. Similar to blood smears, these rapid tests may provide false-negative results in patients with very low parasitemia and should be repeated if results are initially negative and the diagnosis remains unknown.
◦In addition to the rapid diagnostic test listed above (eg, QBC, OptiMal), new molecular techniques such as polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) are also available for diagnosis. They are more sensitive than thick smears but are expensive and unavailable in most developing countries.3