Detection of Parasite Antigens

Rapid diagnostic tests for malaria have been developed that employ immunochromatographic methods based on the detection of malarial antigens present in peripheral blood.  Most tests use monoclonal antibodies and detect particular malarial antigens in blood specimens.  Tests have been developed that detect the histidine-rich protein II (HRP-II), parasite lactate dehydrogenase (pLDH), or both HRP-II and LDH.  These tests generate results within 15 minutes and do not require skilled microscopists.

Commercially available kits for HRP-II detect P. falciparum HRP-II only and therefore diagnose only P. falciparum malaria.  The HRP-II antigen is synthesized and released by trophozoite and immature gametocyte stages and persists in peripheral blood.  Therefore, HRP-II tests can remain positive for up to 2 weeks following chemotherapy and parasite clearance, as confirmed by microscopy.  These tests have low sensitivities for detecting infections with low level parasitemias (<100 parasites/µl) and mature gametocytes.  In contrast, trained microscopists can diagnose infections with parasitemias as low as 5-10 parasites/µl.  The reported specificities of these tests are high (>90%).  Early tests reported false positives due to cross-reactions with rheumatoid factor, but these issues have reportedly been addressed and corrected.

Parasite lactate dehydrogenase (pLDH) is produced by asexual and sexual stages (gametocytes) of malaria parasites.  Test kits that are currently available detect pLDH from all four species of Plasmodium.  They can distinguish P. falciparum from the non-falciparum species, but cannot distinguish between P. malariae, P. ovale, and P. vivax.  Tests that detect pLDH do not generate persistent positive results following chemotherapy, like the HRP-II test.

Although these assays have advantages over microscopic examination of Giemsa stained blood smears, because of their limited usefulness in detecting low-level parasitemias (< 100 parasites/µl) their use is not indicated for diagnosing infection in most clinical presentations of malaria in the US.  These tests are not FDA approved for diagnosis of malaria in the United States and are available only for research studies from vendors outside the United States.

For more information on rapid diagnostic tests for malaria, visit the WHO site.

^a Cellabs, P O Box 421, Brookvale, NSW 2100, Australia
Flow, Inc., 6127 SW Corbett, Portland, OR 97201
MAKROmed Manufacturing, LTD, P O Box 28928, Kensington 2101, South Africa
Orchid, 4390 US Route One North, Princeton, NJ 08540
Omega Diagnostics, LTD, Omega Hense, Carsebridge Court, Whins Road, Alloa, FK10 3LQ, Scotland, United Kingdom
Binax, Inc., 217 Read Street, Portland, ME 04103

^bEIA = enzyme immunoassay; Rapid = rapid immunochromatographic test