Rapid Diagnostic Testing for Malaria — It's Finally Here!

Special Report

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Source: CDC. Notice to readers: malaria rapid diagnostic test. MMWR 2007;56(27):686.

Synopsis: The BinaxNOW® Malaria test, a 15 minute immunochromatographic test with a high sensitivity for the diagnosis of malaria due to Plasmodium falciparaum has been approved for use in the FDA.

The diagnosis and treatment of severe forms of malaria is an emergent matter. However, the microscopic diagnosis of malaria requires skill and experience and the availability of capable personnel at all hours of the day and night is becoming increasingly problematic in U.S. hospitals. A number of effective rapid diagnostic tests (RDT) not requiring the skill of the microscopist have been available in many places of the world, but not in the U.S., for several years. As a result, despite the need for immediate examination of thick and thin blood smears, in some facilities the smears are saved until a qualified individual is available to examine them, or they are sent to outside laboratories. This approach, as well as misdiagnosis, may lead to fatal delays in initiation of therapy for severe malaria due to Plasmodium falciparum.

However, on June 13, 2007, the FDA approved the first malaria RDT authorized for use by laboratories in the U.S., the BinaxNOW® Malaria test (Inverness Medical Professional Diagnostics, Scarborough, Maine). This immunochromatographic test uses whole blood and takes approximately 15 minutes to complete. It targets 2 antigens, one specific to P. falciparum (histidine-rich protein 2 or HRP2) and one found in all 4 human plasmodial parasites (an aldolase).1 Thus, while it specifically identifies P. falciparum, it cannot distinguish among the other species. It is recommended that laboratories using BinaxNOW should have available to them blood containing P. falciparum to serve as a positive control.

Because of their infrequency in trials evaluating the test, available data are inadequate to confidently assess the ability of BinaxNOW to detect cases of infection with either Plasmodium ovale or Plasmodium malariae. Furthermore, it is unable to detect the presence of a second malarial species in patients with mixed infection that include P. falciparum. Finally, it may miss cases of infection with low-level parasitemia. For these reasons, microscopy should be performed in conjunction with the RDT. In cases of a positive RDT test, microscopy allows for confirmation of infection, speciation of non-falciparum parasites, and detection of mixed infection, as well as determination of parasite density. Microscopy may also be considered in patients with a negative test but with a high pre-test probability of infection. This may be especially useful if infection with P. ovale or P. malariae are suspected. Finally, serial microscopy must be used to determine changes in the degree of parasitemia in response to therapy.

The sensitivity and specificity of the test in the diagnosis of P. falciparum infection in Thailand in a cohort with a prevalence of malaria by microscopy was 13% were 100% and 96.2%, respectively.2 The sensitivity for diagnosis of P. vivax infection was 87.3% and the specificity for non-falciparum infections was 100%. In a study in returned travelers in an area not endemic for malaria, the sensitivity and specificity relative to microscopic diagnosis were 98.8% and 98.4%, respectively.3 In another study in returned travelers in which it was compared to diagnosis by PCR, the BinaxNOW test had a sensitivity of 94%-96% in the diagnosis of P. falciparum infection and 84% for non-falciparum infections.4 The overall specificity was 99%. False negatives have been associated with low levels of parasitemia and false positives may occur in the presence of rheumatoid factor.

References:

  1. Moody A. Rapid diagnostic tests for malaria parasites. Clin Microbiol Rev 2002;66-78.
  2. Wongsrichanalai C, et al. Rapid diagnostic devices for malaria: field evaluation of a new prototype immunochromatographic assay for the detection of Plasmodium falciparum and non-falciparum Plasmodium. Am J Trop Med Hyg 2003; 69:26-30.
  3. De Monbrison F, et al. Comparative diagnostic performance of two commercial rapid tests for malaria in a non-endemic area. Eur J Clin Microbiol Infect Dis 2004; 23:784-786.
  4. Farcas GA, et al. Evaluation of the Binax NOW ICT test versus polymerase chain reaction and microscopy for the detection of malaria in returned travelers. Am J Trop Med Hyg 2003; 69:589-592.