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MALARIA: Obstacles and Opportunities
equipment and training would be particularly valuable in field settings. In addition, the medical community's lack of experience in the use of microscopy to diagnose malaria in the United States (and other more developed countries) makes alternative tests potentially valuable for use in domestic hospitals. Research efforts to identify malaria parasite antigens and genes, which could provide the basis for such tests, have spurred the development of a number of new diagnostic methods, through the use of monoclonal antibodies and recombinant DNA techniques, which have been reviewed in detail elsewhere (Bruce-Chwatt, 1987; World Health Organization, 1988; Pammenter, 1988; Wirth et al., 1989; Tharavanij, 1990). These assays are designed to detect specific parasite antigens or nucleic acids with limits of detection equal to or better than that provided by microscopy.
The development of many initially promising assays often has languished because of the difficulty of reproducing the results of laboratory research in field trials. Development has also been slowed by the challenge of creating a simple assay and because improved diagnostic tests have not been a priority for public funding in malaria research.
Immunological techniques that detect malaria parasite antigens have been described since the early 1980s. These tests would be useful in health care facilities where microscopy is not performed, and they could supplement or replace microscopy in other settings. Antigen detection techniques would also be useful epidemiologic tools, providing data for community-based public health intervention measures.
Ideal target antigens for immunological assays should not persist in the blood (or in other specimens, such as urine that might be tested) after the parasite disappears, should be abundant in blood or other clinical specimens to maximize test sensitivity, and should be genus and species specific, without cross-reactivity with host antigens or antigens from other microorganisms (World Health Organization, 1988).
Experimental tests for detecting malaria parasite antigens are based on both antigen-competition and antigen-capture formats, using both enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) methods. Researchers have described the use of both monoclonal antibodies and polyclonal antisera in assays for genus-specific antigens, such as those that cross-react with Plasmodium berghei (Avidor et al., 1985), undefined P. falciparum antigens (Mackey et al., 1982; Avraham et al., 1983; Khusmith et al., 1987), and defined malarial antigens (Fortier et al., 1987), and in idiotype-anti-idiotype detection systems (Zhou and Li, 1987).
Studies of RIA- and ELISA-based tests have demonstrated detection of very low densities of parasitized red blood cells (in the range of 0.01 to