Assays based on Bm14, WbSXP, or BmR1 demonstrate adequate sensitivity for field use. The Bm14 assay appeared to function as a 'pan-filaria' assay, demonstrating antibody reactivity in the sera from patients with W. bancrofti, B. malayi, L. loa and O. volvulus. Although this cross reactivity makes the Bm14 assays useful for monitoring either bancroftian or brugian filariasis, cross reactivity with O. volvulus and L. loa may limit its utility in some areas of sub-Saharan Africa. The BmR1 assays were sensitive for B. malayi infection but relatively insensitive for W. bancrofti infection. They showed excellent specificity for Brugia and Wuchereria, with little reactivity with sera from persons infected with other parasites, including L. loa and O. volvulus. These results suggest that it may be useful to study the W. bancrofti homologue of BmR1 to determine if it is as specific for W. bancrofti as BmR1 is for Brugia. Unfortunately, recent work suggests that this is not the case .
For mapping the distribution of lymphatic filariasis, rapid antibody tests may provide acceptable sensitivity, depending on the geographic area where the mapping is to be done, but the potential for problems with specificity (both in distinguishing past exposure from present infection as well as differentiating filarial from non-filarial infection) still remains. For mapping W. bancrofti, there is minimal value in using antibody tests instead of the antigen tests that are currently used, but because there is no antigen test for Brugia, antibody tests might be an alternative for mapping the distribution of these infections. In Brugia-endemic areas, it will be important to demonstrate, however, the relationship between prevalence rates for microfilaremia and antibodies to validate the assay as a useful tool for programmatic decisions. At this point, it is not clear what antibody prevalence should be considered an indication to initiate mass treatment; no attempt was made in this study to distinguish between antibody responses associated with active infection and those triggered by exposure [24, 25].
Antibody assays almost certainly will find other uses in the context of lymphatic filariasis (LF) elimination programs. For example, antifilarial antibody tests may be sensitive markers of transmission intensity or provide evidence of ongoing exposure to filarial infection long before the development of antigenemia or microfilaremia. Primates develop antibody responses to Bm14 within 4–8 weeks following B. malayi infection . In a longitudinal study in Egypt, microfilaria-negative persons who were positive for Bm14 antibody at baseline were more likely to be microfilaria-positive after one year than were Bm14-negative persons . Less is known about the kinetics of antibody responses to BmR1. Since antibody responses provide an early indicator of infection, assays for antifilarial antibodies should be useful for surveillance following initiation of LF elimination programs.
As LF programs reach their planned end point (5 or more years of > 80% drug coverage in targeted populations), it will be necessary to determine whether or not transmission has been interrupted and whether mass drug administration can be stopped. Parasitologic testing, whether for microfilaremia or antigenemia, will require testing of thousands of persons to demonstrate that infection levels are below 0.1%, the level established by the Global Program as the end point for defining the elimination of LF. Since antibody responses develop in the absence of demonstrable infection, detecting incident antibody responses should provide a more sensitive measure of transmission than microfilaria or antigen detection. Children born following the cessation of transmission should be antibody-negative, while older children and adults may have evidence of residual antibody reactivity [8, 9, 27]. A testing strategy based on screening of children could be exploited for ongoing surveillance in the aftermath of LF programs and may not require screening of as many children as called for by current testing guidelines. The absence of antibody in appropriately chosen populations would strongly suggest that transmission has been interrupted. Additional studies are needed to test the value of antibody testing as a tool for certifying the elimination of filariasis transmission.
Operational use of antibody assays requires far more practical experience with the assays than we now have. Of greatest concern is the specificity of the tests employed. For example, ELISA tests often use a statistical approach to establish cutoff values for positive results. A test that is 99% specific will predictably have some false positive results if large numbers of samples are tested. Further work will be needed to establish rates of antibody positivity that exceed the number that are likely to occur by chance. In addition, it will be necessary to develop and validate algorithms for confirming the presence of infection or ongoing transmission in situations where low antibody prevalence rates are detected. Despite these caveats, we believe that antibody tests based on antigens like Bm14, BmR1, and Wb-SXP will prove to be useful tools that can be used to facilitate decision making by program managers in the context of filariasis elimination programs.