False Positivity of Rapid Antigen Detection Tests for Diagnosis of Plasmodium falciparum Malaria: Issue Appears To Be More Complicated than Presented

We read with interest the letter by Mishra and colleagues (3) suggesting that cross-reactions with rheumatoid factor (RF) that lead to false-positive results with P. falciparum rapid antigen detection tests are a problem confined to the ParaSight-F test (Becton Dickinson, Cockeysville, Md.) only. However, it appears to us that the issue is more complicated than hypothesized by Mishra et al., because their data were derived from a sample size which might have been too small.

As previously described in detail, in a series of 91 RF-positive, malaria-negative specimens, Grobusch et al. (1) found an overall false-positivity rate of 19.8% (18 of 91 specimens) with three different test systems based on the detection of two different plasmodial antigens. Whereas both ParaSight-F and ICT Malaria P.f. (ICT Diagnostics, Sydney, Australia) detect plasmodial histidine-rich protein 2 (HRP-2), OptiMAL (Flow Inc., Portland, Oreg.) detects parasite-specific lactate dehydrogenase (4). Although the problem appears to be most pronounced with the ParaSight-F test (15 of 91 specimens [16.5%]), we found false positives with the ICT Malaria P.f. (6 of 91 specimens [6.6%]) and the OptiMAL (3 of 91 specimens [3.3%]) tests as well.

Mishra et al. explain their findings by arguing that RF is incapable of binding to immunoglobulin M (IgM)-type capture monoclonal antibody, which is used in the ICT test. We are skeptical about this conclusion on the grounds that RF has previously been described to interfere with various test systems by inducing false-positive reactions for specific IgM antibodies in some parasitic and other infectious diseases (2). Based on our findings we assume that, although to varying extents, all currently available rapid immunochromatographic malaria tests may lead to false-positive results due to cross-reaction with RF.