Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Abstract

The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference (“gold”) standard. The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests). According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2–96.9), followed by IVD-ELISA (92.3%, 87.7–96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9–100), followed by IVD-ELISA (97.4%, 95.5–99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity. NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials. The diagnosis of Strongyloides stercoralis infection is usually made by finding larvae of the parasite in the feces. The larval output is orders of magnitude lower than, say, the egg output of Ancylostoma duodenale, therefore the sensitivity of conventional techniques is poor. Sensitivity is enhanced by specific techniques, but the infection can still be missed. Several serologic methods (Strongyloides antibody detection in blood) are considered more sensitive, but they have been assessed so far with fecal tests as the gold standard, which is obviously unsatisfactory considering, precisely, their suboptimal sensitivity. Using a bank of sera from patients surely infected, not infected or doubtful, we assessed the accuracy of five different serologic tests also using a composite reference standard, obtained by combining the results of different tests. The recently developed NIE-LIPS resulted virtually 100% specific, with sensitivity >80%. Two commercially available ELISA tests were also highly specific above a given cut-off. Cross reactions with other parasitic infections were rarer than in previous studies. In conclusion, serologic tests are accurate tools, both for diagnostic purposes and for prevalence studies. Whether or not they can also be reliable markers of cure is currently under study.