Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Background: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.Methods: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).Results: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.Conclusions: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.Fil: Bisoffi, Zeno. Sacro Cuore Hospital; ItaliaFil: Buonfrate, Dora. Sacro Cuore Hospital; ItaliaFil: Sequi, Marco. Istituto Di Ricerche Farmacologiche Mario Negri; ItaliaFil: Mejia, Rojelio. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albonico, Marco. Sacro Cuore Hospital; ItaliaFil: Gobbo, Maria. Sacro Cuore Hospital; ItaliaFil: Bonafini, Stefania. Sacro Cuore Hospital; ItaliaFil: Angheben, Andrea. Sacro Cuore Hospital; ItaliaFil: Requena-Mendez, Ana. Universidad de Barcelona; EspañaFil: Muñoz, José. Universidad de Barcelona; EspañaFil: Nutman, Thomas B.. National Institute Of Allergy And Infectious Diseases; Estados Unido

Diagnostic accuracy of five serologic tests for Strongyloides stercoralis infection.

Background: 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. Methods: 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). Results: 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. Conclusions: 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

ROC curve for NIE-LIPS (composite reference standard).

<p>ROC curve for NIE-LIPS (composite reference standard).</p

ROC curve for Bordier ELISA (composite reference standard).

<p>ROC curve for Bordier ELISA (composite reference standard).</p

ROC curve for NIE-ELISA (composite reference standard).

<p>ROC curve for NIE-ELISA (composite reference standard).</p

Test accuracy on the whole study population.

<p>Test accuracy on the whole study population.</p

Cross reactions with other parasites (Group III b: 62 subjects).

<p>NB Total number of samples differs from <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002640#pntd-0002640-g001" target="_blank">Figure 1</a> (Group III b = 67), as 5 subjects were found positive in at least 3 serologic tests for <i>Strongyloides</i> and then classified as cases according to the composite reference standard.</p

Test accuracy on samples from subjects with certain diagnosis (denominator for sensitivity: 114 subjects with Ss larvae in stool; denominator for specificity: 115 subjects with no Ss larvae in stool and no exposure).

<p>Test accuracy on samples from subjects with certain diagnosis (denominator for sensitivity: 114 subjects with Ss larvae in stool; denominator for specificity: 115 subjects with no Ss larvae in stool and no exposure).</p