Ann Lab Med.  2024 Mar;44(2):155-163. 10.3343/alm.2023.0212.

Head-to-Head Comparison of Nine Assays for the Detection of Anti-Echinococcus Antibodies: A Retrospective Evaluation

Affiliations
  • 1Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Medizinische Fakultät, LMU München, Munich, Germany
  • 2Division of Infectious Diseases and Tropical Medicine, University Hospital Ludwig-Maximilian University Munich, Munich, Germany
  • 3German Centre for Infection Research (DZIF), Munich, Germany
  • 4Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology, Infection and Pandemic Research, Munich, Germany
  • 5Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria

Abstract

Background
Echinococcosis is a neglected tropical disease that is severely underdiagnosed in resource-limited settings. In developed countries, diagnosing echinococcosis is challenging, and reliable serological assays are urgently needed. In the Central European Alps, EM is more common than EG; however, data on the diagnostic performance of assays for EM cases are scarce. We evaluated the suitability of nine antibody assays for routine diagnostics.
Methods
Nine commercially available serological assays for detecting anti-Echinococcus antibodies were compared head-to-head using samples collected from 50 patients with echinococcosis and 50 age- and sex-matched control subjects. The assays are Anti-Echinococcus ELISA (IgG) (Euroimmun), Echinococcus IgG ELISA (DRG), Echinococcus IgG ELISA (IBL International), Echinococcus Western Blot IgG (LDBIO Diagnostics), EUROLINE WB (Euroimmun), Hydatidosis ELISA IgG (VirCell), Hydatidosis VIRCLIA IgG Monotest (VirCell), Ridascreen Echinococcus IgG (R-Biopharm), and Virapid Hydatidosis (VirCell). The cases were ranked according to the WHO-Informal Working Group on Echinococcosis (WHO-IWGE) criteria as confirmed, probable, or possible.
Results
The performance of the assays varied greatly, with overall sensitivities ranging between 50% and 88% and specificities between 62% and 100%. We observed a trend toward better performance with cases classified as “confirmed” using the WHO-IWGE criteria. Combined analysis with sequential screening and confirmatory testing resulted in a maximum sensitivity of 84% and specificity of 100%. Differentiation between EG and EM infections is clinically relevant but was found to be unreliable.
Conclusions
Echinococcus serological assays are highly variable in terms of sensitivity and specificity. Knowledge of the pre-test probability in the patient cohort is required to choose a suitable assay. A combined approach with screening and confirmatory assays may be the best diagnostic strategy in many situations.

Keyword

Alveolar echinococcosis; Antibodies; Comparative study; Cystic echinococcosis; Echinococcosis; Echinococcus granulosus; Echinococcus multilocularis; Hydatidosis; Serology

Figure

  • Fig. 1 Venn diagrams depicting the agreement of different assay systems. (A) Agreement of all measurements for control samples that yielded positive or borderline results. Assays that did not yield false non-negative results are not represented. Intersections without numerals represent instances with zero concordant results. (B) Agreement of positive results between three anti-Echinococcus IgG assays produced by the same manufacturer (VirCell).

  • Fig. 2 Correlation of measured results obtained with the chemiluminescence immunoassay (CLIA) from VirCell and the indicated ELISAs. The gray bars represent regions containing borderline results. The triangle represents a result above the measurement range of the ELISA rBio.

  • Fig. 3 Results obtained for the case and control groups along with ROC curves for each quantitative assay. (A) The gray bars represent regions containing borderline results. The triangle represents a result above the measurement range of the ELISA rBio. (B) Sensitivity is plotted on the Y-axis and 1–specificity is plotted on the X-axis. The gray tick marks on the ROC curve represent the upper and lower cut-offs recommended by the respective manufacturer. Squares mark the cut-offs with the highest Youden’s indices. Abbreviation: AUC, area under the curve.


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