Diagnostic performance of Strongyloides-specific IgG4 detection in urine for diagnosis of human strongyloidiasis

Abstract

Background: Detection of parasite-specific IgG in urine is a sensitive method for diagnosis of strongyloidiasis and gives similar accuracy to serum IgG. However, there are no data concerning detection of IgG subclass in urine. To further explore the utility of diagnosis from urine samples, we evaluated the diagnostic performance of IgG4 in urine compared with parasitological and other immunological methods.

Methods: The urine and sera included proven strongyloidiasis (group 1, n = 93), other parasitic infections (group 2, n = 40) and parasite negatives (group 3, n = 93). The performance of Strongyloides-specific IgG4 in urine for diagnosis of strongyloidiasis using fecal examinations as the reference standard was assessed.

Results: With fecal examination as a gold standard, Strongyloides-specific IgG4 in urine had 91.4% sensitivity and 93.2% specificity while serum IgG4 had 93.6% sensitivity and 91.0% specificity. IgG4 in both urine and serum had almost perfect diagnostic agreements with fecal examination (Cohen's kappa coefficient was > 0.8). Cross-reactivity to Opisthorchis viverrini and Taenia spp. of IgG4 in urine were 7.5% and 12.5% in serum. Concurrent analyses of total IgG in urine and serum showed that the sensitivities (97.9-100%) and specificities (88.7-91.0%) were similar (P > 0.05). The sensitivity for parasitological examination by the formalin-ethyl acetate concentration technique (FECT) was 49.5% and that for agar plate culture technique (APC) it was 92.6%.

Conclusion: Our findings showed that specific IgG4 detection in urine yielded similar diagnostic performance to the same biomarkers in serum. This suggests that accurate diagnosis of strongyloidiasis can be performed using urine samples and IgG4 is a valid choice of diagnostic marker. Further assessment is required to assess the utility of urine IgG4 for measuring the response treatment in strongyloidiasis.

Keywords: Enzyme-linked immunosorbent assay (ELISA); Immunoglobulin G4; Strongyloides stercoralis.

Fig. 1

Flow diagram of the study approach showed the number of participants divided into three groups: Group 1, proven strongyloidiasis with Strongyloides stercoralis larvae in feces; Group 2, other parasite infections; Group 3 parasite negatives

Fig. 2

Measurements of IgG4 in urine (A) and IgG4 in serum (B) in individuals with parasitologically confirmed strongyloidiasis only (n = 60) and those with mixed infections of Strongyloides stercoralis stercoralis and other parasitic infections (n = 33). There was no significant difference in antibody levels between these groups for IgG4 in both serum and urine. The dotted line indicates the cutoff value of each diagnostic method

Fig. 3

Levels of Strongyloides-specific antibodies in samples from individuals infected with Strongyloides stercoralis and other parasites. The levels of urine IgG4 (A), serum IgG4 (B), urine IgG (C) and serum IgG (D) in individuals infected with Ss S. stercoralis, Ov Opisthorchis viverrini, Ech Echinostoma spp., T Taenia spp., MIF minute intestinal flukes, Hw hookworm. The dotted line indicates the cutoff value of each diagnostic method

Fig. 4

Correlations between levels of IgG4 in urine and serum (A), IgG in urine and serum (B), between IgG and IgG4 in urine (C) and between IgG and IgG4 in serum (D). Coefficients of correlation were determined using the Spearman correlation test (rs). Data shown are observed values, and the solid line was calculated from the regression equation (Y = ax + b, Y = log IgG/IgG4, a = slope, x = log IgG/IgG4, b = Y-intercept). Dotted lines (vertical and horizontal) represent the cutoff values