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. 2025 Aug 7;14(7):piaf054.
doi: 10.1093/jpids/piaf054.

Streptococcal Serology Reference Intervals in an Australian Pediatric Cohort

Shu Ki Tsoi  1   2 , Sharon Choo  3 , Lai-Yang Lee  4 , Paul Monagle  5   6   7 , Stephen Hearps  8   9 , Vasiliki Karlaftis  5   6 , Chantal Attard  5   6 , Janet Burgess  10 , Chuong Tran  11 , Sheree Bazeley  12 , Natalie Challen  12 , Andrew C Steer  1   2   5 , Joshua Osowicki  1   2   5 ; HAPPI Kids Study Team
Collaborators, Affiliations

Streptococcal Serology Reference Intervals in an Australian Pediatric Cohort

Shu Ki Tsoi et al. J Pediatric Infect Dis Soc. .

Abstract

Background: Diagnostic criteria for acute rheumatic fever and post-streptococcal glomerulonephritis, the 2 major autoimmune complications of Streptococcus pyogenes infection, include serological evidence of preceding infection. The S. pyogenes proteins, namely streptolysin O and deoxyribonuclease B, are the most widely used targets for clinical streptococcal serology. We aimed to establish age-based reference intervals (RIs) for healthy children in Victoria, Australia, to guide interpretation of anti-streptolysin O (ASO) levels measured by turbidimetry and nephelometry, and anti-deoxyribonuclease B (ADB) levels by nephelometry.

Methods: Serum samples were collected from healthy pediatric cohorts aged 32-week gestation to <18 years at 4 hospitals in Melbourne, Australia, between February 2015 and October 2018. Anti-streptolysin O levels were measured in 2 cohorts: by turbidimetry in cohort 1 and by nephelometry in cohort 2. Anti-deoxyribonuclease B levels were measured by nephelometry in cohort 2. Reference intervals (RIs) for each age group were generated, including 80% upper limit of normal (ULN) cut-offs.

Results: Anti-streptolysin O levels were measured by turbidimetry for 359 samples from cohort 1, and ASO and ADB levels were measured by nephelometry for 360 samples from cohort 2. Anti-streptolysin O levels, measured by turbidimetry, were highest in children 5-9 years of age (80% ULN 346 IU/mL) in cohort 1. For cohort 2, there was a linear age-related increase in ASO levels measured by nephelometry (80% ULN 426 IU/mL in those 15 to <18 years old) and ADB levels were highest in children aged 10-14 years (80% ULN 454 IU/mL).

Conclusions: We established age-specific RI for ASO and ADB levels measured by turbidimetry and nephelometry for healthy Australian children. This study highlights the importance of local method-specific age-based RI to interpret ASO and ADB levels when clinicians suspect acute rheumatic fever or post-streptococcal glomerulonephritis in children.

Keywords: Streptococcus pyogenes; antibodies; child; deoxyribonuclease B; streptolysin O.

Plain language summary

This study established age-specific reference intervals for anti-streptolysin O and anti-DNAse B levels measured by turbidimetry and nephelometry for healthy Australian children. The values are higher than in adults, adding to global data regarding pediatric streptococcal serology values.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Reference Intervals by Age: (A) ASO Level Measured by Turbidimetry (Cohort 1); (B) ASO Level Measured by Nephelometry (Cohort 2); (C) ADB Level Measured by Nephelometry (Cohort 2). Solid Line = 80th Centile; Dotted Lines = 2.5 and 97.5 Centiles; Dashed Line = Median
Figure 2
Figure 2
Bland–Altman Plot of ASO Levels for Cohort 1 Measured by Both Turbidimetry and Nephelometry. Scatter Plot Showing the Mean of ASO Levels Measured by the 2 Methods (X-Axis) and Differences Between ASO Levels Measured by the 2 Methods (Y-Axis). A Mean Difference of −26.4 IU/mL Was Identified (Horizontal Middle Red Dashed Line) With ± 1.96 SD (−100.6 IU/mL, 47.7 IU/mL) Shown in Black Outer Horizontal Dashed Lines
See this image and copyright information in PMC

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