Background: The diagnosis of acute rheumatic fever (ARF) relies on evidence of prior group A streptococcal infection, with antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) titers serving as key markers in the revised Jones Criteria. This study aimed to identify optimal ASO and ADB cut-off values among children living in RHD endemic settings to distinguish healthy children from those with ARF.
Methods: Participants were recruited from Brazil, Malawi, Pakistan, and Timor-Leste, including those with ARF, rheumatic heart disease (RHD), other infections or inflammatory diseases, and healthy controls. Antibody titers were compared across groups using the Kruskal-Wallis test. Receiver operating characteristic (ROC) analysis was performed to determine cut-off values, sensitivity, specificity, and area under the curve (AUC).
Results: A total of 523 participants were analyzed: 133 with ARF, 123 with RHD, 115 with other infections or inflammatory diseases, and 152 healthy controls. ASO and ADB titers were significantly elevated in the ARF group (median ASO = 480 ng/ml, ADB = 540 ng/ml). An ASO cut-off value of 283 ng/ml demonstrated excellent diagnostic performance, with an AUC of 0.94, sensitivity of 0.95, and specificity of 0.82. ADB titers were also diagnostic but less robust, with a cut-off value of 403 ng/ml yielding an AUC of 0.84, sensitivity of 0.88, and specificity of 0.68.
Conclusion: The cutoffs identified here performed well across multiple diverse global populations. This study provides critical baseline data to enhance ARF diagnostic accuracy and refine diagnostic thresholds globally.