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Background: The standard diagnosis of Ascaris lumbricoides and other soil-transmitted helminth (STH) infections relies on the detection of worm eggs by copromicroscopy. However, this method is dependent on worm patency and shows only limited accuracy in low-intensity infection settings. We aimed to decipher the diagnostic accuracy of different antibodies using various Ascaris antigens in reference to copromicroscopy and quantitative PCR (qPCR), four months after national STH preventative chemotherapy among school children in western Kenya. Methodology: STH infection status of 390 school children was evaluated via copromicroscopy (Kato-Katz and mini-FLOTAC) and qPCR. In parallel, Ascaris-specific antibody profiles against larval and adult worm lysates, and adult worm excretory-secretory (ES) products were determined by enzyme-linked immunosorbent assay. Antibody cross-reactivity was evaluated using the closely related zoonotic roundworm species Toxocara cati and Toxocara canis. The diagnostic accuracy of each antibody was evaluated using receiver operating curve analysis and the correspondent area under the curve (AUC). Principal findings: Ascaris was the predominant helminth infection with an overall prevalence of 14.9% (58/390). The sensitivity of mini-FLOTAC and Kato-Katz for Ascaris diagnosis reached only 53.5% and 63.8%, respectively compared to qPCR. Although being more sensitive, qPCR values correlated with microscopic egg counts (R = -0.71, P<0.001), in contrast to antibody levels. Strikingly, IgG antibodies recognizing the ES products of adult Ascaris worms reliably diagnosed active Ascaris infection as determined by qPCR and microscopy, with IgG1 displaying the highest accuracy (AUC = 0.83, 95% CI: 0.75–0.91). Conclusion: IgG1 antibody responses against adult Ascaris-ES products hold a promising potential for complementing the standard fecal and molecular techniques employed for monitoring Ascaris infections. This is of particular importance in the context of deworming programs as the antibody diagnostic accuracy was independent of egg counts. Author summary: Ascaris lumbricoides is the most common human intestinal helminth globally, affecting a quarter of the world's population. Microscopic methods are used to diagnose and monitor Ascaris infections. However, these methods are unsatisfactory for diagnosing low-intensity infections, are prone to human error, their accuracy is greatly affected by the heterogeneous distribution of worm eggs and are limited to detecting only patent infections. qPCR offers an attractive alternative with regard to sensitivity and high-throughput capacity but is also limited by worm patency. Here, we compared the diagnostic accuracy of different antibodies using Ascaris antigen lysates as well as Ascaris excretory/secretory (ES) products using copromicroscopy and qPCR as reference. Our data show that IgG1 antibody responses directed against ES antigens of adult Ascaris worms, but not against the infective third-stage larval or adult worm extracts, reliably decipher between Ascaris-infected and Ascaris-negative participants independent of the microscopic egg counts. Our study is the first to report strong IgG1 responses directed against ES products of adult worms and their potential value as markers for an active Ascaris infection. Our results indicate the potential to develop an antibody-based Ascaris-immunoassay utilizing Ascaris-ES antigens to complement the monitoring of reinfections and transmission dynamics. [ABSTRACT FROM AUTHOR]