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World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworms and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings. Author summary: The prevalence of moderate-to-heavy intensity (M&HI) infections is a key indicator for measuring the success of large-scale deworming programs for intestinal worms because they account for the majority of the worm attributable morbidity. Currently, intestinal worm infections are classified as M&HI when the number of worm eggs that are microscopically detected in stool using a standard diagnostic method exceeds a threshold set by the World Health Organization. Over the years, a variety of new promising diagnostic methods have been introduced for the diagnosis of intestinal worms. Although they have some important advantages over the current standard method, it is not clear whether they can reliably classify M&HI infections. This is because their test results either systematically indicate lower egg counts or are expressed in a unit other than eggs per gram of stool (e.g, concentration of worm DNA), warranting the need for method-specific thresholds. We defined method-specific thresholds and verified whether they increased the correct classification of M&HI infections. Overall, our results indicate that method-specific thresholds improved the classification of M&HI infections, but that further validation is required before they can be recommended for evaluating the occurrence M&HI infections in large-scale deworming programs. [ABSTRACT FROM AUTHOR]