Rethinking soil-transmitted helminth diagnostics in the genomic era: Does genetic variation matter?

Soil-transmitted helminths (STHs) are intestinal parasitic worms that present a significant global health challenge. Traditionally, the diagnosis of STH infections has relied on microscopy; however, molecular tests such as quantitative PCR (qPCR) are now widely adopted for their greater sensitivity, increasingly reduced cost and higher throughput. Recent evidence highlights genetic diversity in both coding and non-coding DNA regions of STHs routinely targeted by molecular diagnostics. Most qPCR assays have been developed using a limited selection of parasite isolates, thus likely overlooking the substantial genetic variation present within and among STH populations worldwide. Such genetic diversity can significantly impact the diagnostic targets of molecular tests, potentially reducing their sensitivity and leading to false-negative results. Therefore, there is growing recognition of the need to develop diagnostic tools that account for this genetic variation. In this Chapter, we outline current advances in STH genomics and review recent work on the assessment of genetic diversity directly from fecal samples, especially as access to adult worms becomes increasingly difficult. These studies emphasize the importance of thoroughly evaluating current and future diagnostic methods prior to their implementation to effectively guide control measures and policy decisions regarding the cessation of STH deworming. Together, these findings lay the groundwork for genomic epidemiology and the sustainable control of STHs as a public health issue.