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Soil-transmitted helminths (STHs) are a group of parasites that are globally distributed and are the most prevalent neglected disease (NTD) in Latin America and the Caribbean (LAC); their presence is associated with health and development problems. In Argentina, their distribution is heterogenous, and there are highly endemic areas in the north of the country. The World Health Organization (WHO) recommends the mass deworming of children as a first-line strategy for the prevention and control of STHs and recently also encourage the development of more sensitive diagnostic tests. The aim of this study was to determine the prevalence of STHs in Tartagal (Salta, Argentina) after four years of deworming interruption with albendazole and ivermectin. A total of 437 fecal samples were analyzed using standard coprological techniques, a subset of which were selected to molecularly typify protozoan parasites; 257 blood samples were analyzed for the presence of specific antibodies to the STH Strongyloides stercoralis. The most prevalent protozoan species were G. intestinalis (19.6–49.2%) and B. hominis (19.1–38.5%). Molecular characterization allowed us to evidence possible zoonotic or human-to-human transmission pathways for Giardia intestinalis or Blastocystis spp., while serology for S. stercoralis proved to be a useful screening tool for monitoring this parasite after treatment. In general, a decrease in the prevalence of STHs was observed in the area, from 60% to 2.9–20% for hookworms and from 51% to 1–9.3% for S. stercoralis four years after treatment, demonstrating the effectiveness and duration of anthelmintic treatment with these two drugs. [ABSTRACT FROM AUTHOR]