Optimizing Strongyloides Testing in an At-Risk US Population - PROJECT SUMMARY Strongyloidiasis, caused by infection with the parasitic nematode Strongyloides stercoralis, remains an important public health problem in tropical and sub-tropical regions, with an estimated 30-100 million infected persons globally. Because S. stercoralis infection is acquired from contact with contaminated soil, those most at risk include the socioeconomically disadvantaged, those with agricultural occupations, and those living in areas with poor sewage control practices. S. stercoralis larval migration during chronic infection is limited to the gastrointestinal tract and lungs and causes few if any symptoms. However, larvae can disseminate and cause severe disease in immunosuppressed individuals. The importance of identifying S. stercoralis infection before immunosuppressive treatments are started has been highlighted by increased use of corticosteroids during the COVID-19 pandemic and related increases in disseminated strongyloidiasis diagnoses. Because disseminated strongyloidiasis is often diagnosed late, after larvae have caused significant and irreversible end-organ damage, the mortality rate of disseminated strongyloidiasis is near 90%. Regional studies and case reports indicate that strongyloidiasis is commonly diagnosed in tropical and sub- tropical regions of the US. We have found 4-10% seropositivity in a Houston solid organ transplant cohort and, more recently, even higher seropositivity (16.5%) in a central Texas community. Other small studies of US immigrants from low- and middle-income countries have indicated infection rates as high as 46.1%. Screening for strongyloidiasis is suboptimal due to poor knowledge of the disease among US healthcare providers and imperfect performance of available diagnostic tests. The clinical gold standard of strongyloidiasis diagnosis is microscopic evaluation of multiple stool specimens for S. stercoralis larva. Unfortunately, it is challenging for patients to submit even one stool specimen in a timely manner, and US clinical laboratory technicians may not have enough training and expertise to reliably identify larvae. Several serologic tests have been developed, but commercially available tests have imperfect test performance and are less sensitive in immunocompromised individuals who may not be able to mount a reliable humoral immune response. Newer serologic and molecular tests based on recombinant antigens have been developed but are not yet commercially available. We propose a prospective study of adult HHS patients undergoing a panel of parasitologic, serologic, and molecular Strongyloides assays, with the following specific aims: (1) to identify a high-performing strongyloidiasis screening strategy for at-risk individuals living in the US and (2) to evaluate each assay as a test-of-cure for strongyloidiasis. Improvement in Strongyloides testing would improve screening and management practices, thereby allowing for timely treatment and reduction of strongyloidiasis related morbidity.
