Strongyloides stercoralis in the non-endemic setting and beyond : an epidemiological, clinical, diagnostic and treatment challenge

Strongyloides stercoralis is a soil-transmitted helminth which can cause a fatal syndrome in immunosuppressed individuals. The infection is mostly present in disadvantaged areas of the world, but can also be diagnosed in industrialized countries. Main objective of this work was to address critical aspects of strongyloidiasis in the non-endemic setting. Specific objectives: to estimate the prevalence of strongyloidiasis at global level and in a non-endemic area; to review the clinical presentation and laboratory profile; to assess the accuracy of diagnostic tests for the diagnosis and post-treatment follow up; to assess the efficacy of different doses of ivermectin for the treatment of chronic strongyloidiasis. The thesis is composed by a collection of published papers, ranging from narrative and systematic reviews, case-control studies, original diagnostic studies and a randomized controlled trial. The first chapter is a narrative review, describing the main characteristics of strongyloidiasis in the non-endemic setting. It reports the state-of-the-art and the grey areas on this topic, and serves as an introduction to the whole work. The second chapter deals with epidemiology. Global prevalence of strongyloidiasis was estimated using a mathematical model, and resulted in 613.9 (95% CI: 313.1–910.1) million people infected. A screening survey of 2701 individuals living in Northern Italy found that eosinophilia was associated with a higher risk of S. stercoralis infection, both in Italians and in migrants. The third chapter is composed by a systematic review with meta-analysis, which demonstrated that about 50% people with chronic infection complain symptoms, and about 77% have eosinophilia at presentation. Both symptoms and eosinophilia tend to clear after treatment. The collection of papers composing the fourth chapter address the diagnostic area. In a narrative review I comment the advantages and disadvantages of the available diagnostic tests for strongyloidiasis, pointing out that the use of highly sensitive diagnostic tests is of primary importance. In a systematic review with meta-analysis I demonstrate that the sensitivity of real-time PCR for S. stercoralis is unsatisfactory (64.4, 95% CI 46.2±77.7). Finally, in an original diagnostic study, I demonstrate that serology can be used for post-treatment monitoring, although time to seroconversion can take up to 12 months. The last chapter is composed by a multicenter randomized controlled trial comparing a single dose versus multiple doses of 200 µg/kg of ivermectin for the treatment of chronic uncomplicated strongyloidiasis. The study showed that a single dose is as effective as multiple doses and better tolerated.