Screening for Leishmania spp. infection in patients treated with biologic agents for immune-mediated inflammatory diseases: results of an Italian multicentric prospective study

Background: Escalation in the use of biologic agents including tumor necrosis factor (TNF)-α inhibitors to treat immune-mediated inflammatory diseases (IMID) is linked to higher susceptibility of severe infections caused by intracellular pathogens, including Leishmania. Methods: This multicentric prospective study assessed the presence of Leishmania spp. infection among patients with IMID under treatment with biologic agents in two Italian clinical centers. We utilized a combination of diagnostic tests: real-time PCR for the detection of parasitic kinetoplast DNA in peripheral blood, Western blot for the identification of serum IgG antibodies, and a Whole blood assay to assess cytokine and chemokine responses following stimulation with parasitic antigen. Results: A total of 126 patients residing in Italy were enrolled. Patients testing positive in at least one assay were classified as Leishmania-positive. Of the 125 asymptomatic individuals, 25 (20%) tested positive for Leishmania infection, revealing a significant rate of subclinical infection. The most frequent marker of infection was positive serology (15/126, 12%) followed by a detectable cell-mediated immune response (9/125, 7%). Parasitic DNA was detected in 3 patients (2%). Conclusions: This study showed a high prevalence of asymptomatic Leishmania infection in Italian patients with IMID under treatment with biologic agents, with a north-to-south gradient. Given the risk of disease reactivation, these patients may benefit from close monitoring. Further research is warranted to clarify the clinical implications of these findings.