Strongyloidiasis hyperinfection syndrome treatment with ivermectin: in-vitro and in-vivo studies

Abstract

Background Strongyloides stercoralis is an intestinal nematode that usually causes asymptomatic infection in immunocompetent individuals and reverts to life-threatening hyperinfection in immunocompromised individuals. Objective The aim of the study was to evaluate the effect of ivermectin (IVM) treatment on S. stercoralis larvae in-vitro cultured forms. In-vivo evaluation was performed by assessment of parasitological, histopathological, and ultrastructural changes in the lungs of mice with Strongyloides hyperinfection syndrome before and after treatment with IVM. Materials and methods S. stercoralis larvae were collected from agar plates cultures of positive stool samples from different areas in Menuofyia Governorate. The in-vitro study involved the examination of S. stercoralis larvae grown in agar plates (APC) after exposure for 2 h to IVM (15 μl/ml) by scanning electron microscope (SEM) and after 24 h for larval motility. In-vivo study involved 96 mice that were divided into four groups (24 mice in each). Group GI was immunosuppressed by dexamethasone and infected with S. stercoralis larvae; GII was immunosuppressed then infected and treated by IVM (0.5 mg/kg); GIII was infected with S. stercoralis larvae; and GIV was infected and treated by IVM. Fecal larval output was carried out on 1 st , 6 th , 11 th , and 13 th days postinfection (dpi); histopathological examination of the lung was conducted on 2 nd , 7 th , 12 th , and 14 th dpi; and lung ultrastructure study by transmission electron microscopy (TEM) was performed on 7 th and 14 th dpi. Results IVM caused severe destruction of S. stercoralis larvae detected by SEM after 2 h and resulted in their death after 24 h. In-vivo results recorded significant decrease in fecal larval output in the treated groups (GII and GIV) and in GIII in comparison with GI. The latter showed significant continuous increase in fecal larval output throughout the period of study. Histopathological and ultrastructural results showed marked pathological changes in GI that were still evident until the last day of the study. IVM induced mild improvement in lung tissues in GII in comparison with GIV. The latter showed obvious improvement with great preservation of lung tissue. In GIII, mild pathological effect of infection was still evident by the end of study. Conclusion Dexamethasone-immunosuppressed mice infected by S. stercoralis showed intestinal and pulmonary hyperinfection. IVM showed significant improvement of all parameters studied mainly in the immune group and was very effective on motility of S. stercoralis larvae in vitro.