Anthelmintic and Antibiotic Therapy Resolves Intestinal Inflammatory Infiltration in Experimental Trichuriasis.

Abstract

Despite significant advances in human health, soil-transmitted helminths (STH) continue to pose a major public health challenge, particularly in impoverished regions. Albendazole has been used to treat STH for over 40 years and remains widely utilized in mass drug administration programs. However, it is estimated that over 1.5 billion people are still infected globally, with Brazil reporting a prevalence of 5.41% for human trichuriasis. The nematode Trichuris muris is widely used in murine models to study trichuriasis due to its impact on the epithelial mucosa, including tissue damage, dysbiosis, bacterial translocation, inflammatory infiltrate, and intestinal layer hypertrophy. These effects contribute to the more severe consequence of high parasite load infections, such as rectal prolapse. Currently, research on the interaction between intestinal helminths and bacteria remains limited, despite its potential contribution to pathological synergy. Drug resistance in conventional STH treatments is a growing concern, highlighting the need for new therapeutic approaches. This study aimed to evaluate the impact of combining the anthelmintic albendazole with the antibiotics piperacillin sodium plus tazobactam on the inflammatory process during chronic experimental trichuriasis. Swiss Webster mice were infected with 150 embryonated T. muris eggs. After 35 days, the mice were divided into four groups: Group 1 (antibiotic treatment), Group 2 (anthelmintic treatment), Group 3 (combined treatment), and Group 4 (control, no treatment). After treatments, the mice were euthanized, and different analyses were conducted. Results showed that untreated mice had a significantly higher number of peritoneal macrophages compared to those that received treatment. Antibiotic-treated mice did not show invading bacteria in the epithelial submucosa, unlike untreated infected mice. The groups that received anthelmintic treatment exhibited a higher number of dead worms compared to the antibiotic-only group. Additionally, the combination of anthelmintic and antibiotic treatments demonstrated more effective control of nematode colonization and bacterial translocation, potentially reducing the secondary impacts of the infection, such as bacterial translocation and the associated inflammatory processes. These findings suggest that our results could pave the way for the development of new treatment protocols for STH, integrating both anthelmintic and antibiotic therapies.