Immunomodulatory treatment with thalidomide in experimental leptospirosis in Golden Syrian hamsters (Mesocricetus auratus)

• Published in: Transactions of the Royal Society of Tropical Medicine and Hygiene 2014-02, Vol.108 (2), p.105-111
• Main Authors: Soares, Luciane Marieta, Macedo, Julio Oliveira, de Azevedo, Everton Cruz, Santos, Cleiton Silva, Sampaio, Marina de Queiroz, Santos, Andréia Carvalho dos, Reis, Mitermayer Galvão dos, Athanazio, Daniel Abensur
• Format: Article
• Language: English
• Subjects: Ampicillin - therapeutic use; Animals; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial diseases; Biological and medical sciences; Cricetinae; Disease Models, Animal; Drug Therapy, Combination; Female; General aspects; Human bacterial diseases; Immunosuppressive Agents - therapeutic use; Infectious diseases; Kaplan-Meier Estimate; Leptospirosis - drug therapy; Leptospirosis - immunology; Medical sciences; Mesocricetus; Miscellaneous; Pharmacology. Drug treatments; Thalidomide - therapeutic use
• ISSN: 0035-9203; 1878-3503
• DOI: 10.1093/trstmh/trt112

Background The benefit of antibiotics in leptospirosis is limited when treatment is started four days after symptoms appear, and new adjuvant therapeutic options are urgently needed. Methods Hamsters (Mesocricetus auratus) were infected by Leptospira interrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results Experiment 1: all hamsters from the groups AMP and AMP-TAL survived (n=8), while all hamsters from groups NONE (n=6) and TAL (n=8) died. The AMP and the AMP-TAL groups showed no renal or liver pathology and absent or very low leptospiral burden in target organs. Experiment 2: lethal outcome was observed in 6/6 hamsters in the NONE group, 8/8 in the TAL group, and 6/8 in both the AMP and AMP-TAL groups. Thalidomide showed no survival benefit when compared to hamsters treated with ampicillin alone. The TAL, AMP and AMP-TAL groups had very low tissue leptospiral counts. Conclusion Thalidomide had minimal impact on survival in the late treatment of leptospirosis hamster model.