title: Kinetics of Leptospira interrogans infection in hamsters after intradermal and subcutaneous challenge.
abstract: BACKGROUND
  Leptospirosis is a zoonosis caused by highly motile, helically shaped bacteria that penetrate the skin and mucous membranes through lesions or abrasions, and rapidly disseminate throughout the body. Although the intraperitoneal route of infection is widely used to experimentally inoculate hamsters, this challenge route does not represent a natural route of infection.
  
  
  RESULTS
  Here we describe the kinetics of disease and infection in hamster model of leptospirosis after subcutaneous and intradermal inoculation of Leptospira interrogans serovar Copenhageni, strain Fiocruz L1-130. Histopathologic changes in and around the kidney, including glomerular and tubular damage and interstitial inflammatory changes, began on day 5, and preceded deterioration in renal function as measured by serum creatinine. Weight loss, hemoconcentration, increased absolute neutrophil counts (ANC) in the blood and hepatic dysfunction were first noted on day 6. Vascular endothelial growth factor, a serum marker of sepsis severity, became elevated during the later stages of infection. The burden of infection, as measured by quantitative PCR, was highest in the kidney and peaked on day 5 after intradermal challenge and on day 6 after subcutaneous challenge. Compared to subcutaneous challenge, intradermal challenge resulted in a lower burden of infection in both the kidney and liver on day 6, lower ANC and less weight loss on day 7.
  
  
  CONCLUSIONS
  The intradermal and subcutaneous challenge routes result in significant differences in the kinetics of dissemination and disease after challenge with L. interrogans serovar Copenhageni strain Fiocruz L1-130 at an experimental dose of 2×106 leptospires. These results provide new information regarding infection kinetics in the hamster model of leptospirosis.
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Centro de Desenvolvimento Tecnologico, Universidade Federal de Pelotas, Pelotas, Brasil; Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
authors.forename: Mariana L
authors.initials: ML
authors.lastname: Coutinho
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Matsunaga
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Long-Chieh
authors.initials: LC
authors.lastname: Wang
authors.affiliation: CEIEPAA Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Tequisquiapan, Querétaro, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: de la Peña Moctezuma
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lewis
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.
authors.forename: Jane T
authors.initials: JT
authors.lastname: Babbitt
authors.affiliation: Centro de Desenvolvimento Tecnologico, Universidade Federal de Pelotas, Pelotas, Brasil.
authors.forename: Jose Antonio G
authors.initials: JA
authors.lastname: Aleixo
authors.affiliation: Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California, United States of America; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America; Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America; Departments of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Haake
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D007279:Injections, Subcutaneous; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D007921:Leptospira interrogans / Q000276:immunology / Q000472:pathogenicity*; D007922:Leptospirosis / Q000097:blood / Q000382:microbiology* / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial