Characterization of virulence of Leptospira isolates in a hamster model

Abstract

Effort has been made to identify protective antigens in order to develop a recombinant vaccine against leptospirosis. Several attempts failed to conclusively demonstrate efficacy of vaccine candidates due to the lack of an appropriate model of lethal leptospirosis. The purposes of our study were: (i) to test the virulence of leptospiral isolates from Brazil, which are representative of important serogroups that cause disease in humans and animals; and (ii) to standardize the lethal dose 50% (LD 50 ) for each of the virulent strains using a hamster (Mesocricetus auratus) model. Five of seven Brazilian isolates induced lethality in a hamster model, with inocula lower than 200 leptospires. Histopathological examination of infected animals showed typical lesions found in both natural and experimental leptospirosis. Results described here demonstrated the potential use of Brazilian isolates as highly virulent strains in challenge experiments using hamster as an appropriate animal model for leptospirosis. Furthermore these strains may be useful in heterologous challenge studies which aim to evaluate cross-protective responses induced by subunit vaccine candidates.

Attenuated Nephritis in Inducible Nitric Oxide Synthase Knockout C57BL/6 Mice and Pulmonary Hemorrhage in CB17 SCID and Recombination Activating Gene 1 Knockout C57BL/6 Mice Infected with Leptospira interrogans

“…In addition, immunodeficiency resulted in high loads of leptospires in the target organs, as seen upon necropsy, in accordance with a previous report on C3H/SCID mice (14). We observed the typical target organ pathology associated with leptospirosis, including acute tubular damage and detrabeculation of hepatocytes, similar to the pathology described in humans and in other models of lethal leptospirosis, such as hamsters (16).…”

“…Among the diverse animal models used in leptospirosis research, guinea pigs and hamsters are the most suitable laboratory rodents for reproducing acute lethal infection (12,16,17). Rats are resistant to acute disease and are more suited to studies focusing on mechanisms of persistent infection (3,13).…”

Experimental Hamster Infection with a Strain of Leptospira borgpetersenii Ballum Isolated from a Reservoir Mouse in New Caledonia

“…[18][19][20][21][22] Interestingly, hamsters infected with virulent strains of leptospires and developing rapid acute lethal infection presented with severe damage of tubular epithelia with cell swelling, whereas hamsters presenting advanced signs of the disease (10 days postinfection) exhibited multifocal moderate nephritis with infiltrates of leukocytes and histiocytes. 23 During chronic infection, interstitial nephritis is commonly associated with fibrosis. Using Masson's trichrome staining, we also recorded evidence of intensive interstitial fibrosis in hamster kidneys during chronic leptospirosis.…”

Genotipificación y evaluación de la dinámica de infección de un aislamiento colombiano de Leptospira santarosai en el modelo experimental hámster

“…La capacidad invasiva de L. santarosai en los órganos blanco (pulmón, riñón) del hámster se pudo demostrar mediante la coloración de WarthinStarry, el aislamiento en cultivo a partir del triturado de estos órganos y el resultado positivo en la PCR lipL32. Esta capacidad invasiva se asoció a las alteraciones macroscópicas y microscópicas de estos órganos estudiados en algunos modelos animales (17,41). A pesar de que la recuperación por cultivo de Leptospira spp.…”

“…Esta cepa fue aislada de un paciente durante el brote de leptospirosis de 1996 asociado a la inundación en Salvador de Bahía, Brasil, y desde entonces ha sido utilizada principalmente para estudios sobre la capacidad patógena en modelos animales (17)(18)(19)(20).…”