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Pathogenic mechanisms of leptospirosis

Leptospirosis is considered to be an emerging, re-emerging and neglected disease of global
significance. It is a notifiable disease in Brazil; from 2007-2011, there were a total of 19,442
confirmed cases and 2,371 deaths. Due to inherent difficulties in the diagnosis of
leptospirosis, these numbers are considered to be underestimates. Human patients suffering
from leptospirosis present with a diverse array of clinical manifestations, including the more
severe and often fatal pulmonary form of the disease. The aetiology of pulmonary
haemorrhage is unclear. Results to date confirm that pathogenic mechanisms of infection are
due in part to the host immune response. Further, it is clear that leptospires regulate gene and
protein expression during infection. The goal of this research project is to advance these
results to provide novel insights into pathogenic mechanism of leptospirosis and facilitate
efficacious diagnostics and therapies.
Selected references:
1. Jarlath E. Nally, Chavit Chantranuwat, Xiao-Yang Wu, Michael C. Fishbein, Martha
M. Pereira, João José Pereira da Silva, David R. Blanco,

and Michael A. Lovett. Alveolar
Septal Deposition of Immunoglobulin and Complement Parallels Pulmonary Hemorrhage in a
Guinea Pig Model of Severe Pulmonary Leptospirosis. 2004. American Journal of
Pathology: 173 (4); 1115-1127.
2. Jarlath E. Nally, Emilie Chow, Michael C. Fishbein, David R. Blanco, and Michael A.
Lovett. Changes in lipopolysaccharide O-antigen content distinguish Leptospira interrogans
in lethal versus chronic infection. 2005. Infection and Immunity; 73 (6) 3251-3260.
3. Jarlath E. Nally, Michael C. Fishbein, David R. Blanco and Michael A. Lovett.
Lethal infection of C3H/HeJ and C3H/SCID mice with an isolate of Leptospira interrogans
serovar Copenhageni. 2005. Infection and Immunity; 73 (10) 7014-7017.

Collaborators in Brazil:
Martha Maria Pereira
Full Researcher and Director of the WHO Collaborating Center for Leptospirosis
Oswaldo Cruz Institute/FIOCRUZ (www.fiocruz.br)
Avenida Brasil, 4365
CEP 21045-900 - Rio de Janeiro

Alan McBride, PhD
Professor Adjunto
Núcleo de Biotecnologia,
Centro de Desenvolvimento Tecnológico,
Universidade Federal do Pelotas,
Pelotas - RS

Ana Lucia T. O. Nascimento, Ph.D.
Centro de Biotecnologia
Instituto Butantan
Av. Vital Brasil, 1500, CEP 05503-001
Sao Paulo, SP