Leptospirosis is a paradigm for an urban slum health problem. Rapid urbanization and expanding urban poverty worldwide have created conditions for rat-borne transmission of the Leptospira spirochete. The investigations of Weill Medical College of Cornell University and Oswaldo Cruz Foundation in the city of Salvador, Brazil raised awareness for a new pattern for leptospirosis, characterized by annual rainfall-associated epidemics that occur in slum communities and cause life-threatening manifestations such pulmonary hemorrhage syndrome. The lack of adequate diagnostics and poor understanding of disease pathogenesis are the major barriers to mounting effective public health responses to urban epidemics. We have established active surveillance for leptospirosis in Salvador and performed long-term prospective studies of urban slum populations. These studies raise specific hypotheses on the pathogen, environment and host-related factors in disease transmission. We propose an ICIDR project which applies state-of-the-art approaches in genomics and proteomics to ongoing field investigations for the aim of elucidating the determinants of urban leptospirosis. In the first project aim, we will identify the pathogen factors which influence disease progression and development of pulmonary hemorrhage syndrome using high-throughput genome sequencing of clinical isolates and genetic tools to manipulate Leptospira. In the second project aim, we will develop molecular assays to measure Leptospira in the environment and determine whether such assays can be used to identify transmission sources, stratify disease risk and prioritize prevention in resource-poor settings. In the third project aim, we will use proteome arrays to systematically identify diagnostic and prognostic markers for leptospirosis, as well as potential vaccine candidates. The information gained may lead to novel strategies for intervention, such as targeted environmental control measures, improved diagnostics and vaccines, which are urgently needed as the world's population residing in slums doubles from one to two billion in the next twenty years. Furthermore the ICIDR project will create the translational research capacity in Brazil to address other neglected infectious diseases.

Public Health Relevance

There is no effective prevention for leptospirosis, a life-threatening bacterial disease which causes epidemics among the urban poor worldwide. The proposed research will apply state-of-the art molecular approaches to field investigations in Brazil for the purpose of characterizing the disease determinants of leptospirosis and identifying novel strategies for intervention, such as improved diagnostics and vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI088752-04
Application #
8518223
Study Section
Special Emphasis Panel (ZAI1-GSM-M (J1))
Program Officer
Mukhopadhyay, Suman
Project Start
2010-08-10
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$681,978
Indirect Cost
$162,313
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Wunder Jr, Elsio A; Figueira, Claudio P; Santos, Gisele R et al. (2016) Real-Time PCR Reveals Rapid Dissemination of Leptospira interrogans after Intraperitoneal and Conjunctival Inoculation of Hamsters. Infect Immun 84:2105-15
Wunder Jr, Elsio A; Figueira, Cláudio P; Benaroudj, Nadia et al. (2016) A novel flagellar sheath protein, FcpA, determines filament coiling, translational motility and virulence for the Leptospira spirochete. Mol Microbiol 101:457-70
Fouts, Derrick E; Matthias, Michael A; Adhikarla, Haritha et al. (2016) What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira. PLoS Negl Trop Dis 10:e0004403
Costa, Federico; Richardson, Jonathan L; Dion, Kirstin et al. (2016) Multiple Paternity in the Norway Rat, Rattus norvegicus, from Urban Slums in Salvador, Brazil. J Hered 107:181-6
Panti-May, Jesús A; Carvalho-Pereira, Ticiana S A; Serrano, Soledad et al. (2016) A Two-Year Ecological Study of Norway Rats (Rattus norvegicus) in a Brazilian Urban Slum. PLoS One 11:e0152511
Hacker, Kathryn P; Minter, Amanda; Begon, Mike et al. (2016) A Comparative Assessment of Track Plates to Quantify Fine Scale Variations in the Relative Abundance of Norway Rats in Urban Slums. Urban Ecosyst 19:561-575
Hagan, José E; Moraga, Paula; Costa, Federico et al. (2016) Spatiotemporal Determinants of Urban Leptospirosis Transmission: Four-Year Prospective Cohort Study of Slum Residents in Brazil. PLoS Negl Trop Dis 10:e0004275
Oliveira, Carlos R; Costa, Gisela S R; Paploski, Igor A D et al. (2016) Influenza-like illness in an urban community of Salvador, Brazil: incidence, seasonality and risk factors. BMC Infect Dis 16:125
Silva, Monaise M O; Rodrigues, Moreno S; Paploski, Igor A D et al. (2016) Accuracy of Dengue Reporting by National Surveillance System, Brazil. Emerg Infect Dis 22:336-9
Torgerson, Paul R; Hagan, José E; Costa, Federico et al. (2015) Global Burden of Leptospirosis: Estimated in Terms of Disability Adjusted Life Years. PLoS Negl Trop Dis 9:e0004122

Showing the most recent 10 out of 42 publications