WCMC's principal research collaborations in Brazil are at the Federal University of Bahia's School of Medicine (UFBa, visit website) and the Oswaldo Cruz Foundation/Brazilian Ministry of Health (Fiocruz, visit website) in Salvador, Brazil.
2009 marks the 45th anniversary of the remarkable collaboration between Weill Cornell Medical College and the Federal University of Bahia, the longest collaboration of its type in the world today. This program has been funded by the Commonwealth Fund and the Rockefeller Foundation (1964-1978), and the NIH (1978 to the present). It has provided training and research opportunities for over 350 US medical students, residents, and fellows, and an equal number of Brazilians. In addition, the NIH is currently supporting a Tropical Medicine Research Center at UFBa.
WCMC's Division of Infectious Diseases also established a research and training program with the Oswaldo Cruz Foundation (Fiocruz) and the Brazilian Ministry of Health in 1996 to address infectious disease problems that have emerged as a result of urban poverty. At present, one billion of the world's population resides in slum settlements. In Brazil, rapid urbanization and migration of the rural poor to the cities has led to greater than 350% growth in the slum population (favelas) in the last 40 years and has created a new pattern of infectious diseases.
In collaboration with seven Brazilian and US research universities and institutes (including Fiocruz), multi-disciplinary research in Brazil focuses on leishmaniasis, tuberculosis, HTLV-1, helminth infections, and leptospirosis. The research program employs approaches from a number of fields, including epidemiology, pathogenesis, genetics, clinical trials, and vaccine development. The two major research programs are led by Dr. Edgar Carvalho, MD, PhD, and Dr. Albert Ko, MD.
Dr. Carvalho, who has been a collaborator with WCMC since finishing his training in 1979, directs the leishmaniasis research at the NIH Tropical Medical Research Center (TMRC). The main Iobjective of the leishmaniasis program, a multi-disciplinary research collaboration of investigators from Brazil and the United States, is to strengthen and expand knowledge of the host-parasite relationship in leishmaniasis that will allow new forms of therapy and control. Research is conducted at field study sites in the state of Bahia, Brazil, the University of Bahia, and the Division of Infectious Diseases at WCMC. Research focuses on immunopathogenesis, clinical manifestations, and management of the disease. The TMRC seeks to define the roles of genetically determined host immune responses, and pathogen virulence factors in determining the outcome of leishmania infection. The Center studies all three forms of endemic leishmaniasis, visceral, cutaneous, and mucosal leishmaniasis, at a field site in Corte de Pedra, 280 km from Salvador. Based on previous immunological studies, clinical trials have been performed using immunomodulatory agents combined with antimony therapy in cutaneous and mucosal leishmaniasis. Ongoing studies are also investigating the spectrum of subclinical and clinical disease in human T-lymphotropic virus I infection in relation to cytokine profiles. Research at Fiocruz focuses on infectious diseases that have emerged as a result of rapid urbanization and extreme poverty. Through the WCMC-Fiocruz program, researchers are exploring disease paradigms that include rat-borne epidemic leptospirosis, bacterial meningitis, and acute respiratory infections.
Epidemiology of Bacterial Meningitis and Pneumococcal Disease. Ko AI, Reis J, Reis M, Riley.
Acute respiratory infections and bacterial meningitis are major causes of mortality in developing countries such as Brazil. WCMC's Division of Infectious Diseases established population-based surveillance for meningitis in the city of Salvador in 1996 and demonstrated penicillin resistance in 15% of the isolates from pneumococcal meningitis cases. The research group at Fiocruz, led by Dr. Albert Ko, has used molecular epidemiology to study transmission of these diseases and has worked on mapping incidence and natural history of leptospirosis and pneumococcal disease. Molecular typing analysis revealed an emergence of penicillin-resistant pneumococcal meningitis due to introduction of a single serotype 14 clone. Ongoing studies focus on evaluating the current interventions, such as the Hib conjugate vaccine, and identifying new approaches for prevention against penicillin-resistant pneumococcal disease. A longitudinal study is measuring the disease burden of acute respiratory infections in a cohort of children from a poor urban slum and identifying factors associated with the acquisition of pneumococcal disease. The overall aim will be to prevent invasive disease due to penicillin-resistant S. pneumoniae by evaluating the use of a conjugate vaccine and controlling inappropriate use of antibiotics. Dr. Ko, Associate Professor of Medicine at WCMC, is also the coordinator of the collaborative Cornell Global Infectious Disease Training Program based in Salvador at the Fiocruz/Brazilian Ministry of Health. The training program has trained more than 60 local laboratory and field staff to date.
Urban Epidemic Leptospirosis in Brazil. Ko, Reis M.
Leptospirosis, a spirochetal disease transmitted by rats causes large epidemics in cities throughout Latin America as a consequence of rapid urbanization and worsening social inequality. Outbreaks occur each year in poor urban slum communities associated with case fatality rates greater than 15%, due to severe clinical forms such as Weil's disease and pulmonary haemorrhage syndrome. In collaboration with the Brazilian Ministry of Health, the Division established active population-based surveillance in the city of Salvador and identified more than 2,500 hospitalized cases during annual rainfall-associated epidemics since 1996. These investigations have lead to national initiatives to sequence the genome of Leptospira interrogans and apply high-throughput strategies towards developing vaccines. Current research focuses on: 1) understanding the natural history of leptospirosis and identifying community-based intervention strategies in a longitudinal study of 9,000 residents from a poor urban slum community; 2) developing rapid diagnostic tests for point-of-care use; 3) identifying candidates for a subunit vaccine for leptospirosis, and 4) characterizing determinants of leptospiral pathogenesis.
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