Weill Cornell Deparment of Medicine | Divisions & Programs | International Medicine & Infectious Diseases

Brazil Program

This year marks the 43rd anniversary of a remarkable collaboration between Cornell University and the Federal University of Bahia. Still growing after four decades, with new partners in Natal, Fortaleza, Rio and the Fiocruz, the Cornell-Bahia program may be the longest collaboration of its type in the world today. To date, over 20 Cornell faculty members and ~100 students and fellows have participated in the program, and over 250 peer reviewed journal publications have emerged from the research. The program has been funded by the Commonwealth Fund and the Rockefeller Foundation, and since 1979, by the NIH. The current NIH funding supports our Tropical Medicine Research Center and a leptospirosis research program in Salvador, Brazil. Presently, a Cornell infectious disease postdoctoral fellow (D. Morgan) and a senior medical student (Tracey Newlove) are conducting advanced research in Salvador, Brazil.

Studies of Leishmaniasis and HTLV-I in Brazil. Carvalho, Johnson, Glesby, Ho, Ko. This is a multi-disciplinary research program with investigators from Brazil and the United States. We seek to define the pathogenesis of these diseases and to develop intervention measures. Research is conducted at field study sites in the state of Bahia, Brazil, the University of Bahia, and the Division of International Medicine and Infectious Diseases at Cornell. We are working to identify host and parasite factors that determine the outcome of leishmania infection. Based on the immunological studies previously performed, 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 HTLV-I infection in relation to cytokine profiles.

Carvalho LP, Passos S, Bacellar O, Lessa M, Almeida RP, Dutra WO, Gollob KJ, Machado P, Ribeiro de Jesus » Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis. Par. Immunol. 29:251-258, 2007.

Morgan DJ, Guimaraes LH, Machado PRL, D'Oliveira Jr A, Almeida RP, Lago EL, Faria DR, Tafuri WL, Dutra WO, Carvalho EM. Cutaneous leishmaniasis during pregnancy: Exuberant lesions and potential fetal complications. Clin. Infect. Dis. 2007; 45: 478-482.

Morgan DJ, Oliveira-Filho, J, Abbeheusen C, Caskey MF, Porto MAF, Muniz AL, Glesby MJ, Carvalho EM. Magnetic resonance imaging does not discriminate between HTLV-I carrier state and HAM/TSP. In press AIDS Res Hum Retroviruses.

Santos SB, Porto AF, Muniz AL, Luna T, Nascimento MC, Guerreiro JB, Oliveira-Filho J, Morgan DJ, Carvalho EM. Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1. NeuroImmunoModulation, 2007; 13:145-151.

Machado PRL, Lessa H, Lessa M, Guimaraes LH, Bang H, Ho JL, Carvalho EM. Oral pentoxifylline combined with pentavalent antimony: A randomized trial for mucosal leishmaniasis. Clin. Infect. Dis. 2007; 44:788-793.

Castro NM, Rodrigues Jr W, Freitas DM, Muniz A, Oliveira P, Carvalho EM. Urinary symptoms associated with human T-cell lymphotropic v’rus type I infection: Evidence of urinary manifestations in large group of HTLV-I carriers. J. Urology 2007; 69(5):813-18.

Caskey MF, Morgan DJ, Porto AF, Giozza SP, Muniz AL, Orge GO, Travassos MJ , Barr—n Y, Carvalho EM , Glesby MJ. Clinical manifestations associated with HTV-1 infection: a cross-sectional study. AIDS Res Hum Retroviruses 2006; 23(3):365-371.

Castellucci L, Menezes E, Oliveira J, Magalhaes A, Guimaraes LH, Lessa M, Ribeiro S, Reale J, Noronha EF, Wilson ME, Duggal P, Geaty TH, Jeronimo S, Jamieson SE, Bales A, Blackwell JM, de Jesus AR, Carvalho EM. IL-6 174 G/C promoter polymorphism influencs susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil. J Infect Dis 2006;194:519-27.

Porto AF, Santos SB, Muniz AL, Basilio V, Rodrigues W Jr, Neva FA, Dutra WO, Gollob KJ, Jacobson S, Carvalho EM. Helminthic infection down-regulates type 1 immune responses in human T-cell lymphotropic virus type 1 (HTLV-1) carriers and is more prevalent in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic parapesis. J Infect Dis 2005;191:612-8.

Morgan DJ, Caskey MF, Abbeheusen C, Oliveira-Filho, J, Porto MAF, Orge MG, Muniz AL, Braga Santos S, Siqueira I, Joia MJ, Araujo C, Glesby MJ, Carvalho EM. Magnetic resonance imaging does not discriminate between HTLV-I carrier state and HAM/TSP. In press AIDS Res Hum Retroviruses.

Emerging Infectious Diseases and Urban Poverty: The Division established a research and training program with the Oswaldo Cruz Foundation (Fiocruz), Brazilian Ministry of Health in 1996 to address infectious disease problems that have emerged due to 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 a more than 350% growth in the slum (favelas) population in the last 40 years and has created a new pattern of infectious diseases. The Cornell-Fiocruz program is conducting research on disease paradigms that include rat-borne epidemic leptospirosis, bacterial meningitis and acute respiratory infections.

Epidemiology of Bacterial Meningitis and Pneumococcal Disease. Ko, Reis J, Reis M, Riley. Acute respiratory infections and bacterial meningitis have become the major infectious disease cause of mortality in increasingly urbanized developing countries such as Brazil. The Division 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. Molecular typing analyses found that the emergence of penicillin-resistant pneumococcal meningitis was due to the introduction of a single serotype 14 clone. On-going 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 evaluate the use of a conjugate vaccine and control of inappropriate antibiotic use as interventions in preventing invasive disease due to penicillin-resistant S. pneumoniae.

Ribeiro GS,Lima JBT, Reis JN, Gouveia EL, CordeiroSM, L™bo TS, Pinheiro RM, Ribeiro CT, Neves AB, Salgado K, Silva HR, Reis MG, Ko AI. Haemophilus influenzae meningitis five years after introduction of the Haemophilus influenzae type B conjugate vaccine in Brazil. Vaccine 2007:25:4420-28.

Ribeiro GS, Reis JN, Cordeiro SM, Lima JBT, Gouveia ELG, Petersen M, Salgado K, Silva HR, Zanella RC, Almeida SCG, Brandileone MC, Reis MG, Ko AI. Prevention of Haemophilus influenzae type B meningitis and emergence of serotype replacement with type A strains following introduction of Hib immunization in Brazil. J Infect Dis 2003;187(1):109-16.

Reis JN, Cordeiro SM, Copolla SJ, Salgado K, Bonfim G, Teixeira LM, Thompson TA, Facklam R, Reis MG, Ko AI. Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil. J Clin Microbiol 2002;40:275-7.

Reis JN, Lima JB, Ribeiro GS, Cordeiro SM, Salgado K, Reis MG, Ko AI. Antimicrobial resistance in Haemophilus influenzae isolated during population-based surveillance for meningitis in Salvador, Brazil. Antimicrobial Agents Chemotherapy. 2002;46(11):3641-3643.

Urban Epidemic Leptospirosis in Brazil. Ko, Reis M, Johnson. Leptospirosis, a spirochetal disease transmitted by rats, has emerged to cause 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 sub-unit vaccine for leptospirosis, and 4) characterizing determinants of leptospiral pathogenesis.

McBride AJ, Athanazio DA, Ries MG, Ko AI. Leptospirosis. Curr Opin Infect Dis 2005;18:376-86.

Cullen PA, Xu X, Matsunaga J, Sanchez Y, Ko AI, Haake DA, Adler B. The surfaceome of Leptospira. Infect Immun 2005;73:4853-63.

Nascimento ATLO, Ko AI, Martins EAL, Monteiro-Vitorello CB, Ho PL, Haake DA et al. Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J Bacteriol 2004;186:2164-72.

Matsunaga J, Barocchi MA, Croda J, Young TA, Sanchez Y, Siqueira I, Bolin CA, Reis MG, Riley LW, Haake DA, Ko AI. Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Mol Microbiol 2003;49(4):929-45.

Sarkar U, Nascimento SF, Barbosa R, Martins R, Nuevo H, Kalafanos I, Grunstein I, Flannery B, Dias J, Riley LW, Reis MG, Ko AI. A population-based case control investigation of risk factors for leptospirosis during an urban epidemic. Am J Trop Med Pub Hyg 2002;66:605-10.

Ko A, Dourado C, Dourado C, Reis M, Johnson WD, Riley L. Urban epidemic of severe leptospirosis in Brazil. Lancet 1999;354:820-5.