Tuberculosis (TB) is a major public health concern in Brazil. This ICIDR proposal builds on a pre-existing collaboration between Drs. Ellner, Dietze, Rodrigues and Palaci and will enhance the scientific infrastructure and training capabilities of the Nucleo de Doengas Infecciosas (NDI) in Vitoria Brazil and provide information essential to address the TB problem. Our hypothesis is that strain variation in Mycobacterium tuberculosis (MTB) is a determinant of the extent of transmission of infection in household contacts with pulmonary TB, the risk of progressing from infection to disease, and the protection conferred by prior mycobacterial infection/vaccination. Our group has discovered a set of synonymous single nucleotide polymorphism (SNP) markers in MTB and used them to construct an unequivocal evolutionary tree of the species making it possible to precisely determine how different clinical strains are related, and to identify strain families likely to share phenotypic traits. We also have discovered new mechanisms for genomic diversity among clinical MTB strains. Overall, these discoveries have uncovered a hitherto unsuspected degree of polymorphism in MTB that may allow it to adapt to host immune responses by antigenic variation and changes in its other cellular functions. A novel household contact design conducted in Vitoria, Brazil will be used to accomplish the following:
Aim 1. To determine whether some clinical strains are more transmissible or cause more disease progression in infected patients, whereas other strains have the opposite phenotype, and to determine whether strains with different phenotypes diverge in the way they interact with the host immune system.
Aim 2. To determine if strains vary in the way that they interact with the innate immune system and the degree to which host differences influence this interaction.
Aim 3. To determine the degree to which adaptive immunity to MTB is strain-specific, and to discover the principal strains or bacterial factors that could be combined in a future vaccine effective against all MTB strains. This program creates a collaboration among leading epidemiologists, immunologists, molecular biologists and microbiologists from the U.S. and Brazil that will enable cutting edge research and training on crucial aspects of tuberculosis biology and immunology in human populations using an innovative epidemiological study design. ? ?
| Fernandes, P; Ma, Y; Gaeddert, M et al. (2018) Sex and age differences in Mycobacterium tuberculosis infection in Brazil. Epidemiol Infect 146:1503-1510 |
| Acuña-Villaorduña, Carlos; Jones-López, Edward C; Fregona, Geisa et al. (2018) Intensity of exposure to pulmonary tuberculosis determines risk of tuberculosis infection and disease. Eur Respir J 51: |
| Colangeli, Roberto; Jedrey, Hannah; Kim, Soyeon et al. (2018) Bacterial Factors That Predict Relapse after Tuberculosis Therapy. N Engl J Med 379:823-833 |
| Vinhas, Solange Alves; Jones-López, Edward C; Ribeiro Rodrigues, Rodrigo et al. (2017) Strains of Mycobacterium tuberculosis transmitting infection in Brazilian households and those associated with community transmission of tuberculosis. Tuberculosis (Edinb) 104:79-86 |
| Jones-López, Edward C; Acuña-Villaorduña, Carlos; Fregona, Geisa et al. (2017) Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil. BMC Infect Dis 17:576 |
| McIntosh, Avery I; Doros, Gheorghe; Jones-López, Edward C et al. (2017) Extensions to Bayesian generalized linear mixed effects models for household tuberculosis transmission. Stat Med 36:2522-2532 |
| Collins, Lauren F; Geadas, Carolina; Ellner, Jerrold J (2016) Diagnosis of Latent Tuberculosis Infection: Too Soon to Pull the Plug on the Tuberculin Skin Test. Ann Intern Med 164:122-4 |
| Salgame, Padmini; Geadas, Carolina; Collins, Lauren et al. (2015) Latent tuberculosis infection--Revisiting and revising concepts. Tuberculosis (Edinb) 95:373-84 |
| Bhatt, Kamlesh; Verma, Sheetal; Ellner, Jerrold J et al. (2015) Quest for correlates of protection against tuberculosis. Clin Vaccine Immunol 22:258-66 |
| Jones-López, Edward C; Kim, Soyeon; Fregona, Geisa et al. (2014) Importance of cough and M. tuberculosis strain type as risks for increased transmission within households. PLoS One 9:e100984 |
Showing the most recent 10 out of 19 publications
