The RU TBRU program is composed of 4 research projects:
Project 1 – Biomarkers to stratify risk of progression from latent TB infection to disease
Project 2 – Validation and application of a model of human TB-like latency in rabbits
Project 4 – Bacterial mechanisms and host pharmacokinetic factors that determine
persistence in paucibacillary TB
Interactions and Synergism Between Projects
Latency and persistence of Mtb infection both depend on bacterial and host-associated factors that are not fully understood and the mechanisms leading to these two outcomes may or may not share common pathways. By studying the two states and using cross-validation in two different models (human and rabbit), we propose an integrative investigation of how latency and persistence occur and correlate, the factors that drive progression from Mtb infection to disease, the biomarkers that can help predict cure or relapse, and the factors that can prevent persistence and establish effective cure.
A Schematic Overview
The Núcleo de Doenças Infecciosas (NDI) in Vitória, Brazil, was created in 1990 as a branch of the Social Medicine and Epidemiology Department at the Universidade Federal do Espírito Santo (UFES). It is located within UFES University’s Health Sciences campus, near the 300-bed affiliated teaching Hospital (Hospital Universitário Cassiano Antonio de Moraes – HUCAM). The NDI has a strong clinical research infrastructure that includes state-of-the-art mycobacteriology and immunology laboratories adhering to international standards of good laboratory practice.
The Clinical Infectious Diseases Research Initiative (CIDRI) at the University of Cape Town (UCT) in Cape Town, South Africa, was established by a Wellcome Trust strategic award and works in partnership with UCT’s Centre for Infectious Disease Epidemiology and Research. The clinical research facilities are in Khayelitsha township at two sites that are five minutes’ drive apart: 1) Khayelitsha site B Ubuntu HIV-TB clinic, and 2) Khayelitsha Hospital (KH). These are augmented by clinical facilities at Tygerberg hospital, approximately 25 minutes’ drive from Khayelitsha. Site staff are experienced in participant recruitment and equipped to conduct the necessary clinical tests and sample collection for studies. The clinical facilities are complemented by established laboratory and administrative infrastructure at the UCT Faculty of Health Sciences campus.