A Centre of Excellence for Biomedical Research and Training In Africa

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Principle Investigator:    John Metcalfe, MD, MPH, Assistant Professor, Division of Pulmonary and Critical Care Medicine

PhD Candidate, Division of Epidemiology

University of California, Berkeley

Between 2000 and 2006, the estimated global incidence of multidrug-resistant tuberculosis (MDR TB) nearly doubled, and extensively drug-resistant tuberculosis (XDR TB) was newly verified in 49 countries. In most settings, patients with drug resistant TB are routinely identified only after multiple failed treatment attempts, leading to mortality exceeding 90% among HIV co-infected patients and the potential for ongoing community transmission. the proposed study seeks to reduce the burden of drug resistant TB by improving early identification of patients with MDR TB and by quantifying the clinical benefits of novel diagnostics.

This work has the potential to:

1. validate or improve upon current international clinical care standards for patients at risk for drug resistant TB,

2. allow for determination of patients most likely to benefit from widely endorsed molecular drug susceptibility testing,

3. be the first prospective study of the contribution of microbial factors on drug resistant TB transmission in a high HIV prevalence setting.

These studies will lay the foundation for an R01-level proposal utilizing longitudinal patient and pathogen-specific data to characterize development of drug resistant TB in real-time. We will use advanced genotyping methods to fully characterize serial drug resistant strains, novel statistical procedures to account fro time-varying clinical covariates (e.g. treatment regimen, adherence, and DC4 count). Our long-term goal is to intelligently design individual and public health interventions to curtail continued expansion of the MDR TB epidemic. the proposal will directly strengthen the Zimbabwe National TB Program (NTP) by:

•  providing the first accurate population-based estimate of MDR TB incidence in the country since 1995 and

• supporting continued scale-up of MDR-TB treatment access in the country