Table 1

Problems with prevention of and treatment for Mtb and shortcomings of current intervention strategies.

Global issueUnderlying regional problems
Failure to provide consistent infrastructure support for health care- Inadequate public health sector in many regions
- Variation in disease manifestations across individuals
Failure to develop effective diagnostic and disease status indicators (biomarkers)- Inadequate testing for drug susceptibility and resistance
- Reliance of current diagnostics mostly on the host immune response
- Poor correlation of bacterial load in sputum with disease status or outcome
- Lack of any indicators of lung pathology or health
Failure of bacillus Calmette-Guérin(BCG) vaccination to protect adult pulmonary TB- Variability in host response to vaccination
- Variability between BCG vaccine strains
- Variability in bacterial strains causing infection
- Variability in host genetics and/or the environment
Failure of chemotherapy to cure many patients with TB- Length of therapy makes compliance difficult
- Individual lesion types respond at different rates
- Drug-tolerant bacteria develop subpopulations
- New drug-resistant strains emerge frequently
Failure of target-based drug discovery programs- Antibiotic killing involves complex biological processes
- Genetic essentiality is not related to target vulnerability
- Whole-cell screenings are not performed under conditions relevant to in vivo infection