TB promotes poverty and bleeds resources from health systems. TB declined throughout the last century, but recently the incidence has increased in Africa, South East Asia, USA, Russia, the Baltics and Eastern Europe. This may be explained by increase in l ife expectancy, HIV, disintegration of health systems and growing inequity. Multi-drug resistance (MDR) multiplied. Factors fueling this “new epidemic” demand new tools and strategies to make TB control effective again.In Archangel “classical factors” ca nnot explain the increase in TB. The spread of WB strains parallel the increase. Patients spreading these strains are younger, much larger clusters of secondary cases and drug resistance are seen far more often than with non-WB. We will perform surveys in South Africa, Sudan and Vietnam to expand the knowledge of the global spread of WB.A mathematical model will be developed with room for an altered biology and used in the context of two defined hypotheses: 1.) WB infects a higher number of contacts than non-WB, and 2.) WB has a shorter latency period than non-WB. The first will be subject to a contact investigation in South Africa and the second to experimental animal studies in Mexico. A preliminary study of BCG in Vietnam indicated no protection again st WB. Our partners in Vietnam will investigate BCG protection against WB. Stable latency rests in one of two genetic mechanisms; inability to enter the right host cell or shift to vegetative growth. WB imposes an increased tendency for primary MDR. WB st rains that acquire resistance without loss of fitness may have defects in DNA repair mechanisms. We will address these specific options and sequence WB strains to look for deletions and mutations in relation to their epidemiological behavior. We need new tools to make early diagnoses of TB. Saliva based rapid assays using antigens and antibodies will be developed. An intervention study will test if early diagnosis of WB/MDR and isolation can control the spread.