The Origin and Maintenance of Tuberculosis Is Explained by the Induction of Smear-Negative Disease in the Paleolithic

Is it possible that the origin of Mycobacterium tuberculosis (Mtb) infection was around 70,000 years before the common era? At that time Homo sapiens was just another primate species with discrete growth and a very low-density geographic occupation. Therefore, it is difficult to understand the origin of a highly virulent obligate human pathogen. We have designed a new SEIR model (TBSpectr) that allows the differentiation of smear-positive and -negative tuberculosis. The model reconciles currently accepted growth rates for the Middle Paleolithic (0.003%/year) and Neolithic (0.1%/year). The obtained data link the origin of Mtb infection in the Middle Paleolithic to the induction of smear-negative TB, and reveal that its persistence required interrelations among hunter–gatherer groups, while the risk of human extinction was negligible. It also highlights the number of people infected per case and the fast progression to disease for Mtb infection maintenance, as well as the link between poor health in the Neolithic with the increased incidence of more severe forms of TB (smear-positive). In conclusion, our data support the origin of TB as a well-tolerated, highly persistent disease, even in low-density populations, showing the difficulty of its eradication and highlighting the necessity for providing better health conditions to humans to reduce its severity.