Origin of tuberculosis in the Paleolithic predicts unprecedented population growth and female resistance

Abstract

Current data estimate the origin of Mycobacterium tuberculosis complex (MtbC) infection around 73,000 years before the common era (BCE), and its evolution to “modern” lineages around 46,000 BCE. Being MtbC a major killer of humanity, the question is how both species could persist. To answer this question, we have developed two new epidemiological models (SEIR type), adapted to sex dimorphism and comparing coinfection and superinfection for different MtbC lineages. We have attributed a higher resistance/tolerance to females to explain the lower incidence noted in this sex, a better health status in the Paleolithic compared to the Neolithic, and a higher dissemination of “modern” lineages compared to “ancient” ones. Our findings show the extraordinary impact caused by “modern” lineages, provoking the extinction of the groups infected. This could only be overcomed by an unprecedented population increase (x20 times in 100 years) and helped with the protection generated by previous infection with “ancient” lineages. Our findings also suggest a key role of female resistance against MtbC. This data obliges us to rethink the growth population parameters in the Paleolithic, which is crucial to understanding the survival of both MtbC and humans, and to decipher the nature of human female resistance against TB.

The Origin and Maintenance of Tuberculosis is Explained by Its Subclinical Course, the Neolithic Revolution Being the Trigger for Its Devastating Deadly Drift

“…Our data also indicates that it was after the change in the living conditions of humans and reduction of standard of living, which came with the Neolithic revolution, that there was an increase in TB severity and mortality. This took place despite the lower virulence of the newly evolved modern lineages, which had a lower inflammatory capacity, but also had higher dissemination abilities 23 .…”

“…We have designed a compartmental mathematical model based on a set of differential equations to describe the dynamics of the evolution of MtbC infection in the population, based on our previous study in several models 23 .…”

“…The assumptions behind each of the equations and values have been discussed at length previously 23 . The main novelty of this update of the model is the distinction between smear positive and smear negative infections.…”

“…Interestingly, modern Mtb lineages appeared by 46,000 BCE, at the time of increasing expansion (reaching as far as Japan, Australia and Europe). This lineage is less aggressive, as it is less proinflammatory, but it has a higher capacity to disseminate through aerosols 23 , and is the one that finally became predominant in humanity 24 . Mtb expansion was fuelled by the Neolithic revolution and the explosive population growth, of around 0.1% annually, thanks to the progressive change towards sedentary life and faming-based activities, which led to higher birth rates (about one child raised every two years), but with a lower quality of life due to the impact of social inequalities 25,26 , harder work duties and less varied nutrition, which caused a reduced life expectancy 21,27 .…”

“…Recently we developed a SEIR model which showed an extraordinary impact of Mtb, which provoked the extinction of the infected groups 23 . This could only be overcome by an unprecedented population increase attributing an annual population growth rate of 1% and 2.6% instead the accepted 0.003% and 0.1% for the Paleolithic and Neolithic 18 .…”