8532f7a430089b95d6a6841015bea03d pathogens_a2022v11n3p366.pdf 80b404739834922434434c45401f4c7d5e0f4754 pathogens_a2022v11n3p366.pdf d0550ba32b474650d32a6e693ccf02fe7ac9d8a84d839e85c69b09db42e6bbde pathogens_a2022v11n3p366.pdf Title: The Origin and Maintenance of Tuberculosis Is Explained by the Induction of Smear-Negative Disease in the Paleolithic Subject: 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. Keywords: Homo sapiens; Mycobacterium tuberculosis; disease spectrum; Paleolithic; Neolithic; demography; resistance; tolerance; chronicity; SEIR model; coinfection; coevolution; eco-immunology; mutualism; inequality; poverty Author: Pere-Joan Cardona, Martí Català and Clara Prats Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 17 11:15:19 2022 CET ModDate: Thu Mar 17 11:26:13 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3023725 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OSMMVR+VnURWPalladioL Type 1 Custom yes yes no 10 0 DKLHJJ+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 QBBSCM+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 NCVIXQ+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 PYPZKK+VnURWPalladioL-Bold Type 1 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DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Mtb Infection in the Paleolithic Was Possible Thanks to High Smear-Negative Proportion (p) Values Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Ancient Lineages Had to Be More Virulent in the Paleolithic in Order to Sustain Mtb Infection but They Offered a Better Recovery Rate Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: The SN Recovered Cases Were Crucial for Maintaining Mtb Infection in the Paleolithic While the Neolithic Era Was Marked by the Arrival of SP Lesions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Persistence of Mtb Infection Required Interrelations among Hunter Gatherer Groups in the Paleolithic While the Risk of Human Extinction Was Negligible Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: The Number of People Infected Per Case and Fast Progression to Disease Are the Most Important Factors in Maintaining TB in Existence Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Methodology Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: TBSpectr Model Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Assessment of Uncertainty and Sensitivity in the System Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Continuous and Discrete Resolution of the Models Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: The Origin and Maintenance of Tuberculosis Is Explained by the Induction of Smear-Negative Disease in the Paleolithic Author: Pere-Joan Cardona, Martí Català and Clara Prats Subject: 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. 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