Tuberculosis caused 20% of all human deaths in the Western world between the 17th and 19th centuries, and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. Here we used 259 whole-genome sequences to reconstruct the evolutionary history of the Mycobacterium tuberculosis complex (MTBC). Coalescent analyses indicate that MTBC emerged about 70 thousand years ago, accompanied migrations of anatomically modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic. This long co-evolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low- and high host densities.
Generalist and specialist species differ in the breadth of their ecological niche. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis Lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that Lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that while the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of Lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
Lockdown measures have been introduced worldwide to contain the transmission of COVID-19. However, the term ‘lockdown’ is not well-defined. Indeed, WHO’s reference to ‘so-called lockdown measures’ indicates the absence of a clear and universally accepted definition of the term ‘lockdown’. We propose a definition of ‘lockdown’ based on a two-by-two matrix that categorises different communicable disease measures based on whether they are compulsory or voluntary; and whether they are targeted at identifiable individuals or facilities, or whether they are applied indiscriminately to a general population or area. Using this definition, we describe the design, timing and implementation of lockdown measures in nine countries in sub-Saharan Africa: Ghana, Nigeria, South Africa, Sierra Leone, Sudan, Tanzania, Uganda, Zambia and Zimbabwe. While there were some commonalities in the implementation of lockdown across these countries, a more notable finding was the variation in the design, timing and implementation of lockdown measures. We also found that the number of reported cases is heavily dependent on the number of tests carried out, and that testing rates ranged from 2031 to 63 928 per million population up until 7 September 2020. The reported number of COVID-19 deaths per million population also varies (0.4 to 250 up until 7 September 2020), but is generally low when compared with countries in Europe and North America. While lockdown measures may have helped inhibit community transmission, the pattern and nature of the epidemic remains unclear. However, there are signs of lockdown harming health by affecting the functioning of the health system and causing social and economic disruption.
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