Historical contingency, rather than higher transmissibility, behind the long-term success of a Mycobacterium tuberculosis outbreak strain

Infectious disease outbreaks are a major public health problem. Tracking their spread and understanding the main factors associated with it are key to assist in disease control. Whole genome sequencing (WGS) of pathogens has been demonstrated to be the best tool to investigate outbreaks, since it helps to answer central questions about their origin and dynamics, and also factors associated with strain success and outbreak evolution. Identification of highly transmissible strains in Mycobacterium tuberculosis is a main area of research. Long-lived outbreak strains have been proposed as candidates with high intrinsic transmissibility. However, limited resolution of available typing methods have prevented testing this hypothesis. Here we study an outbreak strain that started to circulate in Gran Canaria (GC, Canary Islands) in 1993 and has caused around 20% of TB cases since then. By using WGS, and phylodynamics analysis we could trace the origin of the strain to 700 years ago in China and infer its introduction in Gran Canaria in the early 90s. Once established, we document the topology of the outbreak within the Canary Islands. Importantly, we were able to trace the spread of the outbreak beyond the studied area by searching for related sequences within the whole sequence repository, revealing a high success of GC strain in the Canarian archipelago but a limited expansion into the continent. The phylodynamics analyses suggest that determinants associated with the host, instead of higher transmissibility or virulence of the bacteria, are responsible for this long-lived outbreak. We show that historical contingency in the form of a founder effect rather than intrinsic transmissibility explains better the success of the GC strain and probably others of the same nature. Like the GC outbreak strain, many other similar strains in the literature had their origin in the late 20th century suggesting that past epidemics driven by extrinsic factors like HIV are still contributing to the present TB epidemic in local settings.