Genome-based transmission modeling separates imported tuberculosis from recent transmission within an immigrant population

Abstract In many Western countries tuberculosis (TB) incidence is low and largely shaped by immigrant populations originating from high-burden countries. A variable latent period, low rates of evolution and structured social networks, makes separating repeated import from within-border transmission a major conundrum to TB-control efforts in many low-incidence countries. This is the case in Norway, where TB incidence dropped to very low levels during the second half of the 20th century (6 per 100,000 in 2016) and more than 80 per cent of TB cases are now found among immigrants from high-incidence countries. Immigrants from the Horn of Africa constitute the largest group of TB patients in Norway, making up a third of all TB cases in the country over the last decade. One particular genotype-cluster strongly associated with people originating in this region has been identified regularly over a 20-year period. Here we apply transmission modeling methods to whole-genome sequence data to estimate the times at which individual patients were originally infected. By contrasting these estimates with time of arrival in Norway, we estimate on a case-by-case basis whether individual patients were likely to have been infected before or after arrival. Although import was responsible for the majority of cases, we find that transmission is also occurring in Norway. Our approach is very broadly applicable and relevant to many settings where TB control programs can benefit from an understanding of when (and consequently where) individuals have acquired a tuberculosis infection.