Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis

Abstract

The "Beijing" Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is spreading globally and has been associated with accelerated disease progression and increased antibiotic resistance. Here we performed a phylodynamic reconstruction of one of the L2 sublineages, the central Asian clade (CAC), which has recently spread to western Europe. We find that recent historical events have contributed to the evolution and dispersal of the CAC. Our timing estimates indicate that the clade was likely introduced to Afghanistan during the 1979-1989 Soviet-Afghan war and spread further after population displacement in the wake of the American invasion in 2001. We also find that drug resistance mutations accumulated on a massive scale in Mtb isolates from former Soviet republics after the fall of the Soviet Union, a pattern that was not observed in CAC isolates from Afghanistan. Our results underscore the detrimental effects of political instability and population displacement on tuberculosis control and demonstrate the power of phylodynamic methods in exploring bacterial evolution in space and time.

Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis

“…As suggested by the levels of drug resistance reached globally, we are losing the arms race against bacteria including M. tuberculosis (Bañuls et al., 2018). M. tuberculosis , as many pathogens, has a complex ecology and evolution and is also evolving and fluctuating through time and space according to local contexts (Bañuls et al., 2015; Comas et al., 2013; Eldholm et al., 2016; Müller, Borrell, et al., 2013; O'Neill et al., 2015; Trauner et al., 2014). For instance, our review underlines that strains carrying multiple drug‐resistant mutations reveal a high ability to acquire other resistances or compensatory mutations by epistatic interactions in reducing the biological cost imposed on the fitness of bacteria.…”

“…It is worth noting that extrinsic factors such as the economic and social situation of individuals or populations, the major political events (e.g., the fall of the Soviet Union) and the quality of TB control programmes also strongly influence the speed of drug resistance spread (Eldholm et al., 2016; Klopper et al., 2013; Müller, Chihota, et al., 2013). In vivo, the drug resistance acquisition also greatly varies depending on the location of bacterial populations in the body and the characteristics of the drugs (Kempker et al., 2015; Warner et al., 2015).…”

“…In particular, the prevalence of specific drug resistance‐associated mutations also varies within the lineage, such as the frequencies of the rpo B S531L and kat G S315T mutations are greater in the modern (typical) Beijing strains than in ancient (atypical) ones (Hillemann et al., 2005; Lipin et al., 2007; Qian et al., 2002). These differences could be the result of epistatic interactions (see Box 1 and below) and might reflect the adaptation of M. tuberculosis sublineages to the different human populations and the efficiency of treatment and public health strategies (Bañuls et al., 2015; Comas et al., 2013; Eldholm et al., 2016). …”

Latent tuberculosis may be missed by current screening practices: Analysis of interferon‐gamma release assay results from a paediatric refugee clinic

“…In the case of Iran and Syria, these data suggest that using historic TB incidence data may not accurately predict the current likelihood of testing positive. Reasons for this remain unclear; the breakdown of public health infrastructure in Syria, the mass movement of people and crowding in refugee camps are all possible risk factors …”

“…Reasons for this remain unclear; the breakdown of public health infrastructure in Syria, the mass movement of people and crowding in refugee camps are all possible risk factors. 16,17 The discovery of an Australian-born child with a positive IGRA result is cause for concern. The decision whether to screen Australian-born children in HARK is currently made by each individual clinician based on the likelihood of exposure.…”