The Amplifier Model

Borrowing an analogy from Physics, the word 'resistance' is used to describe an impeding force that acts against an object as it tries to get something done. If tubercle bacilli are viewed as an electron flowing through a conductor (host), trying to infect as many hosts as possible to create an epidemic ‘’Hot Zone’’, the drug regimen offers the impedance or resistance. An amplifier magnifies the signal (Voltage) and provides a bigger version of it at the output.

Putting it all into the context of transmission of tuber bacilli and drug resistance, socio economic factors including malnutrition, crowded living spaces, poor ventilation and mental health factors preventing strict adherence to TB regimen provide favourable conditions for amplification of MDR-TB Bacilli. An ideal amplifier would provide the same gain independent of the source and load resistances. By concentrating resources on recent infection, it is possible to achieve more TB control and faster that thought possible.

Mycobacterium tuberculosis is intrinsically resistant to many antibiotics. Resistance to the drugs which are active against M. tuberculosis is conferred by chromosomal mutations. Drug resistance mutations may have pleiotropic effects leading to a reduction in the bacterium's fitness, quantifiable e.g. by a reduction in the in vitro growth rate. Secondary so-called compensatory mutations, not involved in conferring resistance, can ameliorate the fitness cost by interacting epistatically with the resistance mutation.

Drug-resistant M. tuberculosis strains are a major global health concern because treatment of these cases requires second-line drugs not readily available in resource-limited settings. we use the term ‘drug resistance’ to refer to the topic in general, irrespective of specific drug resistance profiles. TB treatment success rates of cases caused by MDR/XDR variants of M. tuberculosis are alarmingly low, with only 54% of MDR and 28% of extensively drug-resistant (XDR—MDR plus resistance to fluoroquinolones and any second-line injectable aminoglycoside/cyclic peptide) cases resulting in cure, compared to 83% of drug-susceptible cases (World Health Organization 2016). The World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease have defined a hot zone as an area where the prevalence of MDRTB cases is >5% (that is, where >5% of current cases are MDRTB).

Sebastian M. Gygli, Sonia Borrell, Andrej Trauner, Sebastien Gagneux, Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives, FEMS Microbiology Reviews, Volume 41, Issue 3, May 2017, Pages 354–373, https://doi.org/10.1093/femsre/fux011

A new multi-strain mathematical model has been developed for understanding the evolution of the hot zones. Monte Carlo sampling methods have been employed to understand the historical effects of poor treatment control programs in creating hot zones for tuberculosis. The results strongly suggest that, in the hot zones, second line drugs should be quickly introduced to disrupt the amplification of resistance. There is an urgent need to develop more complex and region-specific control strategies for regions where MDRTB has reached high levels. (Cohen et al., 2009)