Before the start of treatment, the colony undergoes a clonal expansion until it reaches size N.
We assume the bacillary population grows until it reaches size Nf, the size at which it is likely to produce symptoms and come to clinical diagnosis.
It is easy to see that the total number of cell divisions until the tumor reaches size N does not depend on the quiescence parameters α and β.
While the probability to have 1-hit mutants is independent of the death rate, the average number of 1-hit mutants that are produced and survive by the time the tumor size reaches size N is an increasing function of the death rate.
In contrast to previous estimates that there will be hundreds of INH resistant bacilli present by the time an infection becomes symptomatic (i.e. reaches size 1010) [7], [17], [18], [19], we estimate mean numbers of INH resistant bacilli an order of magnitude higher.
Briefly, we first select the pair of haplotypes with the greatest distance on the tree and add the pair to S. We then sequentially incorporate as the next haplotype in S the haplotype that adds the maximal length to the chosen tree at that step, repeating the process until S reaches size m.
