divisions for RMP. Patients with extensive pulmonary TB have approximately 1012 bacteria in their body, and therefore will likely be harboring approximately 105 EMB-resistant bacteria, 104 STM-resistant bacteria, 104 INH-resistant bacteria and 10² RMP-resistant bacteria. Resistance mutations appear spontaneously and independently, so the chances of them harbouring a bacterium that is spontaneously resistant to both INH and RMP is 1 in 108 × 1 in 1010 = 1 in 1018, and the chances of them harbouring a bacterium that is spontaneously resistant to all four drugs is 1 in 1033. This is, of course, an oversimplification, but it is a useful way of explaining combination therapy. There are other theoretical reasons for supporting combination therapy. The different drugs in the regimen have different modes of action. INH are bacteriacidal against replicating bacteria. EMB is bacteriostatic at low doses, but is used in TB treatment at higher, bactericidal doses. RMP is bacteriacidal and has a sterilizing effect. PZA is only weakly bactericidal, but is very effective against bacteria located in acidic environments, inside macrophages, or in areas of acute inflammation. All TB regimens in use were 18 months or longer until the appearance of rifampicin. In 1953, the standard UK regimen was 3SPH/15PH or 3SPH/15SH2. Between 1965 and 1970, EMB replaced PAS. RMP began to be used to treat TB in 1968 and the BTS study in the 1970s showed that 2HRE/7HR was efficacious. In 1984, a BTS study showed that 2HRZ/4HR was efficacious, with a relapse rate of less than 3% after two years. In 1995, with the recognition that INH resistance was increasing, the British Thoracic Society recommended adding EMB or STM to the regimen: 2HREZ/4HR or 2SHRZ/4HR, which are the regimens currently recommended. The WHO also recommend a six-month continuation phase of HR if the patient is still culture-positive after 2 months of treatment (approximately 15% of patients with fully sensitive TB) and for those patients who have extensive bilateral cavitation at the start of treatment. Monitoring, DOTS, and DOTS-Plus DOTS stands for "Directly Observed Treatment, Short-course" and is a major plank in the World Health Organization (WHO) Global Plan to Stop TB. The DOTS strategy focuses on five main points of action. The first element involves creating increased sustainable financial services and a short and long-term plan provided by the government, dedicated to eliminating tuberculosis. The World Health Organization helps encourage mobilized funding to reduce poverty standards