**5. Conclusion**

resistant to that of drug-susceptible strains have yielded conflicting results: MDR strains can be up to 10 times more or 10 times less transmissible than pan-susceptible strains [36].

Experimental work performed with model organisms has highlighted a level of complexity in the biology of bacterial drug resistance that is generally not considered during standard epidemiological studies of TB transmission. However, much more work is needed to under‐ stand the detailed molecular mechanisms and evolutionary forces that drive drug resistance in this pathogen. Such increased knowledge will allow for better epidemiological predictions and assist in the development of new tools and strategies to fight drug resistant TB [36].

In infectious disease epidemiology, the relevant measure that reflects the reproductive fitness of a pathogen is the number of secondary cases generated; this measure is also known as the basic reproductive rate, R0 [60]. In addition to the absolute number of secondary cases (i.e., absolute fitness), an often more useful measure is that of 'relative fitness', where the success of a particular pathogen variant is compared to the success of another. For example, the fitness of a drug-resistant bacterial strain can be expressed relative to the fitness of a drug-susceptible strain. In addition to epidemiological measures of relative fitness, differences in relative fitness

The results of experimental studies performed with strains resistant to INH, SM or RMP suggested that, in clinical settings, there was a strong selection pressure for drug resistanceconferring mutations that cause minimal fitness defects [61]. Although these findings support the notion that virulence and competitive fitness assays can be predictive of the epidemiology of drug-resistant TB, they do not capture the overall complexity of the life cycle of *M. tuber‐ culosis* [36]. Although several mechanisms of compensatory evolution have been described in

Various molecular tools have been developed to genotype *M. tuberculosis* strains [63]. These tools have been applied to molecular epidemiological investigation of TB transmission for many years. According to the standard concept, patient isolates sharing a particular genotype or DNA 'fingerprint' can be considered epidemiologically linked and represent cases of active TB transmission (i.e., they are clustered TB cases), whereas strains with distinct or 'unique' DNA patterns are thought to reflect reactivation of latent infections. They compared molecular epidemiological fitness estimates from two previous reviews and more recent studies [60, 64]. Overall, the relative fitness estimates for MDR-TB vary dramatically, ranging from an almost 10-fold increased fitness compared to fully drug-susceptible strains found in a study from Russia [65] to about 10-fold lower fitness in Mexico [66] other studies have reported that MDR strains do not cause any secondary cases at all [67]. The reasons for this high variability in relative fitness of MDR strains have likely to do with the differences in study design and setting, differences in sample size and different methodologies and also to the variation in the quality of the TB control programmes [36]. According to Borrell and Gagneux, in addition to methodological, socio-economic and environmental factors, the variation in MDR fitness also reflects biological heterogeneity. Current epidemiological evidence for transmission of MDRand XDR-TB, particularly compared to pan-susceptible TB, is very inconclusive. This can be partially explained by the fact that *M. tuberculosis* is more genetically diverse than is often

other bacteria [62] little work has been done on this topic in *M. tuberculosis.*

can be measured experimentally [36].

194 Tuberculosis - Current Issues in Diagnosis and Management

An understanding of the epidemiology of multidrug resistant tuberculosis (MDR-TB) and the extensively drug-resistant tuberculosis (XDR-TB) is critical for effective control of the global burden of tuberculosis (TB). For a comprehensive study on epidemiology of multidrug resistant tuberculosis (MDR-TB), please refer the reviews in the reference list.
