ReviewMolecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach
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Tuberculosis incidence and transmission in India
According to World Health Organization (WHO),1 about 9 million new cases of tuberculosis (TB) and 1.7 million TB-related deaths occur every year globally. Of the total number of TB cases worldwide, 80% are concentrated in 22 nations, including India, the TB capital of the world1 where it accounts for one fifth of the global burden of tuberculosis (TB), with 1.8 million new cases of active TB each year - more new cases than any other country.2
According to the estimates of the Revised National
The genetic makeup of tubercle bacilli relevant in epidemiology
Downsizing of the genomic content, occurring through serial deletions, is the major underlying force in the emergence of fittest and successful strain variants in the Mycobacterium tuberculosis complex.10 Another minor contribution to genome evolution is through in situ duplication events, most notably in Mycobacterium bovis BCG strains. A few predominant genotypes circulating throughout the world are responsible for the major outbreaks of the recent past and these belong to the so-called
Shortcomings of the ‘gold-standard’ typing method and evolution of secondary genotyping approaches
The presently available typing systems designed for molecular epidemiology16 are not capable of classifying strains on the whole genome basis including various evolutionary changes and random base substitutions.17 Because of these limitations, knowledge about the mycobacterial population structure in India remained largely unexplored and sketchy. There is a need for a genome sequence based classification of predominant lineages and to find out their preponderances etc. so as to assist global
Strain typing in India: from convenient sampling to more systematic analyses
M. tuberculosis genotypes from the Indian sub-continent have largely been described in the context of locally available isolates and in most cases single techniques have been used to define a ’conveniently sampled’ bacterial diversity.19, 20, 51, 52, 53, 54 Such studies, although important, have probably skewed the interpretation of the diversity of M. tuberculosis because of their small-scale, localized, random sampling and or the choice of a single genotyping method. IS6110
Ancestral lineages and adaptive advantage: do ‘docile’ strains offer any promise to the TB control programs?
Some of the early observations showing that the South Indian strains caused low grade pathology,59 lend support to the potential ‘old is gold’ hypothesis.7 However, since M. tuberculosis gene pool diversity was not completely understood at that time, it is not possible to convey if these observations were really destined to explain specific strain advantages. However, in the absence of in vivo experiments to independently confirm such findings, we cannot be 100% sure that the EAI type strains
Toward functional molecular infection epidemiology of TB
Today’s India presents a ‘genetic playground’ with its races, ethnic distributions, cultures, and languages66 with the populations largely categorized as urban and rural dwellers with tribal or mainstream backgrounds. Sixteen hundred different dialects emanating from the four main language families [the largest being Indo European, which is prevalent in North, and the second largest Dravidian group represents languages spoken in the South] are spoken. Such a complex cultural diversity might
Combining systems biology with ‘systems epidemiology’ – the path forward
Large scale, federated availability of the genome sequences from both the pathogen and host sides is likely to usher the discipline of tuberculosis research into a more predictive, interdisciplinary and data intensive discipline called “systems biology”. This new science is perhaps capable of systematically unraveling the differential attributes of this dreaded disease, leading to measurable, biological outcomes of perturbations (system properties) within a ‘system’ comprising of the pathogen
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