Elsevier

Tuberculosis

Volume 91, Issue 5, September 2011, Pages 407-413
Tuberculosis

Review
Molecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach

https://doi.org/10.1016/j.tube.2011.03.006Get rights and content

Summary

Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to be the leading source of mortality and morbidity across the world with India fast emerging as the TB capital of the world. In order to develop effective intervention strategies it is equally important to focus not only on a system of information and efficient methods for localizing sources of infection, but also highlight tools that enable enhanced understanding of the dynamics of spreading of disease. Accurate identification of the underlying strains in an epidemiological setting is therefore of paramount significance. There is no scientific evidence to explain that some strains of the TB bacilli spread faster and transmit more aggressively than others although strains such as M. tuberculosis Beijing/W have been widely reported to cause large scale and fatal outbreaks perhaps linked to their postulated propensity to transmit faster. We provide an overview of the present scenario of molecular epidemiology and dissemination dynamics of M. tuberculosis and discuss how systematic, genome sequence based methods allow decipherment of the population genetic structure of M. tuberculosis in India which was not achievable with traditional fingerprinting methods. We discuss the prevalence of ancestral genotypes in India which perhaps represent less disseminating and more controllable lineages that infect a majority of TB patients in this high burden country. Further, we suggest ‘functional molecular infection epidemiology’ as a new discipline to guide investigation of the impact of pathogen diversity (as juxtaposed to the host response) on the disease phenotype. We also propose systems biology to be a powerful new science to holistically analyze the epidemic through integration of high-throughput multi-omics data to understand the dynamic interactions that occur at the level of host-pathogen cross-talks and to identify potentially novel drivers of the future control strategies.

Section snippets

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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