The past and future of tuberculosis research

Abstract

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance--all of which contribute to susceptibility to TB--global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB's epidemiology, comparative genomics, evolution, and host-pathogen interaction. We argue here, however, that new multidisciplinary approaches--especially the integration of epidemiology with systems biology in what we call "systems epidemiology"--will be required to eliminate TB.

Figure 1. The global incidence of TB.

The number of new TB cases per 100,000 population for the year 2007 according to WHO estimates (adapted from [1]).

Figure 2. Global distribution of the six main lineages of human MTBC.

Each dot represents the most frequent lineage(s) circulating in a country. Colours correspond to the lineages defined in Figure 3 (adapted from [20]).

Figure 3. The global phylogeny of Mycobacterium tuberculosis complex (MTBC).

The phylogenic relationships between various human- and animal-adapted strains and species are largely consistent when defined by using either (A) large sequence polymorphisms (LSPs) or (B) single nucleotide polymorphisms (SNPs) identified by sequencing 89 genes in 108 MTBC strains. Numbers inside the squares in (A) refer to specific lineage-defining LSPs. Colors indicate congruent lineages (adapted from and [29]).

Figure 4. A systems epidemiology approach to TB research.

The spread of TB is influenced by social and biological factors. On the one hand, the new discipline of systems biology integrates approaches that address the host, the pathogen, and interactions between the two. On the other hand, epidemiology addresses the burden of the disease and the social, economic, and ecological causes of its frequency and distribution. There is little crosstalk between these two disciplines at the moment. “Systems epidemiology” is an attempt to take into account the interactions between these various fields of research.