Trends in Microbiology
OpinionEliminating latent tuberculosis
Section snippets
Tuberculosis: a persistent challenge
Tuberculosis (TB) is a leading bacterial cause of death: in 2006, there were 9.2 million new cases and an estimated 1.5 million people died [1]. An increasing proportion of disease is caused by organisms insensitive to first line chemotherapeutic agents (multi-drug resistant TB [MDR-TB]) [2]. Furthermore, it is estimated that one-third of the world's population harbours drug sensitive, and perhaps increasingly drug resistant, TB in the form of latent infection [3]. Thus, understanding latent TB
Rethinking ‘latent’ TB
What is the basis for considering most TB infection in the world to be latent? By analogy, until the mid 1990s, Human Immunodeficiency Virus (HIV-1) infection was characterized as having three phases. After acute seroconversion there was resolution to a minimally symptomatic ‘latent’ phase. Then, after a variable interval of 4–15 years and for reasons that remained vague, an overt clinical AIDS phase of terminal profound immunodeficiency ensued, characterized by serious opportunistic
Microbiology of latent TB
Is there a correlation between an active TB-specific immune response and the presence of viable M. tuberculosis? This question has plagued TB researchers for over a hundred years. A straightforward approach to answer it involves a comprehensive screen of tissue samples for the presence of bacteria by microbiological culture or by inoculation into highly susceptible guinea pigs. Extensive autopsy studies were carried out in the first part of the 20th century, generating an impressive although
Immunology of latent TB
Can we use the immune response as a surrogate measure of bacterial load? Careful analysis of low-level antibody responses, sometimes overlooked as ‘background’ in the development of serodiagnostics, might be a useful indicator of the presence of antigen in latent TB [43]. Changes in the level of T-cell response in persons undergoing treatment of both active and latent infection indicate some relationship to antigen load 44, 45, although measurements using peripheral blood are complicated by the
Interventions in latent TB
Current efforts to control TB focus primarily on attempts to reduce transmission of M. tuberculosis by prompt detection and effective treatment of infectious patients, and it is hoped that optimal implementation of this strategy will achieve the United Nations Millennium Development Goal of a 50% reduction in the global prevalence and mortality of TB by the year 2015. To achieve the more ambitious goal of TB elimination by 2050, it will be necessary to combine the transmission blocking approach
Refining ‘latent TB’ in the research lexicon?
Although the concept of latent TB, defined by the biomarker of antigen-specific T cells in the absence of clinical symptoms, is useful in a clinical context, it can be detrimental in the context of formulating a research agenda. Although the term is unlikely to fall into disuse, we would like to propose that it is subdivided as outlined in Figure 2. We do not envisage these as rigid boxes: individuals might well move back and forth between categories, and the concept of host-pathogen
Acknowledgements
The ideas included in this review have been developed in the context of a consortium funded by the Bill and Melinda Gates Foundation and the Wellcome Trust to explore development of drugs for treatment of latent TB as part of the initiative to address Grand Challenges in Global Health. R.J.W also receives support from the European Union.
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