Biomarkers of Disease Activity, Cure, and Relapse in Tuberculosis

Doherty, T. Mark; Wallis, Robert S.; Zumla, Alimuddin

doi:10.1016/j.ccm.2009.08.008

Cited by 19 publications

(11 citation statements)

References 126 publications

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“…Contacts with greater response to ESAT6 (presumably at greater risk for developing active TB) (36) had higher expression of TNF and Fas, similar to active TB cases. This is consistent with other studies among active cases of TB, in which severe cases were associated with a greater ratio of TNF to TNFR1 (79, 80). The authors suggest these parameters in household contacts are a measure of active infection rather than latency.…”

Section: Immunologic Distinctions Of Active Disease and Latent Infectsupporting

confidence: 93%

Understanding Latent Tuberculosis: A Moving Target

Lin

Flynn

2010

The Journal of Immunology

398

303

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Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be ~2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease.

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Section: Immunologic Distinctions Of Active Disease and Latent Infectsupporting

confidence: 93%

Understanding Latent Tuberculosis: A Moving Target

Lin

Flynn

2010

The Journal of Immunology

398

303

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“…The diagnostic tests in common usage today merely measure whether or not an individual has mounted an immune response to Mtb. Given that progression to disease is determined locally, at the level of the individual granuloma, it is unclear if we will ever be able to develop biomarkers for disease progression based on systemic readouts of immune status (58). Recent advances in PET and CT-based imaging modalities have the potential to fill this gap (Fig.…”

Section: Missing Toolsmentioning

confidence: 99%

Tuberculosis: What We Don’t Know Can, and Does, Hurt Us

Russell

Barry

Flynn

2010

Science

434

368

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Mycobacterium tuberculosis (Mtb) has a penetrance of its host population that would be the envy of most human pathogens. Approximately 1/3 of the human population is skin test positive for the infection and is thus thought to harbor the bacterium. Globally, 22 "high-burden" countries account for over 80% of the active tuberculosis cases in the world, highlighting the inequitable distribution of the disease. There is no effective vaccine against infection and current drug therapies are fraught with problems, predominantly due to the protracted nature of the treatment and the increasing occurrence of drug resistance. Here we focus on the biology of the host-pathogen interaction and discuss new and evolving strategies for intervention.

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“…It is unclear if there is any difference between the systemic immune response in an individual harboring a controlled, persistent infection, versus one with active disease. Certainly programs attempting to identify systemic biomarkers of disease state have met with extremely limited success (Doherty et al, 2009; Wallis et al, 2009). While this has serious implications for monitoring disease progress, or understanding why one granuloma becomes active while others resolve, it has even greater significance for vaccine development because it implies that the best immune response leads to nothing better than containment.…”

Section: Heterogeneity Across the Infectionmentioning

confidence: 99%

Mycobacterium tuberculosis Wears What It Eats

Russell

VanderVen

Lee

et al. 2010

Cell Host & Microbe

172

160

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Mycobacterium tuberculosis remains one of the most pernicious of human pathogens. Current vaccines are ineffective and drugs, although efficacious, require prolonged treatment with constant medical oversight. Overcoming these problems requires a greater appreciation of M. tuberculosis in the context of its host. Upon infection of either macrophages in culture or animal models, the bacterium re-aligns its metabolism in response to the new environments it encounters. Understanding these environments, and the stresses that they place on M. tuberculosis, should provide insights invaluable for the development of new chemo- and immuno-therapeutic strategies.

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Biomarkers of Disease Activity, Cure, and Relapse in Tuberculosis

Cited by 19 publications

References 126 publications

Understanding Latent Tuberculosis: A Moving Target

Understanding Latent Tuberculosis: A Moving Target

Tuberculosis: What We Don’t Know Can, and Does, Hurt Us

Mycobacterium tuberculosis Wears What It Eats

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