The prognosis of latent tuberculosis: can disease be predicted?

Andersen, Peter; Doherty, T. Mark; Pai, Madhukar; Weldingh, Karin

doi:10.1016/j.molmed.2007.03.004

Cited by 164 publications

(138 citation statements)

References 55 publications

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“…However, the effect, if any, seems to be on a minor scale [20]. Reasons for test variability of IGRA may be based on variations of the handling and reading of the tests, variability of the immune system independent of infection status, and differences in the activity of the M. tuberculosis infection, that is, transient infection, low replication of M. tuberculosis with no stimulation of the immune system, high replication of M. tuberculosis with stimulation of the immune system and uncontrolled replication causing active TB [75,76]. In addition, reversions are partly explained by the statistical mechanism of regression toward the population mean [20].…”

Section: Progression From Ltbi To Active Tb In Hcwmentioning

confidence: 99%

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

Nienhaus

Ringshausen

Costa³

et al. 2013

Expert Review of Anti-infective Therapy

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Section: Progression From Ltbi To Active Tb In Hcwmentioning

confidence: 99%

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

Nienhaus

Ringshausen

Costa³

et al. 2013

Expert Review of Anti-infective Therapy

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Section: Introductionmentioning

confidence: 99%

“…Despite the high mortality, most infected people do not immediately develop active disease, but become latently infected -though they may later reactivate their disease, if they become immunocompromised [3]. It is thought that perhaps as much as a third of the world's population is latently infected, [4] complicating control efforts by providing a reservoir from which new cases continually arise. Understanding immunity to Mycobacterium tuberculosis, so that more effective vaccines can be developed, is thus an international priority.…”

Section: Introductionmentioning

confidence: 99%

Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

et al. 2009

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Mycobacterium tuberculosis remains one of the world's deadliest pathogens in part because of its ability to persist in the face of an active immune response. It has been suggested that apoptosis of infected macrophages is one way in which the host deals with intracellular pathogens and that M. tuberculosis can inhibit this process. To assess the relevance of this process for human disease, we compared the expression of multiple genes involved in the activation of the extrinsic (''death receptor initiated'') pathway of apoptosis in 29 tuberculosis patients, 70 tuberculosis contacts and 27 community controls from Ethiopia. We found that there is a strong upregulation of genes for factors that promote apoptosis in PBMC from individuals with active disease, including TNF-a and its receptors, Fas and FasL and proCaspase 8. The anti-apoptotic factor FLIP, however, was also upregulated. A possible explanation for this dichotomy was given by fractionation of PBMC using CD14, which suggests that macrophage/monocytes may regulate several key molecules differently from non-monocytic cells (especially TNF-a and its receptors, a finding confirmed by protein ELISA) potentially reducing the sensitivity to apoptotic death of monocyte/macrophages -the primary host cell for M. tuberculosis. This may represent an important survival strategy for the pathogen. IntroductionDespite vaccination and drug treatment campaigns, tuberculosis (TB) causes an estimated 8-9 million new cases and mortality of 2-3 million deaths annually [1]. The TB epidemic is largely confined to developing countries, and is particularly serious in Sub-Saharan Africa [2], where it is fanned by the HIV epidemic. Despite the high mortality, most infected people do not immediately develop active disease, but become latently infected -though they may later reactivate their disease, if they become immunocompromised [3]. It is thought that perhaps as much as a third of the world's population is latently infected, [4] Eur. J. Immunol. 2010. 40: 291-301 DOI 10.1002 Clinical immunology 291 complicating control efforts by providing a reservoir from which new cases continually arise. Understanding immunity to Mycobacterium tuberculosis, so that more effective vaccines can be developed, is thus an international priority. The response to infection with M. tuberculosis is characterized by a strong inflammatory cell-mediated immune response, with elevated expression of both and . These two cytokines are essential for controlling mycobacterial infections [11][12][13] but in most cases, M. tuberculosis survives to establish a latent infection -which can rapidly reactivate if TNF-a production is blocked [14]. The precise mechanisms involved in this process are still only poorly known. We and others have previously shown that a bias towards IL-4 expression is associated with elevated risk of disease [15] while a bias towards the IL-4 antagonist IL-4d2, or towards IFN-g, is associated with reduced pathology, a better prognosis after infection, recovery after treatment and with ...

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“…If yes, a second cut-off, higher than the diagnostic cut-off, could be used to identify the subgroup that can benefit from preventive therapy. This hypothesis has been proposed 16 and is supported by limited evidence 6 , but again a single test showing an elevated IFNγ response does not provide information on when the response became elevated (whether this was recently or in the past) or whether it has stayed elevated for a long time (whether it has been persistently elevated or not). In summary, current latent TB tests cannot resolve the latent TB spectrum, especially with one-time testing.…”

mentioning

confidence: 98%

The prognosis of latent tuberculosis: can disease be predicted?

Cited by 164 publications

References 55 publications

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

Expression of apoptosis‐related genes in an Ethiopian cohort study correlates with tuberculosis clinical status

Spectrum of latent tuberculosis — existing tests cannot resolve the underlying phenotypes

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