Detection and treatment of subclinical tuberculosis

Robertson, Brian D.; Altmann, Daniel M.; Barry, Clifton E.; Bishai, Bill; Cole, Stewart T.; Dick, Thomas; Duncan, Ken; Dye, Chris; Ehrt, Sabine; Esmail, Hanif; Flynn, JoAnne L.; Hafner, Richard; Handley, G; Hanekom, Willem A.; Helden, Paul van; Kaplan, Gilla; Kaufmann, Stefan H. E.; Kim, Peter; Lienhardt, Christian; Mizrahi, Valerie; Rubín, Eric J.; Schnappinger, Dirk; Sherman, David R.; Thole, Jelle; Vandal, Omar; Walzl, Gerhard; Warner, Digby F.; Wilkinson, Robert J.; Young, Douglas

doi:10.1016/j.tube.2012.06.004

Cited by 32 publications

(23 citation statements)

References 35 publications

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“…This variation is most likely explained by differences in disease progression between individuals within the latent groups. Similar wide disease spectrum is thought to be present also in the human latent TB [2], [3]. To characterize the underlying factors leading to this typical variation in disease outcomes, it would be beneficial to follow the disease progression in individuals instead of heterogeneous groups in studies using in vivo models of TB.…”

Section: Discussionmentioning

confidence: 97%

Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish

et al. 2012

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The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (∼35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5–10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.

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Section: Discussionmentioning

confidence: 97%

Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish

et al. 2012

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“…An estimated 2 billion individuals have immune reactivity towards Mycobacterium tuberculosis without clinical, radiological or microbiological disease. These persons are, per definition, considered to have subclinical infection, traditionally referred to as latent tuberculosis infection (LTBI), and provide an enormous potential reservoir of persons with a future risk of tuberculosis [2,3]. However, the majority will remain healthy in spite of a positive immunodiagnostic test.…”

Section: Introductionmentioning

confidence: 99%

Beyond the IFN- horizon: biomarkers for immunodiagnosis of infection with Mycobacterium tuberculosis

Chegou

Heyckendorf

Walzl

et al. 2013

European Respiratory Journal

142

123

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Latent infection with Mycobacterium tuberculosis (LTBI) is defined by the presence of M. tuberculosis-specific immunity in the absence of active tuberculosis. LTBI is detected using interferon-c release assays (IGRAs) or the tuberculin-skin-test (TST). In clinical practice, IGRAs and the TSTs have failed to distinguish between active tuberculosis and LTBI and their predictive value to identify individuals at risk for the future development of tuberculosis is limited.There is an urgent need to identify biomarkers that improve the clinical performance of current immunodiagnostic methods for tuberculosis prevention, diagnosis and treatment monitoring. Here, we review the landscape of potential alternative biomarkers useful for detection of infection with M. tuberculosis. We describe what individual markers add in terms of specificity for active/latent infection, prediction of progression to active tuberculosis and immunodiagnostic potential in high-risk groups' such as HIV-infected individuals and children. @ERSpublications The field of biomarkers for the guidance of clinical management of patients with tuberculosis is rapidly evolving

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“…These capabilities are important in highly demanding applications, such as rubidium-82 chloride ( 82 Rb) cardiac imaging (24), oncological head and neck imaging (25), radiation therapy procedures in which detecting a hypoxic region is crucial for determining prognosis, radioimmunotherapy imaging (26, 27), or for the early detection of neurodegenerative dementias, for example by imaging tau proteins to detect Alzheimer’s disease using highly specific radiotracers (28). …”

Section: New Detector Technologiesmentioning

confidence: 99%

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

Vaquero

Kinahan

2015

Annu. Rev. Biomed. Eng.

257

183

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Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.

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Detection and treatment of subclinical tuberculosis

Cited by 32 publications

References 35 publications

Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish

Mycobacterium marinum Causes a Latent Infection that Can Be Reactivated by Gamma Irradiation in Adult Zebrafish

Beyond the IFN- horizon: biomarkers for immunodiagnosis of infection with Mycobacterium tuberculosis

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

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