The dual face of central nervous system tuberculosis: A new Janus Bifrons?

Sáenz, Brenda; Hernández-Pando, Rogelio; Fragoso, Gladis; Cárdenas, Graciela

doi:10.1016/j.tube.2012.11.011

Cited by 18 publications

(15 citation statements)

References 43 publications

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“… 3 , 19 Kim and Kim 20 described the term “immunologic paradox” as a therapy-induced increase in the Mycobacterium tuberculosis (MTB)-specific Th1-cell reaction in the CSF or peripheral blood after 2 and 4 weeks, respectively, despite clinical improvement. 21 The humoral and cell-mediated immune reactions are both excessively stimulated by antigens released from the killed bacteria. 20 The recurrent parodoxical manifestation is consistent with a hypothesis from immune response to local antigen release.…”

Section: Discussionmentioning

confidence: 99%

“…The release of mycobacterial cell wall components, including lipoarabinomannan (LAM), and the 30-kDa antigen during mycobacterial destruction by antibiotics may be responsible for an inflammatory host response and production of tumor necrosis factor-alpha (TNF-α) leading to this paradoxical manifestation. 21 An increase in plasma TNF-α level may be associated with transient clinical deterioration observed early in the treatment of severe TB. 22 In addition, regulatory T-cell dysfunction, at a later stage of TB infection, can result in paradoxical manifestation.…”

Section: Discussionmentioning

confidence: 99%

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Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis

et al. 2016

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Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients’ prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients.Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment.Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days.Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up.Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit.Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis

et al. 2016

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“…It is, however, conceivable that the interplay of Tregs and Mtb may differ in infections at immune-privileged sites, such as the CNS or the eye. The assessment of anti-inflammatory mechanisms could be highly relevant in regard to CNS-immune reconstitution syndromes, given their often disastrous outcomes ( 130 ). Several studies have associated plasma biomarkers and CD4 + T-cell activation with the development of HIV-associated immune reconstitution inflammatory syndromes (IRIS), but did not find an association with (CD4 + ) Treg frequencies, both in the development of cryptococcal-IRIS disease ( 131 ) and TB-IRIS disease ( 131 , 132 ).…”

Section: Tregs In Leprosy and Tuberculosismentioning

confidence: 99%

Regulatory T-Cells at the Interface between Human Host and Pathogens in Infectious Diseases and Vaccination

2015

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Regulatory T-cells (Tregs) act at the interface of host and pathogen interactions in human infectious diseases. Tregs are induced by a wide range of pathogens, but distinct effects of Tregs have been demonstrated for different pathogens and in different stages of infection. Moreover, Tregs that are induced by a specific pathogen may non-specifically suppress immunity against other microbes and parasites. Thus, Treg effects need to be assessed not only in homologous but also in heterologous infections and vaccinations. Though Tregs protect the human host against excessive inflammation, they probably also increase the risk of pathogen persistence and chronic disease, and the possibility of disease reactivation later in life. Mycobacterium leprae and Mycobacterium tuberculosis, causing leprosy and tuberculosis, respectively, are among the most ancient microbes known to mankind, and are master manipulators of the immune system toward tolerance and pathogen persistence. The majority of mycobacterial infections occur in settings co-endemic for viral, parasitic, and (other) bacterial coinfections. In this paper, we discuss recent insights in the activation and activity of Tregs in human infectious diseases, with emphasis on early, late, and non-specific effects in disease, coinfections, and vaccination. We highlight mycobacterial infections as important models of modulation of host responses and vaccine-induced immunity by Tregs.

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“…(Rogers, Mastroeni et al 2007; Qian and Flood 2008; Calabrese, Cornelius et al 2009; Tsang and Chung 2009; Streit 2010) Various inflammatory mediators and cytotoxic molecules, such as IL-1α, IL-6, TNF-α, ROS and RNS released by activated microglial cells in response to infection, injury, or endotoxins may trigger neuronal damage and cell death. (Block, Zecca et al 2007; Pacher, Beckman et al 2007; Yang, Lee et al 2007; Olin, Armien et al 2008; Rock, Olin et al 2008; Brown and Neher 2010; Graeber and Streit 2010; Saenz, Hernandez-Pando et al 2013; Isabel and Rogelio 2014; Francisco, Hsu et al 2015)…”

mentioning

confidence: 99%

“…(Rock, Olin et al 2008; Thwaites and Schoeman 2009; Chin and Mateen 2013) With cerebral TB, microglia, neurons and oligodendrocytes are targeted by the invading bacilli (Randall, Hsu et al 2015) and consequent tissue damage and neurodegeneration is caused by infection and excessive cellular mediated immune response and inflammation. (Rock, Olin et al 2008; Saenz, Hernandez-Pando et al 2013; Isabel and Rogelio 2014)…”

mentioning

confidence: 99%

Does Concurrent Use of Some Botanicals Interfere with Treatment of Tuberculosis?

et al. 2016

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Millions of individuals with active TB do not receive recommended treatments, and instead may use botanicals, or use botanicals concurrently with established treatments. Many botanicals protect against oxidative stress, but this can interfere with redox-dependent activation of isoniazid and other prodrugs used for prophylaxis and treatment of TB, as suggested by results of a recent clinical trial of the South African botanical Sutherlandia frutescens (L.) R. Br. (Sutherlandia). Here we provide a brief summary of Sutherlandia's effects upon rodent microglia and neurons relevant to tuberculosis of the central nervous system (CNS-TB). We have observed that ethanolic extracts of Sutherlandia suppress production of reactive oxygen species (ROS) in rat primary cortical neurons stimulated by NMDA, and also suppress LPS- and interferon γ (IFNγ)-induced ROS and nitric oxide (NO) production by microglial cells. Sutherlandia consumption mitigates microglial activation in the hippocampus and striatum of ischemic brains of mice. RNAseq analysis indicates that Sutherlandia suppresses gene expression of oxidative stress, inflammatory signaling and toll-like receptor pathways that can reduce the host's immune response to infection and reactivation of latent Mycobacterium tuberculosis. As a precautionary measure, we recommend that individuals receiving isoniazid for pulmonary or cerebral TB, be advised not to concurrently use botanicals or dietary supplements having antioxidant activity.

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The dual face of central nervous system tuberculosis: A new Janus Bifrons?

Cited by 18 publications

References 43 publications

Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis

Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis

Regulatory T-Cells at the Interface between Human Host and Pathogens in Infectious Diseases and Vaccination

Does Concurrent Use of Some Botanicals Interfere with Treatment of Tuberculosis?

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