Disseminated Infections with<i>Talaromyces</i><i>marneffei</i>in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors

Chan, Jasper F W; Chan, Thomas S. Y.; Gill, Harinder; Lam, Frank Y.F.; Trendell-Smith, Nigel J.; Sridhar, Siddharth; Tse, Herman; Lau, Susanna K.P.; Hung, Ivan Fan-Ngai; Yuen, Kwok‐Yung; Woo, Patrick C. Y.

doi:10.3201/eid2107.150138

Cited by 73 publications

(45 citation statements)

References 18 publications

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“…Eight papers were excluded for the following reasons: pooled analysis ( n = 1), follow‐up of phase I or II trial ( n = 1), sub‐analyses ( n = 2), data on extension phase study with a shorter follow‐up ( n = 2), redundant publications ( n = 2). Five phase III RCTs (3 phase IIIa with their most recently published extended phase (750 patients) and 2 phase IIIb RCTs (283 patients)), 6 phase IV studies (1524 patients) and 28 case report publications (31 patients, of whom 4 were included also in phase III studies and 1 in phase IV study) were included in this systematic review.…”

Section: Resultsmentioning

confidence: 99%

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

et al. 2017

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Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.

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Section: Resultsmentioning

confidence: 99%

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

et al. 2017

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“…T.marneffei is an intracellular fungi, mainly affecting the people with immune de ciency, such as Human Immunode ciency Virus (HIV) positive people, IFN-γ antibody positive people, CD20 antibody positive people and kinase inhibition people [31,32]. It has been reported that the Arg1 expression in lymph nodes and peripheral T cells of HIV patients was negatively correlated with the peripheral CD4 + T cell count and positively correlated with the viral load.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Talaromyces Marneffei Influencing Macrophage RAW264.7 Polarization and Sterilization Ability via Arginine Metabolism Pathway

Shen¹,

Yang²,

Chen³

et al. 2020

Preprint

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Background The opportunistic fungi T. marneffei is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. Macrophages act as pacesetters to resist pathogen invasion and communicators to activate adaptive immunity. During infection, macrophages induce iNOS to generate NO, which kills invading pathogenic microorganisms. Arginase competes with the iNOS for a common substrate L-arginine. We tried to investigate the effect of arginine metabolism on the escape of T. marneffei from macrophage killing. Results We performed qPCR, immunobolt detection, immunofluorescent staining, arginase activity assay and NO production assay when macrophages were co-cultured with T. marneffei. We conducted immunobolt detection, arginase activity assay, NO production assay, phagocytic activity assay and T. marneffei killing assay after adding the arginase specific inhibitor nor-NOHA to the co-culture system. T. marneffei decreased the NO production in macrophages by increasing macrophage arginase activity. With lastingness of infection, T. marneffei induced macrophages towards M2 phenotype polarization, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting the T. marneffei-induced macrophage arginase activity with nor-NOHA restored NO synthesis and strengthened the function of fungal killing. Conclusions T. marneffei potentiated its own survival via regulating arginine metabolism pathway in macrophages during an infection.

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“…In addition, several other individual cases of IFIs in adults receiving rituximab for an array of different indications have been reported: (i) PJP, (ii) aspergillosis, (iii) cryptococcosis, (iv) mucormycosis, (v) candidaemia, (vi) fusariosis, (vii) disseminated infection with Talaromyces marneffei , (viii) Cladophialophora bantiana infection and (viii) Phomopsis spp. and Paraconiothyrium spp.…”

Section: Depletion Of Cd20+ B Cellsmentioning

confidence: 99%

Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors

Kyriakidis

Tragiannidis

Zündorf

et al. 2017

Mycoses

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An expanding list of immunomodulatory or immunosuppressive monoclonal antibodies (mAbs) and biologic therapeutics is currently entering clinical practice, particularly in the areas of oncology, transplantation and autoimmune disorders. These agents are directed against molecules or cells involved in inflammation and immunity and may therefore be associated with serious and opportunistic infections. The purpose of this review was to critically analyse the literature on invasive fungal infections (IFIs) occurring in association with mAbs and fusion proteins other than tumour necrosis alpha (TNF-α) inhibitors, including therapeutics modulating T-cell-mediated pathologies (muromonab, abatacept, belatacept, ipilimumab, basiliximab, daclizumab), inducing lymphopenia (alemtuzumab), depleting CD20+ B cells (rituximab) and interfering with various targets (anakinra, natalizumab, blodalumab, ixekizumab and others) with a focus on children, and to provide a framework of evaluating the risk for IFIs in this population.

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Disseminated Infections withTalaromycesmarneffeiin Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors

Abstract: Clinicians should be aware of these infections, especially in patients from disease-endemic regions.

Cited by 73 publications

References 18 publications

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

Ruxolitinib‐associated infections: A systematic review and meta‐analysis

The Mechanism of Talaromyces Marneffei Influencing Macrophage RAW264.7 Polarization and Sterilization Ability via Arginine Metabolism Pathway

Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors

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