Immune reconstitution inflammatory syndrome in non‐HIV cryptococcal meningitis: Cross‐talk between pathogen and host

Zhou, Linghong; Zhao, Hua-Zhen; Wang, Xuan; Wang, Ruiying; Jiang, Ying-Kui; Huang, Liping; Yip, Ching-Wan; Cheng, Jia-Hui; Que, Chun-Xing; Zhu, Liping

doi:10.1111/myc.13361

Cited by 10 publications

(3 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For immunocompetent individuals, pathogenic cytokine release mediated by PANoptosis through membrane pores and cell lysis could drive lifethreatening damage to host tissues and organs and lead to adverse clinical outcomes (30). MCP-1 was reported to be correlated with CM-associated immune reconstitution inflammatory syndrome (IRIS) in HIV-negative populations (31). In our present study, we demonstrated the diversity of immune mechanisms with higher scores for PC-1 associated with disease severity, suggesting that a combined inflammatory response involving multiple immune mediators may be critical to disease outcome.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid cytokine and chemokine patterns correlate with prognosis of HIV-uninfected cryptococcal meningitis: A prospective observational study

Jiang

Wang²,

Zhou³

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

The cerebrospinal fluid (CSF) immune responses in HIV-uninfected cryptococcal meningitis (CM) have not been well studied. In this study, we aimed to explore the phenotype of CSF immune response during the course of disease and to examine relationships between phenotypes and disease severity. We profiled the CSF immune response in 128 HIV-uninfected CM and 30 pulmonary cryptococcosis patients using a 27-plex Luminex cytokine kit. Principal component analyses (PCA) and logistic regression model were performed. Concentrations of 23 out of 27 cytokines and chemokines in baseline CSF were significantly elevated in CM patients compared with pulmonary cryptococcosis cases. In CM patients with Cryptococcus neoformans infection, IL-1ra, IL-9, and VEGF were significantly elevated in immunocompetent cases. Cytokine levels usually reached peaks within the first 2 weeks of antifungal treatment and gradually decreased over time. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting of Th1, Th2, and Th17 type cytokines. Prognostic analysis showed that higher scores for the PCs loading pro-inflammatory cytokines, IFN-γ, TNF-α, and IL-12; and anti-inflammatory cytokine, IL-4; and chemokines, Eotaxin, FGF-basis, and PDGF-bb; as well as lower scores for the PCs loading RANTES were associated with disease severity, as defined by a Glasgow Coma Scale of <15 or death. In conclusion, combined inflammatory responses in CSF involving both pro- and anti-inflammatory cytokines and chemokines are upregulated in HIV-uninfected CM, and associated with disease severity.

show abstract

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid cytokine and chemokine patterns correlate with prognosis of HIV-uninfected cryptococcal meningitis: A prospective observational study

Jiang

Wang²,

Zhou³

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, previous studies have mainly involved subjects with HIV and CM coinfection in a high HIV burden setting due to increased susceptibility to CM in HIV patients (11). In addition, previous work has also shown that population heterogeneity affects the immune response to the pathogen, resulting in altered clinical symptoms and prognoses (12,13). Recently, a novel predictive model was established for calculating one-year mortality in CM (14).…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study

Wang

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

IntroductionDespite advances in the diagnosis and management, cryptococcal meningitis (CM) is still associated with high mortality due to insufficient knowledge about clinical characteristics and risk factors for poor outcomes. The aim of the present study is to provide additional evidence for regarding clinical characteristics, diagnosis, and factors associated with increased risk of mortality in CM patients.MethodsIn this cohort study, we included eligible patients consecutively admitted to West China Hospital between January 2009 and December 2018. The clinical characteristics and diagnosis method of cerebrospinal fluid culture and India ink stain were analyzed. Independent risk factors were identified by a multivariable logistic regression.ResultsA total of 186 CM patients were included in the analysis. After a 1-year follow-up, 63 patients had died. Headache is the most common presenting symptom (97.3%), followed by vomiting (72%), fever (71.5%), altered consciousness (45.7%), abnormal vision (32.8%), and seizure (15.1%). Older age, altered consciousness or seizures, lower white blood cell count or total protein in cerebrospinal fluid (CSF), and unidentified CSF cryptococcal antigen (CrAg) are all factors associated with increasing risk of death (P < 0.05). We also found a dose-dependent trend between the number of symptoms and risk of death (trend p < 0.001). Multivariate logistic regression revealed that age (P = 0.004, OR = 1.042, 95% CI 1.013–1.071), seizure (P = 0.025, OR = 3.105, 95% CI 1.152–8.369), altered consciousness (P < 0.001, OR=6.858, 95% CI 3.063–15.38), and unidentified CSF CrAg are the independent prognostic factors. In addition, we observed that diagnosis of 28.5% and 22.5% CM could not be established by a single testing of CSF India ink stain or culture, respectively. Use of multiple testing methods or combination of the two assays increases the detection rate.ConclusionOur data show that older age, seizures, altered consciousness, and an inability to detect CSF CrAg are the independent risk factors of death within 1 year in CM patients. Moreover, we recommend use of multiple testing methods with CSF culture and India ink stain. Combined testing with both assays should be considered for initial CM diagnosis.

show abstract

“…Similarly, cryptococcal PIIRS in HIV-negative CM patients is also an immune reconstitution resulting from an interaction between Cryptococcus and host factors. Cryptococcus infection had a local immune suppression effect, which may lead to a subsequent partial immune reconstitution after effective antifungal treatment [ 14 – 16 ].…”

Section: Discussionmentioning

confidence: 99%

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient

et al. 2022

BMC Neurol

View full text Add to dashboard Cite

Background Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome. Case presentation A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions. Conclusions This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Graphical abstract Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.

show abstract

Immune reconstitution inflammatory syndrome in non‐HIV cryptococcal meningitis: Cross‐talk between pathogen and host

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 10 publications

References 32 publications

Cerebrospinal fluid cytokine and chemokine patterns correlate with prognosis of HIV-uninfected cryptococcal meningitis: A prospective observational study

Cerebrospinal fluid cytokine and chemokine patterns correlate with prognosis of HIV-uninfected cryptococcal meningitis: A prospective observational study

Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient

Contact Info

Product

Resources

About