Treatment-Resistant Human Extraparenchymal Neurocysticercosis: An Immune-Inflammatory Approach to Cysticidal Treatment Outcome

Arce-Sillas, Asiel; Cárdenas, Graciela; Álvarez-Luquín, Diana Denisse; Hernández, Marisela; Rey, Adriana del; Besedovsky, Hugo O.; Gómez-Fuentes, Sandra; Fragoso, Gladis; Fleury, Agnès; Sciutto, Edda; Adalid‐Peralta, Laura

doi:10.1159/000491394

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…Although the age of the control patients in our study was higher than in the infection groups, similar levels of cytokines were shown in normal individuals who were under 45 years old and those who were over 65 years old, indicating that age does not influence cytokine production (Kim et al, 2011). Similar to the present study, in which 77% of the study subjects were males, others have reported higher numbers of male subjects in their studies, despite females being more prone to inflammatory diseases (Kashyap et al, 2012;Cavellani et al, 2012;Arce-Sillas et al, 2018). In this study, increased levels of cytokines in more than half of the patients did not correlate with CSF cellularity.…”

Section: Discussionsupporting

confidence: 82%

“…Additionally, in adult patients with NCC, higher levels of IL-6 were detected in CSF from patients with high cerebral blood flow velocity, which is associated with disease severity (Góngora-Rivera et al, 2008;Sáenz et al, 2012). The increased levels of proinflammatory cytokines in NCC have been shown to decrease after cure or in treatmentresistant patients (Arce-Sillas et al, 2018;Harrison et al, 2021). In vitro studies have also shown upregulation of IL-8 in monocytes in response to T. solium antigens (Uddin et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Several molecules, namely, monoclonal antibodies (anti-TNFa inhibitor, etanercept), somatostatin analogues, nonspecific MMP inhibitor (doxycycline), aptamers, and Inonotus obliquus polysaccharide showed promise in experimental systems in the control of parasitic inflammatory responses (Khumbatta et al, 2014;Boshtam et al, 2017;Mahanty et al, 2017;Yan et al, 2021). Interestingly, patients who respond to anti-helminthic drugs show upregulation of several genes involved in pro-and anti-inflammatory and immunomodulatory functions, indicating that a pro-inflammatory environment is related to treatment responsiveness and some of them may have a role in neuroprotection (John et al, 2008;Cárdenas et al, 2014;Arce-Sillas et al, 2018). Prevention of neurotropic parasitic diseases can be achieved by immunization/vaccination when available and eradication of parasitic infections by proper sanitation, use of cooked meat, and safe food handling (Hill & Dubey, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

D.V.

2023

Trop Biomed

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The pathogenesis of chronic parasitic central nervous system (CNS) infections, including granulomatous amoebic meningoencephalitis (GAE), cerebral toxoplasmosis (CT), and neurocysticercosis (NCC), is primarily due to an inflammatory host reaction to the parasite. Inflammatory cytokines produced by invading T cells, monocytes, and CNS resident cells lead to neuroinflammation which underlie the immunopathology of these infections. Immune molecules, especially cytokines, can therefore emerge as potential biomarker(s) of CNS parasitic infections. In this study, cerebral spinal fluid (CSF) samples from suspected patients with parasitic infections were screened for pathogenic free-living amoebae by culture (n=2506) and PCR (n=275). Six proinflammatory cytokines in smear and culture-negative CSF samples from patients with GAE (n = 2), NCC (n = 7), and CT (n = 23) as well as control (n = 7) patients were measured using the Multiplex Suspension assay. None of the CSF samples tested was positive for neurotropic free-living amoebae by culture and only two samples showed Acanthamoeba 18S rRNA by PCR. Of the six cytokines measured, only IL-6 and IL-8 were significantly increased in all three infection groups compared to the control group. In addition, TNFa levels were higher in the GAE and NCC groups and IL-17 in the GAE group compared to controls. The levels of IL-1b and IFNg were very low in all the infection groups and the control group. There was a correlation between CSF cellularity and increased levels of IL-6, IL-8, and TNFa in 11 patients. Thus, quantifying inflammatory cytokine levels in CSF might help with understanding the level of neuroinflammation in patients with neurotropic parasitic diseases. Further studies with clinico-microbiological correlation in the form of reduction of cytokine levels with treatment and the correlation with neurological deficits are needed.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

D.V.

2023

Trop Biomed

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The Local Inflammatory Profile and Predictors of Treatment Success in Subarachnoid Neurocysticercosis

Harrison

Thumm

Nash

et al. 2020

Clinical Infectious Diseases

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Background Subarachnoid neurocysticercosis (SANCC) represents the most severe and difficult to treat form of neurocysticercosis. The inflammatory response contributes significantly to the morbidity and mortality of the disease. This study sought to understand the nature and evolution of the inflammation associated with SANCC, and evaluate for predictors of time to cure. Methods There were 16 subjects with SANCC (basilar cistern, sylvian fissure, and/or spinal involvement) during active infection who had cerebrospinal fluid (CSF) cytokine and chemokine profiling, of whom 9 had a second CSF sample at (or following) the time of cure. The relationships between clinical parameters and cytokine/chemokine results were assessed. Results Compared to pools of healthy donor CSF, those with active SANCC showed a significant (P < .05) increase in chemokines and cytokines associated with Type 1 immunity (interferon [IFN] γ, interleukin [IL] 12p70, C-X-C Motif Ligand 10 CXCL-10); Type 2 immunity (IL-10, IL-13); IFNα2; and the chemokines Macrophage inflammatory protein MIP-1α/CCL3, MIP-1ß/CCL4, and Vascular Endothelial Growth Factor VEGF that appears to be locally (central nervous system [CNS]) produced. Compared to those with active disease, those with CSF taken at the time of cure showed a significant decrease in most of these chemokines and cytokines. Despite this, CSF from cured SANCC patients had levels of IL-10 (P = .039), CXCL-10 (P = .039), and IL-12p70 (P = .044) above those seen in CSF from uninfected subjects. High ratios of IL-12p70/IL-10 early in infections were associated with a shorter time to cure (r = −0.559; P = .027), and a high Taenia solium burden (by quantitative polymerase chain reaction) was associated with longer times to cure (r = 0.84; P = .003). Conclusions SANCC is associated with a marked, CNS-localized cytokine-/chemokine-driven inflammatory response that largely decreases with curative therapy, though some analytes persisted above the normal range. The relative balance between proinflammatory and regulatory cytokines may be an important determinant for a cure in SANCC.

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Murine Extraparenchymal Neurocysticercosis: Appropriate Model for Evaluating Anthelminthic and Anti-Inflammatory Treatment Schedules

Oliveira,

Martins,

Conceição

et al. 2024

TropicalMed

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Background: Experimental models of neurocysticercosis (NCC) are helpful for an improved understanding of the pathophysiological mechanisms of human diseases and for testing novel therapeutic approaches. Controlling inflammation without reducing the effectiveness of anthelmintics is an important challenge in treating neurocysticercosis. This study investigates the effects of currently used drugs (Albendazole and Dexamethasone) in treating murine extraparenchymal NCC. Methods: Twenty-two rats were inoculated with Taenia crassiceps in the subarachnoid space. The animals underwent magnetic resonance imaging to ascertain the success of infection 3 months after inoculation. The infected animals were randomly assigned to one of the three groups (five rats each): control (no treatment), Albendazole (ABZ), or Albendazole + Dexamethasone (ABZ + DXM) for 14 days. The animals were subsequently euthanised for morphological assessment 2 weeks after the end of treatment. Results: Macroscopically integrated cysts were found in all animals. The ABZ + DXM animals demonstrated lower ventricular sizes, lymphocyte infiltration rates, and immunopositivity for IL-6, with statistical differences in lymphocytes within the arachnoid region. Conclusions: This experimental model, which has previously shown similarities to human infections, is also helpful in reproducing the morphological changes upon treatment with Albendazole and Dexamethasone.

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Treatment-Resistant Human Extraparenchymal Neurocysticercosis: An Immune-Inflammatory Approach to Cysticidal Treatment Outcome

Cited by 3 publications

References 26 publications

Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

Cerebrospinal fluid inflammatory cytokine profiles of patients with neurotropic parasitic infections

The Local Inflammatory Profile and Predictors of Treatment Success in Subarachnoid Neurocysticercosis

Murine Extraparenchymal Neurocysticercosis: Appropriate Model for Evaluating Anthelminthic and Anti-Inflammatory Treatment Schedules

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