Dataset Information

Eosinophilic meningitis in New Caledonia: The role of Angiostrongylus cantonensis?

ABSTRACT:

Introduction

Eosinophilic meningitis is a rare form of meningitis with sequelae or death occurring in approximately 2-3% of cases. The most frequent etiological agent is the parasite Angiostrongylus cantonensis. The aim of this study was to characterize New Caledonian cases and to assess the extent to which of A. cantonensis was involved.

Material and methods

We performed a retrospective study of all cases of eosinophilic meningitis (EM) admitted to the Territorial Hospital of New Caledonia, from 2004 to 2019. We performed a descriptive and a multivariate analysis to identify association of variables with severe and fatal cases (or cases with sequelae).

Conclusion

Angiostrongyliasis was confirmed as being responsible for 17 of the 92 reported EM cases in New Caledonia from 2004 to 2019 with most being young adults and non-walking infants, and with two peaks of incidence one during the dry season and one during the rainy season. Considering the high incidence and regularity of cases, the potential reservoirs should be identified to target prevention campaigns.

SUBMITTER: Melot B

PROVIDER: S-EPMC8360557 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Angiostrongylus cantonensis is a parasite endemic in the Southeast Asian and Pacific regions. Humans are incidentally infected either by eating uncooked intermediate hosts or by consuming vegetables containing the living third-stage larvae. The 14-3-3? protein is a cerebrospinal fluid (CSF) marker of neuronal damage during the development of Creutzfeldt-Jakob disease. In addition, increased 14-3-3? protein is also found in CSF from patients with a variety of neurological disorders. The goal of this study is to determine the roles of serum/CSF14-3-3? protein in patients with eosinophilic meningitis. METHODS: In a cohort study among nine Thai laborers with eosinophilic meningitis due to eating raw snails (Pomacea canaliculata), we examined the CSF weekly while patients were still hospitalized and followed up the serum for 6 months. The levels of 14-3-3? protein in CSF were analyzed by western blot and an in-house 14-3-3? enzyme-linked immunosorbent assay (ELISA) measurement was established and tested in an animal model of eosinophilic meningitis. RESULTS: The elevated 14-3-3? level was detected in the CSF from eight out of nine (81%) patients After 2 weeks of treatment, all patients showed a declined level or cleared of 14-3-3? protein in the CSF. By developing an in-house ELISA for measurement of 14-3-3? protein, it was found that the serum 14-3-3? level was significantly increased in patients during initial visit. . This finding was consistent to the animal experiment result in which there was severe blood brain barrier damage three weeks after infection and increased 14-3-3? protein expression in the CSF and serum by western blot and in house ELISA. After treatment, the serum 14-3-3? level in meningitis patients was rapidly returned to normal threshold. There was a correlation between initial CSF 14-3-3? level with severity of headache (r?=?0.692, p?=?0.039), CSF pleocytosis (r?=?0.807, p?=?0.009) and eosinophilia (r?=?0.798, p?=?0.01) in the CSF of patients with eosinophilic meningitis (Spearman's correlation test). CONCLUSIONS: The serum 14-3-3? concentrations may constitute a useful marker for blood brain barrier damage severity and follow up in patients with eosinophilic meningitis caused by A. cantonensis.

Project description:The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after infection. The Evans blue method and BBB junctional protein expressions were used to measure changes in the BBB. Hematoxylin and eosin staining was used to analyze pathological changes in the mice brains following 1-3 weeks of infection with A. cantonensis. The levels of 14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different isoform distributions of 14-3-3 proteins and changes in BBB junctional proteins in the mice brain meninges. Dexamethasone was injected intraperitoneally from the seventh day post infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional proteins. The amounts of Evans blue, tight junction and 14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in 14-3-3 protein isoforms ? and ? in the CSF in the second and third weeks after infection compared to the controls and first week of infection, which were correlated with the severity of BBB damage in brain histology, and Evans blue extravasation. Using IHC to assess the distribution of 14-3-3 protein isoforms and changes in BBB junctional proteins in the mice brain meninges, the expressions of isoforms ?, ?, ?, and ? and junctional proteins occludin and claudin-5 in the brain meninges increased over a 3-week period after infection compared to the controls and 1 week after infection. The administration of dexamethasone decreased the expressions of BBB junctional proteins occludin and claudin-5 in the mice brain meninges. Our findings support that 14-3-3 proteins ? and ? can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic meningitis caused by A. cantonensis.

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