Angiostrongylus cantonensis Eosinophilic Meningitis in an Infant, Tennessee, USA.
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ABSTRACT:
SUBMITTER: Flerlage T
PROVIDER: S-EPMC5621543 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
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Angiostrongylus cantonensis Eosinophilic Meningitis in an Infant, Tennessee, USA.
Flerlage Tim T Qvarnstrom Yvonne Y Noh John J Devincenzo John P JP Madni Arshia A Bagga Bindiya B Hysmith Nicholas D ND
Emerging infectious diseases 20171001 10
Angiostrongylus cantonensis, the rat lungworm, is the most common infectious cause of eosinophilic meningoencephalitis worldwide. This parasite is endemic to Southeast Asia and the Pacific Islands, and its global distribution is increasing. We report A. cantonensis meningoencephalitis in a 12-month-old boy in Tennessee, USA, who had not traveled outside of southwestern Tennessee or northwestern Mississippi. ...[more]
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Project description:IntroductionEosinophilic 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 methodsWe 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).ConclusionAngiostrongyliasis 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.
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Project description:We utilized polymerase chain reaction (PCR) to demonstrate that Angiostrongylus cantonensis was responsible for 67.3% of 55 cases of eosinophilic meningitis from a cohort of 1,690 adult patients with CNS infection at a tertiary hospital in southern Vietnam. Longer duration of illness, depressed consciousness, and peripheral blood eosinophilia were associated with PCR positivity.
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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.
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Project description:Histone deacetylase inhibitor (HDACi) has been used in the treatment of neurodegenerative or autoimmune diseases. Angiostrongyliasis cantonensis caused by Angiostrongylus cantonensis infection is an emerging zoonosis of human eosinophilic meningitis or meningoencephalitis. Progressive neuronal apoptosis is the pathological basis of behavioral dysfunctions in angiostrongyliasis cantonensis. Neurological defects after anthelmintic treatment for angiostrongyliasis cantonensis are still common. In this study, we examined the effects of trichostatin A (TSA), a HDACi, on eosinophilic meningitis induced by A. cantonensis in mice. Intragastric administration of TSA significantly ameliorated brain injury and decreased cognitive impairments in mice at 15 days post-infection. TSA administration effectively reduced the inflammatory factor levels of iNOS, TNF-α, IL-5, IL-6, and IL-13 in infected mice. TSA treatment counteracted apoptosis with reduced expression levels of cleaved caspase-3, -4, -6, and RIP3 in A. cantonensis infected mice. In addition, TSA administration reduced total HDAC activity and increased the acetylation of histone H3 and H4 in the brain tissue of infected mice. The underlying mechanism of TSA on eosinophilic meningitis might be associated with decreased NF-κB p65 nuclear accumulation by inhibiting IκB phosphorylation. Furthermore, a co-expressive network of NF-κB p65 with 22 other genes was constructed according to our previous transcriptomic data in infected mice. We identified the correlations in the gene expression of NF-κB p65 with Lrp10, Il12rb1, Nfkbia, Ube2n, and Ube2d1 in infected mice after TSA administration. Thus, TSA has a protective effect on the progression of eosinophilic meningitis induced by A. cantonensis in mice.
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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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Project description:BackgroundAngiostrongylus cantonensis (rat lungworm) is recognised as the leading cause of human eosinophilic meningitis, a serious condition observed when nematode larvae migrate through the CNS. Canine Neural Angiostrongyliasis (CNA) is the analogous disease in dogs. Both humans and dogs are accidental hosts, and a rapid diagnosis is warranted. A highly sensitive PCR based assay is available but often not readily accessible in many jurisdictions. An alternative DNA amplification assay that would further improve accessibility is needed. This study aimed to assess the diagnostic utility of a newly designed LAMP assay to detect DNA of globally distributed and invasive A. cantonensis and Angiostrongylus mackerrasae, the other neurotropic Angiostrongylus species, which is native to Australia.Methodology/principal findingsCerebrospinal fluid (CSF) from dogs with a presumptive diagnosis of A. cantonensis infection (2020-2022) were received for confirmatory laboratory testing and processed for DNA isolation and ultrasensitive Angiostrongylus qPCR targeting AcanR3390. A newly designed LAMP assay targeting the same gene target was directly compared to the reference ultrasensitive qPCR in a diagnostic laboratory setting to determine the presence of A. cantonensis DNA to diagnose CNA. The LAMP assay (Angie-LAMP) allowed the sensitive detection of A. cantonensis DNA from archived DNA specimens (Kappa = 0.81, 95%CI 0.69-0.92; n = 93) and rapid single-step lysis of archived CSF samples (Kappa = 0.77, 95%CI 0.59-0.94; n = 52). Only A. cantonensis DNA was detected in canine CSF samples, and co-infection with A. mackerrasae using amplicon deep sequencing (ITS-2 rDNA) was not demonstrated. Both SYD.1 and AC13 haplotypes were detected using sequencing of partial cox1.Conclusions/significanceThe Angie-LAMP assay is a useful molecular tool for detecting Angiostrongylus DNA in canine CSF and performs comparably to a laboratory Angiostrongylus qPCR. Adaptation of single-step sample lysis improved potential applicability for diagnosis of angiostrongyliasis in a clinical setting for dogs and by extension, to humans.
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Project description:A red ruffed lemur (Varecia rubra) from a zoo in Louisiana, USA, was euthanized for worsening paresis. Brain and spinal cord histology identified eosinophilic meningoencephalomyelitis with intralesional adult Angiostrongylus sp. nematodes. PCR and sequencing confirmed A. cantonensis infection, indicating this parasite constitutes an emerging zoonosis in the southeastern United States.
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Project description:BACKGROUND:Angiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis. METHODS:Mathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection. The expression level of Chi3l3, the predicted key molecule, was verified using Western blotting and real-time quantitative PCR. Critical cell source of Chi3l3 and its relationship with eosinophils were identified with flow cytometry, immunohistochemistry, and further verified by macrophage depletion using liposomal clodronate. The role of soluble antigens of Angiostrongylus cantonensis in eosinophilic response was identified with mice airway allergy model by intranasal administration of Alternaria alternate. The relationship between Chi3l3 and IL-13 was identified with flow cytometry, Western blotting, and Seahorse Bioscience extracellular flux analyzer. RESULTS:We analyzed the skewed cytokine pattern in brains of Angiostrongylus cantonensis-infected mice and found Chi3l3 to be an important molecule, which increased sharply during the infection. The percentage of inflammatory macrophages, the main source of Chi3l3, also increased, in line with eosinophils percentage in the brain. Network analysis and mathematical modeling predirect a functional association between Chi3l3 and IL-13. Further experiments verified that the soluble antigen of Angiostrongylus cantonensis induce brain eosinophilic meningitis via aggravating a positive feedback loop between IL-13 and Chi3l3. CONCLUSIONS:We present evidences in favor of a key role for macrophave-derived Chi3l3 molecule in the infection of Angiostrongylus cantonensis, which aggravates eosinophilic meningitis induced by Angiostrongylus cantonensis via a IL-13-mediated positive feedback loop. These reported results constitute a starting point for future research of angiostrongyliasis pathogenesis and imply that targeting chitinases and chitinase-like-proteins may be clinically beneficial in Angiostrongylus cantonensis-induced eosinophilic meningitis.
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Project description:Angiostrongylus cantonensis Genome sequencing and assembly
| PRJNA260338 | ENA