Gnathostoma infection after ingestion of raw fish is a probable cause of eosinophilic meningitis in the Brazilian Amazon.

We report a case of eosinophilic meningitis associated with the ingestion of raw fish (Cichla sp.) from the Brazilian Amazon, likely caused by Gnathostoma. A 36-year-old male visited Juruena river on a fishing trip. After 50 days, the patient presented with an intense frontal headache. A cerebrospinal fluid examination revealed 63% eosinophilia. Another individual who ingested raw fish developed linear dermatitis on the abdominal wall. Anti-Gnathostoma serum antibodies were detected, and the patient made a full recovery after treatment with corticosteroids and albendazole. To date, autochthonous Gnathostoma spp. infections in Latin American countries have only caused linear panniculitis. This report raises awareness of gnathostomiasis-causing meningitis.

Regulation of immune response against third-stage Gnathostoma spinigerum larvae by human genes.

Background: Gnathostomiasis is an important zoonosis in tropical areas that is mainly caused by third-stage Gnathostoma spinigerum larvae (G. spinigerum L3). Objectives: This study aimed to prove whether G. spinigerum L3 produces extracellular vesicles (EVs) and investigate human gene profiles related to the immune response against the larvae. Methods: We created an immune cell model using normal human peripheral blood mononuclear cells (PBMCs) co-cultured with the larvae for 1 and 3 days, respectively. The PBMCs were harvested for transcriptome sequencing analysis. The EV ultrastructure was examined in the larvae and the cultured medium. Results: Extracellular vesicle-like particles were observed under the larval teguments and in the pellets in the medium. RNA-seq analysis revealed that 2,847 and 3,118 genes were significantly expressed on days 1 and 3 after culture, respectively. The downregulated genes on day 1 after culture were involved in pro-inflammatory cytokines, the complement system and apoptosis, whereas those on day 3 were involved in T cell-dependent B cell activation and wound healing. Significantly upregulated genes related to cell proliferation, activation and development, as well as cytotoxicity, were observed on day 1, and genes regulating T cell maturation, granulocyte function, nuclear factor-κB and toll-like receptor pathways were predominantly observed on day 3 after culture. Conclusion: G. spinigerum L3 produces EV-like particles and releases them into the excretory-secretory products. Overall, genotypic findings during our 3-day observation revealed that most significant gene expressions were related to T and B cell signalling, driving T helper 2 cells related to chronic infection, immune evasion of the larvae, and the pathogenesis of gnathostomiasis. Further in-depth studies are necessary to clarify gene functions in the pathogenesis and immune evasion mechanisms of the infective larvae.

A case of vocal cord gnathostomiasis diagnosed with sectional morphologies in a histopathological specimen from a Chinese woman living in Korea.

This study aimed to describe a rare case of gnathostomiasis in the vocal cord. A 54-year-old Chinese woman living in Korea visited with a chief complaint of voice change at the outpatient department of otorhinolaryngology in Hallym Sacred Heart Hospital, Hallym University on August 2, 2021. She had eaten raw conger a few weeks before the voice change developed, but her medical history and physical examinations demonstrated neither gastrointestinal symptoms nor other health problems. A round and red cystic lesion, recognized in the anterior part of the right vocal cord, was removed using forceps and scissors through laryngeal microsurgery. The histopathological specimen of the cyst revealed 3 cross-sections of a nematode larva in the lumen of the cyst wall composed of inflammatory cells and fibrotic tissues. They differ in diameter, from 190 µm to 235 µm. They showed characteristic cuticular layers with tegumental spines, somatic muscle layers, and gastrointestinal tracts such as the esophagus and intestine. Notably, intestinal sections consisted of 27-28 lining cells containing 0-4 nuclei per cell. We tentatively identified the nematode larva recovered from the vocal cord cystic lesion as the third-stage larva of Gnathostoma, probably G. nipponicum or G. hispidum, based on the sectional morphologies.

Susceptibility-weighted imaging is helpful in diagnosis of cerebral gnathostomiasis.

PURPOSE: To describe the role of SWI compared with other MR imaging sequences and CT in diagnosis of cerebral gnathostomiasis. MATERIALS AND METHODS: CTs and MRIs of patients with cerebral gnathostomiasis were retrospectively reviewed. The types of intracranial hemorrhage, including intraparenchymal hemorrhage (IPH), subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), and their locations were recorded. RESULTS: Four patients proven as cerebral gnathostomiasis were included. Intracranial hemorrhage was detected in all patients. There was IPH in all patients, SAH in 2 patients, and SDH in 2 patients. All patients (4/4) revealed hemorrhagic tracts which were very conspicuously seen on SWI. Other imaging sequences could also reveal hemorrhagic tracts in 3 patients (3/4) but are less conspicuously seen than SWI. None of the CT brains could detect hemorrhagic tracts. CONCLUSIONS: Intracranial hemorrhage associated with hemorrhagic tract, best demonstrated by SWI, is the key imaging characteristic in diagnosis of cerebral gnathostomiasis.

Intracameral Gnathostomiasis: A Case Report and Literature Review.

PURPOSE: The purpose of this article is to report a case of ocular gnathostomiasis presenting with acute anterior uveitis and uveitis glaucoma. METHODS: observational case report and literature review. RESULTS: A 56-year-old Thai male was referred to a tertiary eye center with acute anterior uveitis and uveitis glaucoma in the right eye. A nematode was found in the right anterior chamber. Surgical removal of the nematode was successfully performed. Gnathostoma spinigerum was the nematode identified on pathological examination. CONCLUSIONS: Early detection of the parasite and timely surgical removal is the key to the management of ocular gnathostomiasis.

Protein and antigen profiles of third-stage larvae of Gnathostoma spinigerum assessed with next-generation sequencing transcriptomic information.

Gnathostomiasis is a food-borne zoonotic disease that can affect humans who eat improperly cooked meat containg infective third-stage larvae. Definitive diagnosis is through larval recovery. However, this is an invasive technique and is impractical if the larvae have encysted in inaccessible areas of the body. Antigen or antibody detection might be more interesting techniques for diagnosis. Proteomic could elucidate diagnostic markers and improve our understanding of parasite biology. However, proteomic studies on Gnathostoma spinigerum are hampered by the lack of a comprehensive database for protein identification. This study aimed to explore the protein and antigen profiles of advanced third-stage G. spinigerum larvae (aL3Gs) using interrogation of mass spectrometry data and an in-house transcriptomic database for protein identification. Immunoproteomic analysis found 74 proteins in 24-kDa SDS-PAGE bands, which is size-specific for the immunodiagnosis of gnathostomiasis. Moreover, 13 proteins were found in 2-DE 24-kDa bands. The data suggest that collagenase 3, cathepsin B, glutathione S-transferase 1, cuticle collagen 14, major antigen, zinc metalloproteinase nas-4, major egg antigen, peroxiredoxin, and superoxide dismutase [Cu-Zn] may be good candidates for novel human gnathostomiasis diagnostic assays. These findings improve our understanding of the parasite's biology and provide additional potential targets for novel therapeutics, diagnostics, and vaccines.

A Rare Case of Eosinophilic Myelitis Due to Gnathostomiasis.

Eosinophilic myelitis is an important cause of transverse myelopathy and has to be considered in an appropriate clinical setting. Eosinophilic myelitis due to parasitic infection should be suspected in cases with cerebrospinal fluid (CSF) eosinophilia along with migratory serpiginous skin lesions and recent travel to endemic areas. We report a case with a 1-month history of fever followed by truncal paresthesias, erythematous creeping skin eruptions, and paraparesis with blood and CSF eosinophilia on a background history of consuming undercooked fish. Magnetic resonance imaging (MRI) spine showed long segment T2 hyperintensities with contrast enhancement. He was tested positive for 24kDa antigenic component of Gnathostoma spinigerum in CSF and serum by immunoblot testing. The patient showed significant improvement with parenteral steroids.

Ocular Gnathostomiasis Presenting as Branch Retinal Artery Occlusion.

PURPOSE: To report a case of ocular Gnathostomiasis presenting as branch retinal artery occlusion. METHOD: Observational case report. RESULT: A 22-year-old Asian woman presented to her ophthalmologist with redness, tearing, and decreased vision in her left eye. Examination revealed anterior uveitis and branch retinal artery occlusion associated with both intra-retinal and vitreous hemorrhage. The patient was treated with topical corticosteroids and cycloplegics. After 3 weeks, she presented in our emergency, with further decrease in vision and worsening pain in the left eye. Slit lamp examination revealed a brown colored live worm on the posterior corneal surface, anterior uveitis, multiple iris holes, and vitreous cells. Indirect ophthalmoscopy showed focal retinal hemorrhages, subretinal tracts, and vitreous hemorrhage. Surgical removal of the worm from anterior chamber was done immediately. CONCLUSION: Branched retinal artery occlusion with intraretinal and vitreous hemorrhage, panuveitis, and multiple iris holes may suggest the presence of an intraocular parasite.

Human gnathostomiasis in Sri Lanka: an underreported disease?

A healthy young man from Sri Lanka, currently living in Switzerland, consulted at the University Hospital of Geneva with a history of painful erythema and swelling of the left forearm. Laboratory tests showed a slight eosinophilia. Western blot serology for Gnathostoma spp, inconclusive at presentation, became positive 2 weeks later.

Evaluation of immunodiagnostic tests for human gnathostomiasis using different antigen preparations of Gnathostoma spinigerum larvae against IgE, IgM, IgG, IgG1-4 and IgG1 patterns of post-treated patients.

OBJECTIVES: The aims of the study were two-fold: (1) antigen (Ag) preparation and evaluation of three antigens of Gnathostoma spinigerum infective larvae (GsL3), crude somatic antigen (CSAg), excretory-secretory antigen (ESAg) and partially purified antigens (namely P1Ag, P2Ag and P3Ag) to differentiate IgE, IgG, IgG1-4 and IgM for human gnathostomiasis diagnosis; and (2) application of the selected ELISA for following up stored sera of patients treated with ivermectin (IVM) and albendazole (ABZ). METHODS: Different antigens were analysed by antibodies of gnathostomiasis cases, other parasite infections and healthy controls using indirect ELISA to differentiate IgE, IgG, IgG1-4 and IgM. Then, prominent antigen and immunoglobulin were used in antibody predictions of gnathostomiasis cases treated with albendazole or ivermectin. RESULTS: Sensitivity of all evaluated ELISAs: IgM-, IgG-, IgG1- and IgG4-ELISA, was 100%. IgM-ELISA with CSAg and P3Ag exhibited the highest specificity of 99%. IgG-ELISA with P2Ag resulted in the highest specificity of 92.3%. IgG1-ELISA with P2Ag and P3Ag showed excellent results with 100% specificity. Finally, P2Ag evaluated IgG1 of the followed-up cases with ABZ and IVM. Decreasing antibody IgG1 levels were mostly found in both treatments at Month 9 and long follow-up was over 12 months. A Gnathostoma worm was extracted from each two treated patients. CONCLUSIONS: Using IgG1-ELISA against P2Ag and P3Ag gave excellent results with 100% sensitivity and specificity. These tests can be an alternative to immunoblotting for gnathostomiasis. IgG1 decreased at least 9 months in most cases, so long-term treatment should be performed over 1 year.

Atypical gnathostomiasis-confirmed cutaneous larva migrans, Vietnam.

We reported a case of gnathostomiasis in a 42-year-old woman with an unclear history of eating high-risk foods and had a non-migratory skin lesion, negative serological testing and normal blood eosinophil counts. A diagnosis of gnathostomiasis was based on a live, third-stage Gnathostoma spinigerum larva that was randomly taken from the patient's skin lesion by herself. The presenting case report demonstrates challenges in correctly diagnose cutaneous gnathostomiasis even in endemic countries due to atypical skin lesions, negative serology testing and the absence of eosinophilia and thus, the widely used classic triad of suggestive evidence of gnathostomiasis is not fulfilled.

Evaluation of Rapid IgG4 Test for Diagnosis of Gnathostomiasis.

Human gnathostomiasis is a parasitic disease caused by Gnathostoma nematode infection. A rapid, reliable, and practical immunoassay, named dot immuno-gold filtration assay (DIGFA), was developed to supporting clinical diagnosis of gnathostomiasis. The practical tool detected anti-Gnathostoma-specific IgG4 in human serum using crude extract of third-stage larvae as antigen. The result of the test was shown by anti-human IgG4 monoclonal antibody conjugated colloidal gold. The sensitivity and specificity of the test were both 100% for detection in human sera from patients with gnathostomiasis (13/13) and from healthy negative controls (50/50), respectively. Cross-reactivity with heterogonous serum samples from patients with other helminthiases ranged from 0 (trichinosis, paragonimiasis, clonorchiasis, schistosomiasis, and cysticercosis) to 25.0% (sparganosis), with an average of 6.3% (7/112). Moreover, specific IgG4 antibodies diminished at 6 months after treatment. This study showed that DIGFA for the detection of specific IgG4 in human sera could be a promising tool for the diagnosis of gnathostomiasis and useful for evaluating therapeutic effects.

An Unusual Case of Gastric Gnathostomiasis Caused by Gnathostoma spinigerum Confirmed by Video Gastroscopy and Morphological and Molecular Identification.

Human gnathostomiasis is a harmful foodborne parasitic infection caused by nematodes of the genus Gnathostoma. Here, we report an unusual case of gastric gnathostomiasis seen in a hospital in Thailand along with the clinical characteristics, treatment, and outcome. A 39-year-old man presented with complaints of epigastric pain, dizziness, and history of passing dark, tarry stools for 2 days. The patient had a history of consuming raw freshwater fish. Supplementary differential diagnosis was performed via rapid serological testing, and presence of the causative agent was confirmed based on video gastroscopy, morphology of the removed parasite, and molecular identification. After its surgical removal from the stomach, the parasite was morphologically identified as Gnathostoma species. Molecular identification was performed via DNA extraction from the recovered worm, and amplification and sequencing of the second internal transcribed spacer (ITS2) region and partial cytochrome c oxidase subunit I (cox1) gene. The ITS2 and cox1 sequences were consistent with those of Gnathostoma spinigerum. Clinicians in endemic areas should therefore be aware of the rare clinical manifestations and use of supplementary serological tests to facilitate early diagnosis and treatment of gastric gnathostomiasis.