Human gnathostomiasis: A review on the biology of the parasite with special reference on the current therapeutic management.

Gnathostoma is a parasitic nematode that can infect a wide range of animal species, but human populations have become accidental hosts because of their habit of eating raw or undercooked meat from a wide variety of intermediate hosts. While gnathostomiasis is considered an endemic disease, cases of human gnathostomiasis have been increasing over time, most notably in nonendemic areas. There are several complexities to this parasitic disease, and this review provides an update on human gnathostomiasis, including the life cycle, diagnosis, treatment, and treatment strategies used to combat drug resistance. Even now, a definitive diagnosis of gnathostomiasis is still challenging because it is difficult to isolate larvae for parasitological confirmation. Another reason is the varying clinical symptoms recorded in reported cases. Clinical cases can be confirmed by immunodiagnosis. For Gnathosotoma spinigerum, the detection of IgG against a specific antigenic band with a molecular weight of 24 kDa from G. spinigerum advanced third-stage larvae (aL3), while for other species of Gnathostoma including G. binucleatum, the 33-kDa antigen protein is being used. This review also discusses cases of recurrence of gnathostomiasis and resistance mechanisms to two effective chemotherapeutics (albendazole and ivermectin) used against gnathostomiasis. This is significant, especially when planning strategies to combat anthelmintic resistance. Lastly, while no new chemotherapeutics against gnathostomiasis have been made available, we describe the management of recurrent gnathostomiasis using albendazole and ivermectin combinations or extensions of drug treatment plans.

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.

Infection levels of Gnathostomatidae (Nematoda) larvae in commercial fishes in north-eastern Australian waters and related food safety concerns.

The majority of research on the safety of marine edible fish has primarily focused on anisakid nematodes, neglecting the potential risks posed by other parasites, including those belonging to the family Gnathostomatidae. In Australia, there have been few reported cases of human infections with gnathostomatid parasites since 2011. However, due to the absence of a standardized diagnostic test in the country, it is believed that the actual number of infections is higher than reported. This study aimed to assess the occurrence and prevalence of infectious gnathostomatid parasites in selected commercial fish species in Australia. A total of 1947 marine fish from northern Australia, representing 9 families, 16 genera, and 30 species, were examined for gnathostomatid nematode infections. Overall, 12.3 % of the fish were found to be infected with at least one gnathostomatid larva. Among the species examined, the yellow-dabbled flounder (Branchypleura novaezeelandiae) exhibited the highest prevalence (83.3 %; n = 6) and the largest number of gnathostomatid larvae. The identification of the gnathostomatid larvae was confirmed as belonging to the genus Echinocephalus based on both morphological characteristics and sequence data. No significant correlation was observed between the prevalence, mean abundance, and mean intensity of infection with the length or weight of the examined fish species. Notably, several of the infected fish species are considered popular choices in the Australian market. Hence, it is imperative to raise awareness among relevant food safety authorities regarding the occurrence of these parasites. The findings from this study should be taken into consideration for the revision of current seafood safety protocols in the country.

Possible zoonotic implications of the discovery of the advanced third stage larva of Gnathostoma turgidum (Spirurida: Gnathostomatidae) in a Mexican fish species.

Gnathostomiasis in humans is acquired by consumption of any infected second intermediate host or paratenic host. This includes amphibians, snakes and poultry as well as fish. In this work we report for the first time in Mexico the presence of an AdvL3 of Gnathostoma turgidum in the musculature of a wild fish (Gobiomorus dormitor, which also acts as intermediate host for the larvae of G. binucleatum and G. lamothei), from the Papaloapan River, Veracruz; previously, larvae of G. turgidum had only been recorded in amphibians in Mexico and in wild swamp eels from Tampa, Florida, USA. The larva found is extremely small (approximately 1,500 by 140 microns in length and width, respectively), and was obtained by artificial digestion with pepsin after examining the musculature against the light between two glass plates, a method by which it went unnoticed. Our finding of an AdvL3 in this fish, together with a previous molecular phylogenetic analysis revealing that the five species involved in human infections do not nest in the same clade, suggest that all species in the genus are potentially zoonotic. In this context, we strongly recommend the identification of larvae extracted from human patients at specific level, in order to know the role played by the 3 species distributed in Mexico in human cases of 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.

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.

Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Subretinal gnathostomiasis: A successful focal laser photocoagulation for a living parasite.

PURPOSE: To report a case of subretinal gnathostomiasis presenting with progressive subretinal tracts of a living parasite and successfully treated with focal laser photocoagulation. METHOD: Observational case report. PATIENT: A 29-year-old Thai male complained of blurred vision and floaters in his left eye for two weeks. An ocular examination showed multiple, whitish, subretinal tracks at the superotemporal retina. After 5 days of oral albendazole, a moving parasite was confirmed by multimodal retinal imaging. An immunoblotting analysis was positive for Gnathostoma species. RESULT: The patient was treated by laser photocoagulation with frequency-doubled Nd:YAG laser around and over the parasite. Oral albendozole was continued and naproxen was prescribed for four weeks. His vision improved to 20/20 and the inflammation subsided completely within three months. The patient has been followed for five years without local and systemic complications. CONCLUSIONS: Focal laser photocoagulation without systemic steroids could be a successful treatment for active subretinal gnathostomiasis with a satisfactory safety profile in a long-term follow-up.

Eosinophilic Granuloma of the Liver Mimicking Metastatic Liver Tumor.

We herein report a case of coagulation necrosis with granulation and eosinophilic infiltration of the liver. A 37-year-old woman was diagnosed with a new mass lesion in the liver 1 month after breast cancer surgery and admitted for a further examination. Because the tumor occurred immediately after surgery, it was considered essential to determine whether or not it was a metastatic liver tumor from breast cancer. A percutaneous liver tumor biopsy revealed eosinophilic granuloma of the liver, which is considered to have a high possibility of visceral larva migrans with suspected gnathostomiasis infection. A detailed medical history and histological diagnosis are important for making a differential diagnosis.

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.

Proteomics of Gnathostomiasis: A Way Forward for Diagnosis and Treatment Development.

Gnathostoma spinigerum is the most common cause of gnathostomiasis in humans. It has a complex life cycle, which requires two intermediate hosts and a definitive host, and poses a high risk for zoonosis. Definitive prognosis of gnathostomiasis relies mainly on the isolation of advanced-stage larvae (aL3), which is very challenging especially if the aL3 is sequestered in difficult-to-reach organs. There is also a lack of a confirmatory diagnostic test for gnathostomiasis. With the ongoing advancement of proteomics, a potential diagnostic approach is underway using immunoproteomics and immunodiagnostics. In addition to this, the employment of mass spectrometry could further elucidate not only understanding the biology of the parasite but also determining potential targets of prospective drugs and vaccines. This article reports the past, present, and future application of proteomics in the study of gnathostomiasis.

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.

Development of Immunochromatographic Test Kit for Rapid Detection of Specific IgG4 Antibody in Whole-Blood Samples for Diagnosis of Human Gnathostomiasis.

Human gnathostomiasis is a harmful food-borne zoonosis caused by roundworms of the genus Gnathostoma. The parasite can occasionally migrate to the central nervous system, causing life-threatening disease and death. Here, we report a new point-of-care (POC) test kit, the gnathostomiasis blood immunochromatographic test (GB-ICT) kit. The kit is based on recombinant Gnathostoma spinigerum antigen and detects specific IgG4 antibody in whole-blood samples (WBSs). The GB-ICT kit showed potentially high diagnostic values with simulated WBSs (n = 248), which were obtained by spiking patients' sera with red blood cells. The accuracy, sensitivity, specificity, and positive and negative predictive values were 95.2%, 100%, 93.8%, 81.5%, and 100%, respectively. Ten WBSs from clinically suspected gnathostomiasis patients were all positive according to the GB-ICT kit, while 10 WBSs from healthy volunteers were negative. The GB-ICT kit is a simple and convenient POC testing tool using finger-prick blood samples: venous blood sampling and serum separation processes are not required. The GB-ICT kit can support clinical diagnosis in remote areas and field settings without sophisticated equipment facilities.

Human gnathostomiasis: a neglected food-borne zoonosis.

BACKGROUND: Human gnathostomiasis is a food-borne zoonosis. Its etiological agents are the third-stage larvae of Gnathostoma spp. Human gnathostomiasis is often reported in developing countries, but it is also an emerging disease in developed countries in non-endemic areas. The recent surge in cases of human gnathostomiasis is mainly due to the increasing consumption of raw freshwater fish, amphibians, and reptiles. METHODS: This article reviews the literature on Gnathostoma spp. and the disease that these parasites cause in humans. We review the literature on the life cycle and pathogenesis of these parasites, the clinical features, epidemiology, diagnosis, treatment, control, and new molecular findings on human gnathostomiasis, and social-ecological factors related to the transmission of this disease. CONCLUSIONS: The information presented provides an impetus for studying the parasite biology and host immunity. It is urgently needed to develop a quick and sensitive diagnosis and to develop an effective regimen for the management and control of human gnathostomiasis.

Autochthonous Gnathostomiasis in Madagascar.

We used molecular tools to identify an autochthonous case of gnathostomiasis in Madagascar. This severe ocular infection, caused by Gnathostoma spinigerum nematodes, led to vision loss in the patient's left eye. Clinicians should be aware of this parasitosis in Madagascar and other countries in Africa.