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Gnathostomiasis, caused by the advanced third-stage larvae of Gnathostoma spinigerum, demands novel treatment avenues. The ethanolic root extract of Stemona collinsiae has been postulated to have anthelminthic properties, suggesting its potential as an alternative remedy. In this study, S. collinsiae roots were collected, identified, and extracted with 95 % ethanol. The crude extracts were standardized using didehydrostemofoline as chemical marker. The efficacy of the S. collinsiae root extract against third-stage larvae of G. spinigerum and its toxicity to Wistar rats were evaluated. Both in vitro and in vivo tests were performed, where the in vitro tests assessed the anthelminthic potential of S. collinsiae extract against G. spinigerum larvae, while in vivo tests examined the extract's efficacy against G. spinigerum larvae in infected Wistar rats and the efficacy was compared with albendazole. Parallelly, Wistar rats underwent acute and sub-chronic toxicity tests to establish the safe dosage of the extract. The in vitro tests showcased significant anthelminthic activity, marked by discernible morphological alterations in the exposed larvae. Acute toxicity proved fatal at 2000 mg/kg body weight, while a dose of 300 mg/kg proved non-toxic. Using the Globally Harmonized Classification System, an LD50 of 500 mg/kg was determined. In vivo trials revealed a pronounced decline in G. spinigerum larvae among rats treated with the S. collinsiae extract. The larvae were also observed to be encysted post-treatment, while those treated with albendazole were not encysted. The S. collinsiae extract, with its noteworthy in vitro efficacy and favorable safety metrics in rodents, can be a potential anthelminthic agent. The diminished inflammatory response compared to albendazole hints at S. collinsiae being a safer gnathostomiasis treatment alternative. The promising results in these preliminary trials warrant a deeper investigation to determine the root extract's optimal dosing, suitable delivery methods, and its broader clinical implications.

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.

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.

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-kB 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. [ABSTRACT FROM AUTHOR]

This study aimed to describe a rare case of gnathostomiasis in the vocal cord. A 54-yearold 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 thirdstage larva of Gnathostoma, probably G. nipponicum or G. hispidum, based on the sectional morphologies. [ABSTRACT FROM AUTHOR]

The purpose of this article is to report a case of ocular gnathostomiasis presenting with acute anterior uveitis and uveitis glaucoma. observational case report and literature review. 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. Early detection of the parasite and timely surgical removal is the key to the management of ocular gnathostomiasis. [ABSTRACT FROM AUTHOR]

Stemona collinsiae Craib., Stemonaceae, has been traditionally used as medicinal plants for insecticides, treatment of parasitic worms and various diseases in Southeast Asian countries. Its ethanolic root extract has been postulated for anthelminthic activities which has a potential for development for human gnathostomiasis drug. To investigate the pharmacokinetic profile, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for the quantification of didehydrostemofoline in rats' plasma was developed and validated. The chromatographic separation was performed on a C 18 column using 1 mM ammonium acetate in water and methanol (50:50, v /v). Tetrahydropalmatine was used as an internal standard. The multiple reaction monitoring mode was used for quantitative analysis. The validated method showed good sensitivity, linearity, precision, and accuracy. The results of stability showed that didehydrostemofoline was stable in the extracted samples in auto-sampler for 24 h and in the plasma samples under room temperature for 24 h, −20 °C for 1 month, and after three freeze-thaw processes. The developed method was applied to the pharmacokinetic study of didehydrostemofoline after oral administration of S. collinsiae root extract. Didehydrostemofoline was rapidly absorbed from the gastrointestinal tract. The time to peak drug concentration was 1.75 ± 0.62 h with maximum drug concentration of 1152.58 ± 271.18 ng/mL. Didehydrostemofoline was rapidly eliminated from the body with terminal half-life of 1.86 ± 0.50 h. Calculated drug clearance of didehydrostemofoline was 96.82 ± 23.51 L/h and volume of distribution was 260.40 ± 96.81 L. The present study provided useful data for understanding drug disposition in the body with dynamic time-course which could be beneficial for further clinical trials. [Display omitted] [ABSTRACT FROM AUTHOR]

Gnathostomiasis is a fish-borne zoonotic infection caused by eating infected seafood or fish parasitized by third-stage nematode larvae of the genus Gnathostoma. Twenty-seven fish specimens of the European eel Anguilla anguilla (Anguillidae) were collected from water coasts of the Mediterranean Sea in Egypt. Of the 27 fish that were studied, 14 fish (51.58%) were parasitized with third-stage larvae (L3) of Gnathostoma sp. (Gnathostomatidae), these larvae were investigated as encapsulated on the surface of different visceral organs and some embedded in muscles of the infected fish. By using both light and scanning electron microscopes, the morphological examination of the recovered nematodes revealed that the main diagnostic features represented by an elongated body, measured 6.5±2 (7.8-9) mm long, and its greatest width observed at the posterior one-third of the body was 0.4±0.02 (0.38-0.44) mm with narrow lateral alae, the presence of a cephalic bulb measured 0.26±0.02 (0.18-0.28) mm long, 0.31±0.02 (0.28-0.34) wide and armed with six transverse rows of spines, mouth opening surrounded by two simple lateral lips, and conical tail terminated with a pointed mucron. The described species was morphologically and morphometrically compared with some of the previously recorded species of the same genus. Based on our detailed description, the present species was identified as Gnathostoma sp. recovered from A.anguilla as the first record in Egypt. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Gnathostomiasis, caused by the advanced third-stage larvae of Gnathostoma spinigerum , demands novel treatment avenues. The ethanolic root extract of Stemona collinsiae has been postulated to have anthelminthic properties, suggesting its potential as an alternative remedy. In this study, S. collinsiae roots were collected, identified, and extracted with 95 % ethanol. The crude extracts were standardized using didehydrostemofoline as chemical marker. The efficacy of the S. collinsiae root extract against third-stage larvae of G. spinigerum and its toxicity to Wistar rats were evaluated. Both in vitro and in vivo tests were performed, where the in vitro tests assessed the anthelminthic potential of S. collinsiae extract against G. spinigerum larvae, while in vivo tests examined the extract's efficacy against G. spinigerum larvae in infected Wistar rats and the efficacy was compared with albendazole. Parallelly, Wistar rats underwent acute and sub-chronic toxicity tests to establish the safe dosage of the extract. The in vitro tests showcased significant anthelminthic activity, marked by discernible morphological alterations in the exposed larvae. Acute toxicity proved fatal at 2000 mg/kg body weight, while a dose of 300 mg/kg proved non-toxic. Using the Globally Harmonized Classification System, an LD50 of 500 mg/kg was determined. In vivo trials revealed a pronounced decline in G. spinigerum larvae among rats treated with the S. collinsiae extract. The larvae were also observed to be encysted post-treatment, while those treated with albendazole were not encysted. The S. collinsiae extract, with its noteworthy in vitro efficacy and favorable safety metrics in rodents, can be a potential anthelminthic agent. The diminished inflammatory response compared to albendazole hints at S. collinsiae being a safer gnathostomiasis treatment alternative. The promising results in these preliminary trials warrant a deeper investigation to determine the root extract's optimal dosing, suitable delivery methods, and its broader clinical implications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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.

Normal cerebrospinal fluid (CSF) does not contain eosinophils. The presence of >10 eosinophils/μL in CSF or at least 10% eosinophils in total CSF leukocyte count confirms eosinophilic meningitis. We present three patients with eosinophilic meningitis from the same locality with peripheral eosinophilia.

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. [ABSTRACT FROM AUTHOR]

Abstract: Gnathostomiasis is a parasitic infection caused by the third larval stage of nematodes of the genus Gnathostoma. The disease is endemic in some countries around the world. In the American continent, the majority of cases is concentrated in Mexico, Ecuador, and Peru. However, due to increasing traveling either at the intercontinental or intracontinental level, the disease is seen each time more frequently in tourists. Furthermore, countries, such as Brazil, that have never been considered endemic are reporting autochthonous cases. The disease usually presents as a deep-seated or slightly superficial migratory nodule in patients with history of eating raw fish, in the form of ceviche, sushi, or sashimi. Along with the clinical presentation, diagnostic criteria include either blood or tissue eosinophilia. In most instances, these criteria are enough for the attending physician to institute therapy. Chances of finding the parasite are low, unless the biopsy is taken from a very specific area that develops after antiparasitic treatment is started. The potential of other organ involvement with more serious consequences should always be kept in mind.

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. [ABSTRACT FROM AUTHOR]

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.

Normal cerebrospinal fluid (CSF) does not contain eosinophils. The presence of >10 eosinophils/µL in CSF or at least 10% eosinophils in total CSF leukocyte count confirms eosinophilic meningitis. We present three patients with eosinophilic meningitis from the same locality with peripheral eosinophilia. [ABSTRACT FROM AUTHOR]

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. • A total of 1947 marine fish were examined for the infection with gnathostomatid nematodes. • Infectious stage of the parasite was found in 12.3 % of the examined fish. • Some of the examined fish such as snapper are among high value and popular fish. • The results are important for revising the current seafood safety protocols in the country. [ABSTRACT FROM AUTHOR]

Gnathostomiasis is a zoonotic nematode parasite disease, most commonly acquired by eating raw or undercooked fish. Although the disease is well known in parts of Asia and Central and South America, relatively few cases have been reported from Africa. Raw fish consumed in the Okavango River delta area of Botswana, and in nearby western Zambia, has previously produced laboratory-proven gnathostomiasis in tourists. The purpose of this communication is to record additional cases of the infection acquired in the Okavango delta, and to alert visitors to the inadvisability of eating raw freshwater fish in the southern African region.

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. [ABSTRACT FROM AUTHOR]

Along with globalization of traveling and trading, fish-borne nematodiases seems to be increasing in number. However, apart from occasional and sporadic case reports or mini-reviews of particular diseases in particular countries, an overview of fish-borne nematodiasis among travelers have never been performed. In this review, we gathered fishborne nematodiasis among travelers for recent 25 years by an extensive global literature survey using appropriate keywords, e.g. travelers diseases, human infection, anisakiasis, gnathostomiasis, capillariasis, sushi, sashimi, ceviche, Gnathostoma, Pseudoterranova, Anisakis, Capillaria, etc., as well as various combinations of these key words. The Internet search engines PubMed, Medline, Google and Googler Scholar were used as much as possible, and the references of every paper were checked in order to identify useful and reliable publications. The results showed unexpectedly high incidence of gnathostomiasis and low incidence of anisakidosis. The different incidence values of the infection with several fish-borne zoonotic nematode species are discussed, as well as some epidemiological aspects of the infections. The difficulties of differential diagnosis in non-endemic countries are emphasized. It is concluded that travelers must avoid risky behaviors which can lead to infection and that physicians and health authorities must advice travelers on the risks of eating behaviors during travel. [ABSTRACT FROM AUTHOR]

Gnathostomiasis is transmitted to humans via ingestion of third-stage larva of genus Gnathostoma. Thailand is considered an endemic area for the disease. We reported a 65-year-old Thai male patient with clinical presentation of a small number of nodular migratory swellings on the face and neck. The histopathology of skin biopsy revealed parasitic material surrounded by eosinophil infiltration and fibrosis in deep dermis. Therefore, we were able to confirm diagnosis of cutaneous gnathostomiasis. After treatment with ivermectin followed by albendazole, the lesions still persisted; thus, surgical excision of lesions may be the necessary curative treatment.

Human gnathostomiasis is a food-borne zoonosis caused by a tissue nematode of the genus Gnathostoma. The disease is highly endemic in Asia, including Thailand. The freshwater swamp eel (Monopterus albus), the second intermediate host of the gnathostome nematode, has an important role in transmitting the infection in Thailand. Surveys on the infective larvae of Gnathostoma spinigerum based on morphological features in freshwater swamp eels have been performed continuously and reported in Thailand. However, there is still limited molecular data on intra-species variations of the parasite. In this study, a total of 19 third-stage larvae of morphologically identified G. spinigerum were collected from 437 liver samples of freshwater swamp eels purchased from a large wholesale market in Bangkok, Thailand. Molecular characterization based on mitochondrial cytochrome c oxidase subunit I (COI) sequences was performed to elucidate their genetic variations and phylogenetic relationship. Among the 19 infective larvae recovered from these eels, 16 were sequenced successfully. Phylogenetic analyses inferred from the partial COI gene showed the presence of three distinct COI haplotypes. Our findings confirm the presence of G. spinigerum as the main species in Thailand. [ABSTRACT FROM AUTHOR]

We describe a case of imported cutaneous gnathostomiasis in a Thai patient living in France. Gnathostomiasis is a zoonosis of food origin. The disease is endemic in Southeast Asia and Latin America. However, over the past 30 years, an increasing number of imported cases has been described in Europe and America. The disease is rare in Western Europe and the majority of cases described had a cutaneous clinical presentation. The disease may sometimes be confused with allergy, leading to a delay in diagnosis. Visceral symptoms are rare but may follow severe attacks. A definitive diagnosis can be obtained by the isolation of larvae from skin biopsies, but these are rarely performed. The diagnosis is usually presumptive, based on a combination of anamnestic, clinical, and biological factors. Several courses of the anti-helminths, albendazole or ivermectin, are often necessary. Although rare, the diagnosis should be evoked systematically in a migrant or traveller returning from an endemic area with cutaneous lesions. [ABSTRACT FROM AUTHOR]

Human gnathostomiasis caused by third-stage Gnathostoma spinigerum larvae ( G. spinigerum L3) is an important zoonotic disease in tropical areas of the world. The excretory-secretory products (ES) that are excreted by infective larva play a significant role in host immune evasion and tissue destruction. To investigate the poorly understood mechanisms of G. spinigerum L3 pathogenesis, we focused on the potential effect of ES on inducing apoptosis in human immune cells by using human peripheral blood mononuclear cells (PBMCs) as a model. Early and late apoptosis of PBMCs were assessed following the exposure of these cells to G. spinigerum L3 ES (0.1, 0.5, and 1.0 μg/ml) for 6-48 h. The apoptotic cells were identified by flow cytometric staining of PBMC with FITC-annexin V and propidium iodide. The expression of regulatory genes related to apoptosis mechanisms in ES-treated PBMCs was investigated using a Human Apoptosis RT Profiler™ PCR Array. The results showed significant levels of early phase apoptosis at 18 h and of late phase apoptosis at 24 h. We speculate that this apoptosis in PBMCs occurs via the extrinsic pathway. Apoptosis in the ES-induced PBMCs was observed as quickly as 90 min after exposure, and the highest effect was observed at 18-24 h. Furthermore, ES can trigger apoptosis lasting for 48 h. Our findings expand the understanding of one of the mechanisms involved, immune-evasive strategy mechanism used by G. spinigerum larvae during human gnathostomiasis. [ABSTRACT FROM AUTHOR]

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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., Competing Interests: The authors hereby declare no conflict of interest., (© 2023 The Authors. Published by Elsevier Inc. on behalf of International Association of Food and Waterborne Parasitology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Puasri, Dechkhajorn, Dekumyoy, Yoonuan, Ampawong, Reamtong, Boonyuen, Benjathummarak and Maneerat.)

As a part of an ongoing project to understand the current distribution of Gnathostoma species in Mexico, 22 species of vertebrates were examined for this nematode in the state of Colima. The fish species Dormitator latifrons ("chococo") and Sciades guatemalensis ("cuatete") from Cuyutlán Lagoon and the reptile Crocodylus acutus from the Amela Lagoon were positive for infection. Morphometric characteristics of the larvae collected in Colima were similar to those of G. binucleatum larvae collected from other regions and host species in Mexico. The low divergence of the ITS sequence obtained in this study from that of G. binucleatum (0.19%) indicates that our material belongs to this species. This is the first record of the AdvL3 of G. binucleatum in Colima, the tenth state in Mexico in which this species has been recorded in wild vertebrates.Como parte de un proyecto para definir la distribución actual de las especies de Gnathostoma en México, examinamos 22 especies de vertebrados en el estado de Colima en busca de este nematodo. Las especies de peces Dormitator latifrons ("chococo") y Sciades guatemalensis ("cuatete") de la laguna de Cuyutlán y el reptil Crocodylus acutus de la laguna de Amela resultaron positivos a la infección. Las características morfométricas de las larvas encontradas en Colima son similares a las de las larvas de G. binucleatum recolectadas en otras regiones y especies de hospederos en México. La escasa divergencia entre las secuencias del ITS obtenidas en este estudio con aquella de G. binucleatum (0.19%) indica que nuestro material pertenece a esta especie. Este es el primer registro de la L3A de G. binucleatum en Colima, siendo éste el décimo estado en México en donde se ha registrado a esta especie en vertebrados silvestres.