RESUMO
Infection by the zoonotic fish-borne trematode, Opisthorchis viverrini, remains a crucial health issue in Thailand and neighboring countries. Recently, molecular analysis revealed two populations of putative O. viverrini: one found primarily in human hosts ("human-specific" population) and the other primarily in cats ("cat-specific" population). It is unclear how the infective stages (metacercariae) of these different populations circulate among definitive and reservoir hosts in nature. To gain an insight into this, mitochondrial cox1 and nad1 gene sequences of metacercariae from fish intermediate hosts were examined. None of 192 metacercariae from cyprinid fish in Lao PDR and Thailand had sequences typical of "cat-specific" O. viverrini, suggesting that cyprinid fish are not the main second intermediate hosts of this population. Interestingly, all 20 O. viverrini-like metacercariae from snakehead fish (Channa striata) shared 99.51-100% sequence identity with eggs from cats naturally infected in a previous study. Hence, we propose a modification of the known transmission dynamics of O. viverrini: consumption of metacercariae within snakehead fish provides another pathway for cats and (occasionally) humans to acquire infection. We also performed morphological comparisons of eggs, metacercariae, and adult flukes (raised in hamsters) of both Opisthorchis populations. The "cat-specific" population has eggs that are narrower and adults that are shorter and wider than in the human-specific population. The metacercaria of the "cat-specific" population is elliptical, while that of the "human-specific" population is oval, occasionally rounded. Our results confirmed that O. viverrini-like metacercariae from snakehead fish are the infective stages of the "cat-specific" fluke. This provides a new insight into the dissemination and transmission of each population in the second intermediate host. The identity of the cat-specific population is discussed.
Assuntos
Doenças dos Peixes , Opistorquíase , Opisthorchis , Animais , Opisthorchis/genética , Opisthorchis/classificação , Opisthorchis/fisiologia , Opisthorchis/anatomia & histologia , Opisthorchis/isolamento & purificação , Gatos , Humanos , Tailândia , Opistorquíase/parasitologia , Opistorquíase/veterinária , Opistorquíase/transmissão , Doenças dos Peixes/parasitologia , Doenças dos Peixes/transmissão , Filogenia , Metacercárias/genética , Metacercárias/anatomia & histologia , Metacercárias/isolamento & purificação , Laos , Doenças do Gato/parasitologia , Doenças do Gato/transmissão , Cyprinidae/parasitologia , Complexo IV da Cadeia de Transporte de Elétrons/genética , Análise de Sequência de DNA , Dados de Sequência Molecular , DNA de Helmintos/genética , NADH Desidrogenase/genéticaRESUMO
Background: Inflammation caused by Opisthorchis viverrini infection increases the risk of cholangitis, cholecystitis, and leads to bile duct cancer (cholangiocarcinoma or CCA). However, only certain infected individuals are susceptible to CCA, suggesting the involvement of host factors in cancer development. In addition, there are reports indicating differences in the locations of CCA. Aim: This study aims to investigate cellular inflammatory responses in the common bile duct (CB), intrahepatic bile duct (IHB), and gallbladder (GB) in susceptible and non-susceptible hosts following O. viverrini infection. Methods: Thirty Syrian golden hamsters (a susceptible host) and 30 BALB/c mice (a non-susceptible host) infected with O. viverrini were studied at six time points (five animals per group). Histopathological evaluations were conducted on samples from the IHB, CB, and GB. Inflammatory cell infiltration was quantitatively assessed and compared between groups and time points. Statistical analysis was performed using one-way ANOVA, with a significance level of p < 0.05. Results: Inflammation was significantly more pronounced in the IHB compared to the other two biliary locations. In comparison between susceptible and non-susceptible hosts, the intensity of inflammation was higher in the OV+H group than in the OV+M group (p < 0.05). Conclusion: This study highlights the association between host response to inflammation, tissue location, and host susceptibility, with the IHB showing particular susceptibility to inflammation and pathological changes. These findings contribute to our understanding of the increased risk of CCA in susceptible hosts.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Opistorquíase , Opisthorchis , Doenças dos Roedores , Cricetinae , Camundongos , Animais , Opistorquíase/complicações , Opistorquíase/patologia , Opistorquíase/veterinária , Opisthorchis/fisiologia , Ductos Biliares Intra-Hepáticos/patologia , Mesocricetus , Colangiocarcinoma/patologia , Colangiocarcinoma/veterinária , Inflamação/veterinária , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/veterináriaRESUMO
Background: Individual host susceptibility is believed to be a risk factor in the interaction between the host and the parasite. Since studying time series in humans is limited, animal models are replaced. Aim: This study aims to explore and compare the pattern of inflammatory cell types along the biliary tract and their association with proliferative lesions in the early development of cholangiocarcinoma from susceptible and nonsusceptible animal models. Methods: Thirty male Syrian golden hamsters and 30 BALB/c mice, serving as the susceptible and nonsusceptible animal models, were used in this comparative study. The animals were infected with 50 Opisthorchis viverrini metacercariae via gastric intubation. At days 1, 2, 7, 14, 28, and 56 postinfection (p.i.), five animals were randomly selected from each group and humanely sacrificed. The hepatobiliary tissues were collected and processed for histopathological study. Histochemical and immunohistochemical staining were applied to differentiate the inflammatory cell types. Kruskal-Wallis and Mann-Whitney tests were applied to assess all semi-quantitative and quantitative variables. The correlation between each variable was also analyzed using Spearman rank at a p-value < 0.05. Results: The results demonstrated that mice had different patterns of infiltrating cell types when compared to hamsters. This suggested that the cellular response to the infection in mice occurred earlier than that in hamsters. The response in mice reached its peak at D7 to D14 and then rapidly declined at D28. In contrast, although the inflammatory response in hamsters started slowly, the response reached the peak at D28 and maintained a high level until D56. Significant differences in the number of inflammatory cells between mice and hamsters were seen at D1 (p = 0.047), D7 (p = 0.049), D28 (p = 0.040), and D56 (p < 0.040). Conclusion: The inflammatory responses to O. viverrini infection in the nonsusceptible animal model occurred and declined earlier while the response in the susceptible animal model occurred later in a gradual manner. Both rodents are suitable animal models for the studies of opisthorchiasis susceptibility.
Assuntos
Neoplasias dos Ductos Biliares , Sistema Biliar , Opistorquíase , Opisthorchis , Cricetinae , Humanos , Masculino , Camundongos , Animais , Opistorquíase/complicações , Opistorquíase/parasitologia , Opistorquíase/patologia , Opistorquíase/veterinária , Fígado/metabolismo , Opisthorchis/fisiologia , Sistema Biliar/metabolismo , Sistema Biliar/patologia , Mesocricetus , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/parasitologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/parasitologia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/veterináriaRESUMO
Opisthorchis viverrini (Ov) infection can cause several disease conditions of the bile duct including hepatobiliary abnormalities (HBAs) and the most severe, cholangiocarcinoma (CCA). Fibrosis occurs when tissues are damaged and normal wound-healing responses are dysregulated. Neutrophils are the first cells to migrate to an infection site to protect the host from intruding extracellular pathogens through a wide range of effector mechanisms such as phagocytosis, production of reactive oxygen species, proteases, or release of neutrophil extracellular traps (NETs). In this work, we used confocal microscopy to assess whether Ov crude antigens can cause release of NETs from neutrophils from Ov-free individuals. We demonstrated for the first time that these antigens could induce release of NETs ex vivo in a dose-dependent manner from neutrophils isolated from Ov-free individuals. Intriguingly, when we measured NETs from neutrophils isolated from Ov-infected patients, we found increased spontaneous production of NETs in patients with HBAs. Interestingly, exposure to Ov crude antigens lowered the level of NETs released by neutrophils from patients with active Ov infection regardless of HBA status. We propose that in the case of acute Ov infection, even when concentration of Ov antigens is relatively low, neutrophils can form NETs. However, when this infection becomes chronic, manifesting as a definite HBA, the levels of NET production are reduced when treated with Ov crude antigens. Excessive production of proinflammatory mediators from these NETs might have effects on the parasites, but may also lead to excessive injury of surrounding tissues resulting in HBAs and may lead eventually to the most severe complications such as CCA.
Assuntos
Neoplasias dos Ductos Biliares , Armadilhas Extracelulares , Opistorquíase , Opisthorchis , Animais , Humanos , Opistorquíase/complicações , Opistorquíase/parasitologia , Opisthorchis/fisiologia , Neutrófilos , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/parasitologiaRESUMO
Dendritic cells (DCs) are antigen-presenting cells (APC) involved in the initiation of immune responses. Maturation of DCs is characterized by the high expression of major histocompatibility complex (MHC) class II and co-stimulatory clusters of differentiation (CD) 40, CD80, and CD86 molecules. Matured DCs are required for T cell differentiation and proliferation. However, the response of DCs to Opisthorchis viverrini antigens has not yet been understood. Therefore, this study sought to determine the expression of surface molecules of JAWSII mouse DCs stimulated by crude somatic (CS) and excretory-secretory (ES) antigens of O. viverrini. ES antigen significantly induced only mRNA expression of CD80 and MHC class II in JAWSII mouse DCs, while CS antigen promoted up-regulation of both mRNA and protein levels of CD80 and MHC class II, indicating relative maturation of JAWII mouse DCs. Moreover, the secreted cytokines from the co-cultures of O. viverrini antigens stimulated JAWSII DC with naïve CD4+ T cells was determined. Significantly increased levels of immunosuppressive cytokines interleukin (IL)-10 and transforming growth factor beta (TGF-ß) were found. The up-regulation of these cytokines may indicate the response of regulatory T cells (Treg) to CS antigen-stimulated JAWSII DC. These findings may lead to a better understanding of the role that DCs play in O. viverrini infection.
Assuntos
Antígenos de Helmintos/metabolismo , Antígeno B7-1/metabolismo , Genes MHC da Classe II , Opisthorchis/fisiologia , Regulação para Cima/genética , Animais , Células Dendríticas/metabolismo , Regulação da Expressão Gênica , Interleucina-10/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Opistorquíase/metabolismo , Opistorquíase/parasitologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
Liver fluke infection through the consumption of raw or undercooked freshwater fish is a major public health problem in the Mekong Region. Despite the extensive efforts of liver fluke health campaigns, Northeast Thailand still reports high human infection prevalence as consumption of raw fish dishes has diminished but not ceased. This study examines the roles of social-cultural factors, particularly the influences of masculinity and misinformation, on liver fluke infection risk. Participant observation, questionnaire surveys and semi-structured interviews were conducted in four villages in Kalasin Province, Thailand, to scrutinize reasons for raw fish consumption, gender differences in raw fish culture, processes of liver fluke information dissemination, and the extent of information mismatch. Our results show that one of the key reasons (76.9%) underlying continued raw fish consumption are deeply embedded cultural practices associated with ways of rural life. About 30% of the participants indicated that they would not avoid eating raw fish, regardless of knowing the health consequences. Gender difference is evident, with 75.6% of males consuming raw fish salad (koi pla), compared to 42.7% of females. Some male participants associate raw meat consumption with virility and strength. Such beliefs underscore the cultural linkage of koi pla consumption with masculinity. Misconceptions of liver fluke life cycle and risk of infection remain, as only 15.3% of the participants correctly selected raw fish as the food source for liver fluke infection while 84.2% misunderstood that other raw foods could lead to infection. The multi-layered and hierarchical structure of public health information dissemination from medical professionals to health officers and village health volunteers to villagers has contributed to information mismatch between different layers. Our study builds on others which call for multi-pronged scientific and social strategies, as well as culturally attuned approaches to public health messaging. The study raises masculinity and misinformation as relevant considerations in disease prevention. Incorporating grounded research and gendered perspectives are part of appreciating the cultural roots of raw fish consumption. Realizing the significant role of village health volunteers in information dissemination and in supplying coherent public health messages is vital for effective health campaigns.
Assuntos
Comunicação , Conhecimentos, Atitudes e Prática em Saúde , Masculinidade , Opistorquíase/epidemiologia , Meio Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Humanos , Masculino , Pessoa de Meia-Idade , Opistorquíase/parasitologia , Opistorquíase/psicologia , Opisthorchis/fisiologia , Prevalência , Tailândia , Adulto JovemRESUMO
The freshwater snail Bithynia siamensis goniomphalos serves as the first intermediate host of liver fluke Opisthorchis viverrini, a foodborne parasite, of which human infection has persisted in Southeast Asia for decades. The snail Filopaludina martensi martensi has been proposed as a biological control agent against B.s. goniomphalos, but knowledge on the snail ecology and population dynamics between the two species remains rudimentary. This study investigated selected abiotic and biotic factors influencing the distribution and abundance of B.s. goniomphalos and F.m. martensi. Water quality, soils, and snails were collected from 34 localities in Northeast Thailand. Soil properties and snail soft tissue elemental concentrations were analyzed. Experiments were performed to examine interspecific competition. Statistical analysis was conducted to explore the associations between water and soil properties and soft tissue elemental concentrations. The results showed that B.s. goniomphalos had the highest mean dominance in streams and red-yellow podzolic soils, while F.m. martensi snails preferred ponds and latosol soils. Negative correlation in species abundances was found between the two species. Interspecific competition was detected, with B.s. goniomphalos growth rates hampered by the presence of F.m. martensi. Despite the possibility of using F.m. martensi to control B.s. goniomphalos, B.s. goniomphalos exhibited a greater adaptability to different water and soil properties, suggesting that the species could colonize a wide range of environmental conditions. This study provides further insights into the ecology of the two snail species, underscoring the importance of considering abiotic factors when assessing the possible biological control agent to control O. viverrini transmission.
Assuntos
Agentes de Controle Biológico , Opistorquíase/prevenção & controle , Opistorquíase/transmissão , Opisthorchis/fisiologia , Caramujos/fisiologia , Animais , Água Doce/parasitologia , Humanos , Opistorquíase/epidemiologia , Caramujos/classificação , Caramujos/parasitologia , Solo/química , Solo/parasitologia , Tailândia/epidemiologiaRESUMO
BACKGROUND: A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile, this phenomenon is far less studied, and with this report, we describe the interactions between the BAs and microbiota in this complex biological matrix. Methodology. Thirty-seven gallstone disease patients of which twenty-one with Opisthorchis felineus infection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acid composition was measured by LC-MS/MS. Gallbladder microbiota were previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acid composition and microbiota were analyzed. RESULTS: Bile acid signature and Opisthorchis felineus infection status exert influence on beta-diversity of bile microbial community. Direct correlations were found between taurocholic acid, taurochenodeoxycholic acid concentrations, and alpha-diversity of bile microbiota. Taurocholic acid and taurochenodeoxycholic acid both show positive associations with the presence of Chitinophagaceae family, Microbacterium and Lutibacterium genera, and Prevotella intermedia. Also, direct associations were identified for taurocholic acid concentration and the presence of Actinomycetales and Bacteroidales orders, Lautropia genus, Jeotgalicoccus psychrophilus, and Haemophilus parainfluenzae as well as for taurochenodeoxycholic acid and Acetobacteraceae family and Sphingomonas genus. There were no differences in bile acid concentrations between O. felineus-infected and noninfected patients. Conclusions/Significance. Associations between diversity, taxonomic profile of bile microbiota, and bile acid levels were evidenced in patients with cholelithiasis. Increase of taurochenodeoxycholic acid and taurocholic acid concentration correlates with bile microbiota alpha-diversity and appearance of opportunistic pathogens.
Assuntos
Ácidos e Sais Biliares/metabolismo , Ductos Biliares/microbiologia , Colelitíase/microbiologia , Microbiota , Adulto , Animais , Ductos Biliares/parasitologia , Biodiversidade , Colelitíase/complicações , Colelitíase/parasitologia , Feminino , Vesícula Biliar/metabolismo , Vesícula Biliar/parasitologia , Humanos , Masculino , Pessoa de Meia-Idade , Opistorquíase/complicações , Opistorquíase/microbiologia , Opisthorchis/fisiologiaRESUMO
Research on the effects of environmental factors influenced by climate change on parasite transmissibility is an area garnering recent attention worldwide. However, there is still a lack of studies on the life cycle of Opisthorchis viverrini, a carcinogenic trematode found in countries of the Lower Mekong subregion of Lao PDR, Cambodia, Myanmar, Vietnam and Thailand. To evaluate the influences of environmental factors water temperature and salinity on the transmissibility of the liver fluke O. viverrini through cercarial stage, longevity of O. viverrini cercaria was examined at different experimental temperatures (22°C, 30°C and 38°C) and salinities (2.5 parts per thousand (PPT), 3.75 PPT and 5 PPT). The results reveal that different temperatures have statistically significant effects on cercarial longevity. The cercariae exhibited a thermostability zone ranging between 22°C and 30°C. Cercarial longevity was significantly shortened when water temperatures reached 38°C. Salinity also plays a key role in cercarial longevity, with cercarial survival significantly shorter at a salinity of 3.75 PPT than at 2.5 PPT and 5 PPT. A combined analysis of salinity and temperature revealed unique trends in cercarial longevity. At all experimental salinities, cercarial longevity was lowest when incubated in 38°C, but statistically significant from cercarial longevity at temperatures of 22°C and 30°C, and salinities of 2.5 PPT and 5 PPT. The results suggest that higher temperatures negatively impact parasite longevity. This reflects that O. viverrini transmission patterns may be impacted by changes in water temperature and salinity resulting from climate change.
Assuntos
Mudança Climática , Longevidade , Opisthorchis/fisiologia , Salinidade , Temperatura , Animais , Sudeste Asiático , Estágios do Ciclo de Vida/fisiologia , Estações do AnoRESUMO
Opisthorchis viverrini is a fish-borne zoonotic trematode that causes significant public health problems in Southeast Asia. Its life cycle requires Bithynia snails as the first intermediate hosts, fish, and human and/or carnivore hosts. This study assessed impacts of land use practice for rice cultivation and seasonality on the transmission dynamics of O. viverrini in Bithynia siamensis goniomphalos in rice paddy field habitats. The transmission of O. viverrini cercariae in B. s. goniomphalos was monitored at monthly intervals over a 4-year period from January 2010 to December 2013. From a total of 59,727 snails examined by standard cercarial shedding, the prevalence of O. viverrini was 0.7% (range, 0.0-4.1%). The prevalence of O. viverrini infection in B. s. goniomphalos varied with the amount of rainfall, with peaks of infection occurring in the cool-dry season, that is, after each rainy season. A shift of peak prevalence from cool-dry to hot-dry season observed in 2013 was associated with the increase in preceding water irrigation to support the production of second annual rice crop. Significant positive correlations were found between the prevalence and intensity of cercarial infection and the size of snails. Our results revealed substantial variation between years so that to have a clear understanding of the population dynamics of this complex system, studies should be conducted over an extended period (> 1 year). Results from this study highlight that water irrigation schemes in rice paddy cultivation and seasonality have a significant effect on the prevalence of O. viverrini in B. s. goniomphalos.
Assuntos
Irrigação Agrícola , Opistorquíase/transmissão , Opisthorchis/fisiologia , Caramujos/parasitologia , Irrigação Agrícola/métodos , Animais , Cercárias/fisiologia , Produção Agrícola , Humanos , Opistorquíase/epidemiologia , Opistorquíase/parasitologia , Oryza , Prevalência , Chuva , Estações do Ano , Tailândia/epidemiologiaRESUMO
Infections caused by Schistosoma haematobium and Opisthorchisviverrini are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.
Assuntos
Anti-Helmínticos/uso terapêutico , Antioxidantes/uso terapêutico , Opistorquíase/tratamento farmacológico , Esquistossomose/tratamento farmacológico , Animais , Anti-Helmínticos/farmacologia , Antioxidantes/farmacologia , Descoberta de Drogas , Reposicionamento de Medicamentos , Quimioterapia Combinada , Humanos , Neoplasias/etiologia , Neoplasias/parasitologia , Opistorquíase/complicações , Opistorquíase/epidemiologia , Opisthorchis/efeitos dos fármacos , Opisthorchis/fisiologia , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Schistosoma/efeitos dos fármacos , Schistosoma/fisiologia , Esquistossomose/complicações , Esquistossomose/epidemiologiaRESUMO
This article reviews the past and present scientific reports regarding Bithynia spp. focusing on the biology, ecology and life cycle of Bithynia snails and their responses to Opisthorchis viverrini infection. Moreover, new data regarding comparative molecular genomics and proteomic approaches have recently revealed novel molecular components involved in the immune defence responses from Bithynia spp., providing additional perspectives for future studies. Studies on the specific interaction between Bithynia snails and their trematodes will contribute to further understanding the snail-parasite relationship with regards to epidemiology and control of Opisthorchiasis and broaden the scope on comparative immunology of gastropod snails.
Assuntos
Opisthorchis/fisiologia , Caramujos/imunologia , Caramujos/parasitologia , Animais , Genômica , Hemócitos/citologia , Hemócitos/parasitologia , Hemolinfa/citologia , Hemolinfa/metabolismo , Hemolinfa/parasitologia , Interações Hospedeiro-Parasita/imunologia , Humanos , Opistorquíase/parasitologia , Opistorquíase/transmissão , Proteômica , Caramujos/genética , Caramujos/metabolismoRESUMO
Opisthorchis viverrini (OV) infection is endemic to the Northeast Thailand where the prevalence of Type 2 Diabetes mellitus (T2DM) is higher whilst the incidence of cardiovascular diseases (CVDs) is lower than the rest of Thailand. Helminth infection has both nutritional and immunological impact on their definitive hosts. Thus, a cross-sectional study was performed to see the effects of OV infection on glucose and lipid profiles. For this purpose, 200 each of OV infected and uninfected residents were recruited and their glycated hemoglobin (HbA1c), total cholesterol, triglycerides, low- and high-density lipoproteins (LDL and HDL) levels and anthropometric measurements, including BMI were examined. Then, as the prospective follow- up study, changes of those metabolic parameters of OV positive subjects (nâ¯=â¯120) before and after Praziquantel (PZQ) treatment were monitored for six months. The results showed that OV infection has a protective effect against hyperglycemia (OR 0.482 and pâ¯=â¯.04) and metabolic disease risk group (OR 0.478 and pâ¯=â¯.03). OV positive participants had lower HbA1c (5.5% Vs. 6.01%, pâ¯=â¯.001) but higher HDL (54.07 Vs. 49.46â¯mg/dL, pâ¯=â¯.001) than OV negative participants that are statistically significant. After PZQ treatment for OV-positive subjects, their serum levels of HbA1c (pâ¯<â¯.05) and HDL (pâ¯<â¯.05) significantly rose during the follow up. Apparently, OV infection lowers HbA1c but increases HDL in definitive human hosts.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/metabolismo , Lipídeos/sangue , Opistorquíase/metabolismo , Opisthorchis/fisiologia , Animais , Anti-Helmínticos/administração & dosagem , Estudos Transversais , Seguimentos , Opistorquíase/parasitologia , Praziquantel/administração & dosagem , Estudos Prospectivos , TailândiaRESUMO
The food-borne liver trematode Opisthorchis felineus causes severe liver damage, including fibrosis. This study shows a comparison of the characteristics between cholangiofibrosis and periductal fibrosis in infected people and in the golden hamster as an experimental model. Comparative evaluation was carried out regarding collagen composition, the number of basic-producing cells, and extracellular-matrix degradation. The results revealed that characteristics of chronic opisthorchiasis due to O. felineus infection in humans and in Syrian hamsters are similar and include well-pronounced development of fibrotic complications in the liver parenchyma. Besides, a difference in fibrogenesis development was demonstrated between chronic O. felineus infection and noninfectious cholecystitis. In this study, we for the first time compared fibrogenesis between humans and model animals against the background of chronic O. felineus infection.
Assuntos
Cirrose Hepática/parasitologia , Mesocricetus/parasitologia , Opistorquíase/parasitologia , Opisthorchis/fisiologia , Animais , Doença Crônica , Colágeno Tipo I/metabolismo , Cricetinae , Modelos Animais de Doenças , Humanos , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Cirrose Hepática/metabolismo , Mesocricetus/metabolismo , Opistorquíase/metabolismoRESUMO
Opisthorchiasis caused by food-borne trematode Opisthorchis felineus is a substantial public health problem, with 17 million persons infected worldwide. This chronic disease is associated with hepatobiliary inflammation, cholangiocyte dysplasia, cholangiofibrosis, intraepithelial neoplasia, and even cholangiocarcinoma among chronically infected individuals. To provide first insights into the mechanism by which O. felineus infection causes precancerous liver lesions, we investigated the level of oxidative stress (lipid peroxidation byproducts and 8-hydroxy-2'-deoxyguanosine) as well as the time course profiles of chronic inflammation and fibrogenesis markers in the dynamics of opisthorchiasis from 1 month to 1.5 years postinfection in an experimental model based on golden hamsters Mesocricetus auratus. For the first time, we showed that O. felineus infection provokes time-dependent accumulation of oxidative hepatobiliary lesions in the injured liver of hamsters. In particular, over the course of infection, lipid peroxidation byproducts 4-hydroxynonenal and malondialdehyde were upregulated; these changes in general correlate with the dynamics of hepatic histopathological changes. We detected macrophages with various immunophenotypes and elevated levels of CD68, COX2, and CD163 in the O. felineus-infected animals. Meanwhile, there was direct time-dependent elevation of TNF-α (R = 0.79; p < 0.001) and CD163 protein levels (R = 0.58; p = 0.022). We also provide quantitative data about epithelial hyperplasia marker CK7 and a marker of myofibroblast activation (α smooth muscle actin). Our present data provide first insights into the histopathological mechanism by which O. felineus infection causes liver injuries. These findings support the inclusion of O. felineus in Group 1 of biological carcinogens.
Assuntos
Doenças do Sistema Digestório/complicações , Doenças do Sistema Digestório/metabolismo , Fígado/metabolismo , Fígado/patologia , Opistorquíase/complicações , Opisthorchis/fisiologia , Estresse Oxidativo , Animais , Biomarcadores/metabolismo , Cricetinae , Dano ao DNA , Doenças do Sistema Digestório/genética , Doenças do Sistema Digestório/patologia , Modelos Animais de Doenças , Peroxidação de Lipídeos , Fatores de TempoRESUMO
BACKGROUND: The liver fluke Opisthorchis viverrini infects several million people in Southeast Asia. Adult flukes live in the bile ducts of humans, where they cause hepatobiliary pathology, including cholangiocarcinoma. Here, we investigated the potential of extracellular vesicles (EVs) secreted by the fluke and defined recombinant proteins derived from EVs to generate protective immunity in a hamster vaccination-challenge model. METHODOLOGY/PRINCIPAL FINDINGS: EVs isolated from the excretory-secretory products of O. viverrini and two recombinant EV surface proteins encoding the large extracellular loops (LEL) of Ov-TSP-2 (rOv-TSP-2) and Ov-TSP-3 (rOv-TSP-3) were adjuvanted and used to vaccinate hamsters intraperitoneally followed by challenge infection with O. viverrini metacercariae. The number of adult flukes recovered from hamsters immunized with EVs, rOv-TSP-2, rOv-TSP-3 and rOv-TSP-2+rOv-TSP-3 were significantly reduced compared to control animals vaccinated with adjuvant alone. The number of eggs per gram feces was also significantly reduced in hamsters vaccinated with rOv-TSP-2 compared to controls, but no significant differences were found in the other groups. The average length of worms recovered from hamsters vaccinated with EVs, rOv-TSP-2 and rOv-TSP-3 was significantly shorter than that of worms recovered from the control group. Anti-EV IgG levels in serum and bile were significantly higher in hamsters vaccinated with EVs compared to control hamsters both pre- and post-challenge. In addition, levels of anti-rOv-TSP antibodies in the serum and bile were significantly higher than control hamsters both pre- and post-challenge. Finally, antibodies against rOv-TSP-2 and rOv-TSP-3 blocked uptake of EVs by human primary cholangiocyte in vitro, providing a plausible mechanism by which these vaccines exert partial efficacy and reduce the intensity of O. viverrini infection. CONCLUSION/SIGNIFICANCE: Liver fluke EVs and recombinant tetraspanins derived from the EV surface when administered to hamsters induce antibody responses that block EV uptake by target bile duct cells and exert partial efficacy and against O. viverrini challenge.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Vesículas Extracelulares/imunologia , Proteínas de Helminto/imunologia , Opistorquíase/prevenção & controle , Opisthorchis/imunologia , Tetraspaninas/imunologia , Animais , Cricetinae , Feminino , Humanos , Masculino , Mesocricetus , Opistorquíase/imunologia , Opistorquíase/parasitologia , Opisthorchis/fisiologia , VacinaçãoRESUMO
Contaminated liver fluke egg in the environment has led to the high prevalence of human opisthorchiasis associated with cholangiocarcinoma in Southeast Asia. To find the effective lessening methods of Opisthorchis viverrini eggs in the contaminated environment, we investigated the temperature conditions for killing of these trematode eggs in vitro. Numerous O. viverrini eggs were obtained in the proximal part of uteri of adult worms from experimental hamsters. Mature eggs with miracidium were allocated by experimental groups (2 control: positive and negative and 4 treatment: 50, 60, 70, and 80°C) with 0.85% saline, and treated by the experimental plan. Eggs in each experimental groups were observed under the confocal microscope after stain with Propidium Iodide (PI) to evaluate the effect of temperatures. Eggs in 70 and 80°C groups were all killed after over 10 min heated. Majority of eggs in 60°C (10, 15, and 30 min heated), 70 and 80°C (5 min heated) groups were inactivated. However in 50°C group, below half of eggs were to be killed in all time lapse (10, 15 and 30 min). In order to prevent O. viverrini infection and cholangiocarcinoma, direct treatment of sewage by heating at 70 or 80°C at least 10 min is essential. Therefore, treatment of O. viverrini eggs at a high temperature is a potential method for controlling egg contamination in sewage.
Assuntos
Temperatura Alta , Opisthorchis/fisiologia , Opisthorchis/efeitos da radiação , Zigoto/fisiologia , Zigoto/efeitos da radiação , Animais , Cricetinae , Corantes Fluorescentes/metabolismo , Microscopia Confocal , Propídio/metabolismo , Coloração e Rotulagem , Análise de SobrevidaRESUMO
The omics technologies have improved our understanding of the molecular events that underpin host-parasite interactions and the pathogenesis of parasitic diseases. In the last decade, proteomics and genomics in particular have been used to characterize the surface and secreted products of the carcinogenic liver fluke Opisthorchis viverrini and revealed important roles for proteins at the host-parasite interface to ensure that the flukes can migrate, feed and reproduce in a hostile environment. This review summarizes the advances made in this area, primarily focusing on discoveries enabled by the publication of the fluke secreted proteomes over the last decade. Protein families that will be covered include proteases, antioxidants, oncogenic proteins and the secretion of exosome-like extracellular vesicles. Roles of these proteins in host-parasite interactions and pathogenesis of fluke-induced hepatobiliary diseases, including cholangiocarcinogenesis, are discussed. Future directions for the application of this knowledge to control infection and disease will also be discussed.
Assuntos
Proteínas de Helminto/metabolismo , Interações Hospedeiro-Parasita , Opisthorchis/fisiologia , Proteoma , Animais , Proteínas de Helminto/genética , Humanos , Hepatopatias Parasitárias/etiologia , Hepatopatias Parasitárias/patologia , Opistorquíase/complicações , Opistorquíase/parasitologia , Opistorquíase/patologiaRESUMO
In Italy, food-borne outbreaks of opisthorchiasis have occurred since 2003, all of them originating from some lakes in Central Italy where the only European liver fluke, Opisthorchis felineus (Rivolta, 1884) is endemic. The aim of the present study is to investigate the factors that may facilitate the life cycle of O. felineus in the area of Bolsena Lake, the knowledge of the local population about opisthorchiasis, and preventative healthcare measures. We performed a descriptive observational study through the submission of questionnaires to three target populations: fishermen who fish exclusively in Bolsena Lake, restaurateurs whose businesses are close to the lake and general population living in the province of Viterbo. Results showed hazardous behaviours and eating habits in the three target populations, as well as a poor knowledge of opisthorchiasis and preventative healthcare measures.
Assuntos
Comportamento Alimentar , Conhecimentos, Atitudes e Prática em Saúde , Atividades Humanas , Opistorquíase/epidemiologia , Adulto , Idoso , Animais , Humanos , Itália/epidemiologia , Lagos , Masculino , Pessoa de Meia-Idade , Opistorquíase/parasitologia , Opistorquíase/prevenção & controle , Opistorquíase/psicologia , Opisthorchis/crescimento & desenvolvimento , Opisthorchis/fisiologia , Fatores de RiscoRESUMO
BACKGROUND: Cholangiocarcinoma (CCA) is a fatal bile duct cancer associated with infection by the liver fluke, Opisthorchis viverrini, in the lower Mekong region. Numerous public health interventions have focused on reducing exposure to O. viverrini, but incidence of CCA in the region remains high. While this may indicate the inefficacy of public health interventions due to complex social and cultural factors, it may further indicate other risk factors or interactions with the parasite are important in pathogenesis of CCA. This systematic review aims to provide a comprehensive analysis of described risk factors for CCA in addition to O. viverrini to guide future integrative interventions. MAIN BODY: We searched five international and seven Thai research databases to identify studies relevant to risk factors for CCA in the lower Mekong region. Selected studies were assessed for risk of bias and quality in terms of study design, population, CCA diagnostic methods, and statistical methods. The final 18 included studies reported numerous risk factors which were grouped into behaviors, socioeconomics, diet, genetics, gender, immune response, other infections, and treatment for O. viverrini. Seventeen risk factors were reported by two or more studies and were assessed with random effects models during meta-analysis. This meta-analysis indicates that the combination of alcohol and smoking (OR = 11.1, 95% CI: 5.63-21.92, P < 0.0001) is most significantly associated with increased risk for CCA and is an even greater risk factor than O. viverrini exposure. This analysis also suggests that family history of cancer, consumption of raw cyprinoid fish, consumption of high nitrate foods, and praziquantel treatment are associated with significantly increased risk. These risk factors may have complex relationships with the host, parasite, or pathogenesis of CCA, and many of these risk factors were found to interact with each other in one or more studies. CONCLUSIONS: Our findings suggest that a complex variety of risk factors in addition to O. viverrini infection should be addressed in future public health interventions to reduce CCA in affected regions. In particular, smoking and alcohol use, dietary patterns, and socioeconomic factors should be considered when developing intervention programs to reduce CCA.