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1.
Clin Microbiol Rev ; 37(1): e0000923, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38169283

RESUMO

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.


Assuntos
Clonorquíase , Clonorchis sinensis , Opistorquíase , Opisthorchis , Animais , Humanos , Opistorquíase/diagnóstico , Opistorquíase/tratamento farmacológico , Opistorquíase/epidemiologia , Clonorquíase/diagnóstico , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Morbidade
3.
PLoS Negl Trop Dis ; 16(11): e0010909, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36350897

RESUMO

BACKGROUND: Clonorchis sinensis requires bile acid transporters as this fluke inhabits bile juice-filled biliary ducts, which provide an extreme environment. Clonorchis sinensis sodium-bile acid co-transporter (CsSBAT) is indispensable for the fluke's survival in the final host, as it circulates taurocholate and prevents bile toxicity in the fluke; hence, it is recognized as a useful drug target. METHODOLOGY AND PRINCIPAL FINDINGS: In the present study, using structure-based virtual screening approach, we presented inhibitor candidates targeting a bile acid-binding pocket of CsSBAT. CsSBAT models were built using tertiary structure modeling based on a bile acid transporter template (PDB ID: 3zuy and 4n7x) and were applied into AutoDock Vina for competitive docking simulation. First, potential compounds were identified from PubChem (holding more than 100,000 compounds) by applying three criteria: i) interacting more favorably with CsSBAT than with a human homolog, ii) intimate interaction to the inward- and outward-facing conformational states, iii) binding with CsSBAT preferably to natural bile acids. Second, two compounds were identified following the Lipinski's rule of five. Third, other two compounds of molecular weight higher than 500 Da (Mr > 500 Da) were presumed to efficiently block the transporter via a feasible rational screening strategy. Of these candidates, compound 9806452 exhibited the least hepatotoxicity that may enhance drug-likeness properties. CONCLUSIONS: It is proposed that compound 9806452 act as a potential inhibitor toward CsSBAT and further studies are warranted for drug development process against clonorchiasis.


Assuntos
Clonorquíase , Clonorchis sinensis , Fasciola hepatica , Simportadores , Animais , Humanos , Clonorchis sinensis/metabolismo , Fasciola hepatica/metabolismo , Simulação de Dinâmica Molecular , Sódio , Carcinógenos , Proteínas de Helminto/metabolismo , Clonorquíase/tratamento farmacológico , Clonorquíase/diagnóstico , Ácidos e Sais Biliares/farmacologia
4.
Korean J Parasitol ; 60(3): 187-193, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35772737

RESUMO

The positive rate of Clonorchis sinensis is the highest among intestinal parasites in the Republic of Korea (Korea). More than 1.2 million people were at risk of C. sinensis infection in Korea in 2012. An intensive control program is being implemented for residents of the 5 major river basins to reduce helminthic infections, including C. sinensis infection. This study evaluated the continuous intensive control program for parasitic diseases including clonorchiasis in areas near the 5 major river basins in Korea over the past 10 years (2011-2020). A total of 335,020 fecal samples (one sample per resident) prepared by the modified sedimentation technic were microscopically examined. Those who expelled helminth eggs were treated with anthelmintics through local health centers and re-examined 3 months later. The overall positive rate of helminths egg was 7.1%. The annual positive rates were dramatically decreased from 14.4% (2011) to 5.9% (2020). The egg positive rate was highest in C. sinensis (5.3%), followed by heterophyid flukes (1.5%) and Trichuris trichiura (0.2%). The prevalence of C. sinensis was significantly higher in males (7.6%) than in females (3.7%), and the highest in the 50-59 years (7.0%) age group. Our results are beneficial to establish prevention and control policies against helminthiases including clonorchiasis in endemic areas in this country.


Assuntos
Clonorquíase/epidemiologia , Clonorchis sinensis , Helmintíase/epidemiologia , Fatores Etários , Animais , Anti-Helmínticos/uso terapêutico , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Clonorquíase/prevenção & controle , Clonorchis sinensis/isolamento & purificação , Fezes/parasitologia , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/prevenção & controle , Helmintos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Rios , Fatores Sexuais
5.
Lancet Microbe ; 3(8): e616-e624, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35697047

RESUMO

BACKGROUND: Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three most important human liver fluke species in the Opisthorchiidae family, infecting approximately 25 million people worldwide. Drug treatment is needed to control morbidity and is also useful in lowering transmission. Several drugs used in various regimens are available to treat these infections, but their comparative efficacy is uncertain. We aimed to compare the efficacy in terms of cure rate and egg reduction rate of currently registered drugs against human liver fluke infection. METHODS: We conducted a systematic review using readily available electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, KoreaMed, China National Knowledge Infrastructure, and Wanfang Data) without language restrictions from inception until June 29, 2021. Clinical trials with pairwise comparison of drugs (praziquantel, albendazole, mebendazole, tribendimidine, or combinations of these drugs) against C sinensis, O viverrini, and O felineus were eligible, including trials comparing these drugs or their combinations with placebo. We compared efficacy in terms of cure rate by network meta-analysis. We conducted mixed binomial regression analyses for each species to derive predicted median cure rates for each drug regimen. The models included treatment and infection intensity as fixed factors, year of publication as covariate, and random effects of the different studies assumed to be normally distributed. We also assessed the quality of the included studies. This study was registered with PROSPERO (CRD42018109232). FINDINGS: Overall, 26 trials from 25 studies were included, of which 18 involved C sinensis, seven studied O viverrini, and one focused on O felineus. These trials included a total of 3340 participants. The two long-term treatment courses against C sinensis infection using 400 mg of albendazole (400 mg twice a day for 5 days and 400 mg twice a day for 7 days) resulted in cure rates of 100%, while two other multiple-dose regimens of albendazole resulted in high predicted cure rates: 300 mg twice a day for 5 days (93·9% [95% CI 49·6-99·6]) and 400 mg twice a day for 3 days (91·0% [50·9-99·0]). The WHO-recommended praziquantel regimen (25 mg/kg three times a day for 2 days) also showed a high predicted cure rate (98·5% [85·4-99·9]) in C sinensis infection, and predicted cure rates were above 90% for several other multiple-dose praziquantel regimens, including 20 mg/kg three times a day for 3 days (97·6% [74·7-99·8]), 14 mg/kg three times a day for 5 days (93·9% [44·8-99·7]), and 20 mg/kg twice a day for 3 days (91·0% [50·9-99·0]). In O viverrini infection, the regimen of 50 mg/kg and 25 mg/kg of praziquantel given in a single day showed the highest predicted cure rate (93·8% [85·7-97·5]), while a single dose of 50 mg/kg praziquantel also resulted in a high predicted cure rate (92·1% [64·9-98·6]). The single dose of 400 mg tribendimidine showed a high predicted cure rate of 89·8% (77·5-95·8). A low quality of evidence was demonstrated in most studies, especially those published before 2000. Selection bias due to poor random sequence generation and allocation concealment was high, and performance and detection biases were frequently unreported. INTERPRETATION: Praziquantel shows high efficacy against clonorchiasis and opisthorchiasis. Tribendimidine might serve as a treatment alternative and warrants further investigation. Although albendazole is efficacious when long treatment schedules (5 days or 7 days) are applied, limited size of studies and high risk of bias affect the interpretation of results. More high-quality studies are needed to promote the establishment of treatment guidelines for human liver fluke infection. FUNDING: Fourth Round of Three-Year Public Health Action Plan (2015-2017; Shanghai, China) and Swiss National Science Foundation.


Assuntos
Anti-Helmínticos , Clonorquíase , Fasciolíase , Opistorquíase , Opisthorchis , Albendazol , Animais , Anti-Helmínticos/uso terapêutico , China , Clonorquíase/tratamento farmacológico , Fasciolíase/tratamento farmacológico , Humanos , Metanálise em Rede , Opistorquíase/tratamento farmacológico , Praziquantel/uso terapêutico
6.
PLoS Negl Trop Dis ; 16(5): e0010429, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35605030

RESUMO

Clonorchiasis is an important food-borne parasitic disease caused by Clonorchis sinensis infection. The evaluation of long-term cost-effectiveness of control strategies is important for disease control and prevention. The present study aimed to assess the cost-effectiveness of the three recommended strategies (i.e., WHO, Chinese and Guangdong strategies) and different combinations of commonly used measures (i.e., preventive chemotherapy, information, education, and communication (IEC) and environmental improvement) on clonorchiasis. The study area, Fusha town in Guangdong Province, was a typical high endemic area in China. The analysis was based on a multi-group transmission model of C. sinensis infection. We set the intervention duration for 10 years and post-intervention period for 50 years. The corresponding costs and DALYs were estimated. Strategies with incremental cost-effectiveness ratios (ICERs) less than 1/5 of the willingness-to-pay threshold were identified as highly cost-effective strategies. The optimal control strategy was obtained using the next best comparator method. The ICERs of Guangdong strategy were $172 (95% CI: $143-$230) US for praziquantel and $106 (95% CI: $85-$143) US for albendazole, suggesting the highest cost-effectiveness among the three recommended strategies. For praziquantel, 470 sets of control strategies were identified as highly cost-effective strategies for achieving infection control (prevalence<5%). The optimal strategy consisted of chemotherapy targeted on at-risk population, IEC and environmental improvement, with coverages all being 100%, and with the ICER of $202 (95% CI: $168-$271) US. The results for transmission control (prevalence<1%) and albendazole were obtained with the same procedures. The findings may help to develop control policies for C. sinensis infection in high endemic areas. Moreover, the method adopted is applicable for assessment of optimal strategies in other endemic areas.


Assuntos
Clonorquíase , Clonorchis sinensis , Doenças Transmitidas por Alimentos , Albendazol/uso terapêutico , Animais , China/epidemiologia , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Clonorquíase/prevenção & controle , Análise Custo-Benefício , Doenças Transmitidas por Alimentos/epidemiologia , Praziquantel/uso terapêutico
7.
Acta Trop ; 230: 106330, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35090859

RESUMO

Tribendimidine (TBD) is a broad-spectrum anthelmintic drug that is also significantly effective in treating clonorchiasis. In this study, the altered metabolomes of Clonorchis sinensis (C. sinensis) in rats after TBD administration were quantified by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) to explore the possible active sites of TBD against clonorchiasis through altered metabolites and metabolic pathway analysis, and the results are expected to provide a target for the future design of anti-Clonorchis sinensis drugs. The worm burden reduction rate and scanning electron microscopy demonstrated that praziquantel (PZQ, positive control drug) and TBD had significant effects on C. sinensis in rats after treatment at a single dose of 200 mg/kg for 24 h. For the MS-based metabolomic analysis, a total of 173 standard metabolites (126 amino acids, 10 phospholipids and 37 fatty acids) were utilized as a reference metabolite database for metabolome identification. In total, 32 amino acids, 71 phospholipids and 27 fatty acids were detected in the C. sinensis of each group. Among these metabolites, 10 amino acids were significantly decreased in both drug-treated groups. Four lysophosphatidyl cholines (LPCs), six lysophosphatidyl ethanolamines (LPEs) and one phosphatidyl inositol (PI) were significantly increased after treatment with TBD. There were no significant changes in fatty acids among the control group and the two drug-treated groups. The results indicated that TBD administration caused a decrease in amino acids involved in the metabolic pathways of energy consumption and an increase in lysophospholipids, which are the hydrolysis products of phospholipase2 (PLA2) in the phospholipid metabolic pathways. The increased lysophospholipid content can destroy the cell membrane, increase membrane permeability, and even cause exposure to internal antigens that can be attacked by host antibodies. Perhaps the destroyed membrane, the exposed internal antigens and the consumed energy are the cause of the damage and death of C. sinensis after TBD administration. This is an interesting problem that can be examined in future research.


Assuntos
Clonorquíase , Clonorchis sinensis , Aminoácidos , Animais , Clonorquíase/tratamento farmacológico , Ácidos Graxos , Metaboloma , Fenilenodiaminas , Fosfolipídeos/farmacologia , Fosfolipídeos/uso terapêutico , Ratos , Espectrometria de Massas em Tandem
8.
J Infect Dis ; 225(3): 481-491, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375427

RESUMO

BACKGROUND: To understand Clonorchis sinensis reinfection and the determinants of reinfection in endemic areas is important in establishment of control measures. METHODS: A prospective cohort study was implemented in Hengxian County, Guangxi, China. Individuals with C. sinensis infection were completely treated, and those cured were enrolled as study subjects and followed up for 3, 6, and 12 months. The reinfection frequency and incidence were calculated, and a multivariable Cox proportional hazard model was constructed to capture reinfection determinants. RESULTS: Among 635 enrolled subjects, 436 (68.7%) completed follow-up. Of these, 177 (40.6%) were reinfected; 133 (75.1%) were reinfected once, 41 (23.2%) twice, and 3 (1.7%) three times. The incidence of reinfection was 64.0 per 100 person-years. Men (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.14-2.44), those with underlying diseases (aHR, 1.41; 95% CI, 1.02-1.95), and those with moderate- or heavy-intensity infections (aHR, 1.45; 95% CI, 1.14-1.85) had increasing reinfection probabilities. CONCLUSIONS: C. sinensis reinfection is high in endemic areas. Men and high-intensity infection are important determinants of reinfection. Repeated chemotherapy is necessary to control reinfection and its associated morbidities, especially in high-risk individuals. In addition, behavioral education is advised to decrease overall reinfection in endemic areas.


Assuntos
Clonorquíase , Clonorchis sinensis , Animais , China/epidemiologia , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Reinfecção
9.
Infect Dis Poverty ; 10(1): 136, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34933693

RESUMO

BACKGROUND: Clonorchiasis is attributed to the ingestion of raw freshwater fish harboring Clonorchis sinensis. Morbidity control is targeted through the administration of antihelminthics. This study modelled the cost yield indicated by effectiveness and utility of different treatment strategies against clonorchiasis. METHODS: About 1000 participants were enrolled from each of 14 counties selected from four provincial-level administrative divisions namely Guangxi, Guangdong, Heilongjiang and Jilin in 2017. Fecal examination was adopted to detect C. sinensis infection, while behavior of ingesting raw freshwater fish was enquired. Counties were grouped into four categories based on prevalence, namely low prevalence group (< 1%), moderate prevalence group (1-9.9%), high prevalence group (10-19.9%) and very high prevalence group (≥ 20%), while population were divided into three subgroups, namely children aged below 14 years old, adult female and adult male both aged over 14 years old. The average of cost effectiveness indicated by the cost to treat single infected cases with C. sinensis and of cost utility indicated by the cost to avoid per disability-adjusted life years (DALYs) caused by C. sinensis infection was calculated. Comparisons were performed between three treatment schedules, namely individual treatment, massive and selective chemotherapy, in which different endemic levels and populations were considered. RESULTS: In selective chemotherapy strategy, the cost to treat single infected case in very high prevalence group was USD 10.6 in adult male, USD 11.6 in adult female, and USD 13.2 in children. The cost increased followed the decrease of endemic level. In massive chemotherapy strategy, the cost per infected case in very high prevalence group was USD 14.0 in adult male, USD 17.1 in adult female, USD 45.8 in children, which were also increased when the endemic level decreased. In individual treatment strategy, the cost was USD 12.2 in adult male, USD 15.0 in adult female and USD 41.5 in children in very high prevalence group; USD 19.2 in adult male, USD 34.0 in adult female, and USD 90.1 in children in high prevalence group; USD 30.4 in adult male, USD 50.5 in adult female and over USD 100 in children in moderate prevalence group; and over USD 400 in any population in low prevalence group. As to cost utility, the differences by treatment strategies, populations and endemic levels were similar to those in cost effectiveness. CONCLUSIONS: Both cost effectiveness and cost utility indicators are highly impacted by the prevalence and population, as well as the treatment schedules. Adults especially men in the areas with a prevalence over 10% should be prioritized, in which selective chemotherapy was best and massive chemotherapy was also cost effective. In moderate endemic areas, the yield is not ideal, but selective chemotherapy for adult male may also be adopted. In low endemic areas, all strategies were high costly and new strategies need to be developed.


Assuntos
Clonorquíase , Clonorchis sinensis , Adolescente , Adulto , Animais , Criança , China/epidemiologia , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Clonorquíase/prevenção & controle , Anos de Vida Ajustados por Deficiência , Fezes , Feminino , Humanos , Masculino , Prevalência
10.
Wiad Lek ; 74(9 cz 1): 2232-2234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34725307

RESUMO

Clonorchiasis is a parasitic disease caused by Clonorchis sinensis. Parasite colonies can develop not only in the bile and pancreatic ducts but also in the gastric wall. This is confirmed by the described clinical case of perforated gastric ulcer, the morphological study of which revealed parasite colonies in the wall of the organ.


Assuntos
Clonorquíase , Clonorchis sinensis , Parasitos , Animais , Bile , Clonorquíase/complicações , Clonorquíase/diagnóstico , Clonorquíase/tratamento farmacológico , Humanos
11.
Uisahak ; 30(2): 317-354, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34663774

RESUMO

The Korean parasite control program is regarded as one of the most successful examples of health care movement in Korea. This 'Parasite Eradication Program' which was conducted from 1969 to 1995, involved testing and treating of 300 million people. In cooperation with Japan, parasitologists and activists who participated in the parasite control program formed a common system called the 'Mass Testing, Mass Treatment.' This study focuses on the localization process of Praziquantel, Clonorchiasis treatment production and its application in Clonorchiasis control program. Parasitologists rapidly introduced newly developed Praziquantel, and Korean chemists quickly reverse engineered the compound to evade patent issues. This allowed for the mass production of Praziquantel at a lower price, which in turn enabled a nationwide Clonorchiasis control program. At the same time, low price and stable supply opened the private market for Praziquantel. However, acceptance and understanding of the Praziquantel differed significantly among the stakeholders. For the government, it was a means for policy propaganda, and for the health agencies, it was a means for mass scale control program, while for the public, it was a means for maintaining conventional eating habits without risk of infection. This study reveals how the material end of a disease control policy is accepted and interpreted by different actors.


Assuntos
Clonorquíase , Clonorchis sinensis , Animais , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Clonorquíase/prevenção & controle , Humanos , Japão , Praziquantel/uso terapêutico , República da Coreia
12.
Genomics ; 113(3): 1605-1615, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33677057

RESUMO

The Chinese liver fluke, Clonorchis sinensis, causes the disease clonorchiasis, affecting ~35 million people in regions of China, Vietnam, Korea and the Russian Far East. Chronic clonorchiasis causes cholangitis and can induce a malignant cancer, called cholangiocarcinoma, in the biliary system. Control in endemic regions is challenging, and often relies largely on chemotherapy with one anthelmintic, called praziquantel. Routine treatment carries a significant risk of inducing resistance to this anthelmintic in the fluke, such that the discovery of new interventions is considered important. It is hoped that the use of molecular technologies will assist this endeavour by enabling the identification of drug or vaccine targets involved in crucial biological processes and/or pathways in the parasite. Although draft genomes of C. sinensis have been published, their assemblies are fragmented. In the present study, we tackle this genome fragmentation issue by utilising, in an integrated way, advanced (second- and third-generation) DNA sequencing and informatic approaches to build a high-quality reference genome for C. sinensis, with chromosome-level contiguity and curated gene models. This substantially-enhanced genome provides a resource that could accelerate fundamental and applied molecular investigations of C. sinensis, clonorchiasis and/or cholangiocarcinoma, and assist in the discovery of new interventions against what is a highly significant, but neglected disease-complex.


Assuntos
Clonorquíase , Clonorchis sinensis , Animais , Sequência de Bases , China , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Clonorquíase/genética , Clonorchis sinensis/genética , Clonorchis sinensis/metabolismo , Humanos , Federação Russa
13.
Int Immunopharmacol ; 85: 106512, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454418

RESUMO

Clonorchis sinensis could induce inflammation, epithelial hyperplasia and fibrosis in the intrahepatic bile duct as a food-borne parasite, which was associated with the development of cholangiocarcinoma (CCA). Praziquantel was the most effective drug on treatment of this kind of parasite. However, new drugs with minimal toxicity to the host were urgently needed due to the side effects of Praziquantel and its CCA risk. In this study, helminth mitochondria respiratory chain blocker Wortmannilatone F (WF) and IL-8 analogue CXCL8 (3-72) K11R/G31P were used to treat BALB/C mice infected by Clonorchis sinensis. We investigated the gross and histopathological morphology of the liver, inflammation-associated cytokine IL-6, lipid peroxidation-related proteins cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), collagen fiber accumulation and fibroblast-specific protein 1 (FSP1), malignant markers proliferating cell nuclear antigen (PCNA) and cytokeratin 19 (CK19), as well as the disinfection effect on these parasites in vitro. WF inhibited and killed the worms dramatically, and the combination of WF with G31P improved the condition of the hepatobiliary duct tissue greatly. These outcomes indicated that the combination of WF and G31P was a potential therapeutic method to treat the Clonorchis sinensis infection.


Assuntos
Anti-Helmínticos/uso terapêutico , Clonorquíase/tratamento farmacológico , Interleucina-8/uso terapêutico , Macrolídeos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Animais , Anti-Helmínticos/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Clonorquíase/metabolismo , Clonorquíase/parasitologia , Clonorquíase/patologia , Clonorchis sinensis/efeitos dos fármacos , Colágeno/metabolismo , Ciclo-Oxigenase 2/metabolismo , Interleucina-6/sangue , Interleucina-8/farmacologia , Queratina-19/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Macrolídeos/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/farmacologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo
14.
PLoS Negl Trop Dis ; 14(3): e0008220, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32226018

RESUMO

Human clonorchiasis, caused by Clonorchis sinensis, is endemic in East Asian countries. C. sinensis metacercariae excyst in the duodenum of mammalian hosts, migrate to the intrahepatic bile duct, and mature into adults in the milieu of bile. We have previously shown that newly excysted juvenile C. sinensis move chemotactically toward bile and bile acids. Here, the chemotactic behavior of adult C. sinensis (CsAd) toward bile and bile acids was investigated. CsAds moved toward 0.05-5% bile and were most attracted to 0.5% bile but moved away from 10% bile. Upon exposure to 1-10% bile, CsAds eventually stopped moving and then died quickly. Among bile acids, CsAds showed strong chemotaxis toward cholic acid (CA) and deoxycholic acid. On the contrary, CsAds repelled from lithocholic acid (LCA). Moreover, at higher than 10 mM LCA, CsAds became sluggish and eventually died. Dopamine D1 receptor antagonists (LE-300 and SKF-83566), D2/3 receptor antagonists (raclopride and its derivative CS-49612), and a dopamine re-uptake inhibitor inhibited CA-induced chemotaxis of CsAds almost completely. Clinically used antipsychotic drugs, namely chlorpromazine, haloperidol, and clozapine, are dopaminergic antagonists and are secreted into bile. They completely inhibited chemotaxis of CsAds toward CA. At the maximum doses used to treat patients, the three tested medicines only expelled 2-12% of CsAds from the experimentally infected rabbits, but reduced egg production by 64-79%. Thus, antipsychotic medicines with dopaminergic antagonism could be considered as new anthelmintic candidates for human C. sinensis infections.


Assuntos
Anti-Helmínticos/farmacologia , Antipsicóticos/farmacologia , Quimiotaxia/efeitos dos fármacos , Clonorchis sinensis/efeitos dos fármacos , Clonorchis sinensis/fisiologia , Antagonistas de Dopamina/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Antipsicóticos/administração & dosagem , Bile/metabolismo , Fatores Quimiotáticos/metabolismo , Ácido Cólico/metabolismo , Clonorquíase/tratamento farmacológico , Modelos Animais de Doenças , Antagonistas de Dopamina/administração & dosagem , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Ácido Litocólico/metabolismo , Coelhos , Análise de Sobrevida , Resultado do Tratamento
15.
Acta Trop ; 202: 105246, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31672488

RESUMO

Oriental liver fluke disease (clonorchiasis), caused by Clonorchis sinensis, is endemic in 81 counties in Guangdong province, China. This study was conducted following increasing lack of clonorchiasis awareness and increased consumption of raw freshwater fish and raw fish porridge at home and restaurants, which has been attributed to improved living standards in China, and is considered to have led to a higher C. sinensis infection rate in the country. A total of 61,517 individuals were investigated from 123 sites during a provincial survey in 1988, with average C. sinensis infection rate of 1.82% that increased to 4.08% (335/8217) in 1997. Higher infection rate was observed in adult men than women, with heavy infection rate in fishermen and businessmen because they have access and means to get raw fishes for consumption. Thus, clonorchiasis has become a serious public health problem in Guangdong province. Efforts targeting clonorchiasis prevention and control in Guangdong province started in the 1990s. These included carrying out large-scale surveys and chemotherapy in epidemic regions, research on promotion of environmental sanitation and methods for freshwater aquaculture. Establishment and promotion of clonorchiosis demonstration plots for comprehensive control measures, as well as the development of clonorchiasis-prevention community-out-patient clinics were initiated and their effectiveness was evaluated. However, there seem to be no obvious decline in the prevalence of C. sinensis with 4.90% (608/12,401) in 2015, at Guangdong province due to the people's habit of eating raw fishes in endemic areas. This has led to increasing calls to improve environmental sanitation in the aquaculture industry. It is, however, believed that control efforts on clonorchiosis in the province are at an early stage and require strengthening through the cooperation of different departments to work out effective strategies for sustainable field application of control mechanisms.


Assuntos
Anti-Helmínticos/uso terapêutico , Clonorquíase , Doenças Transmitidas por Alimentos/parasitologia , Alimentos Crus/parasitologia , Adulto , Animais , Aquicultura , China/epidemiologia , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Clonorquíase/prevenção & controle , Clonorquíase/transmissão , Clonorchis sinensis/parasitologia , Atenção à Saúde/organização & administração , Comportamento Alimentar , Feminino , Peixes/parasitologia , Água Doce/parasitologia , Humanos , Masculino , Prevalência , Saúde Pública/métodos , Alimentos Marinhos/parasitologia , Inquéritos e Questionários
16.
Korean J Parasitol ; 57(3): 299-302, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31284354

RESUMO

A clonorchiasis case in a captive leopard cat, Prionailurus bengalensis euptilurus, was confirmed by ultrasonographic findings and egg morphologies found in the bile juice sample in the Korea. The leopard cat was introduced from the wild habitat of Gyeongsangnam-do, to Cheongju Zoo in Cheongju-si, Chungcheongbuk-do, Korea in August 2014. Physical examinations were basically performed for quarantine and check-up health. The cat was comparatively good in health except anorexia. The cyst-like bile duct dilation and the increased echogenicity of gall bladder wall and hepatic parenchyma were observed by ultrasonography. Ultrasound-guided needle biopsy was conducted for collecting bile juice and the specimens were observed under light microscope. The numerous small trematode eggs were detected in the bile juice sample of the light microscopy. The eggs were 25-33 (28±3) µm by 18-22 (20±1) µm in size and showed typical characteristics of Clonorchis sinensis egg, i.e., a dominantly developed operculum, shoulder rim and dust-like wrinkles in surface. To treat the liver fluke infection, 20 mg/kg of praziquantel was orally administered only once to the case. Follow-up studies including fecal examinations were conducted during 2 years after treatment. But no more eggs were detected from the case. In the present study, we described the first clonorchiasis case of leopard cat, which was confirmed by ultrasonographic findings and egg morphologies from the bile juice sample in Korea.


Assuntos
Clonorquíase/veterinária , Clonorchis sinensis/isolamento & purificação , Panthera/parasitologia , Animais , Anti-Helmínticos/uso terapêutico , Bile/parasitologia , Tamanho Celular , Clonorquíase/diagnóstico por imagem , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Clonorchis sinensis/efeitos dos fármacos , Clonorchis sinensis/crescimento & desenvolvimento , Óvulo/citologia , Óvulo/efeitos dos fármacos , Óvulo/crescimento & desenvolvimento , Praziquantel/uso terapêutico , República da Coreia , Ultrassonografia
17.
BMC Infect Dis ; 19(1): 115, 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30727977

RESUMO

BACKGROUND: Clonorchiasis is the common parasitic infection in the general population of the Republic of Korea, however, taeniasis is scarcely reported recently. Here, we describe a case of co-infection with the cestode T. saginata in a patient with subclinical clonorchiasis diagnosed by a combination of diagnostic tools in Korea. CASE PRESENTATION: A 56-year-old man visited the hospital having passed proglottids in his stool for the past two months and brought a stool sample with segments to our hospital. He had no abdominal symptoms, such as nausea, vomiting, abdominal pain, diarrhea, or constipation. He used to consume raw beef and fish frequently. We could not find evidence of gravid proglottids which contain fully developed uteri filled with ova or branched uterine structures, within the submitted sample. To identify the tapeworm species, we carried out molecular analyses on the proglottids. The cox1 and ef1a sequences had a 100% match with those of T. saginata and differed from the sequences of the other Taenia species. Upon examination of stool samples fixed by formalin-ether concentration method, no Taenia species ova were observed in 10 slides. Instead, C. sinensis ova were observed, despite the level of IgG specific to C. sinensis being within the normal range. The patient was treated with praziquantel (25 mg/kg, three times a day) for 3 days, and subsequently C. sinensis ova were not found in his stool. CONCLUSION: Our case indicates that a combination of morphological, serological, and molecular diagnostic tools should be used for the accurate diagnosis of subclinical parasitic infections.


Assuntos
Clonorquíase/diagnóstico , Taenia saginata/genética , Teníase/diagnóstico , Animais , Bovinos , Clonorquíase/tratamento farmacológico , Clonorquíase/etiologia , Coinfecção/complicações , Coinfecção/parasitologia , Ciclo-Oxigenase 1/genética , Fezes/parasitologia , Proteínas de Helminto/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fator Tu de Elongação de Peptídeos/genética , Praziquantel/uso terapêutico , República da Coreia , Taenia saginata/patogenicidade , Teníase/tratamento farmacológico , Teníase/etiologia
18.
BMC Infect Dis ; 19(1): 33, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621611

RESUMO

BACKGROUND: Hepatic clonorchiasis is one of the most prevalent food-borne parasitic diseases worldwide. Clonorchis sinensis, the pathogen, is the major parasitic trigger contributing to cholangitis, cholelithiasis, and even cholangiocarcinoma. Unfortunately, unspecific clinical manifestations of patients with hepatic clonorchiasis tend to mislead clinicians to neglect or misdiagnose them, following ignorance of appropriate therapy. Our case report may shed light on definite diagnosis of clonorchiasis with concomitant cholelithiasis, methodology for surgical drainage of the parasites, and postoperative anthelmintic therapy. CASE PRESENTATION: Two patients with habit of eating infected raw or undercooked freshwater fish were hospitalized due to right upper quadrant pain and jaundice. Magnetic resonance cholangiopancreatography (MRCP)/computed tomography (CT) detection indicated cholangiolithiasis and cholangiolithiasis with concurrent cholecystolithiasis, respectively. Fecal examinations were both negative for adult worms or eggs of parasites. However, adults of Clonrochis sinensis were detected within hepatobiliary tracts during laparoscopic cholecystectomy. Postoperative drainage and anthelmintic therapy contributed to complete recovery with good prognosis. CONCLUSIONS: Clonorchiasis provokes cholangiolithiasis and cholecystolithiasis. Standardized treatments for these gallstone patients with concomitant clonorchiasis include surgical removal of the calculus, postoperative T tubule drainage and anthelmintic therapy. Serological test or polymerase chain reaction (PCR)-based approaches might be helpful for diagnosis of clonorchiasis when no eggs are found by stool microscopy. Public health promotion on ceasing to eat raw freshwater fish is essential for prevention and control of clonorchiasis.


Assuntos
Sistema Biliar/diagnóstico por imagem , Sistema Biliar/parasitologia , Colangiopancreatografia por Ressonância Magnética/métodos , Clonorquíase/diagnóstico , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/parasitologia , Laparoscopia/métodos , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/parasitologia , Colecistectomia Laparoscópica , Clonorquíase/complicações , Clonorquíase/tratamento farmacológico , Clonorquíase/cirurgia , Clonorchis sinensis/isolamento & purificação , Feminino , Cálculos Biliares/diagnóstico , Cálculos Biliares/tratamento farmacológico , Cálculos Biliares/parasitologia , Cálculos Biliares/cirurgia , Humanos , Icterícia Obstrutiva/tratamento farmacológico , Icterícia Obstrutiva/cirurgia , Masculino , Pessoa de Meia-Idade
19.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 30(5): 513-517, 2018 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-30567021

RESUMO

OBJECTIVE: To analyze the current drug treatment against clonorchiasis in China, in order to promote the standardization of drug treatment and national deworming for clonorchiasis. METHODS: All the 10 provinces were enrolled, which reported clonorchiasis in the work report for important helminthiasis in 2016. Then, 20 counties were selected from these 10 provinces. The data on drug treatment including both mass chemotherapy and individual treatment against clonorchiasis were collected and compared. RESULTS: All the 10 provinces had no guideline for mass chemotherapy, while only 3 had that for individual treatment against clonorchiasis. Out of 20 counties, only 1 implemented mass chemotherapy. Among these 20 counties, 13 applied praziquantel in individual treatment, while other 7 employed albendazole. In the 12 counties with clear protocol for praziquantel, the total dosage for a man of 60 kg ranged from 3.6 to 18.0 g, the days and times for administration ranged from 1 to 6 and from 3 to 18, respectively. In the 4 counties with clear protocol for albendazole, the total dosage for a man of 60 kg ranged from 0.8 to 8.4 g, the days and times for administration ranged from 2 to 7 and from 2 to 14, respectively. CONCLUSIONS: Nowadays, the guideline on mass chemotherapy for clonorchiasis is inadequate in China. Although individual treatment is applied in many areas, the protocols vary in drugs, dosage, and days and times for treatment. Thus, the national guideline of mass chemotherapy for clonorchiasis should be established, while the protocols for individual treatment should be standardized.


Assuntos
Clonorquíase , Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , China , Clonorquíase/tratamento farmacológico , Guias como Assunto , Humanos , Masculino , Praziquantel/administração & dosagem
20.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 30(2): 219-221, 2018 Feb 22.
Artigo em Chinês | MEDLINE | ID: mdl-29770671

RESUMO

OBJECTIVE: To understand the prevalence of Clonorchis sinensis infection among residents in two communities of Zhongshan City, and evaluate the effect of albendazole treatment, so as to offer the evidence for formulating the strategy of clonorchiasis prevention and control. METHODS: The stool specimens were collected from the residents of two comprehensive demonstration areas, and the eggs of C. sinensis were detected by Kato-Katz technique. Those who were tested positive were treated with albendazole (0.4, twice a day for 4 days in adults, and half dosage for children aged 16 years or below). Three weeks after the treatment, the stool specimens were recollected and retested to evaluate the effect. RESULTS: A total of 532 people were investigated and 96 were tested positive, with an infection rate of 18.05%. The infection rate was 28.63% (69/241) in the males and 9.28% (27/291) in the females, and there was a significant difference between them (χ2 = 334.99, P < 0.01). The infection rate increased with the increase of the age (χ2 = 63.84, P < 0.01). Among the 96 positive residents, 94 received the albendazole treatment, and 86 were retested after the treatment with a negative conversion rate of 91.86% (79/86). Of the 7 residents without the conversion, 5 had irregular medication. No severe adverse reactions were reported during the period of treatment. CONCLUSIONS: The infection rate of C. sinensis among residents in the two communities of Zhongshan City is high, especially among the males and aged people. The effect of albendazole is good in the treatment of C. sinensis infection. In the future, the general survey and treatment should be strengthened in order to lower the infection rate.


Assuntos
Albendazol/uso terapêutico , Clonorquíase/tratamento farmacológico , Clonorquíase/epidemiologia , Fatores Etários , Animais , China/epidemiologia , Cidades , Clonorchis sinensis , Fezes/parasitologia , Feminino , Humanos , Masculino , Contagem de Ovos de Parasitas , Prevalência
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