Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of h...Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.展开更多
AIM： To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory （ES） product. METHODS： NIH-3T3, mouse fibroblast cells were treated with O. viverrini...AIM： To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory （ES） product. METHODS： NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA （cDNA） array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR. RESULTS： Among a total of 15 000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O.viverrini ES product, The expression level of signal transduction genes, pkC, pdgfra, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC,eps 8 and tgfβ3 1/4 which are the downstream signaling molecules of either epidermal growth factor （EGF） or transforming growth factor-β （TGF-β） showed statistical significance （P 〈 0.05）.CONCLUSION： O. viverrini ES product stimulates the significant changes of gene expression in several functional categories and these mainly include transcripts related to cell proliferation. The TGF-β and EGF signal transduction pathways are indicated as the possible pathways of O. viverrini-driven cell proliferation.展开更多
Objective:To determine the influence of geographic,knowledge and behavioral factors on Opisthorchis(O.)viverrini infection in the Northeast of Thailand.Methods:This cross-sectional study was conducted by using four da...Objective:To determine the influence of geographic,knowledge and behavioral factors on Opisthorchis(O.)viverrini infection in the Northeast of Thailand.Methods:This cross-sectional study was conducted by using four datasets of years 2016 and 2017.Generalized linear mixed model was employed to analyze association between geographic,knowledge and behavioral factors and O.viverrini infection.Results:Totally there were 1885 participants.The prevalence of O.viverrini infection was 10.03%.Geographic factors that showed statistically significant association with O.viverrini infection in the Northeast region were featured by at least a dam and reservoir(Adj.OR=4.21,95%CI:2.49-7.13,P<0.001),at least a weir(Adj.OR=1.74,95%CI:1.09-2.77,P=0.020),>50 dogs and cats per village(Adj.OR=3.40,95%CI:2.17-5.31,P<0.001),and rice fields covered>50%of its areas(Adj.OR=1.91,95%CI:1.04-4.01,P=0.036),as well as low to moderate levels of knowledge(Adj.OR=1.60,95%CI:1.32 to 1.94,P<0.001),consumed raw fish(Adj.OR=1.90,95%CI:1.02 to 3.52,P=0.040)and consumed processed raw fish(Adj.OR=3.03,95%CI:2.20 to 4.18,P<0.001).Other significant covariates were gender and age of the respondents.Conclusions:O.viverrini infection still remains a public health problem of the Northeast of Thailand.Geographic and demographic factors,knowledge,and consumption behaviors of raw fish products are significantly associated with O.viverrini infection.展开更多
Objective: To apply lectin affinity chromatography and glycoproteomics-based LC-MS/MS to preliminarily investigate the possible potential plasma biomarkers of Opisthorchis viverrini(OV)-associated CCA in OV/dimethylni...Objective: To apply lectin affinity chromatography and glycoproteomics-based LC-MS/MS to preliminarily investigate the possible potential plasma biomarkers of Opisthorchis viverrini(OV)-associated CCA in OV/dimethylnitrosamine(DMN)-induced CCA hamster model. Methods: Nine Syrian hamsters were divided into 3 groups as follows(n=3 each): normal(healthy control group); OV group; and OV/DMN group(CCA group). Pooled plasma samples collected from animals in each group at the 6th month post-infection with OV metacercarae were subjected to glycoproteomics analysis. Glycoproteins in the pooled sample from each group were initially isolated by concanavilin A(Con A)-based affinity chromatography. The expression of glycoproteins isolated by both enrichment methods were determined using LCMS/MS. Results: Among the 24 Con A-binding glycoproteins isolated, two proteins, N-myc downstream regulated gene 1(NDRG1) and fetuin-B(FETUB) were found up-regulated only in the samples from the OV and control groups, but not in the OV/DMN(CCA) groups. On the other hand, one protein, i.e., NSFL1 cofactor p47 isoform x3(NSFL1C) was found only in the samples from OV/DMN(CCA) and control groups, but not in the OV group. The remaining 21 proteins were upregulated in the samples from all groups. Conclusions: NDRG1, FETUB and NSFL1 C glycoproteins isolated by Con A-based affinity chromatography could be potential biomarkers for CCA. Plasma samples with negative for NDRG1 and FETUB proteins but positive for NSFL1 C are likely to be OV-associated CCA. Nevertheless, this conclusion remains to be confirmed whether this battery test can discriminate OV-associated CCA from other risk factors.展开更多
Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicid...Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.展开更多
Objective: To investigate the maturity development of miracidia in uterine eggs from four portions of the Opisthorchis viverrini uterus and environmental factors possibly affected in maturation and infectivity of dist...Objective: To investigate the maturity development of miracidia in uterine eggs from four portions of the Opisthorchis viverrini uterus and environmental factors possibly affected in maturation and infectivity of distal part uterine eggs.Methods: Uteri of adult worms were divided into 4 equal parts.Development of eggs was determined under light microscope.Only embryonated eggs were used to evaluate the effects of physicochemical factors: temperature, salinity, acidity, ultraviolet A, B, C.Infection success was evaluated by feeding treated eggs to intermediate host snails and determining by using a PCR approach.Results: Eggs obtained from the uterus closest to the ovary(regions 1 and 2) failed to develop in vitro.Eggs from region 4 of the uterus(close to the genital pore) were used to study effects of physicochemical factors.The highest survival and infection success was in groups of eggs kept at 30 ℃(95.20%).The calculated period of loss infection success(LI_(50) and LI_(95)) on miracidia in distal uterine eggs by exposure to UV-A, UV-B and UV-C were 73 and 1 523 d; 8 and 20 d; 1 and 2 d, respectively.Lethal concentrations(LC_(50) and LC_(95)) of salinity, HCl and NaOH on miracidia in distal uterine eggs were 45.43 and 120.09 ppt, 0.01 and 0.25 M; 0.01 and 0.11 M, respectively, after 24 h exposure.Conclusions: Opisthorchis viverrini eggs display a high tolerance to environmental conditions, especially after snail host eating for infection.展开更多
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 reducin...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.展开更多
Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administrat...Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administration,education and communication campaigns.New approaches are required to advance helminth control.Methods:An ecohealth study was conducted on two Mekong islands in Southern Laos.Demographic and behavioural data were collected by questionnaire.Human and animal reservoir stools were examined.Bithynia spp.and Neotricula aperta snails were examined using shedding.Fresh water fish were examined using digestion technique.Multivariate random-effects analysis was used to find risk factors associated with helminth infections.Results:Human infection rates with O.viverrini,hookworm,S.mekongi,Trichuris trichiura,Ascaris lumbricoides and Taenia spp.were 60.7%,44.1%,22.2%,4.1%,0.6%and 0.1%,respectively.Heavy intensity infections were 4.2%,3.6%and 1.8%for O.viverrini,S.mekongi and hookworm,respectively.O.viverrini and S.mekongi infection rates among dogs and cats were 25.0%and 14.7%,respectively.Of the cats tested,53.1%were infected with O.viverrini.Prevalence of O.viverrini and S.mekongi in snails was 0.3%and 0.01%,respectively.Overall prevalence of O.viverrini infection in fresh water fish was 26.9%,with the highest infection rates occurring in Hampala dispa(87.1%),Cyclocheilichthys apogon(85.7%)and Puntius brevis(40.0%).Illiteracy and lower socioeconomic status increased the risk of O.viverrini infection,while those aged 10-16 years and possessing latrines at home were less likely to be infected.Household dogs and cats that consumed raw fish were significantly and positively associated with O.viverrini infection of the household members.For S.mekongi,children under 9 years old were exposed significantly to this infection,compared to older age groups.Conclusions:There is a pressing need to design and implement an integrated helminth control intervention on the Mekong Islands in southern Lao PDR.Given the highly dynamic transmission of O.viverrini,S.mekongi,STH and extended multiparasitism,annual mass-drug administration is warranted along with environmental modifications,health education and improved access to clean water and adequate sanitation to consolidate morbidity control and move towards elimination.Trail registration number:Our findings presented here are from a cross-sectional study,therefore,it has not been registered.展开更多
Background:Foodborne trematodiasis(FBT)is a significant global health problem,with the liver flukes Opisthorchis viverrini,O.felineus,and Clonorchis sinensis contributing to half of the global burden of FBT.North-east...Background:Foodborne trematodiasis(FBT)is a significant global health problem,with the liver flukes Opisthorchis viverrini,O.felineus,and Clonorchis sinensis contributing to half of the global burden of FBT.North-eastern Thailand where O.viverrini is endemic and un-cooked fish dishes remain an integral part of the food culture has the highest reported incidence of opisthorchiasis,including associated cholangiocarcinoma.Both food sharing and eating practices are potentially important factors in FTB,suggesting an important role for the social ecology of disease transmission in these rural communities.Methods:Two rural Thai-Lao villages that were part of a 12-village project in Northeastern Thailand were selected for detailed investigation of O.viverrini infection risk associated with sharing of raw fish dishes among households.The project included screening individuals for infection and cholangiocarcinoma,a household questionnaire,and offering treatment options for positive individuals.Social network mapping was used to construct raw fish dish-sharing networks and create a proxy variable capturing variability in the degree of food sharing(DFS),measured as the number of different households with which each household shared fish dishes.Measures of associations between DFS,O.viverrini infection,the frequency of raw fish consumption,and the number of raw fish dishes consumed were generated using binary logistic regression,proportional odds ordinal logistic regression,and Poisson regression.Results:The results showed that the probability that a household has members infected with O.viverrini increased by~7%(P<0.01)for each additional household included in its network.Moreover,the frequency and number of types of raw fish dishes consumed increased significantly as the DFS increased.Of the two villages,that with the highest infection prevalence(48%versus 34.6%)had significantly higher social connectivity overall(P<0.001).Conclusions:Our findings suggest that the social ecology of human settlements may be key to understanding the transmission dynamics of some FBT.In the case of O.viverrini in Thai-Lao communities,for which food sharing is a traditional practice supporting social cohesion,food sharing network mapping should be incorporated into community-based interventions.These should encourage fish dish preparation methods that minimize infection risk by targeting households with high DFS values.展开更多
Background:Opisthorchis viverrini infection is highly prevalent in northeast Thailand.This liver fluke is classified as a carcinogen due to its causal links with cholangiocarcinoma(CCA)development.Although treatment w...Background:Opisthorchis viverrini infection is highly prevalent in northeast Thailand.This liver fluke is classified as a carcinogen due to its causal links with cholangiocarcinoma(CCA)development.Although treatment with praziquantel(PZQ)effectively cures O.viverrini infection,the prevalence remains high due to the traditional consumption of raw fish.Therefore,re-infection is common in the endemic community,leading to severe hepatobiliary morbidities including the fatal CCA.In this study,we evaluate the association between the frequency of previous PZQ treatment and current O.viverrini infections among Thai adults living in the endemic area of northeast Thailand.Methods:This study includes all participants who were screened for O.viverrini infection in the Cholangiocarcinoma Screening and Care Program(CASCAP),northeast Thailand.History of PZQ treatment was recorded using a health questionnaire.O.viverrini infections were diagnosed using urine antigen detection.Associations between PZQ and O.viverrini were determined by adjusted odds ratio(aOR)and 95%confidence interval(CI)using multiple logistic regression.Results:Among participants,27.7%had previously been treated once with PZQ,8.2%twice,2.8%three times,and 3.5%more than three times.Current O.viverrini prevalence was 17%(n=524).Compared with participants who never used PZQ,the aOR for infection among those who used the drug once was 1.09(95%CI:0.88-1.37),twice was 1.19(95%CI:0.85-1.68),three times was 1.28(95%C/:0.74-2.21),and more than three times was 1.86(95%C/:1.18-2.93;P=0.007).Conclusions:The population with a frequent history of PZQ use and still continued raw fish consumption showed high levels of repeated reinfection with O.viverrini.They were infected,treated and re-infected repeatedly.These findings suggest that certain participants continue raw fish consumption even after previous infection.This is a particular problem in highly endemic areas for O.viverrni and increases the risk of CCA.展开更多
AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patient...AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N -nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA. RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-kB gene expression. CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.展开更多
Opisthorchiasis caused by Opisthorchis viverrini （Oviverrini） remains a major public health problem in many parts of Southeast Asia including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with...Opisthorchiasis caused by Opisthorchis viverrini （Oviverrini） remains a major public health problem in many parts of Southeast Asia including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobUiary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis, cholelithiasis and cholangiocarcinoma. The liver fluke infection was induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas of Thailand. Health education programs to prevent and control opisthorchiasis are still required in high-risk areas.展开更多
Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in dete...Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.展开更多
Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention a...Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.展开更多
Schistosoma mekongi and other intestinal helminth infections remain public health concerns in Lao People's Democratic Republic, especially in remote areas where access to sanitation is limited.We performed an expe...Schistosoma mekongi and other intestinal helminth infections remain public health concerns in Lao People's Democratic Republic, especially in remote areas where access to sanitation is limited.We performed an experimental study in four villages where latrine construction was coupled with two rounds of mass drug administration (MDA) with praziquantel and albendazole, and compared with two control villages that only received two rounds of MDA. The prevalence of helminth infections before (baseline) and after (follow-up) intervention were compared. Additionally, the prevalence in intervention and control villages were compared 12 months post-intervention. Kato–Katz, formalin-ethyl acetate concentration and Baermann techniques were employed to assess helminth infections.We found infection prevalence of S. mekongi in the intervention and control villages was 28.6% and 1.8%, respectively. The prevalences of other helminth infections were as follows: Opisthorchis viverrini, 79.5% and 71.8%;hookworm, 48.8% and 65.6%;and Strongyloides stercoralis, 43.1% and 38.3%. Other helminth species were detected in less than 5% of the study participants. Latrine intervention coupled with two rounds of MDA in the intervention villages reduced the prevalence of S. mekongi infection by 6.0% (from 28.6% to 22.6%;P < 0.001), O. viverrini infection by 11.3% (from 79.5% to 68.2%;P < 0.001), hookworm infection by 22.6% (from 48.8% to 26.2%;P < 0.001), and S. stercoralis infection by 12.0% (from 43.1% to 31.1%;P < 0.001). The observed reductions were not significantly different when compared to the control villages, where only two rounds of MDA were implemented (P > 0.05). Study participants in both groups commonly engaged in behaviours such as open defecation, bathing in the Mekong River, consuming raw or undercooked fish dishes and walking barefoot. These practices and behaviours are associated with helminth infections. Concluding, this study showed only a marginal impact associated with latrine use in intervention communities. There is a need for longer term studies with integrated interventions, such as effective health education to foster behavioural changes related to open defecation, raw or undercooked food consumption, wearing protected footwear outdoors, and personal hygiene.展开更多
Background Helminth infections, includingOpisthorchis viverrini, hookworm, andTrichuris trichiura, are prevalent in Khong district, Champasack province, southern Lao People’s Democratic Republic (PDR). Schistosomiasi...Background Helminth infections, includingOpisthorchis viverrini, hookworm, andTrichuris trichiura, are prevalent in Khong district, Champasack province, southern Lao People’s Democratic Republic (PDR). Schistosomiasis caused bySchistosoma mekongi is of public health concern on the islands of the Khong district. This study aimed to assess the impact of an Eco-Health/One-Health approach in combination with mass drug administration (MDA) to reduce these helminth infections.Methods We conducted a community intervention using a stepped-wedge trial approach on two endemic islands (Donsom and Donkhone) of the Khong district, Champasack province, Lao PDR, between April 2012 and March 2013. In each study village, 30–40 households were randomly selected. All members of selected households, who were at home during the study period were invited to participate in the study. A baseline study was conducted to assess helminth infections, knowledge attitudes and practices towardSchistosoma mekongi infection, behavior of open defecation and availability of latrine at home. After the baseline (T0), the Eco-Health/One-Health approach was implemented on Donsom (intervention) and Donkhone island (control). An assessment was conducted in 2014 (T1), one year after the completion of intervention implementation, to assess the short-term impact of the Eco-Health/One-Health approach on helminth infections and compare intervention and control islands. Later in 2015, the Eco-Health/One-Health approach was implemented on control island (Donkhone). After the implementation of intervention, the parasitological assessments were conducted annually in humans in 2015 (T2), in 2016 (T3) and in 2017 (T4), and in dogs in 2017 (T4) to evaluate the long-term impact of the intervention on helminth infections. Frequency was used to describe the prevalence of helminth infections. Logistic regression was applied to associate the KAP (knowledge, attitudes, and practices and open defecation behavior) and the reduction of helminth infections between intervention and control islands. The reduction in prevalence pre- and post-intervention was associated using a McNemar test. A two-independent samplet-test was applied to compare the mean eggs per gram (EPG) of helminth infections between control and intervention islands. A paired t-test test was used to compare the mean EPG of stool samples before (baseline) and after (follow-up) interventions for the two islands separately. AP-value lower than 0.05 was considered statistically significant.Results Eco-Health/One-Health approach appears to be associated with reduction in prevalence ofS. mekongi by 9.0% [odds ratio (OR) = 0.49,P = 0.003] compared to the use of mass drug administration alone (control island). Additionally, this intervention package significantly reducedO. viverrini infection by 20.3% (OR = 1.92,P < 0.001) and hookworm by 17.9% (OR = 0.71,P = 0.045), respectively. Annual parasitological assessments between 2012 and 2017 showed that the Eco-Health/One-Health approach, coupled with MDA, steadily reduced the prevalence ofS. mekongi on the intervention island from 29.1% to 1.8% and on the control island from 28.4% to 3.1%, respectively.Conclusions The study findings suggest that the Eco-Health/One-Health approach appears to be associated with a significant reduction in prevalence ofS. mekongi and helminth co-infections, particularly hookworm andT. trichiura. Therefore, implementing the Eco-Health/One-Health approach in schistosomiasis-endemic areas could accelerate the achievement of national goals for transmission interruption by 2025 and elimination by 2030.展开更多
Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentrati...Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz method.Although the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of opisthorchiasis.Methods A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV.The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted withO.viverrini were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical analyses.Results Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal FECT.Urinary OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,respectively.Cross-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence ofO.viverrini between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen ELISA.The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT(86.6%)and urinary antigen ELISA(80.5%)were similar(P>0.05).Conclusions The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis.The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening,control and elimination of opisthorchiasis,thereby contributing to a reduction in the disease burden in Southeast Asia.展开更多
基金the Division of Research Promotion,Ubon Rajthanee UniversityDivision of Research, College of MedicinePublic Health, Ubon Rajthanee University
文摘Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.
基金the Thailand Research Fund, Grant No. TRG4880004 and the Grants of Khon Kaen University 2004 and 2006 Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan the Grant for Student of Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, 2003-2005
文摘AIM： To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory （ES） product. METHODS： NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA （cDNA） array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR. RESULTS： Among a total of 15 000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O.viverrini ES product, The expression level of signal transduction genes, pkC, pdgfra, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC,eps 8 and tgfβ3 1/4 which are the downstream signaling molecules of either epidermal growth factor （EGF） or transforming growth factor-β （TGF-β） showed statistical significance （P 〈 0.05）.CONCLUSION： O. viverrini ES product stimulates the significant changes of gene expression in several functional categories and these mainly include transcripts related to cell proliferation. The TGF-β and EGF signal transduction pathways are indicated as the possible pathways of O. viverrini-driven cell proliferation.
文摘Objective:To determine the influence of geographic,knowledge and behavioral factors on Opisthorchis(O.)viverrini infection in the Northeast of Thailand.Methods:This cross-sectional study was conducted by using four datasets of years 2016 and 2017.Generalized linear mixed model was employed to analyze association between geographic,knowledge and behavioral factors and O.viverrini infection.Results:Totally there were 1885 participants.The prevalence of O.viverrini infection was 10.03%.Geographic factors that showed statistically significant association with O.viverrini infection in the Northeast region were featured by at least a dam and reservoir(Adj.OR=4.21,95%CI:2.49-7.13,P<0.001),at least a weir(Adj.OR=1.74,95%CI:1.09-2.77,P=0.020),>50 dogs and cats per village(Adj.OR=3.40,95%CI:2.17-5.31,P<0.001),and rice fields covered>50%of its areas(Adj.OR=1.91,95%CI:1.04-4.01,P=0.036),as well as low to moderate levels of knowledge(Adj.OR=1.60,95%CI:1.32 to 1.94,P<0.001),consumed raw fish(Adj.OR=1.90,95%CI:1.02 to 3.52,P=0.040)and consumed processed raw fish(Adj.OR=3.03,95%CI:2.20 to 4.18,P<0.001).Other significant covariates were gender and age of the respondents.Conclusions:O.viverrini infection still remains a public health problem of the Northeast of Thailand.Geographic and demographic factors,knowledge,and consumption behaviors of raw fish products are significantly associated with O.viverrini infection.
基金supported by the National Research University Project(NRU)of Thailand Office of Higher Education Commission,Ministry of Education of Thailand and Thammasat University(Excellence Center in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma)
文摘Objective: To apply lectin affinity chromatography and glycoproteomics-based LC-MS/MS to preliminarily investigate the possible potential plasma biomarkers of Opisthorchis viverrini(OV)-associated CCA in OV/dimethylnitrosamine(DMN)-induced CCA hamster model. Methods: Nine Syrian hamsters were divided into 3 groups as follows(n=3 each): normal(healthy control group); OV group; and OV/DMN group(CCA group). Pooled plasma samples collected from animals in each group at the 6th month post-infection with OV metacercarae were subjected to glycoproteomics analysis. Glycoproteins in the pooled sample from each group were initially isolated by concanavilin A(Con A)-based affinity chromatography. The expression of glycoproteins isolated by both enrichment methods were determined using LCMS/MS. Results: Among the 24 Con A-binding glycoproteins isolated, two proteins, N-myc downstream regulated gene 1(NDRG1) and fetuin-B(FETUB) were found up-regulated only in the samples from the OV and control groups, but not in the OV/DMN(CCA) groups. On the other hand, one protein, i.e., NSFL1 cofactor p47 isoform x3(NSFL1C) was found only in the samples from OV/DMN(CCA) and control groups, but not in the OV group. The remaining 21 proteins were upregulated in the samples from all groups. Conclusions: NDRG1, FETUB and NSFL1 C glycoproteins isolated by Con A-based affinity chromatography could be potential biomarkers for CCA. Plasma samples with negative for NDRG1 and FETUB proteins but positive for NSFL1 C are likely to be OV-associated CCA. Nevertheless, this conclusion remains to be confirmed whether this battery test can discriminate OV-associated CCA from other risk factors.
基金The Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,though the Health Cluster(SHePGMS),Khon Kaen University to student,Miss Phornphitcha Pechdee and advisor,Assoc.Prof.Dr.Smarn Tesana for financial support of this work
文摘Objective:To explore larvicidal effects of anthelmintic drugs on Opisthorchis viverrini(O.viverrini) for alternative approach to interrupting its cycle for developing a field-based control program.Methods:The larvicidal activities of albendazole(A1),artesunate(Ar),praziquantel(Pzq) and miltefosine(Mf) on O.viverrini cercariae and mature metacercariae were investigated.Lethal concentrations(LC_(50) and LC_(95)) of these drugs were determined.Mature metacercariae previously exposed to various concentrations of the drugs were administered to hamsters.Worms were harvested 30 d post infection and worm recovery rates calculated.Al,Ar,Pzq and Mf produced morphological degeneration and induced shedding tails of cercariae after 24 h exposure.Results:The LC_(50) and LC_(95) of Al,Ar,Pzq and Mf on cercariae were 0.720 and 1.139,0.350 and 0.861,0.017 and 0.693,and 0.530 and 1.134 ppm,respectively.LC_(50) and LC_(95) of Ar on mature metacercariae were 303.643 and 446.237 ppm and of Mf were 289.711 and 631.781 ppm,respectively but no lethal effect in Pzq-and Al-treated groups(up to 1 ppt).No worms were found in hamsters administered Pzq-treated metacercariae.The adult worms from Al-treated metacercariae were significantly bigger in size compared to the control group(P<0.05).Fecundity and body width were greater in adults from Mf-treated metacercariae compared to the control group(P<0.05).Conclusions:The larvicidal effects of these drugs were high efficacy to O.viverrini cercariae but lesser efficacy to metacercariae.It should be further studied with the eventual aim of developing a field-based control program.
文摘Objective: To investigate the maturity development of miracidia in uterine eggs from four portions of the Opisthorchis viverrini uterus and environmental factors possibly affected in maturation and infectivity of distal part uterine eggs.Methods: Uteri of adult worms were divided into 4 equal parts.Development of eggs was determined under light microscope.Only embryonated eggs were used to evaluate the effects of physicochemical factors: temperature, salinity, acidity, ultraviolet A, B, C.Infection success was evaluated by feeding treated eggs to intermediate host snails and determining by using a PCR approach.Results: Eggs obtained from the uterus closest to the ovary(regions 1 and 2) failed to develop in vitro.Eggs from region 4 of the uterus(close to the genital pore) were used to study effects of physicochemical factors.The highest survival and infection success was in groups of eggs kept at 30 ℃(95.20%).The calculated period of loss infection success(LI_(50) and LI_(95)) on miracidia in distal uterine eggs by exposure to UV-A, UV-B and UV-C were 73 and 1 523 d; 8 and 20 d; 1 and 2 d, respectively.Lethal concentrations(LC_(50) and LC_(95)) of salinity, HCl and NaOH on miracidia in distal uterine eggs were 45.43 and 120.09 ppt, 0.01 and 0.25 M; 0.01 and 0.11 M, respectively, after 24 h exposure.Conclusions: Opisthorchis viverrini eggs display a high tolerance to environmental conditions, especially after snail host eating for infection.
文摘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.
基金We are grateful to the International Development Research CentreForeign Affairs,Trade and Development Canada(through the Global Health Research Initiative)the Australian Agency for International Development for funding support。
文摘Background:Prevalence of Opisthorchis viverrini,Schistosoma mekongi and soil-transmitted helminths(STH)remains high in Lao People’s Democratic Republic(Lao PDR),despite control efforts including mass-drug administration,education and communication campaigns.New approaches are required to advance helminth control.Methods:An ecohealth study was conducted on two Mekong islands in Southern Laos.Demographic and behavioural data were collected by questionnaire.Human and animal reservoir stools were examined.Bithynia spp.and Neotricula aperta snails were examined using shedding.Fresh water fish were examined using digestion technique.Multivariate random-effects analysis was used to find risk factors associated with helminth infections.Results:Human infection rates with O.viverrini,hookworm,S.mekongi,Trichuris trichiura,Ascaris lumbricoides and Taenia spp.were 60.7%,44.1%,22.2%,4.1%,0.6%and 0.1%,respectively.Heavy intensity infections were 4.2%,3.6%and 1.8%for O.viverrini,S.mekongi and hookworm,respectively.O.viverrini and S.mekongi infection rates among dogs and cats were 25.0%and 14.7%,respectively.Of the cats tested,53.1%were infected with O.viverrini.Prevalence of O.viverrini and S.mekongi in snails was 0.3%and 0.01%,respectively.Overall prevalence of O.viverrini infection in fresh water fish was 26.9%,with the highest infection rates occurring in Hampala dispa(87.1%),Cyclocheilichthys apogon(85.7%)and Puntius brevis(40.0%).Illiteracy and lower socioeconomic status increased the risk of O.viverrini infection,while those aged 10-16 years and possessing latrines at home were less likely to be infected.Household dogs and cats that consumed raw fish were significantly and positively associated with O.viverrini infection of the household members.For S.mekongi,children under 9 years old were exposed significantly to this infection,compared to older age groups.Conclusions:There is a pressing need to design and implement an integrated helminth control intervention on the Mekong Islands in southern Lao PDR.Given the highly dynamic transmission of O.viverrini,S.mekongi,STH and extended multiparasitism,annual mass-drug administration is warranted along with environmental modifications,health education and improved access to clean water and adequate sanitation to consolidate morbidity control and move towards elimination.Trail registration number:Our findings presented here are from a cross-sectional study,therefore,it has not been registered.
基金This work was partially supported by the Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,through the Health Cluster(SHeP-GMS)Khon Kaen University,Thailand+3 种基金the Thailand Research Fund(RTA 5680006)the National Institute of Allergy and Infectious Diseases(NIAID),National Institute of Health(NIH)award number P50AI098639The content is solely the opinion of the authors and does not necessarily represent the official views of NIAID,the NIH,or the funders.
文摘Background:Foodborne trematodiasis(FBT)is a significant global health problem,with the liver flukes Opisthorchis viverrini,O.felineus,and Clonorchis sinensis contributing to half of the global burden of FBT.North-eastern Thailand where O.viverrini is endemic and un-cooked fish dishes remain an integral part of the food culture has the highest reported incidence of opisthorchiasis,including associated cholangiocarcinoma.Both food sharing and eating practices are potentially important factors in FTB,suggesting an important role for the social ecology of disease transmission in these rural communities.Methods:Two rural Thai-Lao villages that were part of a 12-village project in Northeastern Thailand were selected for detailed investigation of O.viverrini infection risk associated with sharing of raw fish dishes among households.The project included screening individuals for infection and cholangiocarcinoma,a household questionnaire,and offering treatment options for positive individuals.Social network mapping was used to construct raw fish dish-sharing networks and create a proxy variable capturing variability in the degree of food sharing(DFS),measured as the number of different households with which each household shared fish dishes.Measures of associations between DFS,O.viverrini infection,the frequency of raw fish consumption,and the number of raw fish dishes consumed were generated using binary logistic regression,proportional odds ordinal logistic regression,and Poisson regression.Results:The results showed that the probability that a household has members infected with O.viverrini increased by~7%(P<0.01)for each additional household included in its network.Moreover,the frequency and number of types of raw fish dishes consumed increased significantly as the DFS increased.Of the two villages,that with the highest infection prevalence(48%versus 34.6%)had significantly higher social connectivity overall(P<0.001).Conclusions:Our findings suggest that the social ecology of human settlements may be key to understanding the transmission dynamics of some FBT.In the case of O.viverrini in Thai-Lao communities,for which food sharing is a traditional practice supporting social cohesion,food sharing network mapping should be incorporated into community-based interventions.These should encourage fish dish preparation methods that minimize infection risk by targeting households with high DFS values.
基金Khon Kaen University(KKU)through CASCAP(Grant No.CASCAP 1/60)the National Research Council of Thailand through the Medical Research Network of the C onsortium of Thai Medical Schools(Grant No.MRF 59-076)National Research Council of Thailand(NRCT/2559-134)。
文摘Background:Opisthorchis viverrini infection is highly prevalent in northeast Thailand.This liver fluke is classified as a carcinogen due to its causal links with cholangiocarcinoma(CCA)development.Although treatment with praziquantel(PZQ)effectively cures O.viverrini infection,the prevalence remains high due to the traditional consumption of raw fish.Therefore,re-infection is common in the endemic community,leading to severe hepatobiliary morbidities including the fatal CCA.In this study,we evaluate the association between the frequency of previous PZQ treatment and current O.viverrini infections among Thai adults living in the endemic area of northeast Thailand.Methods:This study includes all participants who were screened for O.viverrini infection in the Cholangiocarcinoma Screening and Care Program(CASCAP),northeast Thailand.History of PZQ treatment was recorded using a health questionnaire.O.viverrini infections were diagnosed using urine antigen detection.Associations between PZQ and O.viverrini were determined by adjusted odds ratio(aOR)and 95%confidence interval(CI)using multiple logistic regression.Results:Among participants,27.7%had previously been treated once with PZQ,8.2%twice,2.8%three times,and 3.5%more than three times.Current O.viverrini prevalence was 17%(n=524).Compared with participants who never used PZQ,the aOR for infection among those who used the drug once was 1.09(95%CI:0.88-1.37),twice was 1.19(95%CI:0.85-1.68),three times was 1.28(95%C/:0.74-2.21),and more than three times was 1.86(95%C/:1.18-2.93;P=0.007).Conclusions:The population with a frequent history of PZQ use and still continued raw fish consumption showed high levels of repeated reinfection with O.viverrini.They were infected,treated and re-infected repeatedly.These findings suggest that certain participants continue raw fish consumption even after previous infection.This is a particular problem in highly endemic areas for O.viverrni and increases the risk of CCA.
基金Supported by The Commission on Higher Education, Thailand(Strategic Scholarships for Frontier Research Network for the PhD Program Thai Doctoral degree)Khon Kaen University Research Foundation, Invitation Research from Faculty of Medicine, No. I55113he Higher Education Research Promotion and National Research University Project of Thailand, Office ofthe Higher Education Commission, through the Health Cluster(SHeP-GMS), Thailand
文摘AIM: To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). METHODS: Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N -nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA. RESULTS: In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-kB gene expression. CONCLUSION: ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.
文摘Opisthorchiasis caused by Opisthorchis viverrini （Oviverrini） remains a major public health problem in many parts of Southeast Asia including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobUiary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis, cholelithiasis and cholangiocarcinoma. The liver fluke infection was induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas of Thailand. Health education programs to prevent and control opisthorchiasis are still required in high-risk areas.
基金Supported by Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology Japan
文摘Cholangiocarcinoma(CCA) is a difficult cancer to diagnose in the early stage and to treat by curative resec-tion. The incidence of CCA in the northeast of Thailand is the highest in the world. To make progress in detecting a high risk group and in the prevention and detection of CCA, we have been analyzing the risk factors for CCA. Although liver fluke infection is known to be a risk factor, there are patients who are not infected with the liver fluke and not all people infected with the liver fluke will suffer from the disease. Therefore, it is of the utmost importance to analyze the risk factors and the mechanism to prevent the disease and also to detect the disease in its early stage to save patients' lives. Through collaboration among Thai and Japanese researchers, we analyzed the genetic and environmental determinants of risks for CCA. Also, we have been trying to develop methods to detect the disease in a non-invasive way. Without repeating findings reported in various reviews on CCA, we will first discuss the environmental and genetic determinants of the risks for CCA. Second, we will discuss the properties of CCA, including the etiological agents and the mechanism of cholangiocarcinogenesis, and finally, we will discuss future approaches to prevent and cure CCA from the standpoint of evidence-based medicine. We will discuss these points by including the data from our laboratories. We would like to emphasize the importance of the genetic data, especially whole genome approaches, to understand the properties of CCA, to find a high risk population for CCA and to develop effective preventative methods to stop the carcinogenic steps toward CCA in the near future. In addition, it is of the upmost importance to develop a non-invasive, specific and sensitive method to detect CCA in its early stage for the application of modern medical approaches to help patients with CCA.
文摘Various kinds of organisms, including viruses, bacteria, trematodes and fungi are known carcinogens that cause cancer. Infectious identification related to cancer may lead to better treatment for both the prevention and targeting of cancer therapy. Although nearly 20% of all cancers are caused by an infection of a microbe, the amount of evidence and information regarding the mechanisms associated with oncogenesis varies dramatically from one organism to the next. This review cannot be exhaustive because we are not aware of all infections worldwide in addition to their potential mechanisms for oncogenesis. More research is required for all of the species mentioned in this review.
基金funded by the World Health Organization,National Centres of Competence in Research,North-South and the Forlen Foundation.The project was also partially supported by the International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion(no.21410750200)from Shanghai Municipality Government.
文摘Schistosoma mekongi and other intestinal helminth infections remain public health concerns in Lao People's Democratic Republic, especially in remote areas where access to sanitation is limited.We performed an experimental study in four villages where latrine construction was coupled with two rounds of mass drug administration (MDA) with praziquantel and albendazole, and compared with two control villages that only received two rounds of MDA. The prevalence of helminth infections before (baseline) and after (follow-up) intervention were compared. Additionally, the prevalence in intervention and control villages were compared 12 months post-intervention. Kato–Katz, formalin-ethyl acetate concentration and Baermann techniques were employed to assess helminth infections.We found infection prevalence of S. mekongi in the intervention and control villages was 28.6% and 1.8%, respectively. The prevalences of other helminth infections were as follows: Opisthorchis viverrini, 79.5% and 71.8%;hookworm, 48.8% and 65.6%;and Strongyloides stercoralis, 43.1% and 38.3%. Other helminth species were detected in less than 5% of the study participants. Latrine intervention coupled with two rounds of MDA in the intervention villages reduced the prevalence of S. mekongi infection by 6.0% (from 28.6% to 22.6%;P < 0.001), O. viverrini infection by 11.3% (from 79.5% to 68.2%;P < 0.001), hookworm infection by 22.6% (from 48.8% to 26.2%;P < 0.001), and S. stercoralis infection by 12.0% (from 43.1% to 31.1%;P < 0.001). The observed reductions were not significantly different when compared to the control villages, where only two rounds of MDA were implemented (P > 0.05). Study participants in both groups commonly engaged in behaviours such as open defecation, bathing in the Mekong River, consuming raw or undercooked fish dishes and walking barefoot. These practices and behaviours are associated with helminth infections. Concluding, this study showed only a marginal impact associated with latrine use in intervention communities. There is a need for longer term studies with integrated interventions, such as effective health education to foster behavioural changes related to open defecation, raw or undercooked food consumption, wearing protected footwear outdoors, and personal hygiene.
基金This intervention study was funded by the International Development Research CentreForeign Affairs,Trade and Development Canada(through the Global Health Research Initiative),the Australian Agency for International Development for funding support,under funding number 105509-027the International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion from Shanghai Municipality Government(No.21410750200).
文摘Background Helminth infections, includingOpisthorchis viverrini, hookworm, andTrichuris trichiura, are prevalent in Khong district, Champasack province, southern Lao People’s Democratic Republic (PDR). Schistosomiasis caused bySchistosoma mekongi is of public health concern on the islands of the Khong district. This study aimed to assess the impact of an Eco-Health/One-Health approach in combination with mass drug administration (MDA) to reduce these helminth infections.Methods We conducted a community intervention using a stepped-wedge trial approach on two endemic islands (Donsom and Donkhone) of the Khong district, Champasack province, Lao PDR, between April 2012 and March 2013. In each study village, 30–40 households were randomly selected. All members of selected households, who were at home during the study period were invited to participate in the study. A baseline study was conducted to assess helminth infections, knowledge attitudes and practices towardSchistosoma mekongi infection, behavior of open defecation and availability of latrine at home. After the baseline (T0), the Eco-Health/One-Health approach was implemented on Donsom (intervention) and Donkhone island (control). An assessment was conducted in 2014 (T1), one year after the completion of intervention implementation, to assess the short-term impact of the Eco-Health/One-Health approach on helminth infections and compare intervention and control islands. Later in 2015, the Eco-Health/One-Health approach was implemented on control island (Donkhone). After the implementation of intervention, the parasitological assessments were conducted annually in humans in 2015 (T2), in 2016 (T3) and in 2017 (T4), and in dogs in 2017 (T4) to evaluate the long-term impact of the intervention on helminth infections. Frequency was used to describe the prevalence of helminth infections. Logistic regression was applied to associate the KAP (knowledge, attitudes, and practices and open defecation behavior) and the reduction of helminth infections between intervention and control islands. The reduction in prevalence pre- and post-intervention was associated using a McNemar test. A two-independent samplet-test was applied to compare the mean eggs per gram (EPG) of helminth infections between control and intervention islands. A paired t-test test was used to compare the mean EPG of stool samples before (baseline) and after (follow-up) interventions for the two islands separately. AP-value lower than 0.05 was considered statistically significant.Results Eco-Health/One-Health approach appears to be associated with reduction in prevalence ofS. mekongi by 9.0% [odds ratio (OR) = 0.49,P = 0.003] compared to the use of mass drug administration alone (control island). Additionally, this intervention package significantly reducedO. viverrini infection by 20.3% (OR = 1.92,P < 0.001) and hookworm by 17.9% (OR = 0.71,P = 0.045), respectively. Annual parasitological assessments between 2012 and 2017 showed that the Eco-Health/One-Health approach, coupled with MDA, steadily reduced the prevalence ofS. mekongi on the intervention island from 29.1% to 1.8% and on the control island from 28.4% to 3.1%, respectively.Conclusions The study findings suggest that the Eco-Health/One-Health approach appears to be associated with a significant reduction in prevalence ofS. mekongi and helminth co-infections, particularly hookworm andT. trichiura. Therefore, implementing the Eco-Health/One-Health approach in schistosomiasis-endemic areas could accelerate the achievement of national goals for transmission interruption by 2025 and elimination by 2030.
基金supported by the Cholangiocarcinoma Research Institute,Khon Kaen University,Thailand.This project is funded by the National Science Research Council of Thailand(NRCT)the Post-Doctoral Training Program from Khon Kaen University,Thailand(PD2565-02-01)supported by the Thailand Centre of Excellence for Life Sciences(TCELS)SDT-R was funded by the Wellcome Trust ISSF grant at Imperial College London.
文摘Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz method.Although the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of opisthorchiasis.Methods A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV.The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted withO.viverrini were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical analyses.Results Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal FECT.Urinary OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,respectively.Cross-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence ofO.viverrini between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen ELISA.The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT(86.6%)and urinary antigen ELISA(80.5%)were similar(P>0.05).Conclusions The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis.The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening,control and elimination of opisthorchiasis,thereby contributing to a reduction in the disease burden in Southeast Asia.
