Accuracy of a new rapid diagnostic test for urinary antigen detection and assessment of drug treatment in opisthorchiasis.

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 urinary Opisthorchis 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 with O. 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 of O. 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.

Rapid assessment of Opisthorchis viverrini IgG antibody in serum: A potential diagnostic biomarker to predict risk of cholangiocarcinoma in regions endemic for opisthorchiasis.

BACKGROUND: Opisthorchiasis is caused by an infection with fish-borne liver flukes of the genus Opisthorchis. Opisthorchiasis frequently leads to chronic inflammation in the biliary tract and is classified as a group 1 biological carcinogen by the International Agency for Research on Cancer: a definitive risk for cholangiocarcinoma (CCA). METHODS: We used the rapid immunochromatographic test (ICT) to detect anti-Opisthorchis viverrini IgG and IgG4 subclass antibodies in sera of patients with CCA. The ICT kits were developed based on soluble antigens excreted and secreted by O. viverrini adult worms. RESULTS: ICT indicated sera was positive for IgG and IgG4 antibodies, respectively, in 22 (61.1%) and 15 (41.6%) participants of the 36 study participants diagnosed with CCA (P > 0.05). Our study also included groups with other cancers and with liver cirrhosis, where the IgG ICT and IgG4 ICT kits were 27.7% (13/47) and 25.5% (12/47) positive, respectively (P > 0.05). Neither total the IgG ICT nor the IgG4 ICT yielded positive results in a control group of 20 healthy participants. Moreover, the percentage positivity rate using the ICT for total IgG between the CCA group and the other cancers and liver cirrhosis group was significantly different (P < 0.05). By contrast, no significant difference between these groups was apparent in the ICT for IgG4 antibody. The CCA group was 6.53 times more likely to have positive anti-O. viverrini IgG antibody (odds ratio 6.53, P < 0.001) and 3.27 times more likely to have positive anti-O. viverrini IgG4 antibody (odds ratio 3.27, P = 0.010) than the non-CCA group. CONCLUSION: This information is of potential value for the development of a diagnostic biomarker to predict risk for O. viverrini infection-associated CCA.

The Socioeconomic Burden of Cholangiocarcinoma Associated With Opisthorchis viverrini Sensu Lato Infection in Northeast Thailand: A Preliminary Analysis.

The northeast of Thailand, which is the poorest region of the country, has the highest incidence of cholangiocarcinoma (CCA) worldwide. This is associated with infection with the liver fluke Opisthorchis viverrini. Although an estimated 20,000 people die every year of this disease, the socioeconomic impact of this mortality on the victims' family and the community in which he or she lived remains unknown. Here, we provide background information on the socioeconomic groups most effected by CCA and provide a qualitative estimate of the likely financial burden on the family and community. Most victims of CCA are small-scale farmers. Mortality occurs most commonly in males between the ages of 40 and 65, having either children or grandchildren to support. Costs can be divided between premortality with the family paying for transport and accommodation to the hospital, as well as costs not covered by the Thai Universal Health Coverage scheme. The main costs, however, are likely to be postmortem with loss of income and potentially the loss of a major contributor to farm work. What is urgently required is a quantitative estimate of the costs of CCA and long-term studies of the families and communities affected to determine where and how the burden of CCA falls.

Role of socio-cultural and economic factors in cyprinid fish distribution networks and consumption in Lawa Lake region, Northeast Thailand: Novel perspectives on Opisthorchis viverrini transmission dynamics.

Opisthorchis viverrini (Ov) is a fish-borne parasite endemic in parts of Lao PDR, Cambodia, southern Vietnam and Northeast Thailand (Isaan) where an estimated 10 million people are infected. Human Ov infection, associated with hepatobiliary complications, including cholangiocarcinoma (CCA), occurs when infected fish are consumed raw or undercooked, a longstanding cultural tradition in the region. This mixed- methods descriptive study was carried out in Isaan villages around Lawa Lake, Khon Kaen Province, known for their Ov endemicity. Focus group discussions (FGDs) and in depth interviews (IDIs) were used to explore socio-cultural determinants underlying raw fish consumption practices, and global positioning system (GPS) devices to map local fish distribution networks. Qualitative data affirmed major socio-cultural and dietary lifestyle transitions occurring consequent on recent decades of modernization policies and practices, but also the persistence of Isaan traditional raw-fish eating practices and incorrect beliefs about infection risk avoidance. Fish traders/middlemen purchase most of the catch at the lakeshore and play the dominant role in district market fish distribution networks, at least for the larger and less likely infected, fish species. The lower economic value of the small potentially-infected cyprinid fish means local fishermen typically distribute them free, or sell cheaply, to family and friends, effectively concentrating infection risk in already highly Ov infected villages. Our study confirmed the persistence of traditional Isaan raw-fish meal practices, despite major ongoing socio-cultural lifestyle transitions and decades of Ov infection health education programs. We contend that diffuse socio-cultural drivers underpin this practice, including its role as a valued cultural identity marker. A "fish economics" factor was also evident in the concentration of more likely infected fish back into local villages due to their low economic value at district market level. The complexity of factors supporting "risky" fish-eating traditions in Isaan underscores the importance of integrated liver fluke infection control strategies to draw on transdisciplinary knowledge beyond biomedicine and also embrace participatory protocols for engaging communities in developing, implementing and evaluating interventions.

Re-Examination of Opisthorchis viverrini in Nakhon Ratchasima Province, Northeastern Thailand, Indicates Continued Needs for Health Intervention.

Opisthorchis viverrini infection is associated with cholangiocarcinoma particularly in the cases of chronic or re-infection. This presents a serious health problem in northeastern and northern Thailand. A community base approach is required for surveillance. Therefore, in a pilot project, re-examination of O. viverrini infection was conducted in the 3 districts of Nakhon Ratchasima province, Thailand, during June and October 2015. A total of 355 participants from a 194,152 population, was selected through multi-stage sampling. O. viverrini infection was determined using modified Kato Katz thick smear technique. Participants were 229 males and 126 females, and aged ≥30 years old. Prevalence of O. viverrini infection was 2.25% (8/355 participants). O. viverrini infection was slightly higher in females (3.17%), and age group between 41-50 years (4.49%). Mueang Yang district had a highest of O. viverrini infection rate (2.82%), and followed by Bua Yai (2.48%), and Chum Phuang (1.84%), respectively. O. viverrini infection rate was increased from year 2012 to 2015 particularly in Bua Yai and Mueang Yang. These re-examinion results indicate that opisthorchiasis is still problem in community of Nakhon Ratchasima province, therefore, the provincial-wide scale is need required. Furthermore health education is need intervened in the infected group, and screening of cholangiocarcinoma is urgently concerned.

Re-examination of Opisthorchis viverrini Infection in Northeast Thailand.

BACKGROUND: Liver fluke infection caused by the parasite Opisthorchis viverrini (O. viverrini), a human carcinogen, is endemic in north-eastern Thailand and remains a major health problem. OBJECTIVES: The objectives of the study were to (1) resurvey the prevalence of O. viverrini infection in a field site from the Khon Kaen Cohort Study (in newly recruited subjects as well as previous cohort subjects surveyed in 1992); (2) investigate how subjects' lifestyle habits and their exposure to health promotion initiatives influence changes in prevalence of O. viverrini infection. MATERIALS AND METHODS: The prevalence of O. viverrini infection in the cohort subjects (as well as new subjects) was investigated using faecal egg counts. Information on demographic factors, lifestyle and awareness of health promotion initiatives were obtained through questionnaires. RESULTS: O. viverrini infection rates in the same individuals of the cohort were lower in 2006 than in 1992. Also, by studying the period effect, the current 35-44 year olds had a 12.4% (95% CI 3.9% to 20.9%) lower prevalence of O. viverrini infection than the 35-44 year olds in 1992 (24.2% versus 11.8%). Lifestyle choices showed that smoking and alcohol consumption were associated with an increased chance of acquiring O. viverrini infection with adjusted odds ratios of 10.1 (95%CI 2.4-41.6) and 5.3 (95%CI 1.2-23.0), respectively. CONCLUSIONS: Our study has demonstrated that although the prevalence of O. viverrini infection over a 14-year period has decreased, unhealthy lifestyle was common with smoking and alcohol consumption being associated with increased chances of infection, emphasising the double burden of disease which developing countries are facing.

Epidemiology of Strongyloides stercoralis on Mekong islands in southern Laos.

Strongyloides stercoralis is a neglected helminth infection potentially that can lead to systemic infection in immunocompromised individuals. In Lao People's Democratic Republic (Lao PDR, Laos), information on S. stercoralis infection is scarce. We assessed S. stercoralis infection and associated risk factors and symptoms on the Mekong islands in Southern Laos. Baermann and Kato-Katz techniques were performed on two stool samples from each individual to detect S. stercoralis larvae and concomitant helminth infections. Among 729 individuals, 41.0% were infected with S. stercoralis. Men were at higher risk than women (OR 1.97, 95% CI 1.45-2.67). Urticaria and body itching was associated with S. stercoralis infection (OR 2.4, 95% CI 1.42-4.05). Infection with Opisthorchis viverrini (72.2%), Schistosoma mekongi (12.8%), and hookworm (56.1%) were very common. Few infections with Trichuris trichiura (3.3%), Ascaris lumbricoides (0.3%) and Taenia spp. (0.3%) were detected. The majority of helminth infections were of light intensity, with prevalences of 80.4%, 92.9%, 64.5%, 100% and 100%, for O. viverrini, hookworm, S. mekongi, T. trichiura and A. lumbricoides, respectively. Nevertheless, heavy infection intensities were observed for O. viverrini (1.0%), S. mekongi (14.0%) and hookworm (2.9%). S. stercoralis is highly endemic on the islands of Khong district, Champasack province, Southern Laos. The national helminth control programme should take action to control this helminth infection.

Risk biomarkers for assessment and chemoprevention of liver fluke-associated cholangiocarcinoma.

Human liver fluke, Opisthorchis viverrini (Ov), is the major risk factor of cholangiocarcinoma (CCA) in northeastern Thailand. Our approach focuses on genetic progression and molecular changes in the carcinogenic pathway of liver fluke-associated CCA aimed at assessing patients at risk of CCA and using chemoprevention as the secondary cancer prevention to reduce the incidence of CCA. This review summarizes altered gene expressions, biomolecules and their modification, i.e. DNA adducts, oxidized proteins, oxysterols and fibrotic markers in hamster- and human-CCA. Potential risk biomarker(s) and chemopreventive agent(s) criteria and selection were based on results from experimental and epidemiological studies identifying hepatobiliary disease, including CCA. Laboratory results reveal that oxidative stress induced by Ov infection leads to bimolecular damage, tissue remodeling especially periductal fibrosis and alteration of gene expressions, which could be involved in all steps of CCA carcinogenesis. Some of these molecules are reported to change their levels in opisthorchiasis, periductal fibrosis diagnosed by ultrasonography and CCA. Chemoprevention in experimental CCA tumorigenesis is discussed. These multiple risk biomarkers could now be explored for screening including chemopreventive intervention of subjects living in endemic areas where the prevalence of opisthorchiasis remains high.

Ultrasonography assessment of hepatobiliary abnormalities in 3359 subjects with Opisthorchis viverrini infection in endemic areas of Thailand.

A cross sectional study on hepatobiliary abnormalities in opisthorchiasis was performed in 8936 males and females aged from 20 to 60 years from 90 villages of Khon Kaen province, Northeast Thailand. All were stool-examined for Opisthorchis viverrini infection by standard quantitative formalin/ethyl acetate concentration technique. Of these, 3359 participants with stool egg positive underwent ultrasonography of the upper abdomen. The hepatobiliary abnormalities detected by ultrasound are described here. This study found a significantly higher frequency of advanced periductal fibrosis in persons with chronic opisthorchiasis (23.6%), particularly in males. Risks of the fibrosis included intensity of infection, and age younger than 30 years. Height of left lobe of the liver, cross-section of the gallbladder dimensions post fatty meal, sludge, and, interestingly, intrahepatic duct stones were significantly associated with the advanced periductal fibrosis. Eleven suspected cholangiocarcinoma (CCA) cases were observed. This study emphasizes the current status of high O. viverrini infection rate and the existence of hepatobiliary abnormalities including suspected CCA in opisthorchiasis endemic areas of Thailand.

Cost comparison of rapid questionnaire screening for individuals at risk of clonorchiasis in low- and high-prevalence communities in northern Vietnam.

Clonorchiasis is an emerging food-borne trematode infection in Vietnam. Due to the absence of cost-effective preventive measures its control largely relies on morbidity reduction by chemotherapy with praziquantel. We performed a comparative cost estimation of three different diagnostic and intervention approaches in areas of high and low prevalence of clonorchiasis in northern Vietnam in order to select more cost-effective chemotherapy. Our study confirmed that a questionnaire investigating the habit of eating raw, freshwater fish was a rapid, cost-effective and operationally feasible tool for identifying individuals at risk of clonorchiasis in both high-prevalence and low-prevalence areas. The cost of diagnosis and intervention per person and per true positive case was 20-fold higher in low-prevalence areas, regardless of the type of approach. Geographical mapping of high-risk areas prior to screening is, therefore, recommended to maximize the cost-effectiveness of the intervention activities.

Opisthorchis viverrini: an underestimated parasite in world health.

Infection with Opisthorchis viverrini and its associated cholangiocarcinoma (CCA) is an underestimated problem in the Mekong region of Southeast Asia, despite the widespread use of praziquantel and health education measures for parasite control. Although data from Cambodia, Laos and Vietnam are rare, data from Thailand often show wide-ranging variability in epidemiological parameters, including human morbidity and the prevalence and incidence of CCA. The recent discovery of high levels of population genetic variability in O. viverrini in different wetlands in Thailand and Laos, which indicates the presence of sibling species, suggests that we have underestimated the complexity of this epidemiological situation. Future research should determine the relationship between the genetic variability of O. viverrini and patterns of opisthorchiasis-related disease.

Assessment of the relationship of chronic opisthorchiasis to Epstein-Barr virus infection as well as some cytogenetical and immunological parameters in two comparable Siberian regions.

Previous studies have shown an increase in the frequency of chromosomal abnormalities in the peripheral blood lymphocytes from opisthorchiasis patients. Some evidence suggests that there is an association between chronic opisthorchiasis and certain herpes viruses. To study the relationship of opisthorchiasis to the reactivation of Epstein-Barr virus (EBV) infection as well as the influence of opisthorchis infection on some cytogenetical and immunological parameters, we used the indirect immunofluorescence for measuring some virus specific antibodies, the cytokinesis-block lymphocyte micronucleus assay, and the quantitative immunodiffusion method for measuring immunoglobulin concentrations in serum. A total of 1,580 people were monitored in two comparable Siberian regions: in the Ob River region which is endemically related to opisthorchiasis caused by Opisthorchisfelineus and in the nonendemic control Yenisey River region. There was no significant difference in each of the tested parameters between two uninfected controls from the endemic Ob and nonendemic Yenisey regions. We have found significant difference (p < 0.01) in the frequency of micronucleated cytokinesis-block lymphocytes and the antibody levels against certain EBV antigens between the examined inhabitants of the opisthorchis-infected Ob and uninfected Yenisey regions. Furthermore, there were a good correlation (r = + 0.72) between the increase in titres of antibody to the EBV capsid antigen and the high frequency of micronucleated lymphocytes in the opisthorchis-infected Ob population. Also, levels of both IgG and IgM were increased in opisthorchiasis patients. This study confirms an association between chronic opisthrochiasis and reactivation of EBV which may be implicated in the development of cancer in opisthorchiasis patients.

Infection with Helicobacter pylori and parasites, social class and cancer.

Three genera of parasites are known or suspected risk factors for cancer in humans: Schistosoma, Opisthorchis and Clonorchis. No adequate information is available on the determinants of infections related to social class. Infection with the bacterium Helicobacter pylori is an important cause of stomach cancer. Studies, in particular from the United Kingdom and the United States of America, strongly suggest that social class factors, especially those acting during childhood, are determinants of the infection, with odds ratios of seroprevalence of the order of 1.5-5 for lower social class as compared with higher social class. A conservative estimate of the contribution of social class, acting through an increased prevalence of H. pylori infection, to the burden of stomach cancer gives a figure of over 50,000 stomach cancers per year worldwide, or 8% of all stomach cancers. In countries with both high and low prevalence of infection with H. pylori, it is likely that a sizeable proportion of this difference is due to social-class-related risk factors of infection.

Food-borne parasitoses in Malaysia epidemiological assessment and research needs.

Food-borne parasitic zoonoses have emerged as a major public health problem in many countries and are posing a medical challenge. They are not only important from the economic point of view but also because of their severe sequelae. In Malaysia, these parasitoses are a tip of an iceberg problem. The article documents all the food-borne parasitic zoonoses reported in Malaysia. An epidemiological assessment of the diseases with research needs is highlighted.

[A quantitative assessment of risk factors in helminthiases]. / Kolichestvennaia otsenka faktorov riska pri gel'mintozakh.

Presents a quantitative assessment of some risk factors leading to enterobiasis and opisthorchiasis. Suggests a division of these factors into those that can be eliminated easily, conditionally, or not at all.

Preliminary estimates of economic impact of liver fluke infection in Thailand and the feasibility of irradiation as a control measure.

Liver fluke infection by Opisthorchis viverrini is the leading cause of food-borne parasitic disease in Thailand. Approximately one third of the population in the northeastern region of the country, ie, 6-7 million, are infected by this parasite through the habit of consuming raw or insufficiently cooked freshwater fish, especially those of cyprinoid family. A recent survey showed that 60% of the work force in the Northeast between the age of 15 and 60 is infected. The estimated wage loss of this population may be approximately Baht 1,620 million (US$65 million) per annum. The estimated direct cost of medical care may be as high as Baht 495 million (US$19.4 million) per annum. Thus, the total direct cost of the infected work force is estimated to be Baht 2115 million (US$84.6 million) per annum. Irradiation of fish flesh infected by metacercaria of O. viverrini has been demonstrated as an effective method of control. A minimum dose of 0.1 kGy is effective without changing physiochemical properties of the fish flesh. This technology, therefore, shows promise as a method to control infection by O. viverrini acquired by the habit of consuming raw freshwater fish in the country. Preliminary economic analyses indicate that the public health benefit from preventing infection with this parasite could outweigh the investment cost of irradiation facilities. Detailed economic feasibility studies should be carried out to demonstrate the practical efficacy and cost-effectiveness of the treatment as a public health intervention measure in the country.

[An assessment of the situation regarding opisthorchiasis in the area of the Irtysh-Karaganda canal]. / Otsenka situatsii po opistorkhozu v zone kanala Irtysh-Karaganda.

The opisthorchiasis situation in Irtysh--Karaganda canal zone were studied. 615 men (by coprological method), 319 men (by serological method), 26 domestic cats, and molluscs (gen. Codiella)--were investigated. In the canal zone the situation of opisthorchiasis infection at present is favourable. Some of the infections are connected with the fish out of Shiderty River.

[An assessment of the opisthorchiasis situation in the area of Irtysh-Karaganda Canal]. / K otsenke situatsii po opistorkhozu v zone kanala Irtysh-Karaganda.

Helminthological investigation of the Irtysh-Karaganda Canal area was performed in the summer of 1989. In 9 storage ponds on the Shiderta and Olenta rivers 900 fish individuals, whose size was suitable for fishery have been examined, samples of water have been taken and the epidemiological assessment of modern conditions of opisthorchiasis agent circulation have been presented. The whole canal is at present favourable in view of opisthorchiasis infection. Local cases of infection are associated with fish from Shiderta and Olenta rivers.