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Prof. Dr. Peter Odermatt

Department of Public Health
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Projects & Collaborations

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Towards early detection of severe morbidity associated with Asian liver fluke infection in Lao PDR

Research Project  | 2 Project Members

Asian liver fluke infections, namely infection with the trematode helminths Opisthorchis viverrini, O. felineus and Clonorchis sinensis, are highly endemic in many settings in Asia and Eastern Europe. Deeply culturally rooted habits of raw and undercooked fish dishes consumption are the origin of the infection. Asian liver fluke infections are typically prevalent in rural, resource-poor settings with little access to quality health services. The presence of adult fluke worms in the biliary ducts in combination with other socio-culturally, behavioural and geographically rooted risk factors such as nitrosamine rich diets, smoking, alcohol consumption, concomitant viral hepatitis infections and other factors determine the severity of developing morbidity. Chronic infection may induce cholangiocarcinoma (CCA), a fatal bile duct cancer. In most Asian liver fluke endemic settings, the true extent of liver fluke induced liver morbidity is unknown and underestimated, resulting in an inadequate allocation of resources for prevention and control. The lack of easily measurable morbidity markers are a fundamental problem. Also lacking are detailed risk pattern assessments for the hepatobiliary morbidity. In Lao PDR, about half of the population is infected with O. viverrini.Objectives: Our project pursues the following objectives: (i) to assess the prevalence of different hepatobiliary pathologies associated with O. viverrini infection in adult residents living in central and southern Lao PDR; (ii) to identify factors associated with the risk and presence of moderate (periductal fibrosis) and severe morbidity (advanced periductal fibrosis and precancerous lesions) in O. viverrini-infected adults in central and southern Lao PDR, with particular emphasis on PZQ treatment history; (iii) to assess the predictive capacity for the presence of O. viverrini-induced (advanced) periductal fibrosis and CCA as assessed by ultrasound in a new O. viverrini-endemic setting of candidate, CCA-related biomarkers (i.e. CA19-9, alpha 1-fetoprotein mucin-5AC, CYFRA21-1, serum IL-6, serum ES exosomes, urinary 8-oxodG, urinary miR-21 and miR-192) and to investigate how the concentration level of these biomarkers is influenced by behavioural and PZQ treatment factors associated with severe hepatobiliary morbidity (see Objective 2); (iv) to establish a population-based biobank consisting of urine, serum and stool aliquots from an O. viverrini-infected (Ov+) case-control sample (Ov+ cases: persons with different severity stages of hepatobiliary pathology; Ov+ controls: persons without evidence hepatobiliary pathology) for future research on (i) the validation of novel CCA-related candidate biomarkers and (ii) the identification of novel diagnostic biomarkers through agnostic or targeted -omics approaches.Methods: The study consists of three parts: (i) a cross-sectional survey in two provinces of Lao PDR (Champasack and Saravane) in which randomly selected adults (>25 years) will be enrolled and examined on the presence of O. viverrini infection (Ov+) with a parasitological stool examination and on liver morbidity (healthy, PF+, APF+, CCA-like lesions) by using ultrasonography and on risk factors by using a questionnaire. A total of 2,625 participants will be enrolled; (ii) a case-control study will be embedded in the cross-sectional study. A case-group 1 with severe morbidity (APF+, Ov+), a case-group 2 with moderate morbidity (PF+, Ov+) will be compared to age, sex and village of residence matched controls which have no morbidity (PF-, Ov+). All participants are O. viverrini positive (Ov+). In cases and controls the concentration of the new biomarkers, ES exosomes of O. viverrini and 8-oxodG will be measured as well as other known factors contributing to morbidity development. In total 945 patients will be enrolled in the case-control study, 315 patients per group; and (iii) a biobank containing aliquots (full blood, serum, stool and urine) of each participant in the case-control study, will be established.Expected results: The study will provide detailed information on the amount of hepatobiliary morbidity present in two provinces of Lao PDR. Furthermore, it will elucidate the risk pattern responsible for severe morbidity development in addition to O. viverrini infection and therefore provide new mechanistic insights. In particular, it will show whether history of treatment may results in morbidity increase, which has direct implications for control in Lao PDR and other Asian liver fluke endemic settings and will inform treatment policy.

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Food-borne trematodiasis: role in hepatobiliar and intestinal morbidity and risk patterns for infection in ecological and socio-economic distinct settings of Southeast Asia

Research Project  | 1 Project Members

In the Mekong River basin parasitic infections are of major public health, economic and veterinary importance. Besides malaria, food- and water-borne trematode infections (worms) persist. Liver flukes (Opisthorchis viverrini) and intestinal flukes (Fasciolopsis buski, Haplorchis sp.) are responsible for hepatobiliar and intestinal diseases, respectively. Schistosoma mekongi is the endemic water-borne trematode affecting the liver and intestinal tract. Food- and water-borne trematodes exhibit a complex life cycle in which either aquatic snails, or crustacean, or fish, or water plants act as intermediate host(s). Raw or undercooked consumption of these animals and plants or exposure to contaminated water leads to infection. Ecological features of the Mekong River basin ascertain the presence of the environmental reservoir. The low socio-economic status governs the exposure of mainly rural populations and infections with two or more parasites are very frequent. The socio-ecological setting determines which parasites can be transmitted, and hence the characteristics of the multiple infections change according to the setting and as a consequence the combined morbidity. Further complications arise as the distinction of these parasites with standard laboratory diagnostic techniques is difficult and therefore misdiagnosis is common. The goal of the project is to analyse the characteristics and dynamics of polyparasitism of trematodes in the Mekong River basin area and its community-attributable burden. The study will provide a basis for the design and implementation of control strategies. The project will be conducted in distinctly different socio-ecological setting in Lao PDR. They represent the variety of socio-ecological setting present in the Mekong River basin and bordering areas. Hospital- and community-based studies will be performed. This project will provide qualitative and quantitative, hospital and community based assessments of trematode infections, their interrelationship and association with other intestinal parasitic infections in Lao PDR. It will allow risk mapping and prediction and will help to tailor cost-effective control and surveillance strategies. This project is financed by the Research Partnership Initiative of the Swiss National Research Foundation (SNF) and the Swiss Development Cooperation. Research capacity building in Lao PDR is an explicit operational aim of the project.