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

English title Towards early detection of severe morbidity associated with Asian liver fluke infection in Lao PDR
Applicant Odermatt Peter
Number 160930
Funding scheme r4d (Swiss Programme for Research on Global Issues for Development)
Research institution Swiss Tropical and Public Health Institute
Institution of higher education University of Basel - BS
Main discipline Tropical Medicine
Start/End 01.03.2017 - 31.12.2020
Approved amount 500'000.00
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All Disciplines (2)

Discipline
Tropical Medicine
Infectious Diseases

Keywords (11)

periductal liver fibrosis; Opisthorchis viverrini; Clonorchis sinensis; risk factors; tumour markers; hepatobiliary morbidity; Asian liver fluke; Lao PDR; Opisthorchis felineus; cholangiocarcinoma; biobank

Lay Summary (German)

Lead
Zu den Asiatischen Leberegeln (ALE) gehören die drei humanpathogenen Wurmparasiten Opisthorchis viverrini, O. felineus und Clonorchis sinensis. Sie sind in Asien und Europa endemisch. Die Ansteckung erfolgt durch den Konsum von rohem Fisch. Adulte ALE leben in den Gallengängen der Leber, wo sie zu pathologischen Veränderung führen. Chronische Infektionen können zum tödlichen Gallengangkrebs führen. Neben dem ALE sind auch weitere Faktoren für die Bildung der Pathologien verantwortlich. In vielen ALE endemischen Gebieten sind die gesundheitlichen Folgen der ALE Infektionen und die zusätzlichen Risikofaktoren, nicht bekannt. Zum Beispiel in Laos, sind die Infektionsraten mit dem ALE sehr hoch (häufig über 50%) aber nur spärliche Informationen liegen in Bezug auf die Leberschäden vor. Ein Hauptgrund dafür ist, dass deren Messung sehr umständlich ist und spezifische diagnostische Techniken nötig sind.
Lay summary

Inhalt und Ziel des Forschungsprojekts

Mit unserem Forschungsprojekt verfolgen wir vier Ziele. Erstens, werden wir die Leberpathologien erfassen, die durch den ALE in hochendemischen Gebieten in Laos verursacht werden. Zweitens, werden wir Risikofaktoren identifizieren, die für die Entstehung der besonders schweren Leberpathologien verantwortlich sind. Drittens, werden wir die Nützlichkeit von heute bestehenden Biomarkern evaluieren. Und, viertens, werden wir eine Biobank erstellen (Blut, Urin und Stuhlproben der Patienten) welche dazu dienen wird, neue Biomarker zu entwickeln, die Frühstadien der Leberpathologien diagnostizieren können.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unsere Resultate werden einen Überblick der Häufigkeit und des Schweregrads der Leberschäden geben, die durch den ALE und die zusätzlichen anderen Risikofaktoren in Laos zuzuschreiben sind. Diese Erkenntnisse werden die Bekämpfungsstrategien des Parasiten direkt beeinflussen und die nötigen Schritte identifizieren, die zur Bekämpfung des Gallengangkrebses nötig sind.


Direct link to Lay Summary Last update: 18.11.2016

Responsible applicant and co-applicants

Publications

Publication
Cross-reaction of POC-CCA urine test for detection of Schistosoma mekongi in Lao PDR: a cross-sectional study
Homsana Anousin, Odermatt Peter, Southisavath Phonesavanh, Yajima Aya, Sayasone Somphou (2020), Cross-reaction of POC-CCA urine test for detection of Schistosoma mekongi in Lao PDR: a cross-sectional study, in Infectious Diseases of Poverty, 9(1), 114-114.

Collaboration

Group / person Country
Types of collaboration
Radiology, Anaesthesia, Surgery, Intensive Care Unit, at Mahosot hospital Laos (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. Paiboon Sithithaworn, University of Khon Kaen, Department of Parasitology Thailand (Asia)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Nittaya Chamadol, Faculty of Medicine, University of Khon Kaen Thailand (Asia)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Narong Khuntikeo, Faculty of Medicine, University of Khon Kaen Thailand (Asia)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
2nd Asian conference of cholangiocarcinoma 2019 Talk given at a conference Epidemiology and carcinogenesis of CCA (symposium) 13.12.2019 Vientiane, Laos Odermatt Peter;
2nd Asian conference of cholangiocarcinoma 2019 Talk given at a conference Cholangiocarcinoma major public health problem: Experience from Lao PDR 12.12.2019 Viuentiane, Laos Somphou Sayasone;
Cholangiocaricnoma UK Annual Conference 2019 Talk given at a conference Cholangiocarcinoma and liver fluke infection in Lao PDR 14.11.2019 Nottingham, Great Britain and Northern Ireland Odermatt Peter;
National Health Research Forum, Vientiane, Lao PDR 2019 Talk given at a conference Cholangiocarcinoma, a fatal disease associated with liver fluke infection “Opisthorchis viverrini” in Lao PDR 17.10.2019 Vientiane, Laos Somphou Sayasone;
Belt and Road Tropical Medical Alliance 2019 Talk given at a conference Opisthorchis infection and risk for cholangiocarcinoma in Lao PDR 11.10.2019 Hainan, China Somphou Sayasone;
National Health Research Forum, Vientiane, Lao PDR 2018 Talk given at a conference Severe liver morbidity on Khong Islands: a starting point for cholangiocarcinoma screening and care in Lao People’s Democratic Republic 16.10.2018 Vientiane, Laos Somphou Sayasone;
BASEL LIFE 2018 Talk given at a conference Imaging and Biobanking towards the Understanding Dual Disease Burden in Laos 14.09.2018 Basel, Switzerland Odermatt Peter;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
What to do with sex and gender in health research? (Webinar) Talk 26.11.2019 Basel, Switzerland Odermatt Peter;
Needs assessment workshop: Grant Application for "Combating Cholangiocarcinoma in Laos" (CCAL) Workshop 10.03.2017 Khon Kaen, Thailand Somphou Sayasone; Odermatt Peter;


Communication with the public

Communication Title Media Place Year

Associated projects

Number Title Start Funding scheme
185644 New tools for the regional control of Asian liver fluke infection and associated severe liver diseases 01.01.2020 Bilateral programmes

Abstract

Background: 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. Our study will show the predictive capacity of new biomarkers. The biobank will lay the foundation for biomarker work which has a high potential to generate further disease risk and disease diagnostic markers in future. Our study will clarify the public health dimension of O. viverrini in Lao PDR and help generate adequate resources to combat the disease. Our study will contribute to increase primary and secondary prevention of cancer in Lao PDR and other Southeast Asia.
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