Liver fluke infestation and cholangiocarcinoma (CCA) remain one of the major health problems of populations in the northeast of Thailand, as well as the neighboring countries of Laos, Vietnam and Cambodia. In Thailand alone, over 6 million people harbor the liver fluke (Opisthorchis viverrini). Infection with this parasite is the major risk factor for developing CCA. Each year 20,000 people develop CCA in Thailand alone, most of whom come from the northeast of the country. As Khon Kaen University was the first university established in the northeast region, we have a commitment to provide health care and reduce the disease burden of this cancer. Our research group was initially formed from individuals who were interested in research on liver fluke and CCA. The group has been supported by the Research Affairs of the Faculty of Medicine since 1996, and eventually evolved into the Liver Fluke and Cholangiocarcinoma Research Center (LFCRC) in 2002 on the initiative of visionary staff of the University. Members of the Center come from all health science faculties. In 2016, the Research Center was upgraded to be the Cholangiocarcinoma Research Institute (CARI) of which Dr. Khuntikeo is now the director.

CARI has the biggest CCA biobank in the world, comprising both samples from CCA patients as well as from the risk population from regional communities. We have produced more than 400 international, peer-reviewed publications and more than 150 graduate students. The Center is currently heavily involved in multidisciplinary research which is summarized below:

• Novel approaches for risk assessment of CCA and long-term measures for the prevention and control of opisthorchiasis in endemic communities
• Carcinogenesis of CCA caused by infection and inflammation in order to develop prevention and therapeutic approaches
• The development of treatment and care approaches for CCA patients to improve their quality of life
• Development of a new diagnostic platform for CCA in the northeast of Thailand

In addition, the Cholangiocarcinoma Screening and Care Program (CASCAP), led by Dr. Khuntikeo, was initiated in 2014 by Khon Kaen University with the aim of establishing a comprehensive program for the long-term control and elimination liver fluke infection and CCA. The program has the facilities summarized below:

• The Isan Cohort software (https://cloud.cascap.in.th/) was established in 2014 and has been in daily use since this time. This is an online and real-time database system used for nation-wide at-risk population registration, data recording, monitoring, evaluation and reporting to the Thai Ministry of Health, as well as to the general public. The registration and inclusion of the high-risk population takes place at primary health care hospitals. The at-risk individuals are then transferred for ultrasound screening to district hospitals and suspected CCA cases are referred for further investigation and treatment to super-tertiary care hospitals. Screening is performed simultaneously for up to 500 at risk members of the local population at the primary health care units. To date, there are more than 3,000 health care units enrolled in our diagnostic network.
• An ultrasound screening system has been developed, composed of ultrasound machines with mini-PACS, which allows the transfer of ultrasound images through the internet into the Isan Cohort database. This system also includes online-based consultation where the images can be reviewed by an expert radiologist for confirmatory diagnosis. In addition to increasing the screening capability, hepatobiliary ultrasonography training courses are offered for radiologists and general practitioners.
• Network hospitals are designated for the diagnosis and treatment of CCA and for further management of suspected CCA cases identified by ultrasound screening. This network comprises all 7 super-tertiary care hospitals in the northeast of Thailand. Moreover, hepatobiliary and pancreatic surgery training courses are provided to increase the number of specialist surgeons available to perform potentially curative or palliative surgery.

Significantly, Dr. Khuntikeo established the Cholangiocarcinoma Center of Excellence in 2015 at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, which enables patients in the first stages of the disease to undergo surgical, potentially curative, treatment. The Center has the mission to offer training to doctors, nurses and staff members in the treatment of the more than 20,000 patients from the northeast provinces if Thailand. These patients have liver fluke infection and come from large hospitals throughout the region. The center has an operation room for CCA patients as well as 2 intensive care unit beds and a patient ward for 19 people.

Furthermore, we are working together with the Data Management and Statistical Analysis Center (DAMASAC), lead by Dr. Thinkhamrop at the Faculty of Public Health, Khon Kaen Univiersity. The DAMASAC is excellent center for data management and statistical analysis for health science research who provides regular workshops on statistics, data analysis and manuscript writing for the research organizations requiring intensive regulatory environments. DAMASAC also train graduate students in data analysis and scientific writing

In 2018, The CARI in collaboration with Lao Tropical and Public Health Institute (Lao TPHI), Lao Ministry of Public Health under the support of the Kadoorie Charitable Foundation and Imperial College London (ICL) are running “Combating Cholangiocarcinoma in Lao PDR (CCAL) project, which seeks to leverage the CASCAP program to the Mekong Basin River Country of Lao PDR, where OV infection and OV-induced CCA are major public health challenges. Investment now is allow a multidisciplinary approach for the first time and with Lao PDR now awakening to the problem and the combined parasitological, zoological, water disinfection, sanitation, epidemiological, sociological and anthropological approach to disease prevention, combined with better means of disease detection with population screening, improved imaging and biomarkers for early detection – and for those with incurable cancer, improved end of life care, will allow the problem to be addressed in an integrated way for the first time. We are also aiming to expand the program to the others great Mekong sub-region countries where face the same burden.

Figure 1 The timeline for combating liver fluke and cholangiocarcinoma

CKDNET recognizes the importance of preventing and reducing kidney disease and is committed to expanding the academic roles of Khon Kaen University in solving health problems in rural areas where population may lack knowledge and access to adequate medical services.   The project is a network of cooperation between departments within Khon Kaen University, from 8 faculties (Faculty of Medicine, Faculty of Nursing, Faculty of Public Health, Faculty of Pharmacy, Faculty of Medical Technology, Faculty of Engineering, Faculty of Science and the Faculty of Agriculture), the Institute for Strategic Research and Collaboration for Northeastern Development and organizations outside the University such as the Institute of Defense Technology and the Provincial Public Health Office, hospitals, Ministry of Interior (such as Governor, Provincial Administrative Organization, District Administrative Organization, Municipality, Sub-district, Village headmen) to support medical / health sciences personnel and Village Health Volunteers, and Family Health Volunteers working on care and prevention of kidney disease. The project has ongoing government funding through Khon Kaen University, Research grants from the Thailand Science Research and Innovation (TSRI), through Program Management Unit for Competitiveness (PMUC), Office of the National Council for Higher Education, Science, Research and Innovation Policy, and the National Research Office (NRCT) since 2016.

CKDNET has carried out a number of 8 projects, [i.e., Prevention and reduction of kidney disease in urban communities; Prevention and reduction of chronic kidney disease in rural communities; Development of a rigorous and comprehensive chronic kidney disease patient care program; Cost-Effective Analysis of the Rigorous CKD Care Program; Digital Development Project for Kidney Disease Prevention; Innovative project for screening and treating chronic kidney disease; Project on study effects of environmental pollution and global warming on the occurrence of NCDs.; A population-wide assessment and treatment project for urinary tract stones for kidney disease at-risk groups and patients with kidney disease and to review of multiple strategies for maximum efficiency, and cost-savings covering the entire health service system, care and treatment system, and social welfare system, (fuller details in www.ckd.kku.ac.th and QR codes at the end of the document).

The project has mentored researchers at primary care units and hospitals in Khon Kaen Province to develop patient treatment guidelines, including new treatment approaches such as the Khon Kaen People’s Healthy Kidney Project.  This project is a collaboration between Khon Kaen University, Provincial Public Health Office, Khon Kaen Municipality, Khon Kaen Hospital, and has been presented the Governor of Khon Kaen Province, and expanded to other Northeast areas, into the 12th health zone in Southern Thailand area

CKDNET has also collaborated with the National Science and Technology Development Agency (NSTDA) through the National Electronics and Computer Technology Center (NECTEC) to develop quality innovations, such as, marker sensors for screening and monitoring symptoms of early kidney disease, via substances like “NGAL” (Neutrophil Gelatinase-associated Lipocalin) using electro-chemistry techniques, and the National Center for Nanotechnology (NANOTEC) to develop a kit for quantitative and qualitative determination of albumin in urine for point-of-care testing to prevent and slow chronic kidney disease in the community, and also to develop water quality monitoring kits, especially for heavy metal, herbicide, and pesticide contamination in Ubonrat Dam and  for 35 km along the Phong River.

Project outputs:

-A patient registration system has been created for managing patients, and test results in various medical institutions

-Training opportunity has been organized for doctors, nurses, pharmacists and information officers.

– Four MOUs have been signed, licensing 24 innovation projects, 24 titles, 29 manuscripts have been published research in international journals and 8 in national journals,

– Educational, media materials and manuals for the general public and patients have been produced in a variety of formats to suit varying age, economic and educational level and over 400,000 pieces have been distributed in communities.

– CKDNET’s products have been requested by 142 agencies from 33 provinces for patient care work.

– Seventeen agencies/organizations have requested biobank database and blood and urine samples for research.

-Three models of the “Suksala”, health check machine innovation, have been produced for application with Village Health Volunteers, patients, people at risk of kidney disease and the general public.

– A new technique for measuring NGAL biomarkers for nephrotic patients was developed.

– A model was created for community behavior change to reduce health problems in both urban and rural communities.   It included rigorous, multidisciplinary patient care training to educate health service personnel, village health volunteers, community leaders participation, and promoting community, interest and awareness of local health issue.

– Systems for village health volunteer screening and monitoring patients’ symptoms were strengthened.  This included the use of concrete practice innovations (such as reading blood pressure and sugar levels from a meter, noting urine color the color changes that represent kidney function changes, using a salinity meter for testing food salinity meter for testing salinity level.

The above are all aimed at preventing and slowing the progression of “non-communicable diseases” (NCD) and CKD, through better control of diabetes and blood pressure, and reducing smoking and alcohol consumption in the community (details in QR codes at the end of document).

In addition, CKDNET’s economic and health cost-effectiveness impacts on the country were evaluated through cost-effectiveness analysis of the project implementation, compared to normal care.  Results indicated could reduce chronic kidney disease patients’ worsening from stage 3 to 4 by approximately 75,400 people per year, and from stage 4 to 5, by about 41,300 people per year, clearly a best by intervention.

In addition, there is a basic sciences research on animals to be published on the effect of monosodium glutamate (MSG), Liver fluke infection, and changes in gut bacteria (microbiome), on the kidney pathology development.

Future plans include developing a seamless, sustainable remote health system (KKU CKD Telehealth platform) connection model for health care from the community primary care to tertiary hospital care.  This will be specific for kidney disease and “non-communicable diseases” patients using web and mobile applications combined with some CKDNET project innovations.  This will extend the CKDNET hospital registry system for using by Village Health Volunteers for reporting on individual patient health outcomes (via Raktai Application), including public health measurement data from the Suk-sala machine.   This KKU CKD telehealth system will promote multidisciplinary care and integrates treatment, prevention, health promotion, and health restoration whilst making travel and other practice-cost savings.

Further research will focus on the impact of water pollution and agrochemical contamination on kidney disease incidence in rural communities, especially idiopathic kidney and other related diseases.

A joint project with NANOTEC plans to develop screening innovations for early kidney disease with further albumin analysis kits: portable quantitative and semi-quantitative urine creatinine kits.  It is also planned to develop economically prices sensors for detecting small quantities of drinking water chemical contaminants by focusing on easily use inspection techniques.  For example, to detect level of ferrous metals (Fe), manganese (Mn), aluminum (Al) and pesticides, including glyphosate and paraquat, in the local areas.  There is an existing sensors technology base that can be developed for local and rural use to monitor and improve water quality.

CKDNET project has already surveyed and found that households and community water sources quality is lower standard in some of these areas.  Local innovations through community and industrial sites collaboration could test effective pragmatic practice to rectify this situation, which could then be further developed into a national policy.

ภาคผนวก

สรุปผลงาน CKDNET

1.รวมสื่อประชาสัมพันธ์ CKDNE

https://drive.google.com/drive/u/0/folders/1QcC55z26LjdRuAkN6J5-iMN1oDSh_cDP

2. ผลงานลิขสิทธิ์ จำนวน 24 เรื่อง

https://drive.google.com/drive/u/0/folders/1tYxOE8_JwDqBOUcr0xatJtGd2soSe4-F

3.วารสารโครงการ CKDNET

https://drive.google.com/drive/u/0/folders/1tnJZ4N2a_K-6gAkNrp-m8mj_VUmC5TYW

4.วารสารฉบับพิเศษ

https://drive.google.com/drive/u/0/folders/1MY87prBOFWghZO9NWslz85wM1PJDXzOO

5.CKDNET paper

https://drive.google.com/drive/u/0/folders/1e3KxQ9RqkFeF0nTHxgS1GT4IGe87nqwB

6.คลิป VDO นวัตกรรมตู้ตรวจสุขภาพอัจฉริยะ “สุขศาลา”

https://drive.google.com/drive/u/0/folders/1fiK9jRTLEfHA9KX1jgJqaE2j4lk-pzvT

7.สรุปงานภาพรวม CKDNET

https://drive.google.com/drive/u/0/folders/1oJVzfRfvkmoPeYLl3VSpCJltZ36xFGJ

รูปภาพประกอบ

คณะผู้ร่วมโครงการป้องกันและชะลอโรคไตในภาคตะวันออกเฉียงเหนือ (Chronic Kidney Disease Prevention in the Northeast of Thailand: CKDNET)

สรุปการดำเนินงานตั้งแต่ พ.ศ. 2559-ปัจจุบัน

การสร้างรูปแบบป้องกันโรคไตในชุมชน และคัดกรองโรคไตเรื้อรังและปรับเปลี่ยนพฤติกรรม

นวัตกรรมในการตรวจคัดกรองและติดตามอาการผู้ป่วยโรคไต

การสำรวจมลภาวะทางน้ำและพัฒนาชุดตรวจวัดคุณภาพของแหล่งน้ำและน้ำที่ใช้ในครัวเรือนภายใต้โครงการ อว. เพื่อสำรวจปัญหาสุขภาพและคุณภาพน้ำ ในแหล่งน้ำและน้ำที่ใช้สำหรับอุปโภค-บริโภค ในพื้นที่เขื่อนอุบลรัตน์และอำเภอน้ำพอง  จังหวัดขอนแก่น