Human liver flukes in China and ASEAN: Time to fight together

Abstract

In particular, only three parasites are definite carcinogens, including both C. sinensis and O. viverrini [7], which are responsible for a conservative estimate of 7,000 new cases of cholangiocarcinoma yearly [8]. [...]China and ASEAN member countries are highly afflicted with cholangiocarcinoma [9]. [...]research and development on liver flukes have already achieved some breakthroughs in different countries—e.g., mapping and surveillance in China, drug development in China and Laos, the carcinogenic mechanism, diagnosis and management of cholangiocarcinoma in Thailand, and the management of aquaculture in Vietnam [14–19]. [...]there exist good cooperative platforms, such as the Regional Network for Asian Schistosomiasis and other Helminth Zoonoses (RNAS+), of which all countries endemic for clonorchiasis and opisthorchiasis viverrini are members [20]. First report and molecular identification of Opisthorchis viverrini infection in human communities from Lower Myanmar.

About the Authors:

Men-Bao Qian

Affiliations National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China, Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China, Chinese Center for Tropical Diseases Research, Shanghai, China, WHO Collaborating Center for Tropical Diseases, Shanghai, China

Xiao-Nong Zhou

* E-mail: [email protected]

Affiliations National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China, Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China, Chinese Center for Tropical Diseases Research, Shanghai, China, WHO Collaborating Center for Tropical Diseases, Shanghai, China

ORCID logo http://orcid.org/0000-0003-1417-8427

Citation: Qian M-B, Zhou X-N (2019) Human liver flukes in China and ASEAN: Time to fight together. PLoS Negl Trop Dis 13(4): e0007214. https://doi.org/10.1371/journal.pntd.0007214

Editor: jong-Yil Chai, Seoul National University College of Medicine, REPUBLIC OF KOREA

Published: April 25, 2019

Copyright: © 2019 Qian, Zhou. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: M-BQ and X-NZ were financially supported by the Forth Round of Three-Year Public Health Action Plan (2015-2017) in Shanghai (grant No. GWTD2015S06). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

The second forum on health cooperation between China and the Association of Southeast Asian Nations (ASEAN) was held in Guangxi, China, on September 19 and 22, 2018 [1]. Important resolutions, including those on the cooperation between China and ASEAN member countries on traditional medicine, management of hospitals, youth exchanges, and the prevention and control of diseases, were proposed at the regional forum [1]. This regional cooperation provides a platform and a potential opportunity to fight the menace of human liver flukes together. Two human liver flukes—namely, Clonorchis sinensis and Opisthorchis viverrini—exert a huge burden in China and Southeast Asia [2, 3]. Infections due to these human liver flukes are predominantly endemic in China and several ASEAN member countries as a result of the traditional and rooted dietary habit of ingesting raw freshwater fish. There are about 15 million people infected with C. sinensis globally, out of which 13 million are domiciled in China and 1 million in northern Vietnam [2]. O. viverrini infection accounts for about 8.6 million cases, with distribution in the following ASEAN member countries: Thailand (6 million cases), Laos (2 million cases), and Cambodia (0.6 million cases) [3]. O. viverrini infection is also endemic in southern Vietnam. Recent findings have revealed the distribution of O. viverrini infection in Myanmar, which has given us more insight on human liver fluke distribution in the region [4]. Thus, China and ASEAN member countries share more than 90% of the clonorchiasis burden and about 100% of the opisthorchiasis viverrini burden. Both infections pose significant health concerns in the region. Long and chronic infections could lead to high morbidity in liver and the biliary system (e.g., gallstone, cholecystitis, and cholangitis) [2, 5, 6]. In particular, only three parasites are definite carcinogens, including both C. sinensis and O. viverrini [7], which are responsible for a conservative estimate of 7,000 new cases of cholangiocarcinoma yearly [8]. Thus, China and ASEAN member countries are highly afflicted with cholangiocarcinoma [9].

In spite of the persistent high burden, human liver flukes are yet to receive adequate attention compared with other neglected tropical diseases, and this enhances the disease persistence in the region. For example, Guangxi, where the health cooperation meeting was held, is highly endemic with clonorchiasis. Most neglected tropical diseases have been effectively controlled in Guangxi, especially lymphatic filariasis, which was eliminated in 1985 [10], and schistosomiasis transmission, which was interrupted in 1988 [11]. However, there has been an increasingly widespread distribution and prevalence of clonorchiasis over the past decades [12, 13].

A basis for the potential cooperation between China and ASEAN on human liver flukes already exists. First, C. sinensis and O. viverrini belong to the same family, and thus they have many similarities in biology, pathobiology, carcinogenicity, epidemiological determinants, diagnosis, treatment, control, and prevention [2, 3]. Second, research and development on liver flukes have already achieved some breakthroughs in different countries—e.g., mapping and surveillance in China, drug development in China and Laos, the carcinogenic mechanism, diagnosis and management of cholangiocarcinoma in Thailand, and the management of aquaculture in Vietnam [14–19]. All of these efforts provide a basis for future cooperation. Third, there exist good cooperative platforms, such as the Regional Network for Asian Schistosomiasis and other Helminth Zoonoses (RNAS+), of which all countries endemic for clonorchiasis and opisthorchiasis viverrini are members [20]. Numerous training courses, which have attracted more than 400 participants, have been held through this network since 2000, and several collaborative projects have been completed through RNAS+, some of which are still ongoing.

The objective of fighting liver flukes via cooperation could be achieved through diverse approaches such as talent development; joint research and development of tools, products, and strategies; and the establishment of cooperative pilot projects. The health cooperation forum provides a potential opportunity for cooperation by targeting the promotion of effective and sustainable control of liver flukes in the region [2, 21–24].

Some special objectives that require attention are as follows:

1. To construct the regional database. Accurate endemic maps for human liver flukes in the region are yet to be available, and this hinders control activities. This should not be limited to prevalence data; data on ecological and socioeconomic factors should also be included.

2. To estimate the disease burden. A full evaluation of disease burden should contain both health loss and economic cost. Regarding health loss, fatal cholangiocarcinoma, chronic liver and biliary conditions, and early nonspecific symptoms need to be evaluated comprehensively. Economic burden should include direct and indirect costs related to hospitalization, loss of productivity due to disability, premature mortality, etc.

3. To explore the determinants. Cultural, psychological, and behavioral factors contribute to the persistence of liver flukes in endemic areas. Providing insights on these determinants would greatly benefit the design of effective measures and sustainable strategies. More importantly, attitudinal change by doing away with eating raw freshwater fish will facilitate primary prevention of liver fluke infections, and this is key for long-term and sustainable control, which could eventually lead to disease elimination as a public health problem.

4. To develop screening and diagnostic tools. Rapid and simple screening tools are required to detect endemic communities and individuals at risk. Sensitive and specific serologic tests are needed in clinical settings. Rapid diagnostic tests, such as dipsticks, are important for field tests. Additionally, field-friendly molecular diagnostic methods need to be explored, and they should have the ability to differentiate among different species of human liver flukes as well as between human liver flukes and other minute intestinal flukes.

5. To develop and evaluate new drugs. As an alternative to praziquantel, albendazole efficacy needs to be evaluated further, and the regimens should be optimized. Previous studies have shown the promising efficacy and safety of tribendimidine against both C. sinensis and O. viverrini. Further trials are expected to verify and optimize its usage before application.

6. To study the potential spread of the two liver flukes. The two flukes are usually believed to have separate preferences for transmission sites in endemic areas because of the different distributions of their respective first intermediate hosts. However, the potential to spread to opposite endemic areas and other nonendemic areas also requires attention and should be studied, especially considering global climate change.

7. To strengthen modeling application. Studies using the application of modeling techniques are grossly inadequate for human liver flukes. These techniques help illustrate transmission dynamics, predict risk maps, design control measures, determine the cost-effectiveness, etc.

8. To explore new control measures. The strategies, effectiveness, cost, and sustainability of different measures including chemotherapy; information, education, and communication techniques; control of animal reservoirs; establishment of sanitation; management of aquaculture; and the integration of diverse measures should be investigated and evaluated.

The necessity, urgency, and feasibility of controlling human liver flukes through technical cooperation could be demonstrated to the governments in endemic countries, and this would promote its potential inclusion in national health policy. Then, multisectoral cooperation could be established between health departments and other departments, especially education and agriculture, which will guarantee its effectiveness and sustainability. We therefore expect that human liver flukes will be effectively tackled through our cooperation mechanism, and this will corroborate the achievements of other cooperation in this region.

Citation: Qian M-B, Zhou X-N (2019) Human liver flukes in China and ASEAN: Time to fight together. PLoS Negl Trop Dis 13(4): e0007214. https://doi.org/10.1371/journal.pntd.0007214

References

1. [The 2nd China-ASEAN Forum on Health Cooperation]. [cited 2018 Nov 23]. Available from: http://www.gxhfpc.gov.cn/cahcforum/.Chinese.

2. Qian MB, Utzinger J, Keiser J, Zhou XN. Clonorchiasis. Lancet. 2016;387(10020):800–10. pmid:26299184

3. Sithithaworn P, Andrews RH, Nguyen VD, Wongsaroj T, Sinuon M, Odermatt P, et al. The current status of opisthorchiasis and clonorchiasis in the Mekong Basin. Parasitol Int. 2012;61(1):10–6. pmid:21893213

4. Aung WPP, Htoon TT, Tin HH, Thinn KK, Sanpool O, Jongthawin J, et al. First report and molecular identification of Opisthorchis viverrini infection in human communities from Lower Myanmar. PLoS ONE. 2017;12(5):e0177130. pmid:28472153

5. Qian MB, Chen YD, Fang YY, Xu LQ, Zhu TJ, Tan T, et al. Disability weight of Clonorchis sinensis infection: captured from community study and model simulation. PLoS Negl Trop Dis. 2011;5(12):e1377. pmid:22180791

6. Ayé Soukhathammavong P, Rajpho V, Phongluxa K, Vonghachack Y, Hattendorf J, Hongvanthong B, et al. Subtle to severe hepatobiliary morbidity in Opisthorchis viverrini endemic settings in southern Laos. Acta Trop. 2015;141(Pt B):303–9. pmid:25275346

7. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens—Part B: biological agents. Lancet Oncol. 2009;10(4):321–2. pmid:19350698

8. Qian MB, Zhou XN. Global burden of cancers attributable to liver flukes. Lancet Glob Health. 2017;5(2):e139. pmid:28104177

9. Shin HR, Oh JK, Masuyer E, Curado MP, Bouvard V, Fang Y, et al. Comparison of incidence of intrahepatic and extrahepatic cholangiocarcinoma—focus on East and South-Eastern Asia. Asian Pac J Cancer Prev. 2010;11(5):1159–66. pmid:21198257

10. De-Jian S, Xu-Li D, Ji-Hui D. The history of the elimination of lymphatic filariasis in China. Infect Dis Poverty. 2013;2(1):30. pmid:24289733

11. Zhang LJ, Li SZ, Wen LY, Lin DD, Abe EM, Zhu R, et al. The establishment and function of schistosomiasis surveillance system towards elimination in the People's Republic of China. Adv Parasitol. 2016;92:117–41. pmid:27137445

12. Qian MB, Chen YD, Yang YC, Lu MF, Jiang ZH, Wei K, et al. Increasing prevalence and intensity of foodborne clonorchiasis, Hengxian County, China, 1989–2011. Emerg Infect Dis. 2014;20(11):1872–5. pmid:25340976

13. Jiang ZH, Yang YC, Wan XL, Li CH, Huang FM. [Preliminary analysis of geographical and basin distribution characteristics of clonorchiasis sinensis in Guangxi. China Tropical Medicine]. 2015;15(9):1057–61. Chinese.

14. Lai YS, Zhou XN, Pan ZH, Utzinger J, Vounatsou P. Risk mapping of clonorchiasis in the People's Republic of China: A systematic review and Bayesian geostatistical analysis. PLoS Negl Trop Dis. 2017;11(3):e0005239. pmid:28253272

15. Qian MB, Chen YD, Zhu HH, Zhu TJ, Zhou CH, Zhou XN. [Establishment and role of national clonorchiasis surveillance system in China]. Zhonghua Liu Xing Bing Xue Za Zhi. 2018;39(11):1496–1500. Chinese. pmid:30462961

16. Qian MB, Yap P, Yang YC, Liang H, Jiang ZH, Li W, et al. Efficacy and safety of tribendimidine against Clonorchis sinensis. Clin Infect Dis. 2013;56(7):e76–82. pmid:23223597

17. Sayasone S, Keiser J, Meister I, Vonghachack Y, Xayavong S, Senggnam K, et al. Efficacy and safety of tribendimidine versus praziquantel against Opisthorchis viverrini in Laos: an open-label, randomised, non-inferiority, phase 2 trial. Lancet Infect Dis. 2018;18(2):155–161. pmid:29153938

18. Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E, et al. The tumorigenic liver fluke Opisthorchis viverrini—multiple pathways to cancer. Trends Parasitol. 2012;28(10):395–407. pmid:22947297

19. Clausen JH, Madsen H, Van PT, Dalsgaard A, Murrell KD. Integrated parasite management: path to sustainable control of fishborne trematodes in aquaculture. Trends Parasitol. 2015;31(1):8–15. pmid:25466608

20. Zhou XN, Olveda R, Sripa B, Yang GJ, Leonardo L, Bergquist R. From gap analysis to solution and action: the RNAS⁺ model. Acta Trop. 2015;141(Pt B):146–9. pmid:23831926

21. Utzinger J. A research and development agenda for the control and elimination of human helminthiases. PLoS Negl Trop Dis. 2012;6(4):e1646. pmid:22545174

22. Tang ZL, Huang Y, Yu XB. Current status and perspectives of Clonorchis sinensis and clonorchiasis: epidemiology, pathogenesis, omics, prevention and control. Infect Dis Poverty. 2016;5(1):71. pmid:27384714

23. Li HM, Qian MB, Yang YC, Jiang ZH, Wei K, Chen JX, et al. Performance evaluation of existing immunoassays for Clonorchis sinensis infection in China. Parasit Vectors. 2018;11(1):35. pmid:29334990

24. Khuntikeo N, Thinkhamrop B, Bundhamcharoen K, Andrews RH, Grundy-Warr C, Yongvanit P, et al. The socioeconomic burden of cholangiocarcinoma associated with Opisthorchis viverrini sensu lato infection in Northeast Thailand: a preliminary analysis. Adv Parasitol. 2018;102:141–163. pmid:30442308