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Expected rate of liver fluke-related cholangiocarcinoma in endemic area of liver fluke with antiparasitic drug distribution program for disease control in Thailand


 Department of Community Medicine, Dr Dy Patil University, Pune, Maharashtra, India; Department of Biological Science, Joseph Ayo Babalola University, Ikeji-Arakeji, Osun, Nigeria; Department of Medical Science, Faculty of Medicine, University of Nis, Serbia; Department of Laboratory Medicine, Chulalongkorn University, Bangkok, Thailand

Date of Submission30-Sep-2019
Date of Decision22-Nov-2019
Date of Acceptance07-Jan-2020
Date of Web Publication03-Oct-2020

Correspondence Address:
Viroj Wiwanitkit,
140 Wiwanitkit House, Bangkhae 1 Road, Bangkok, 10160

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_783_19

 > Abstract 


Objective: Parasitic-induced cancer is an important problem in tropical oncology. Liver fluke-related biliary tract cancer of cholangiocarcinoma is an important kind of endemic cancer in Southeast Asia. This cancer is related to the liver fluke infection. The local public health policies for disease control include antiparasitic drug, praziquantel, distributing aiming at getting rid of risk factor, and opisthorchiasis. In the present report, the authors reappraise on the local epidemiological data on liver fluke infection among the local people in endemic area Thailand under antiparasitic drug distribution program for further assessment for expected rate of cholangiocarcinoma.
Materials and Methods: The present study is a clinical mathematical modeling study. First, the retrospective reappraisal on the available local data on liver fluke infection among the local people in endemic area of Thailand, a tropical country in Indochina, with a different history of previous exposure to antiparasitic drug is done. Then, a mathematical model based on predictive modeling and probability assignment technique is developed for the assessment of estimated rate of cholangiocarcinoma.
Results: According to the present study, the expected rate of liver fluke-related cholangiocarcinoma is equal to 0.0564%. There is a strong relationship between expected rate of liver fluke-related cholangiocarcinoma and number of previous exposure to praziquantel (r = 0.99, P = 0.02).
Conclusion: According to the study, the high expected rare of cholangiocarcinoma is observed despite the use of general antiparasitic drug distribution policy. It implies finding for new adjusted public health manipulation for disease prevention and management.

Keywords: Cholangiocarcinoma, distribution, endemic, liver fluke, praziquantel



How to cite this URL:
Wiwanitkit V. Expected rate of liver fluke-related cholangiocarcinoma in endemic area of liver fluke with antiparasitic drug distribution program for disease control in Thailand. J Can Res Ther [Epub ahead of print] [cited 2020 Oct 28]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=297203




 > Introduction Top


Cancer is an important problem in medicine. Infectious disease-related cancer is an important group of malignancy. The good example of the cancer in this group is human papillomavirus-related cervix caner.[1] Another important cancer in this group is liver fluke-related hepatobiliary tract malignancy of cholangiocarcinoma.[2],[3],[4],[5] As an infectious-related cancer, the primary prevention for the cancer usually focuses on the management of the basic risk, the infection. For cervix cancer, the cervix cancer vaccine is presently available and becomes the hope for eradication of human papillomavirus-related cervix caner.[6] Regarding liver fluke-related cholangiocarcinoma, there is still no specific vaccine. The main primary prevention is the prevention for getting liver fluke infection.[2],[3],[4],[5]

At present, liver fluke-related cholangiocarcinoma is common in several countries. In tropical Southeast Asia, the cancer is highly endemic. In Indochina, the cholangiocarcinoma is strongly related to a kind of liver fluke infection, opisthorchiasis.[7] In this area, opisthorchiasis is very common. The local food intake habit of local people is considered problematic risk health behavior. The intake of local uncooked or poorly cooked fish dishes is the main cause of opisthorchiasis among local people in this area. In general, metacercariae of the liver fluke parasite can infect the freshwater fish, and if the local people eat the contaminated fish without good cooking, the infection might occur. In the previous study, it is proven that many local cooking techniques of local people are not appropriate for getting rid of contaminated fluke metacercariae.[8],[9] The infective fluke metacercariae of the parasite can well tolerate to poorly cooking technique and the survival infective metacercariae can further infect anyone who eats contaminated fish dish.[8],[9]

After getting opisthorchiasis, a chronic infection might occur. The chronic liver fluke might result in chronic insult to the biliary tract and can finally result in malignant change. The biliary tract cancer or cholangiocarcinoma is a very common cancer in Thailand. Extremely high incidence can be observed in the country.[10] The patient is usually from rural area with poor food sanitation. The patient usually visits to the physician with a late clinical presentation.[11] The patient usually has severe jaundice, and the tumor is usually not resectable.[11] The prognosis of disease is usually grave.[11] Most patients die within a short period after the first diagnosis.[11]

At present, cholangiocarcinoma becomes an important public health threat in Indochina. Thailand, a country in this area, is also affected. The great burden due to a huge number of cholangiocarcinoma patients leads to the public health consideration by Local Thai Ministry of Public Health.[12],[13] Several public health campaigns are launched, aiming at control of opisthorchiasis and liver fluke-related cholangiocarcinoma.[12],[13] The health education and promotion for local people are provided.[12],[13] The campaign for no eating of raw fish is heavily promoted. In addition, universal screening for liver fluke infection by stool examination and universal distribution of antiparasitic drug, praziquantel, are also implemented as national health policies for controlling of disease.[12],[13]

Despite there are several control measures, the disease is still prevalent in Thailand, and it is still needs for continuous disease control and management.[13] The surveillance of the local situation is necessary. Reanalysis of the current situation is useful for monitoring the effectiveness of the local public health control program. In the present study, the author performed a clinical informatics study and used clinical mathematical model for determined expected rate of liver fluke-related cholangiocarcinoma in endemic area of liver fluke with antiparasitic drug distribution program for disease control in Thailand.


 > Materials and Methods Top


General methodology

The present study is a clinical mathematical modeling study with a reference to the public local available epidemiological data. The aim of this study is to predict for an estimated rate of liver fluke infection-related cholangiocarcinoma among the local people in endemic area with different history of oral praziquantel treatment under antiparasitic drug distribution program. The setting of the present study is northern region of Thailand, a tropical country in Indochina. In this region, there is a very high incidence of cholangiocarcinoma, and the liver fluke infection is very common. The general antiparasitic drug distribution program has been set in this region for several years according to the National Policy of Thai Ministry of Public Health.

The development of clinical mathematical model

First, the retrospective reappraisal on the available local data on liver fluke infection among the local people in endemic area of Thailand, a tropical country in Indochina, with a different history of previous exposure to antiparasitic drug is done. Then, a mathematical model based on predictive modeling and probability assignment technique is developed for the assessment of estimated rate of cholangiocarcinoma.

Focusing on the primary data, the available data from the recent publication on local epidemiology study on opisthorchiasis among the local people in northeastern region of Thailand are collected and used.[14] The primary parameters from the available epidemiological report are as follows: (a) rate of opisthorchiasis, (b) the number of previous receipt of praziquantel according to antiparasitic drug distribution program, and (c) frequency of individuals at different history of number of the previous receipt of praziquantel according to antiparasitic drug distribution program.[14]

First, the author predicted the rate of liver fluke-related cholangiocarcinoma based on the previously observed relationship between the rate of liver fluke infection and rate of liver fluke-related cholangiocarcinoma in the study setting.[15] The previous report by Kamsa-Ard et al. showed the relationship between rate of cholangiocarcinoma and liver fluke infection identified from stool examination as the “logit cholangiocarcinoma rate = 0.69 × liver fluke infection rate.[15]” The mentioned equation is simplified written by mathematic mean as “log (cholangiocarcinoma rate/1-cholangiocarcinoma rate) =0.69 × liver fluke infection rate.” By solving this equation, the expected cholangiocarcinoma rate in each group can be predicted.

A specific expected rate for individuals with different groups of history of previous exposure to praziquantel is calculated. Then, the finalized expected rate was calculated based on the probability assignment technique. Briefly, the final expected is the summation of path expected rate in each group. The path expected rate in each group is equal “expected rate in that group × probability frequency) in that group.” The probability in each is directly referred to the data in the previous epidemiological study.[15]

The authors also assessed the relationship between expected rate of liver fluke-related cholangiocarcinoma and number of previous exposure to praziquantel. For this assessment, the correlation analysis was done.

Ethical consideration

The present study is a pure mathematical modeling study, which is a kind of clinical informatics research. It does not deal with any human or animal subjects. No written informed consent or ethical approval by ethical committee is required.


 > Results Top


Expected rate liver expected rate of liver fluke-related cholangiocarcinoma

The expected rate of liver fluke-related cholangiocarcinoma in different groups of individuals with a different history of previous exposure to praziquantel is shown in [Table 1].
Table 1: The expected rate of liver fluke-related cholangiocarcinoma in different groups of subjects with different history of previous exposure to praziquantel

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For the final expected rate of liver, fluke-related cholangiocarcinoma, the path expected rate in each group is calculated and presented in [Table 2]. The final expected rate from the summarization of all path expected rates from all groups is equal to 0.0564% or 56.4 cases/100,000 population.
Table 2: Path expected rate of liver fluke-related cholangiocarcinoma

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Relationship between expected rate of liver fluke-related cholangiocarcinoma and number of previous exposure to praziquantel

From correlation analysis, there is a strong relationship between expected rate of liver fluke-related cholangiocarcinoma (Y) and number of previous exposure to praziquantel (X), as presented in [Figure 1]. The correlation coefficient ® to represent the relationship between expected rate of liver fluke-related cholangiocarcinoma and number of previous exposure to praziquantel is equal to 0.99 (P = 0.02).
Figure 1: The relationship between expected rate of liver fluke relate cholangiocarcinoma (Y) and number of previous exposure to praziquantel (X)

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 > Discussion Top


Cholangiocarcinoma is an important common cancer seen in Southeast Asia. This deadly cancer is difficult to manage. The patient usually has severe clinical diseases, and the curative treatment is usually not possible. The local government raises several public health campaign for the management of the problem. The main focus for disease management is the control of liver fluke infection, which is the rooted cause of liver-related cholangiocarcinoma in this region.[13] In Thailand, the public health worker usually plays an important role in disease screening in the rural village. The distribution of antiparasitic drug aiming at parasitic eradication is also parallel performed. Nevertheless, the repeated infection is a common problem. In several studies,[14],[16] there are many cases of local people in endemic area, northeastern region of Thailand, who are identified to have liver fluke infection and already have a history of previous praziquantel drug treatment.

In a recent report,[14] it was surprisingly found that the group with a history of more previous times of praziquantel treatment had more rate of opisthorchiasis detection from stool test.[14] Thinkhamrop et al. mentioned that the reinfection might be the explanation.[14] However, an additional explanation might be the antiparasitic resistance induced by universal repeated antiparasitic drug distribution. In fact, praziquantel resist fluke infection is observable in blood fluke and relationship with poor control of antiparasitic drug use is proposed as a possible cause.[17] Nevertheless, the universal antiparastitic drug distribution is still the main public health policy for disease control in Thailand. The effect of the program on the epidemiology of liver fluke-related cholangiocarcinoma is an interesting topic for researching.

In the present report, the author studies on the expected rate of expected rate of liver fluke-related cholangiocarcinoma in endemic area of liver fluke with antiparasitic drug distribution program for disease control. Based on the present study, it can show that the rate of cholangiocarcinoma in the study setting is still very high despite there is a universal antiparasitic drug distribution program. It implies for the requirement for readjustment of the present public health policies regarding disease control.


 > Conclusion Top


The author uses clinical mathematical modeling technique for determining the expected rate of liver fluke-related cholangiocarcinoma in endemic area of liver fluke with antiparasitic drug distribution program for disease control in Thailand and can identify a very high expected rate. This finding calls for attention to readjust the present public health program for more proper disease prevention and management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Small W Jr., Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, et al. Cervical cancer: A global health crisis. Cancer 2017;123:2404-12.  Back to cited text no. 1
    
2.
Zheng S, Zhu Y, Zhao Z, Wu Z, Okanurak K, Lv Z. Liver fluke infection and cholangiocarcinoma: A review. Parasitol Res 2017;116:11-9.  Back to cited text no. 2
    
3.
Liu GX, Wu XP, Wang ZJ, Bai X, Liu MY. Research progress on the relationship between three kinds of liver fluke infections and cholangiocarcinoma. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi 2010;28:301-5.  Back to cited text no. 3
    
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Hughes T, O'Connor T, Techasen A, Namwat N, Loilome W, Andrews RH, et al. Opisthorchiasis and cholangiocarcinoma in Southeast Asia: An unresolved problem. Int J Gen Med 2017;10:227-37.  Back to cited text no. 4
    
5.
Buisson Y. Control of Opisthorchis viverrini infection for cholangiocarcinoma prevention. Bull Soc Pathol Exot 2017;110:61-7.  Back to cited text no. 5
    
6.
Harper DM, DeMars LR. HPV vaccines – A review of the first decade. Gynecol Oncol 2017;146:196-204.  Back to cited text no. 6
    
7.
Steele JA, Richter CH, Echaubard P, Saenna P, Stout V, Sithithaworn P, et al. Thinking beyond Opisthorchis viverrini for risk of cholangiocarcinoma in the lower Mekong region: A systematic review and meta-analysis. Infect Dis Poverty 2018;7:44.  Back to cited text no. 7
    
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Wiwanitkit V, Nithiuthai S, Suwansaksri J, Chongboonprasert C, Tangwattakanont K. Survival of heterophyid metacercariae in uncooked Thai fish dishes. Ann Trop Med Parasitol 2001;95:725-7.  Back to cited text no. 8
    
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Wiwanitkit V, Nithiuthai S, Suwansaksri J. Motility of minute intestinal fluke, Haplorchinae spp, metacercariae in fish dishes prepared by different uncooked methods. MedGenMed 2002;4:8.  Back to cited text no. 9
    
10.
Wilcox BA, Echaubard P. Balancing biomedical and ecological perspectives in research framing of liver fluke and cholangiocarcinoma in NE Thailand. Parasitol Int 2017;66:372-7.  Back to cited text no. 10
    
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Wiwanitkit V. Clinical findings among 62 Thais with cholangiocarcinoma. Trop Med Int Health 2003;8:228-30.  Back to cited text no. 11
    
12.
Khuntikeo N, Titapun A, Loilome W, Yongvanit P, Thinkhamrop B, Chamadol N, et al. Current perspectives on opisthorchiasis control and cholangiocarcinoma detection in Southeast Asia. Front Med (Lausanne) 2018;5:117.  Back to cited text no. 12
    
13.
Jongsuksuntigul P, Imsomboon T. Opisthorchiasis control in Thailand. Acta Trop 2003;88:229-32.  Back to cited text no. 13
    
14.
Thinkhamrop K, Khuntikeo N, Sithithaworn P, Thinkhamrop W, Wangdi K, Kelly MJ, et al. Repeated praziquantel treatment and Opisthorchis viverrini infection: A population-based cross-sectional study in northeast Thailand. Infect Dis Poverty 2019;8:18.  Back to cited text no. 14
    
15.
Kamsa-Ard S, Promthet S, Sithithaworn P, Vatanasapt P, KhuntiKao N, Pimchan N, et al. Predictive statistical model for the risk of cholangiocarcinoma in Northeast Thailand. Srinagarind Med J 2009;24:231-9.  Back to cited text no. 15
    
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Kaewpitoon SJ, Kaewpitoon N, Rujirakul R, Ueng-Arporn N, Matrakool L, Tongtawee T. The carcinogenic liver fluke Opisthorchis viverrini among rural community people in northeast Thailand: A cross-sectional descriptive study using multistage sampling technique. Asian Pac J Cancer Prev 2015;16:7803-7.  Back to cited text no. 16
    
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Wang W, Wang L, Liang YS. Susceptibility or resistance of praziquantel in human schistosomiasis: A review. Parasitol Res 2012;111:1871-7.  Back to cited text no. 17
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

 
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