Clonorchiasis

Clonorchiasis is one of the most important foodborne trematodiasis (Fürst, Keiser, & Utzinger 2012). It is caused by infection with the Chinese liver fluke, Clonorchis sinensis (Lun et al. 2005).

1.1.3.1 Parasite and life cycle

The adult fluke C. sinensis is a leaf-shaped slender digenetic trematode, 15–20 mm long and 3–4 mm wide (Hong & Fang 2012). Eggs laid by hermaphroditic adult worms reach the intestine with bile fluids and are emitted with the faeces into the water (Qian et al. 2016) (Figure 1.7). The first intermediate hosts, freshwater snails, ingest the eggs, which are further hatch into miracidiae. Inside the nails, miracidiae subsequently develop to sporocysts, rediae and cercariae, through asexual reproduction (Lun et al. 2005). The free-swimming cercariae leave the snails and adhere to the second intermediate host, freshwater fish or shrimp, in

which cercariae develop into mature metacercariae (Hong & Fang 2012). The definite hosts, human beings or other piscivorous mammals, get infected by eating raw or insufficient cooked infected fish. Metacercariae reach the human small intestine and further navigate to the liver, where they develop into adult flukes and reach the stage of sexual reproduction (Rim 1986). The egg productivity of an adult worm in human is estimated at around 4000 per day (Kim et al. 2011). Usually after four weeks of infection, eggs can be detected in faeces (Hsü & Wang 1938).

Figure 1.7: Life cycle of Clonorchis sinensis (source: CDC)

1.1.3.2 Clinical conditions

The clinical manifestations of clonorchiasis tend to relate to worm burden but are variable and unspecific (Kim et al. 2011;Lun et al. 2005;Rim 1986). People with small infection intensity have few or mild symptoms (e.g., abdominal discomfort, diarrhea, and/or malaise), while people with moderate to high infection intensity present more pronounced symptoms (e.g., fever, chills, anorexia, weight loss, colic, fatigue, and/or abdominal distension) (Lun et al. 2005). Typical physical signs of clonorchiasis include jaundice, hepatomegaly, and liver tenderness. Chronic infection usually results in complications in liver and biliary systems (e.g., cholelithiasis, cholangitis, and cholecystitis) (Qian et al. 2016). Furthermore, C. sinensis is classified as a definite carcinogen, as infection can increase the risk of cholangiocarcinoma, according to different studies (Bouvard et al. 2009;Fürst et al. 2012;Qian et al. 2012;Shin et al. 2010).

1.1 Neglected tropical diseases 15

1.1.3.3 Epidemiology

Figure 1.8: Endemic regions of clonorchiasis (source: WHO 2013)

It was estimated conservatively that around 15 million people were infected with

C. sinensis in 2004, predominantly in countries of Asia, particularly in China, South Korea,

northern Vietnam and parts of Russia (Fürst et al. 2012;Qian et al. 2012;Qian et al. 2016;Qian, Chen, & Yan 2013) (Figure 1.8). China accounts for around 85% of the global infected people, corresponding to 12.5 million people infected (Qian et al. 2012). Two major endemic regions were identified for human clonorchiasis in China, namely the provinces of Guangdong and Guangxi in the south and the provinces of Heilongjiang and Jilin in the north- east (Lun et al. 2005;Qian et al. 2012;Qian et al. 2016). In South Korea, C. sinensis infection is the major intestinal parasitic infection, with an estimation of 1.2 million people infected, according to a nationwide survey in 2004 (Kim et al. 2009). High endemic areas were reported along the four major rivers (Nakdong-fang, Seomjin-gang, Zoungsan-gang, and Guem-gang) in the southern part of the country (Cho et al. 2008). Around one million people in Vietnam (mainly the northern part) and 3000 people in the far east of Russia were reported to be infected with C. sinensis by a WHO report in 1995, however, there is no updated country-level reports for the two countries since then (Chau et al. 2001;Kino et al. 1998;WHO 1995).

Clonorchiasis was estimated to attribute to a disease burden of 275 thousand DALYs in 2005 (Fürst et al. 2012). However, the burden was considered to be largely underestimated due to the exclusion of light to moderate infections in the calculation (Qian et al. 2016). In general, males show higher prevalence than women and the prevalence increases with age (Fang et al. 2008;Qian et al. 2012).

1.1.3.4 Risk factors

Environmental and climatic factors affect the endemicity of C. sinensis infection, mainly thought influencing the distribution of the intermediate hosts. For example, temperature and climatic change have an impact on the activities, survival and reproduction rate of the intermediate hosts, thus are regarded as potential risk factors (Li et al. 1983;Petney et al. 2013). Factors such as precipitation, land cover/usage, and aquaculture that affect the presence, quality, and current of fresh water bodies (reservoirs for intermediate hosts), can also be potential risk factors (Keiser & Utzinger 2005). Areas adjacent to water bodies were reported to correlate with high infection risk of C. sinensis, however, such situation may be changing due to improvement of trade and transportation channels (Keiser & Utzinger 2005;Sripa et al. 2010).

One the other hand, socioeconomic factors and consumption of raw freshwater fish are important in understanding the epidemiology of clonorchiasis (Phan et al. 2011). Consumption of raw fish dishes is a traditional rooted culture practice in some areas of China, while in other areas it is considered delicious or highly nutritious by some people (Qian et al. 2013a;Tang et al. 1963a;Zheng 2009). In addition, lack of self-protection awareness of food hygiene influencing people’s behavior of raw-fish-consumption, can be an important risk factor (Han et al. 2013).

1.1.3.5 Diagnosis and treatment

The gold standard of diagnosis for C. sinensis infection is the detection of eggs in stool (Qian et al. 2016). Kato-Katz method is the most widely used technique with the advantages of simplicity, low cost and the ability to quantify the infection intensity, but the sensitivity is low (Hong et al. 2003;Qian et al. 2016). Direct stool smear and formalin-ether concentration technique are sometimes used but also with low sensitivity (Hong et al. 2003;Qian et al. 2013b). Multiple Kato-Katz thick smears are recommended to increase the accuracy of diagnosis (Qian et al. 2013b). On the other hand, immunodiagnostic techniques are employed as supplementary methods, among which serodiagnosis by the enzyme-linked immunosorbent assay (ELISA) is the most commonly used one (Qu, Chen, & Zeng 1980). However, the main limitations of ELISA is its cross-reactivity and inability to differentiate between past and active infection (Chen, Hu, & Shen 1988). Other immunodiagnostic techniques such as complement fixation, agglutination, and immunoelectrophoresis are seldom used in epidemiological studies (Qian et al. 2016). Molecular biological methods such as PCR- based/coupled technologies and loop-mediated isothermal amplification (LAMP) technique have been developed showing high performance and accuracy, however, they are inconvenient for large-scale epidemiological surveys due to the need for laboratory facilities, trained personnel, and financial supports (Han et al. 2012;Huang et al. 2012). In addition, imaging diagnosis is a complementary method for clonorchiasis in clinical practices (Choi & Hong 2007).

1.2 Geographical distribution of disease risk 17