Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos

Abstract

Liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Thailand and the Lao People's Democratic Republic (Lao PDR; Laos). Currently, more than 600 million people are at risk of infection with these fish-borne trematodes and/or their close relatives. Opisthorchiasis has been studied extensively in Thailand, where about 8 million people are infected with the liver fluke. Here we review the pathogenesis, control and re-emergence of O. viverrini infection, in particular in Thailand and, to a lesser extent in Lao PDR given the contiguous geographical range of O. viverrini through these two regions. We also review the association of O. viverrini infection and cholangiocarcinoma, bile duct cancer, and highlight new findings on pathogenesis of liver fluke-induced cholangiocarcinogenesis. Last, we comment on national control strategies in Thailand for the control of O. viverrini infection aimed at reduction in the prevalence of O. viverrini-associated liver cancer in the longer term.

Figure 1. Montage of images relating to transmission of Opisthorchis viverrini infection in Khon Kaen Province, Thailand

Panel A. Bithynia species nails, the intermediate host of Opisthorchis viverrini; Chonnabot district, Khon Kaen province, Thailand. Panel B. A fisherman in Chonnabot district, Khon Kaen province, Thailand. Panel C. Cyprinoid fish, about 10 cm in length, caught in natural water courses in Chonnabot district, Khon Kaen Province, Thailand (http://en.wikipedia.org/wiki/Amphoe_Chonnabot). D. A plate of koi-pla, a traditional, widely consumed dish prepared from un-cooked cyprinoid fish (as shown in panel C), salad vegetables and condiments. Koi-pla is frequently contaminated with viable, infectious metacercariae of O. viverrini.

Figure 2. Photomicrographs of an egg of Opisthorchis viverrini (panel A) and eggs from two microscopic intestinal flukes (MIF), Phaneropsolus bonnei (B) and Prosthodendrium molenkampi (C)

All three eggs were passed in human feces. The average dimensions of these eggs are 27 × 15 (O. viverrini), 30 × 15 (P. bonnei) and 24 × 12 µm (P. molenkampi) (Kaewkes et al, 1991). When stained with iodine, there is an iodophilic body in the miracidium of embryonated MIF (lecithodendrid) eggs, which is absent from O. viverrini eggs.

Figure 3

Opisthorchis viverrini infection in Thailand in relationship to the incidence of cholangiocarcinoma (CCA) by province.

Figure 4. Immunolocalization of cathepsin F cysteine protease (Ov-CF-1) in Opisthorchis viverrini infected hamster liver

Thin sections of paraffin embedded liver tissues were probed with rabbit antiserum (panel A) Representative section of liver from an uninfected hamster, spanning a portal triad including a secondary bile duct, probed with rabbit anti-Ov-CF-1serum (negative control). Infected hamster liver in the vicinity of the secondary bile ducts too small in internal diameter to include an adult fluke, probed with the rabbit anti-Ov-CF-1 serum (panels B and C). Immunoperoxidase stain (brown) indicates the presence of Ov-CF-1 in bile ducts epithelial cells (B) and in sinusoidal Kupffer and mononuclear cells (panel C). Section through bile duct containing an adult O. viverrini, showing strong reactivity to organs and tissues of the fluke (including the gut), and to the epithelial cells lining the infected bile duct (panel D). Immunoperoxidase staining, original magnification, ×100 (from Pinlaor et al. 2009).