Current status of human liver fluke infections in the Greater Mekong Subregion

Sripa, Banchob; Suwannatrai, Apiporn; Sayasone, Somphou; Trung, Dung; Khieu, Virak; Yang, Yue

doi:10.1016/j.actatropica.2021.106133

Cited by 72 publications

(61 citation statements)

References 141 publications

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“…Indeed, antibodies raised against liver fluke granulin block its ability to drive proliferation of CCA cell lines (14) and, hence, bootstrap support for a vaccination strategy targeting Ov -GRN-1 in the gastro-intestinal tract, for example through induction of mucosal IgA and IgG responses (23, 61). Such an intervention might contribute a productive component to a multivalent, orally administered, anti-infection and anti-cancer vaccine (1, 23), which in turn would augment current tools for the public health intervention and control of this neglected tropical disease and its cancer burden (62, 63).…”

Section: Discussionmentioning

confidence: 99%

Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini

Chaiyadet

Tangkawattana

Smout

et al. 2021

Preprint

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Infection with the food-borne liver fluke Opisthorchis viverrini is the principal risk factor for cholangiocarcinoma (CCA; bile duct cancer) in the Lower Mekong River Basin countries including Thailand, Lao PDR, Vietnam, Myanmar and Cambodia. Using gene edited liver flukes in a hamster model of CCA involving concurrent infection and administration of sub-carcinogenic levels of nitrosamine, we explored the role of the fluke granulin-like growth factor Ov-GRN-1 in malignancy. We produced programmed gene knockout flukes (ΔOv-grn-1) by delivery of a CRISPR/Cas9/gRNA system by square wave electroporation. Targeted genome sequencing confirmed Cas9-catalyzed mutations in target parasite genes, and the rapid depletion of transcripts and the targeted proteins. Hamsters were infected with gene edited larval parasites and exposed to sub-carcinogenic levels of dimethyl nitrosamine in drinking water. Whereas Ov-grn-1 gene-edited parasites colonized the biliary tract of hamsters and developed into adult flukes, less hepatobiliary tract disease manifested during chronic infection with ΔOv-grn-1 worms in comparison to hamsters infected with control parasites. Specifically, immunohistochemical analysis of thin sections of hamster livers revealed markedly less fibrosis surrounding flukes and less global liver fibrosis as a result of infection with ΔOv-grn-1 worms, minimal biliary epithelial cell proliferation, and markedly fewer mutations of TP53 in biliary epithelial cells. Moreover, fewer hamsters developed high grade CCA when infected with ΔOv-grn-1 flukes compared to controls. The clinically-relevant pathophysiological phenotype of the livers of the hamsters confirmed a role for this parasite secreted growth factor in morbidity and malignancy during opisthorchiasis.

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Section: Discussionmentioning

confidence: 99%

Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini

Chaiyadet

Tangkawattana

Smout

et al. 2021

Preprint

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“…Animals can act as reservoirs for FBTs, so epidemiological studies aimed at determining the zoonotic and zooanthroponotic transmission of parasites are of great https://doi.org/10.1017/S0031182022000877 Published online by Cambridge University Press importance. Since cats are well-known hosts of the Thai liver fluke (Sripa et al, 2021), Sota et al analyse the circulation of O. viverrini between domestic cats and humans in an endemic area of Thailand (Sota et al, 2022). A population genetics analysis performed in >100 cat and ~1,500 human samples demonstrated the presence of at least three different O. viverrini populations in cats and humans.…”

Section: In Their Review Article Coogle Et Al Highlight the Emergence...mentioning

confidence: 99%

Foodborne trematodes: old foes, new kids on the block and research perspectives for control and understanding host–parasite interactions

Robinson

Sotillo

2022

Parasitology

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Foodborne trematodes (FBTs) have a worldwide distribution (with particular prevalence in south-east Asia) and are believed to infect almost 75 million people, with millions more living at risk of infection. Although mortality due to trematodiasis is low, these infections cause considerable morbidity and some species are associated with the development of cancer in hyperendemic regions. Despite this, FBTs are often side-lined in terms of research funding and have been dubbed neglected tropical diseases by the World Health Organisation. Thus, the aim of this special issue was to provide an update of our understanding of FBT infections, to shine a light on current work in the field and to highlight some research priorities for the future. With contributions from leading researchers, many from endemic regions, we review the major FBT species. In doing so we revisit some old foes, uncover emerging infections and discover how outbreaks are being dealt with as a result of new approaches to parasite control. We also report advances in our understanding of the interactions of FBTs with their mammalian hosts and uncover new interplay between trematodes and host microbiome components. We hope that this article collection will stimulate discussion and further research on the FBTs and help raise them from their neglected status.

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“…Pharmaceuticals 2022, 15, x FOR PEER REVIEW 3 of 10 3 Another category of parasites for which there appear to be no commercially available antibodies are liver flukes, which are important, because they have been shown to induce cholangiocarcinoma via chronic inflammation of the bile ducts [11]. The liver flukes, Clonorchis sinensis and Opisthorchis viverrini, affect tens of millions of people worldwide with by far the greatest concentration in Asia [12]. Rapid microscopic detection of the fluke's eggs in human fecal smears is challenging.…”

Section: When No Commercial Antibodies Exist or Are Very Difficult To...mentioning

confidence: 99%

Applications in Which Aptamers Are Needed or Wanted in Diagnostics and Therapeutics

Bruno

2022

Pharmaceuticals

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One strategy for bringing aptamers more into the mainstream of biomedical diagnostics and therapeutics is to exploit niche applications where aptamers are truly needed or wanted for their innate differences versus antibodies. This brief review article highlights some of those relatively rare applications in which aptamers are necessary or better suited to the user requirements than antibodies with explanations for why the aptamer is a necessary or superior choice. These situations include when no commercial antibody exists, when antibodies are excessively difficult to develop against a particular target because the target is highly toxic to host animals, when antibodies fail to discriminate closely related targets, when a smaller size is preferable to penetrate a tissue, when humanized monoclonal antibodies are too expensive and when the target is rapidly evolving or mutating. Examples of each are provided to illustrate these points.

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Current status of human liver fluke infections in the Greater Mekong Subregion

Cited by 72 publications

References 141 publications

Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini

Knockout of liver fluke granulin, Ov-grn-1, impedes malignant transformation during chronic infection with Opisthorchis viverrini

Foodborne trematodes: old foes, new kids on the block and research perspectives for control and understanding host–parasite interactions

Applications in Which Aptamers Are Needed or Wanted in Diagnostics and Therapeutics

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