Fig. 2. A dynamic view of O. viverrini infection and associated clinical risks.

A) Liver fuke infection may vary from beneficial to costly depending on the infection intensity which for sake of simplicity in the figure we categorize as Low (L), Moderate (M) or High (H). The infection intensity will influence the relative dominance of anti-inflammatory and beneficial TH2 responses vs pro-infammatory harmful/costly TH1 responses. In case of chronic immuno-modulation by the Fluke and associated reduction of inflammation, the benefits can be a reduced risk of autoimmune and allergic diseases as well as metabolic disorders including obesity, cardiovascular and type 2 diabetes (in the figure lowest panel (L) the benefits (+) outweight the costs (−)). In case of chronic inflammation when Th1 response dominates and impart costs to the host (i.e. in the upper panel of the figure, costs (−) are higher than benefits (+)). Costs of infection range from anemia, hepathobiliary abnormalities to more severe pathologies such as fibrosis, cholangitis, hepatoegaly and in combination with other risk factors such as alcohol, Cholangiocarcinoma. The thresholds (the line represented in the middle of the figure) - beyond which infection intensity triggered hyper-inflammation and where the costs outwheight the benefits - are dynamic and change in relation to the host genetic background, diet and lifestyle as well as microbiome. B) Health assessments incoprorating knowledge about infection intensity, genetic predisposition to inflammation as well as lifestyle is necessary to refine interventions and avoid disrupting possible beneficial settings. When costs of infection are found to outwheight potential benefits, intervention, likely drug administration (chemotherapy) is warranted. When the benefits are thought to outwheight the costs (in case of low intensity infection) intervention and drug administration may be nuanced as possibly administrering drug in this case can lead to unwanted clinical conditions that are more detrimental than having a low worm burden. This « trade-off » rationale should help design epidemiological investigation where risk groups (risk of developping severe hepathobiliary conditions) are defined based on infection intensity and if possible other biological and socio-economic attributes as advocated by the WHO (Montresor et al. 1998).