The objective of this study was to examine the association between helminth infections and atherosclerosis in a population residing in an area highly endemic for STH. The hypothesis being tested is that helminth infections may have a beneficial effect on the development of atherosclerosis, both by influencing conventional CVD risk factors and systemic inflammation. Although this beneficial effect has been illustrated in animal studies 
, no human studies on the relationship between STH infections and atherosclerosis have been published before.
We found a negative association between helminth infections and conventional CVD risk factors, including BMI, WHR and serum cholesterol levels, which was independent of age and gender. In addition, with increasing number of helminth species, the negative association with CVD risk factors increased. The association was similar when we analyzed TIgE as a marker of exposure to helminth infections and reflects not only current but also prior exposure to helminth infection 
The finding of lower lipid levels in individuals with infections in our study area is similar to what was found in Tsimane 
or Shipibo 
population. The lipids measured included HDL, which might seem surprising as decreased HDL level is considered to be a CVD risk factor. Interestingly, the anti-atherogenic properties of HDL might be dependent on the composition of HDL and the context in terms of type of inflammation 
. It would be important to investigate whether helminth infections affect the type of HDL or its role in cholesterol transport.
With regards to cytokine production, we found a positive association of TNF production in response to LPS stimulation with helminth infections as well as with TIgE. These data suggest that helminths are associated with pro-inflammatory responses. Although higher TNF and pro-inflammatory cytokines have been found in the circulation of helminth infected patients with pathology 
, most studies of subjects infected with helminths with no overt pathology, report an anti-inflammatory effect of these parasites on the immune system. However, the before mentioned have focused on the adaptive responses and include Tregs 
. It should be noted that, in line with the current data, a recent study in Gabon found that S. haematobium
infected children develop a more pro-inflammatory TLR-mediated response 
. We did not observe substantial differences in STH species and their effects on CVD risk factors.
Although we showed a relationship between helminth infections and traditional CVD risk factors, we did not find an association between helminth infections and cIMT. The following explanations may account for the absence of a relationship between helminth infection status and cIMT. In our study, helminth infection was assessed at one time-point. Theoretically, it may be possible that helminth-negative subjects in our study have only recently become helminth negative. In this situation, the beneficial effects of helminths can be seen on some of the traditional CVD risk factors, but not atherosclerosis development, as the dewormed state may have been too short to affect cIMT. As the development of atherosclerosis is a chronic process, ideally, lifetime exposure to helminth infections should be assessed in relation to atherosclerosis development. Although this is not feasible, the association was also not significant when TIgE, reflecting current and prior helminth infection, was considered. Another explanation is that the population studied has a low cardiovascular risk profile. Although the association of CVD risk factors and IMT in the Flores population was similar to other studies 
, mean IMT in the study population was lower than comparable age groups in Europe 
, the USA 
, and Japan 
. Indeed most other CVD risk parameters were well within the normal reference range. In this situation, the absolute levels of CVD risk factors may be below the threshold for accelerated atherosclerosis development.
In conclusion, in a large cross-sectional study in an area endemic for helminth infections, we found an association between STH infection and conventional risk factors for CVD. The effect of helminth infections on CVD was at least partially mediated by an effect on BMI. However, no direct association between helminth infections and IMT was found. Nevertheless we believe that this study shows that in the explanation of increase in CVD in non-western societies, changes in infectious pressure should be taken into account. Further studies are necessary to assess the causal relationships between helminth infections and atherosclerosis.