Nematodes and human therapeutic trials for inflammatory disease

Helminth infections likely provide a protective influence against some immune-mediated and metabolic diseases because helminth infection dramatically decreased in developed countries shortly before the explosive rise in the prevalence of these diseases. The capacity of helminths to activate immune-regulatory circuits in their hosts and to modulate the composition of intestinal flora appears to be the mechanisms of protective action. Animal models of disease show that various helminth species prevent and/or block inflammation in various organs in a diverse range of diseases. Clinical trials have demonstrated that medicinal exposure to Trichuris suis or small numbers of Necator americanus is safe with minor, if any, reported adverse effects. This includes exposure of inflamed intestine to T. suis, asthmathic lung to N. americanus and in patients with atopy. Efficacy has been suggested in some small studies, but is absent in others. Factors that may have led to inconclusive results in some trials are discussed. To date, there have been no registered clinical trials using helminths to treat metabolic syndrome or its component conditions. However, the excellent safety profile of T. suis or N. americanus suggests that such studies should be possible.