Mechanisms of immunity in hydatid disease: Implications for vaccine development

The Echinococcus organisms, the cause of echinococcosis (hydatid disease), are parasitic helminths with life cycles involving a carnivorous definitive host (usually dog or fox) and an intermediate host (human, ungulate, or rodent). They are complex multicellular pathogens that, despite being under constant barrage by the immune system, are able to modulate antiparasite immune responses and persist and flourish in their mammalian hosts. Understanding how the immune system deals with these parasites is a major challenge. Recent application of modern molecular and immunological approaches has revealed insights on the nature of immune responses generated during the course of hydatid infection, although many aspects of the Echinococcus-host interplay remain unexplored. This review summarizes current understanding of the immunology of echinococcosis, indicates areas where information is lacking, and shows how knowledge of host protective immunity has been translated into the design and development of anti-Echinococcus vaccines for application in intermediate hosts.

Hydatid disease is a chronic, cyst-forming, parasitic helminthic disease of human beings as well as domestic and wild animals. It is caused by infection with the larval (metacestode) stages of dog/fox tapeworms (cestodes) belonging to the genus Echinococcus (family Taeniidae) and is also referred to as echinococcosis. The two major species of medical and public health importance are Echinococcus granulosus and Echinococcus multilocularis, which cause cystic echinococcosis (CE)³ and alveolar echinococcosis (AE), respectively. Human cystic echinococcosis is the most common presentation and probably accounts for >95% of the estimated 3 million global cases, with human alveolar echinococcosis causing ∼0.3–0.5 million cases (all in the Northern Hemisphere).

The life cycle of the two tapeworms is shown in Fig. 1⇓. Hydatid cysts of E. granulosus develop in internal organs (mainly liver and lungs) of humans and intermediate hosts (herbivores such as sheep, horses, cattle, pigs, goats, and camels) as unilocular fluid-filled bladders. These consist of two parasite-derived layers, an inner nucleated germinal layer and an outer acellular laminated layer surrounded by a host-produced fibrous capsule. Brood capsules and protoscoleces bud off from the germinal membrane. Definitive hosts are carnivores such as dogs, wolves, and foxes. Sexual maturity of adult E. granulosus occurs in the host small intestine within 4–5 wk of ingesting offal containing viable protoscoleces. Gravid proglottids or released eggs are shed in the feces and, following their ingestion by a human or ungulate host, an oncosphere larva is released that penetrates the intestinal epithelium into the lamina propria. This is then transported passively through blood or lymph to the target organs where it develops into a hydatid cyst.