The human immune response to helminth infections is associated with elevated levels of IgE, tissue eosinophilia and mastocytosis, and the presence of CD4+ T cells that preferentially produce IL-4, IL-5, and IL-13 [1
]. Th2-mediated mechanisms are considered to mediate protective immunity against these parasites [13
]. Parasites in the tissues stimulate a strong localized Th2 response, characterized by an eosinophil-rich inflammatory infiltrate. A classic example is the Th2 granoluma that develops around schistosome eggs in the liver or wall of the intestine [14
Individuals exposed to helminth infection may have allergic inflammatory responses to parasites and parasite antigens (). Individuals with limited exposures to helminths such as expatriates or recent migrants often develop allergic-type clinical manifestations () [15
], a probable host response to isolate and kill the parasites (). A classic example is the asthma-like illness, Loeffler's syndrome, caused by the passage of A.lumbricoides
larvae through the lungs. Helminth parasites in endemic areas tend to cause chronic infections - individual adult parasites may survive for many years in their human host - that are associated with few allergic-type reactions and a more tightly controlled Th2 response. Regulation of the Th2 response may be important for parasite survival and may allow the host to escape potentially damaging inflammation in the tissues.
Figure 1 Examples of allergic-type reactions to helminth parasites. A. Immediate hypersensitivity reaction to Paragonimus mexicanus antigen extract injected into the forearm of child. B. Cutaneous larva migrans showing serpiginous track of dog hookworm larvae (more ...)
Allergic-type reactions associated with human helminth parasites and possible associations between helminth infections and atopic diseases.
For example, during infections with the tissue helminth, Onchocerca volvulus
, the skin may be populated by millions of larval microfilariae and these appear to elicit little in the way of a host inflammatory response (). This state of hyporesponsiveness may be reversed rapidly after the killing of microfilariae by chemotherapy - treated individuals may develop allergic-type reactions () that are associated with the development of eosinophilic abscesses in the superficial dermis () within hours after treatment. The onset and severity of these reactions are associated with the release of allergic mediators such as tryptase and eosinophil degranulation products into the peripheral circulation [16
]. The hyporesponsiveness associated with chronic helminth infections appears to be actively regulated and may require the presence of live parasites.
Figure 2 Allergic-type inflammatory reactions to Onchocerca volvulus microfilariae in the skin. The Figure shows effect of treatment with the microflaricidal drug diethylcarbamazine. Pre-treatment skin biopsy (A) shows microfilariae in the dermis with few associated (more ...)
Geohelminth parasites that are confined to the intestinal lumen may be less likely to induce strong systemic immune regulation although the tissue migratory life cycle stages of parasites such as Ascaris lumbricoides
may induce strong allergic reactions in infected individuals living in regions where transmission of infection is seasonal. The comparative rarity of such reactions in endemic populations with year-round transmission [17
] may reflect difficulties in diagnosis or perhaps suppression of the inflammatory response.
Many zoonotic helminth infections cannot develop to maturity in the human host and the helminth larvae may migrate for prolonged periods in the tissues (). Examples are infections with Toxocara spp, Ascaris suum, and dog hookworms. Such infections cause allergic type syndromes such as cutaneous () and visceral larva migrans [18
]. Tissue damage is caused by allergic inflammation directed against the migrating larvae. During such infections there appears to be a failure of immune regulation probably because host and parasite have not co-evolved.