Letters to the Editor

TUBERCULIN SKIN TESTS AND B.C.G. VACCINATION IN HYPERENDEMIC AREA OF ONCHOCERCIASIS

Helminthic infections occur worldwide, especially in developing countries. About one-quarter of the world's population, i.e., 1.5 billion, are infected with one or more of the major soil-transmitted helminths, including hookworms, ascarids, and whipworms. Schistosomes infect more than 200 million people worldwide with 600 million at risk in 74 countries. The interaction between helminths and the host's immune system provokes particular immunomodulatory and immunoregulatory mechanisms that ensure their survival in the host for years. However, these changes might impair the immunologic response to bystander bacterial, viral, and protozoal pathogens and to vaccination. Modulation of the immune system by infection with helminthic parasites is proposed to reduce the levels of allergic responses and to protect against inflammatory bowel disease. In this section, we summarize the immunologic milieu associated with helminthic infections and its impact on hepatitis C virus, and HIV in humans and experimental animals.

Over 2 billion people worldwide are infected with helminths (worms). Similarly, infection with Mycobacterium tuberculosis (Mtb) occurs in over a third of the world's population, often with a great degree of geographical overlap with helminth infection. Interestingly, the responses induced by the extracellular helminths and those induced by the intracellular Mtb are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infecting pathogens. In this review, we outline the nature of the immune responses induced by infections with helminths and tuberculosis (TB) and then provide data from both experimental models and human studies that illustrate how the immune response engendered by helminth parasites modulates Mtb-specific responses in helminth–TB coinfection

This chapter discusses onchocerciasis and lymphatic filariasis. Microfilariae of Onchocerca volvulus in superficial connective tissues, rather than in blood, are taken up by biting arthropod vectors, namely, the species of Simulium blackflies. There, they complete their development into third-stage infective juveniles. Infected vectors release 3L forms on biting new hosts, thereby completing the transmission cycle as 3L migrate and eventually mature to adults over a period of 6–12 months. In contrast, microfilariae of Wuchereria and Brugia circulate in peripheral blood, thereby completing their development to infective forms in a wide range of mosquito vectors. The 3L of these species migrate to lymphatic vessels maturing over a period of months. Eventually, they liberate microfilariae that make their way with the course of lymph flow into the peripheral blood. Live microfilariae of O. volvulus in enormous quantities may coexist with healthy human tissues, whereas severely affected onchocerciasis patients, disfigured and debilitated as a consequence of their infection, may have few or no live microfilariae detectable in their tissues.

Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P = 0.0002), and IgG3 (P = 0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.