Eradication of helminthic infections may be essential for successful vaccination against HIV and tuberculosis.

The current epidemics of tuberculosis and acquired immunodeficiency syndrome (AIDS) (caused, respectively, by infection with Mj,cobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV)) are a major cause for concern. No successful or effective anti-HIV vaccine has been yet developed, and Bacille Calmette-Guarin (13CG) has failed to confer protection against tuberculosis in developing countries. Nevertheless, apart from the use of social and educational measures, the only plausible way to overcome these epidemics is through mass vaccination. An effective protective vaccine against MTB or HIV infection should generate a potent cellular immune response, which is dependent on a dominant T-helper type 1 (TH1) cellular response, rather than a T-helper type 2 (TH2) humoral immune response. These two cch types cross-regulate each other and thus cytokines produced by one T-helper subset can suppress the production and/or activity of the other. Helminthic infections affect more than a third of the world's population, and have a similar geographical distribution to that of HIV and tuberculosis. In developing countries, children born in areas where intestinal nematodes are endemic harbour worms for most of their lives. Individuals with helminth infections are chronically immune-activated and have a very pronounced TH2 immune profile. We have hypothesized that the chronic immune activation and TH2 immune profile caused by helminthic infections make the host more susceptible to HIV infection and less able to cope with it once infected. This may play a major role in the pathogenesis of AIDS in Africa (Bentwich Z et al. Immunology Today, 1995, 16: 187-191) and account for the widespread tuberculosis in developing countries (]3entwich Z et al. Immunology Today, 1995, 201 485-487). Furthermore, intestinal helminth infections may also compromise the generation of protective immunity upon vaccination for both HIV and tuberculosis. This hypothesis is based on the following observations: several populations in Africa and South-east Asia have a pre-existent dominant TH2 cytokine profile and extremely high immune activation (e.g. Bentwich Z et al. Clinical and Experimental Immunology; 1996, 103: 239-243); lymphocytes isolated from Ethiopian immigrants recently arrived in Israel had very impaired signal transduction and anergy following stimulation; there was a clear inverse correlation between immune activation in these Ethiopian immigrants and the capacity of their lymphocytes to proliferate and secrete chemokines following stimulation with tuberculin purified protein derivative (PPD) (r= -0.58, P [is less than] 0.002); helminthinfected Ethiopian immigrants responded poorly to PPD skin test compared with such immigrants following deworming (P [is less than] 0.005) (Borkov G. et al. Journal of Clinical Investigation, in press). Why do the populations of developing countries exhibit such immune profiles? Though several factors could contribute to it, such as constant exposure to infectious diseases, poor hygiene and malnutrition, we have proposed that it is mainly a consequence ofhelminthic infections (e.g. Kalinkovich A et al. Clinical and Experimental Immunology, 1998,114: 414-421). This conclusion is largely based on the following evidence: the high prevalence of helminthic infections among the Ethiopian immigrants in Israel ([is greater than] 90% were infested with at least one parasite, while some had even 5 different parasitic infections); the immune profile of the Ethiopian immigrants returned to normal following the eradication of the helminthic infections; helminth eradication had also a clear effect on the HIV infection/ disease, i.e. once their helminth infections had been eradicated the response of the Ethiopian immigrants to highly active antiretroviral treatment was similar to that of other Israeli. inhabitants (Weisman Z et al. Journal of AIDS, 1999, 21: 157-163); preliminary results of a study carried out in Ethiopia show that eradication of helminthic infections in people infected with both these and HIV is associated with significant decreases in HIV plasma viral load. …