Perspectives 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 infectionwithMycobacterium tuberculosis (MTB) andhuman immunodeficiency virus (HIV)) are amajor cause for concern.No successful or effective anti-HIV vaccine has been yet developed, and Bacille Calmette– Guérin (BCG) 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 againstMTB 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 cell 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. Thismay play amajor 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 (Bentwich 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<0.002); helminthinfected Ethiopian immigrants responded poorly to PPD skin test compared with such immigrants following deworming (P<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 consequenceofhelminthic 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 (>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. Furthermore, HIV viral load was correlated with helminthic ‘‘load’’ (number of eggs found in stools of HIV and helminth-infected individuals). The following observations further support our hypothesis: in Africa, faster progression to AIDS 1 Senior Scientist, R. Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot, Israel. 2 Professor and Head, R. Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, Rehovot 76100, Israel (email: bentwich@agri. huji.ac.il). Correspondence should be addressed to this author.