Immune activation is a dominant factor in the pathogenesis of African AIDS Zvi Bentwich, Alexander Kalinkovich and Ziva Weisman zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON The AIDS epidemic in Africa is very different from the epidemrc in the West. As suggested here by ZzG Bentwich, Alexander Kalinkovicb afrd Ziua W eisman, this appears to be primarily a consequence zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR of the oz’cr- activation of the immune system in the African population, owing to the extremely high prevalence of infections, particularly belmintbic, in Africa. Such activation shifts the cytokine halance towards a T helper O/2 (TbOl2)-type response, which makes the host more susceptible to infection with human immunodeficiency virus (HIV) and less able to cope ulith it. Several features of the AIDS epidemic in Africa mark it as a distinct entity from the disease that is present in North America and Europe: (1) it is primarily a hetero- sexually transmitted disease with a male-to-female ratio of l:l, and lacks the known ‘classical’ risk groups of male homosexuals and intravenous (i.v.) drug usersl.L; (2) it is probably transmitted more easily’-“; (3) the progression of infection and disease is faster - the time from infection to onset of clinical manifestations and overall survival may be shorter’m7; and (4) the clinical manifestations are different, particularly the zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED m a in opportunistic infections and the main organ systems involved6. It is probably because of these features that the AIDS epidemic in Africa has reached such catastrophic dimensions, with a prevalence of human immuno- deficiency virus (HIV) infection in the general popu- lation reaching 30% or more in several African countries and with mounting numbers of AIDS patientsi,X. This pattern of epidemic is also fast emerging in other parts of the world, particularly in the developing countries of Southeast Asia (Thailand and India) and of South America and the Caribbeanx. Common to all regions showing this pattern is the pivotal role of prostitutes, who constitute the major, initial ‘reservoir’ of the virus and the source of its further spread into the general population as a sexually transmitted disease (STD)‘.‘. Quite remarkably, this pattern of spread has not been observed in the West or in other developed countries such as Japan, Australia or New Zealand, where the prevalence of HIV infection among prostitutes has remained surprisingly low and is mostly associated with i.v. drug use*. Hypothesis Our view is that profound changes in the host immune response may account for the dramatic differ- ences in the behavior of the AIDS epidemic in Africa and in other developing countries. Such changes make the host more susceptible to HIV infection and less capable of controlling the infection once it is acquired. Infectious diseases, mostly helminth infections endemic 111 Mrica and the developing countries, activate the immune system and alter its balance in such a way that tnakes the host more receptive to HIV and more vul- nerable to its effects. This altered ‘backgound’ immune response must be taken into consideration when designing vaccines and devising new therapies for HIV in .4frica and other developing countries. Type and variety of infections The average African host is exposed to a huge nutn- ber of infectious diseases from early childhood on- wards. These include various bacterial, viral and para- sitic infections”‘~‘“. Noteworthy is the wide prevalence of helminth infections, malarta and tuberculosis in most parts of Africa: especially in sub-Saharan Africa, and in East and West ,4frica”‘,“.“m’-. Also of central importance is the very high prevalence of STDs, par- ticularly genital ulcer diseases (GIJDs), which play an important role in facilitating the dissemination of HIV infection into the general populationz.“. Although there are only a few controlled studies addressing this sub- ject, there clearly appears to be a high rate of HIV transmission in Africa. Furthermore, recent studies on HIV transmission among army recruits in Thailand have shown a 50-fold higher rate of transmission when compared with rates of transmission observed in the Westi8; this could not be accounted for by STDs aloneix, indicating the involvement of other, as yet undefined, factors. It is very plausible that a similar situation also exists in Africa. Israel has received two waves of immigration from Ethiopia during recent years, and it has been possible to studv this Ethiopian population shortly after their arrival in Israel. These studies have revealed a very high prevalence of most infections, helminth infections being almost universal”‘. Immune activation in Africans With the high background of infections in Africa, it could be expected that increased signs of immune acti- vation occur in the general African population. Although the number of studies addressing this question has been small, increased immune activation has been