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6 Epstein, J. H. (1978) Natl CancerInst. Monogr. 50, 13-25 7 Kripe, M. L. (1984) Transplant. Proc. 16, 474-475 8 Stingl, L. A., Sander, D. N., Iljima, M., Wolff, K., Pehamburger, H. and Stingl, G. (1983)J. Immunol. 130, 1586-1591 9 Parrish, J. A., White, H. A. D. and Pathak, M. A. (1979) in Derrnatology in General Medicine (Fitzpatrick, T. B., Eisen, A. Z., Wolff, K., Freedberg, I. M. and Austen, K. F., eds), 2nd edn, pp. 942-994, McGraw-Hill, New York 10 Roelandts, R. (1984) Arch. DermatoL 120, 662-669 11 Belsito, D. V., Flotte, T . J . , Lira, H. W., Baer, R. L., Thorbecke, G . J . and Gigli, I. (1982)J. Exp. Med. 155, 291-302

12 Koranda, F. C., Loeffier, R. T., Koranda, D. M. and Penn, I. (1975) Surg. Forum 26, 145-146 13 Nathanson, R. B., Forbes, P. D. and Urbach, F. (1973) Proc. Am. Assoc. Cancer Res. ]4, 46 14 Kelly, G. E., Sheil, A. G. R. and Taylor, R. (1984) Transplantation 37, 368-372 15 Sontheimer, R. D., Bergstresser, P. R., Gailiunas, P., Jr, Helderman, J. H. and Gilliam, J. N. (1984) Transplantation 37, 168-174 16 Lytte, C. D. (1978) Natl CancerInst. Monogr. 50, 145-I49 17 Belsito, D. V., Sanchez, M. R., Baer, R. L., Valentine, F. and Thorbecke, G. J. (1984) N. EngL J. Med. 310, 1279-1282

AIDS in Africa An intriguing aspect of the acquired immunodeficiency syndrome (AIDS) story has been the detection of a focus of an AIDS-like illness in central Africa. An association between AIDS and central Africa first came to light following the observation by Belgian and French physicians of an AIDS-like illness in Africans, predominantly people from Zaire but now living in Europe 1'2. The clinical features of 23 African patients with an AIDS-like illness, seen in Belgium between 1979 and 1983, have recently been reviewed 3. Two patients came from Rwanda, two from Burundi, one from Chad and the remainder from Zaire. All were heterosexual and nine were female. None were known to be drug abusers. They presented symptoms characteristic of AIDS: fever, weight loss and chronic diarrhoea, complicated by unusual secondary infections and disseminated Kaposi's sarcoma. Immunological findings included diminished lymphocyte responsiveness to T-cell mitogens and a low O K T 4 / O K T 8 lymphocyte ratio. Several patients in this series had come to Belgium for treatment, suggesting that they had acquired their illness in Africa and that an AIDS-like illness might be prevalent in Zaire. This supposition has now been confirmed. Two one-month-surveys undertaken in 1983 in Kinshasa, Zaire and in Kigali, capital of neighbouring Rwanda, identified 55 probable cases of AIDS and several further patients who may have had an AIDS prodromal syndrome 4's. Attack rates in Kinshasa and Kigali were approximately 17 and 80 per 100000 population per year, respectively, rates as high as those recorded in New York and San Francisco. The clinical features of the patients seen in these two surveys were very similar. Nearly one half were female and, with one possible exception, all were heterosexual. Several were promiscuous. Most came from the small upper and middle class sections of their communities. A wide variety of secondary infections were seen: oesophageal candidiasis was prominent in Kigali, as noted among AIDS patients in Haiti6; disseminated Kaposi's sarcoma was relatively infrequent, being seen in only nine patients. Low O K T 4 total lymphocyte counts and a low O K T 4 / O K T 8 T lymphocyte ratio were seen in both series. Eleven of the 55 patients died during the short observation period. Can we accept that the AIDS-like illness seen in these African patients is the same disease as AIDS in American and European homosexuals and drug abusers? Diagnosis of AIDS is difficult in tropical Africa where infectious diseases that can produce a similar clinical picture are prevalent. Furthermore, lymphocyte subpopulations may be perturbed by infections such as malaria 7'8 and

tuberculosis 4 which are widespread in Africa. Despite these provisos, the evidence is convincing that at least the majority of the patients seen in Kinshasa and Kigali had true AIDS. Their clinical features, apart from a lower prevalence of Kaposi's sarcoma, were similar to those described in AIDS patients elsewhere and, in most patients, lymphocyte changes were so marked that it is unlikely that these were caused by an intercurrent infection. The view that African and American AIDS is the same disease has been strengthened by recent reports of the isolation of lymphadenopathy-associated virus ( L A V / H T L V III), the putative cause of AIDS 9, from a Zairian patient with AIDS in France 1°. Furthermore, antibodies to L A V have been detected in a high proportion of African patients with the syndrome 11. Detection of a focus of AIDS in central Africa raises a number of intriguing epidemiological questions. Is AIDS a new disease in central Africa or has it occurred there in the past but remained unrecognized? It is unlikely that this question will ever be answered, but there is evidence which suggests that the present high incidence of AIDS in Zaire and Rwanda is a new phenomenon. Both Kinshasa and Kigali (see Fig. 1) have had relatively good medical facilities for many years, and it is difficult to imagine how an outbreak of AIDS, on the present scale, could have continued unnoticed for several years. A recent increase in the number of reported cases of cryptococcal meningitis 12 and oesophageal candidiasis 5, in Kinshasa and Kigali respectively, supports this view. It is possible that further information on the chronology of AIDS could be obtained by serological surveys. Antibodies to L A V are found now in about 5 % of Zairian blood donors. It is likely that sera collected in Zaire some years previously, for parasitological or other surveys, are still available. A low positivity for L A V antibodies in these sera would provide evidence for the recent spread of the lymphadenopathy-associated virus in Zaire. If evidence is found of the recent spread of L A V in Zaire and Rwanda it would be interesting to see if this could be chronologically related to any sociological or environmental changes that have occurred recently in these communities. Retrospective analysis of case records of patients seen in Europe suggests that AIDS has been present in Zaire since at least 1976 (see Refs 13 and 14) - about two years before the first cases occurred in the USA or Haiti. These clinical anecdotes suggest that central Africa may be the original focus of the AIDS-agent, which has spread from Zaire to Haiti, with which Zaire has close links, and also to the USA. So far, there is no direct evidence to support this view and spread across the Atlantic could have taken place in the opposite direction. It has been suggested that © 1984,ElsevierScienceP//bllshcrsB.V.,Amsterdam 0167- 4919/84/$02.00

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Fig. 1. M a p of Africa showing location of Kinshasa (Zaire) and Kigali (Rwanda) both of which have a high incidence of AIDS. No such outbreaks have been noted in West and East Africa, and although there has been an increase in the occurrence of Kaposi's sarcoma in Zambia there has been no outbreak of AIDS.

H T L V I, the human T-cell leukaemia-lymphoma virus which is closely related to the AIDS-agent, also originated in central Africa and spread from there to foci in Japan, the Caribbean and parts of South America ~5. The origin of AIDS, a subject which evokes strong national reactions, may never be definitely determined, but serological analysis of stored sera might provide some further clues. Is the African focus of AIDS limited to Zaire and its neighbours, or is the disease occurring in other parts of Africa but passing unrecognized? An increase in the incidence of Kaposi's sarcoma, associated with lymphocyte changes similar to those described in AIDS, has been reported from Zambia ~6, Zaire's eastern neighbour, but the reported patients do not have all the characteristic features of AIDS. It seems unlikely that an outbreak of AIDS would pass unnoticed for several years in the large and well-doctored cities of West and East Africa, such as Dakar, Abidjan, Lagos and Nairobi (see Fig. 1). Furthermore, AIDS has not been reported so far among the many West African immigrants and visitors to Western Europe. Thus, it is probable that, at present, a high prevalence of AIDS is restricted to central Africa. Why this area in particular should be at risk is not obvious, but a tantalizing clue is provided by the fact that this is the area of Africa that has always had the highest incidence of Kaposi's sarcoma. Although endemic, Kaposi's sarcoma differs in a number of ways from Kaposi's sarcoma associated with AIDS, this is a lead worth further investigation, If there are no special geographical or cultural reasons

for the emergence of AIDS in central Africa then there may be no reason why it should not spread to other areas of tropical Africa. This could be a major medical disaster for an area which already has a multitude of medical problems. An outbreak, with an attack rate comparable to that described in Kigali, would result in something approaching 10 000 cases of AIDS a year in the large cities of southern Nigeria alone. If the spread of AIDS in Africa is to be prevented the way in which the disease is transmitted in Africa must be clearly established. The occurrence of two clusters of AIDS in Zairois linked by sexual contact 4 suggets that heterosexual transmission is important, but why should this mode of transmission be important in Zaire but not in the USA? Is there something unusual about the sexual mores of Kinshasa which differ from those of other large African or American cities? Could the AIDS-agent be transmitted by scarification, unsterile syringes, bloodsucking insects or arthropods in a manner analogous to that suggested for the hepatitis B virus? A detailed case control study of African patients with AIDS, undertaken by investigators with an intimate knowledge of local customs and practices, is urgently needed to identify special risk factors for the transmission of AIDS in Africa and also, to determine if there are any ways in which the spread of the condition can be prevented. ~T] B. M. G R E E N W O O D M R C Laboratories, Fajara, Banjul, The Gambia

References 1 Clumeck, N., Mascart-Lemone, F., de Maubeuge, J., Brenez, D. and Mareelis, L., (1983) Lancet (i), 642 2 8ruent, J. B., Bouvet, E., Leibowitch, J., Chaperon, J., Mayaud, C., Gluckman, J. C., Pieard, O., Kernbaum, S., gevuz, J., IOatzman, D., gosenbaum, W., Laehiver, D., Villalonga, J., Wesselberg, C. (1983) Lancet (i), 700-701 3 Clumeck, N., Sonnet, J., Taelman, H., Mascart-Lemone, F., de Bruyere, M., Vandeperre, P., Dasnoy, J., Marcelis, L., Lamy, M., Jonas, C., Eyckmans, L., Noel, H., Vanhaeverheek, M. and Butzler, J-P. (1984) N Engl. J. Med. 310, 492-497 4 Plot, P., Qninn, T. C., Taelman, H., Feinsod, F. M., Minlangu, K. B., Wobin, O., Mbendi, N., Mazebo, P., Ndangi, K., Stevens, W., Kalambayi, K., Mitchell, S., Bridts, C. and McCormick, J. B. (1984) Lancet (ii) 65-69 5 Van de Perre, P., Rouvray, D., Lepage, P., Bogaerts, J., Kestelyn, P., Kayihigi, J., Hekker, A. C., Butzler, J-P. and Clumeek, N. (1984) Lancet (ii) 62-65 6 Pape, J. W., Liantaud, B., Thomas, F., Mathurln, J-R., St. Amand, M-M. A., Boney, M., Penn, V., Pamphile, M., Laroche, A. C. and Johnson, W. D. (1983) N. Engl. J. Med. 309, 945-950 7 Troye-Blomberg, M., Sj6holm, P. E., Perlmann, H., Patarroyo, M. E. and Pertmann, P. (1983) Clin. Exp. Immunol. 53, 335-344 8 Whittle, H. C., Brown, J., Marsh, K., Greenwood, B. M., Sidelin, P., Tighe, H. and Wedderbum, L. Nature (London) (in press) 9 Pinching, A. (1984) Immunol. Today 5, 196-199 10 Ellrodt, A., Barre-Sinoussi, F., Le Bras, Ph., Nugeyere, M. T., Palazzo, L., Rey, F., Brun-Vezinet, F., Rouzioux, C., Segond, P., Caquet, R., Montagnier, L. and Chermann, J. C. (1984) Lancet (i) 1383-1385' 11 Montagnier, L., McCormick, J. B., Quinn, T. and Piot, P. Science (in press) 12 Lamey, B. and Melameka, N. (1982) Med. Trop. (Marseille) 42,507-511 13 Bygbjerg, I. C. (1983) Lancet (i), 925 14 Vandepitte,J., Verwilghen, R. and Zachee, P. (1983)Lancet (i), 925-926 15 Gallo, R. C., Sliski, A. and Wang-Staal, F. (1983) Lancet (ii), 962-963 16 Downing, R. G., Eglin, R. P. and Bayley, A. C. (1984) Lancet (i), 478-480

For technicalreasonswe ave unableto reproducethesefiguresin colourin this edition--see the Octoberissueof ImmunologyTodayfor full colourillustration.

AIDS in Africa.

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