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The AIDS epidemic and commercial plasmapheresis
Medical Hypotheses (1997) 49, 521-523 © Harcourt Brace & Co Ltd 1997
The AIDS epidemic and commercial plasmapheresis P. VOLKOW Instituto Nacional de Cancerologia, San Fernando 22, CoL Tlalpan, C. P. 14000, M#xico
Abstract - - In 1986 an epidemic of HIV infection among paid plasma donors was identified in Mexico; paid donors were iatrogenically infected in a plasmapheresis center. These paid donors sold both plasma and blood: they provided one-third of blood consumed in 1986. This led to infection of blood recipients, mainly women of childbearing age. Blood transfusion is the leading cause of AIDS in women in Mexico. The male:female ratio decreased from 30:1 in 1986 to 5:1 1990; that coincided with the increase of transfusion-associated AIDS cases. Mexico prohibited the blood trade in 1987, ending the epidemic in paid donors and recipients. latrogenic infection of paid donors in plasmapheresis facilities could help to explain the explosive AIDS epidemic in central Africa and Haiti in the 1980s. There is a temporal and geographical coincidence in the early eighties between that AIDS epidemic, high numbers of hepatitis B asymptomatic carriers and an increased production of serum inactivated hepatitis B vaccine. Plasmapheresis facilities in these developing countries may have taken advantage of the high prevalence of hepatitis B asymptomatic carriers in their populations to obtain plasma for exportation through brokers to developed countries where the vaccine and other plasma products were manufactured. This hypothesis is relevant to establishing preventive policies and warrants further investigation.
Introduction
Blood and plasma industry in the worm As early as 1975, long before the discovery of AIDS, members of the World Health Organization were seriously concerned about the possible health and ethical problems involved in the trade of blood, mainly regarding plasmapheresis on a commercial basis (1). At that time, the plasmapheresis industry was already operating in Mexico, central and South America and spreading to Africa and Asia. It was an expanding industry that produced therapeutic (coagulation factors, albumin, anti-Rho immunoglobulin,
etc.), diagnostic (blood typing), and vaccine (hepatitis B serum vaccine) products. By 1990, 30 million doses of inactivated hepatitis B serum vaccine, processed by 12 manufacturers, had been administered (2). Some Pacific countries received inactivated vaccine processed in Japan in exchange for plasma positive for HBsAg. Where did the plasma to produce the vaccines used in the USA and western Europe come from? It is well documented that several developed countries bought cheap plasma and blood from developing countries (3). Developing countries consume mainly whole blood or red blood cells because
Date received 11 June 1996 Date accepted 24 October 1996
521
522 industrialized plasma derivatives are expensive (4). Plasmapheresis in poor countries was mainly used to obtain plasma for export to the USA and Europe.
MEDICALHYPOTHESES Fourth, the Mexican government prohibited blood commercialization in 1986, ending the epidemic in paid donors and, consequently, the epidemic in blood product recipients.
Commercial plasmapheresis in developing countries Commercial plasma banks exist only in cities, because the purchase of plasma is a phenomenon of areas with high rates of unemployment, characteristically located where poor rural migrants settle while searching for work (3). Paid donors in the developing world differ from those described in the USA (5); they are men and women who earn or supplement their incomes by selling plasma and who are not involved in regular illicit drug use. Intravenous drug abuse is uncommon in most of these areas of the world, since it is too costly. HIV epidemic among plasmapheresis donors in Mexico and its relation to Mexican HIV epidemic Mexico offered a unique opportunity to show how commercial plasmapheresis was capable of transmitting HIV very efficiently in a short period of time (6). First, an epidemic of HIV infection in paid plasma donors was documented in Mexico (besides the sexually transmitted HIV epidemic). HIV seroprevalence increased from 6% to 54% in only 6 months in a group of paid donors (7). Paid plasma donors in Mexico donated every month up to 12 times through apheresis in addition to one or two units of blood (8). They were probably infected during the procedure of donation by reuse of disposable material or injection of human serum. Blood recipients in developing countries are mainly women of childbearing age since the principal reasons for blood transfusion are gynecological emergencies. Transfusion has been the main risk factor for AIDS in Mexican women: in 1990 61% of AIDS in women in Mexico was associated with transfusion (4). Second, the establishment of AIDS surveillance in 1987 allowed the development of a registry of AIDS cases by different risk groups and observation of the occurrence of these cases over time. Infection of women rapidly decreased the male:female ratio of AIDS cases from 30:1 in 1986, to 5:1 in 1990 (5). Women of childbearing age infected via transfusion also contributed to perinatal AIDS. Third, the transition of the HIV epidemic to women is clearly related to blood transfusion because prostitution is not linked to drug abuse in Mexico and, as of 1994, seroprevalence in female sex workers remained low at about 2% (9). This is in contrast with countries such as the USA, where seroprevalence in prostitutes is much higher and associated with IV drug abuse (10).
Origins of global HIV epidemic It is speculated that the AIDS epidemic originated in Africa and from there it was transmitted to other countries of the world. The mechanism of AIDS dissemination in Africa has been attributed to sexual promiscuity, political instability, migration, and industrialization leading to concentration of people in urban areas (11). These hypotheses, however, are not definitely proven. I postulate that the commercial plasmapheresis industry also had a major role in the dissemination of AIDS observed in central Africa and in other countries such as Haiti and Honduras. Plasmapheresis paid donation and transfusion could have led to a rapid and efficient transmission of HIV in central Africa and Haiti where there is a high prevalence of asymptomatic hepatitis B carriers. In the early 1980s this high prevalence was attractive to the commercial plasma industry as a source of inexpensive plasma needed to produce the hepatitis B vaccine and other plasma derivatives. The price of plasma in developing countries was 10 to 20 times cheaper than in developed countries (3). The role of the hepatitis B serum vaccine in HIV dissemination is difficult to assess. The hepatitis B serum vaccine used in published and well-known trials has been considered safe for HIV infection. However, the possibility of HIV contamination of earlier or less well-known vaccine prototypes made with serum from developing countries remains. AIDS is mainly an urban phenomenon in central Africa (6,12-15). Seroprevalence in rural areas of Zaire and Rwanda has shown stability after 10 years of the AIDS epidemic. Fear of acquiring AIDS from donating blood was recognized in Africa (16) and also in Mexico in the late 1980s but is unknown in developed countries with adequate sanitary regulations. A similar process to that described in Mexico could explain the high seroprevalence among pregnant women seen in some cities of central Africa. A rapid dissemination through the infection of paid donors in plasmapheresis centers could explain the outburst of HIV infection in Africa in the early 1980s and its consequence, the AIDS epidemic in the mid-1980s. There is a geographic and temporal coincidence between the high number of hepatitis B carriers, the extended program of vaccination with serum inactivated hepatitis B vaccine, and the aforementioned explosion of the HIV epidemic in
AIDS AND PLASMAPHERESIS
the mid-1980s. Plasmapheresis banks were located in Kinshasha, Zaire, other central African countries, and in Port-au-Prince, Haiti, and plasma reached developed countries through plasma brokers (17). Haiti had at least one plasmapheresis bank, the Caribbean Plasmapheresis Bank, which was apparently closed in 1975; however, in 1985, Haiti and Honduras still appeared as countries in America with 'blood trade' (3). In the mid-1980s, commercial plasmapheresis in Africa and other countries may have decreased mainly because of concern about transmission of AIDS and because of the availability of recombinant hepatitis B vaccine. Plasmapheresis industries moved away from areas with high HIV infection prevalence to other places with lower prevalence, such as India. In this context, the situation in India is also consistent with this hypothesis. In the last 4 years, the male to female ratio of AIDS cases has steadily decreased towards unity in regions with a known plasmapheresis industry where outbreaks of HIV infection in paid donors have been described (18,19). However, in India, intravenous drug abuse and prostitution have also played a prominent role in dissemination of the HIV epidemic (20). In summary, we observed in Mexico a very efficient mechanism of HIV transmission through the infection of paid donors in plasmapheresis banks. Those centers did not comply with standard sanitary regulations. Sometimes HIV screening was lacking or positive donors were not rejected. Each donor provided multiple donations each month that infected mainly women of childbearing age. Plasmapheresis banks could have played a major role in the dissemination of HIV-1 in Haiti and Central Africa. This hypothesis is relevant to establishing preventive policies and warrants further investigation.
References 1. Utilization and supply of human blood and blood product, WHO Document A28/WP/6, May 1975. 2. Hollinger B F. Hepatitis B. In: HolIinger B F. Viral hepatitis, 2nd edn. New York: Raven Press, 1990: 73-122.
523 3. World Health Organization. Blood and blood products: Report by the Director-General, Executive Board document EB/79/Add. Geneva: WHO, 1987. 4. Britten A F. Worldwide supply of blood and blood products. World J Surg 1987; 11: 82-85. 5. Walsh J H, Purcell R H, Morrow A G, Chanock R M, Schrnidt P J. Post-transfusion hepatitis after open-heart operations. J Am Med Assoc 1979; 211: 261-265. 6. Sepfilveda A J, Garcia L G, Dom/nguez T J, Vaidespino J L. Prevencfon de la transmisi6n sanguinea del VIH: La experieucia mexicana. In: SIDA, Perfil de una Epidemia. MExico: OPS 1989: 163-172. 7. Avila C, Stetler H, Sepfilveda J e t al. The epidemiology of HIV transmission among paid donors, Mexico City. AIDS 1989; 3: 631-633. 8. Uribe F, Hem~ndez-Avila M, Conde C, Ju~ez L, Uribe P, del Rio C, De Zalduondo P. STDs prevalence among PCSW from Mexico City: A population based study. PCO353 (Abstract). International Conference on AIDS-IV STD World Congress, Berlin, Germany, 6-11 June 1993. 9. Harawi S J. Epidemiology. In: Harawi S J, O'Hara C J. Pathology and pathophysiology of AIDS and HtV-related diseases. Great Britain: Mosby 1989: 1-20. 10. Volkow P. Prrez-Padilla R, del Rio C, Mohar A. The role of plasmapheresis banks in the AIDS epidemic in Mexico. Submitted for publication. 11. Quinn T. Population migration and spread of types 1 and 2 human immunodeficiency viruses. Proc Natl Acad Sci USA 1994; 91: 2407-2414. 12. Nizilambi N, De Cock K, Forthal D N et al. The prevalence of infection with human immunodeficiency virus over a 10 year period in rural Zaire. N Engl J Med 1989; 320: 1172-1176. 13. The HIV Pandemic Status and Trends. In: Mann J, Tarantola D J M, Netter Th W, eds AIDS in the World: A Global Report. Cambridge, MA: Harvard University Press, 1992: 40-7. 14. Piot P, Quinn T C, Taelman H et al. Acquired immunodeficiency syndrome in a heterosexual population in Zaire. Lancet 1984; 2: 65-69. 15. Van Perre P, Rouvroy D, Lepage P e t al. Acquired immunodeficiency syndrome in Rwanda. Lancet 1984; ii: 6245. 16. Emmanuel J, Britten A. Reducing HIV transmission through blood. In: AIDS Prevention Handbook, pp. 70-82. 17. Jones P. AIDS: the African connection? Br Med J 1985; 290: 932. 18. Banerjee K, Rodrigues J, Kulkami S, Israel Z, Thakar M. Outbreak of HIV seropositivity among commercial plasma donors in Pune, India. Lancet 1989; ii: 166. 19. Bhimani G V, Gilada I S. HIV prevalence in people with no fixed abode--A study of blood donorship patterns and risk determinants. Proc VIII Int Conf on AIDS/STD World Congress, Amsterdam, The Netherlands, 19-24 July, 1992. 20. India confronts the epidemic. The AIDS Report (Harvard AIDS Institute) 1994; Spring: 8-t0.
The AIDS epidemic and commercial plasmapheresis P. VOLKOW Instituto Nacional de Cancerologia, San Fernando 22, CoL Tlalpan, C. P. 14000, M#xico
Abstract - - In 1986 an epidemic of HIV infection among paid plasma donors was identified in Mexico; paid donors were iatrogenically infected in a plasmapheresis center. These paid donors sold both plasma and blood: they provided one-third of blood consumed in 1986. This led to infection of blood recipients, mainly women of childbearing age. Blood transfusion is the leading cause of AIDS in women in Mexico. The male:female ratio decreased from 30:1 in 1986 to 5:1 1990; that coincided with the increase of transfusion-associated AIDS cases. Mexico prohibited the blood trade in 1987, ending the epidemic in paid donors and recipients. latrogenic infection of paid donors in plasmapheresis facilities could help to explain the explosive AIDS epidemic in central Africa and Haiti in the 1980s. There is a temporal and geographical coincidence in the early eighties between that AIDS epidemic, high numbers of hepatitis B asymptomatic carriers and an increased production of serum inactivated hepatitis B vaccine. Plasmapheresis facilities in these developing countries may have taken advantage of the high prevalence of hepatitis B asymptomatic carriers in their populations to obtain plasma for exportation through brokers to developed countries where the vaccine and other plasma products were manufactured. This hypothesis is relevant to establishing preventive policies and warrants further investigation.
Introduction
Blood and plasma industry in the worm As early as 1975, long before the discovery of AIDS, members of the World Health Organization were seriously concerned about the possible health and ethical problems involved in the trade of blood, mainly regarding plasmapheresis on a commercial basis (1). At that time, the plasmapheresis industry was already operating in Mexico, central and South America and spreading to Africa and Asia. It was an expanding industry that produced therapeutic (coagulation factors, albumin, anti-Rho immunoglobulin,
etc.), diagnostic (blood typing), and vaccine (hepatitis B serum vaccine) products. By 1990, 30 million doses of inactivated hepatitis B serum vaccine, processed by 12 manufacturers, had been administered (2). Some Pacific countries received inactivated vaccine processed in Japan in exchange for plasma positive for HBsAg. Where did the plasma to produce the vaccines used in the USA and western Europe come from? It is well documented that several developed countries bought cheap plasma and blood from developing countries (3). Developing countries consume mainly whole blood or red blood cells because
Date received 11 June 1996 Date accepted 24 October 1996
521
522 industrialized plasma derivatives are expensive (4). Plasmapheresis in poor countries was mainly used to obtain plasma for export to the USA and Europe.
MEDICALHYPOTHESES Fourth, the Mexican government prohibited blood commercialization in 1986, ending the epidemic in paid donors and, consequently, the epidemic in blood product recipients.
Commercial plasmapheresis in developing countries Commercial plasma banks exist only in cities, because the purchase of plasma is a phenomenon of areas with high rates of unemployment, characteristically located where poor rural migrants settle while searching for work (3). Paid donors in the developing world differ from those described in the USA (5); they are men and women who earn or supplement their incomes by selling plasma and who are not involved in regular illicit drug use. Intravenous drug abuse is uncommon in most of these areas of the world, since it is too costly. HIV epidemic among plasmapheresis donors in Mexico and its relation to Mexican HIV epidemic Mexico offered a unique opportunity to show how commercial plasmapheresis was capable of transmitting HIV very efficiently in a short period of time (6). First, an epidemic of HIV infection in paid plasma donors was documented in Mexico (besides the sexually transmitted HIV epidemic). HIV seroprevalence increased from 6% to 54% in only 6 months in a group of paid donors (7). Paid plasma donors in Mexico donated every month up to 12 times through apheresis in addition to one or two units of blood (8). They were probably infected during the procedure of donation by reuse of disposable material or injection of human serum. Blood recipients in developing countries are mainly women of childbearing age since the principal reasons for blood transfusion are gynecological emergencies. Transfusion has been the main risk factor for AIDS in Mexican women: in 1990 61% of AIDS in women in Mexico was associated with transfusion (4). Second, the establishment of AIDS surveillance in 1987 allowed the development of a registry of AIDS cases by different risk groups and observation of the occurrence of these cases over time. Infection of women rapidly decreased the male:female ratio of AIDS cases from 30:1 in 1986, to 5:1 in 1990 (5). Women of childbearing age infected via transfusion also contributed to perinatal AIDS. Third, the transition of the HIV epidemic to women is clearly related to blood transfusion because prostitution is not linked to drug abuse in Mexico and, as of 1994, seroprevalence in female sex workers remained low at about 2% (9). This is in contrast with countries such as the USA, where seroprevalence in prostitutes is much higher and associated with IV drug abuse (10).
Origins of global HIV epidemic It is speculated that the AIDS epidemic originated in Africa and from there it was transmitted to other countries of the world. The mechanism of AIDS dissemination in Africa has been attributed to sexual promiscuity, political instability, migration, and industrialization leading to concentration of people in urban areas (11). These hypotheses, however, are not definitely proven. I postulate that the commercial plasmapheresis industry also had a major role in the dissemination of AIDS observed in central Africa and in other countries such as Haiti and Honduras. Plasmapheresis paid donation and transfusion could have led to a rapid and efficient transmission of HIV in central Africa and Haiti where there is a high prevalence of asymptomatic hepatitis B carriers. In the early 1980s this high prevalence was attractive to the commercial plasma industry as a source of inexpensive plasma needed to produce the hepatitis B vaccine and other plasma derivatives. The price of plasma in developing countries was 10 to 20 times cheaper than in developed countries (3). The role of the hepatitis B serum vaccine in HIV dissemination is difficult to assess. The hepatitis B serum vaccine used in published and well-known trials has been considered safe for HIV infection. However, the possibility of HIV contamination of earlier or less well-known vaccine prototypes made with serum from developing countries remains. AIDS is mainly an urban phenomenon in central Africa (6,12-15). Seroprevalence in rural areas of Zaire and Rwanda has shown stability after 10 years of the AIDS epidemic. Fear of acquiring AIDS from donating blood was recognized in Africa (16) and also in Mexico in the late 1980s but is unknown in developed countries with adequate sanitary regulations. A similar process to that described in Mexico could explain the high seroprevalence among pregnant women seen in some cities of central Africa. A rapid dissemination through the infection of paid donors in plasmapheresis centers could explain the outburst of HIV infection in Africa in the early 1980s and its consequence, the AIDS epidemic in the mid-1980s. There is a geographic and temporal coincidence between the high number of hepatitis B carriers, the extended program of vaccination with serum inactivated hepatitis B vaccine, and the aforementioned explosion of the HIV epidemic in
AIDS AND PLASMAPHERESIS
the mid-1980s. Plasmapheresis banks were located in Kinshasha, Zaire, other central African countries, and in Port-au-Prince, Haiti, and plasma reached developed countries through plasma brokers (17). Haiti had at least one plasmapheresis bank, the Caribbean Plasmapheresis Bank, which was apparently closed in 1975; however, in 1985, Haiti and Honduras still appeared as countries in America with 'blood trade' (3). In the mid-1980s, commercial plasmapheresis in Africa and other countries may have decreased mainly because of concern about transmission of AIDS and because of the availability of recombinant hepatitis B vaccine. Plasmapheresis industries moved away from areas with high HIV infection prevalence to other places with lower prevalence, such as India. In this context, the situation in India is also consistent with this hypothesis. In the last 4 years, the male to female ratio of AIDS cases has steadily decreased towards unity in regions with a known plasmapheresis industry where outbreaks of HIV infection in paid donors have been described (18,19). However, in India, intravenous drug abuse and prostitution have also played a prominent role in dissemination of the HIV epidemic (20). In summary, we observed in Mexico a very efficient mechanism of HIV transmission through the infection of paid donors in plasmapheresis banks. Those centers did not comply with standard sanitary regulations. Sometimes HIV screening was lacking or positive donors were not rejected. Each donor provided multiple donations each month that infected mainly women of childbearing age. Plasmapheresis banks could have played a major role in the dissemination of HIV-1 in Haiti and Central Africa. This hypothesis is relevant to establishing preventive policies and warrants further investigation.
References 1. Utilization and supply of human blood and blood product, WHO Document A28/WP/6, May 1975. 2. Hollinger B F. Hepatitis B. In: HolIinger B F. Viral hepatitis, 2nd edn. New York: Raven Press, 1990: 73-122.
523 3. World Health Organization. Blood and blood products: Report by the Director-General, Executive Board document EB/79/Add. Geneva: WHO, 1987. 4. Britten A F. Worldwide supply of blood and blood products. World J Surg 1987; 11: 82-85. 5. Walsh J H, Purcell R H, Morrow A G, Chanock R M, Schrnidt P J. Post-transfusion hepatitis after open-heart operations. J Am Med Assoc 1979; 211: 261-265. 6. Sepfilveda A J, Garcia L G, Dom/nguez T J, Vaidespino J L. Prevencfon de la transmisi6n sanguinea del VIH: La experieucia mexicana. In: SIDA, Perfil de una Epidemia. MExico: OPS 1989: 163-172. 7. Avila C, Stetler H, Sepfilveda J e t al. The epidemiology of HIV transmission among paid donors, Mexico City. AIDS 1989; 3: 631-633. 8. Uribe F, Hem~ndez-Avila M, Conde C, Ju~ez L, Uribe P, del Rio C, De Zalduondo P. STDs prevalence among PCSW from Mexico City: A population based study. PCO353 (Abstract). International Conference on AIDS-IV STD World Congress, Berlin, Germany, 6-11 June 1993. 9. Harawi S J. Epidemiology. In: Harawi S J, O'Hara C J. Pathology and pathophysiology of AIDS and HtV-related diseases. Great Britain: Mosby 1989: 1-20. 10. Volkow P. Prrez-Padilla R, del Rio C, Mohar A. The role of plasmapheresis banks in the AIDS epidemic in Mexico. Submitted for publication. 11. Quinn T. Population migration and spread of types 1 and 2 human immunodeficiency viruses. Proc Natl Acad Sci USA 1994; 91: 2407-2414. 12. Nizilambi N, De Cock K, Forthal D N et al. The prevalence of infection with human immunodeficiency virus over a 10 year period in rural Zaire. N Engl J Med 1989; 320: 1172-1176. 13. The HIV Pandemic Status and Trends. In: Mann J, Tarantola D J M, Netter Th W, eds AIDS in the World: A Global Report. Cambridge, MA: Harvard University Press, 1992: 40-7. 14. Piot P, Quinn T C, Taelman H et al. Acquired immunodeficiency syndrome in a heterosexual population in Zaire. Lancet 1984; 2: 65-69. 15. Van Perre P, Rouvroy D, Lepage P e t al. Acquired immunodeficiency syndrome in Rwanda. Lancet 1984; ii: 6245. 16. Emmanuel J, Britten A. Reducing HIV transmission through blood. In: AIDS Prevention Handbook, pp. 70-82. 17. Jones P. AIDS: the African connection? Br Med J 1985; 290: 932. 18. Banerjee K, Rodrigues J, Kulkami S, Israel Z, Thakar M. Outbreak of HIV seropositivity among commercial plasma donors in Pune, India. Lancet 1989; ii: 166. 19. Bhimani G V, Gilada I S. HIV prevalence in people with no fixed abode--A study of blood donorship patterns and risk determinants. Proc VIII Int Conf on AIDS/STD World Congress, Amsterdam, The Netherlands, 19-24 July, 1992. 20. India confronts the epidemic. The AIDS Report (Harvard AIDS Institute) 1994; Spring: 8-t0.