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A new approach to the etiopathogenesis of AIDS
Medical Hypotheses
A New Approach to the Etiopathogenesis
of Al DS
J. L. SCAR0 National
University of Jujuy, Department
of Erital (CONICET),
4600 San S de Jujuy, Argentina
Abstract-This hypothesis proposes as an explanation for the origin of the Acquired Immune-Deficiency Syndrome (AIDS), the homosexual transmission of spermatozoons. The male gamete may possess a depressing action on the immuno-competence of the egg aimed to prevent the rejection of the spermatozoon material. The female organism may be able to inactivate this action, an ability that might be absent in the male organism. As a consequence of the loss of its immunological competence, the body is invaded by a variety of microorganisms, among which certain elemental classes of viruses would strive successfully for long periods of time. Their permanence in the depressed organism would enable them to overcome the immune barriers present in normal subjects, becoming thus, transmissible and in some cases even pathogenic for the new host.
Introduction AIDS, the most serious epidemic disease of modem medicine, has caused a global response of scientists in search of means for controlling its expansion (1, 2, 3). However, in spite of the vast amount of information now available, no significant progress has been made in the understanding of the biology of the viruses involved. Researchers now are scrutinizing its molecular details looking for a more meaningful understanding of the behavior of these viruses that prove so peculiar and far removed from other families of these agents. On the other hand, the immunological side of the disease has not yet received the same intense consideration. Problems with the existing theory Two species of AIDS viruses have already clearly been recognized through their genetic differences and
both were found pathogenic, the HIV1 and HIVZ The first is overwhelmingly responsible for AIDS in the United States, whereas the second though more frequently found in Africa, is now expanding to other arcas. Among the obstacles to designing a vaccine is the ability of both classes of viruses to mutate and hide in immune cells. The concept that the transmission of the virus occurs by the transfer of body fluids containing infected blood cells, is compatible with the transmission via blood transfusion and through the use of non sterile syringe needles. However, the infection of male homosexuals, which is the largest group of individuals with high risk of infection with HIV1 and ultimate development of the disease, is only inferential. In this case, it is assumed that the infected cells get access into the circulation through minor lesions of the rectal membrane. This explanation also implies the existence of bleeding areas in the male genital
Date received 30 January 1993 Date accepted 7 April 1993
306
THE ETIOPATHOGENESIS
307
OF AIDS
New hypothesis
explained by this hypothesis as those means prevent the spermatozoon from invading another male organism. The recent observations using the Polymerase Chain Reaction to detect the presence of pro virus sequences in the saliva (Z-8) support the possibility that the salival route may have a significant share in the transmission of the infection. The large number of AIDS cases in Africa as well as in India, which are associated with the presence of the HIV2 virus, could be interpreted as caused originally by the deterioration of the immunologic system, which is due to the severe degree of malnutrition existing in these areas. The development of the disease in this case, in addition to its affecting a large number of children, shows no difference in the proportion of male and female subjects which is in line with the fact that malnutrition affects all ages and both sexes in equal proportion (9).
There are facts that support the possibility that homo-
Conclusion
tract to make possible the mixture of the seminal fluid with traces of blood containing the infected cells. The high incidence of the disease in this group contmdicts the admitted practical absence of transmission through the saliva1 route. It is widely admitted that the virus is not transmitted by this means, and yet there is a far greater probability that the gums should bleed than there is of the existence of bleeding in the male genital or gastrointestinal tracts. Also, the wide occurrence of mouth to mouth kisses adds doubts to the appropriateness of excluding this means as a significant route of the transmission. There is no clear explanation for the continuously expanding gap between the number of infected subjects and the number that develop AIDS. Neither is the notion of the AIDS Related Complex (4) in patients that develop AIDS in the absence of the virus at all clear.
sexual transmission of spermatozoans could play a role in the production of the acquired immunodeficiency syndrome. This hypothesis is in line with the well known fact that the male gamete contains in its head substances capable of inducing a change in the egg membrane that prevent the entrance of a second spermatozoon. This fact gives ground to suggest the presence in the male gamete of other factors or substances capable of causing a temporary immunological paralysis in the egg, aimed at preventing the rejection of the spermatozoon as their materials have obviously different antigenic identities. After fertilization has taken place, female individuals would be able to neutralize or eliminate the immune depressing action contributed by the spermatozoon. This ability would not have developed in the male, who, after repetitive exposures to the mentioned depressing action would end up with the loss of his immunologic competence. The existence of viral forms of life greatly depends on their ability to overcome the biological barriers of the infected subject. Once this barrier deteriorates or disappears, virus families with low virulence and complexity can invade and proliferate in the defenseless organism. The virus at this stage of the disease would mutate actively, turning into more complex forms capable of being transmitted and even to become dangerously pathogenic or even lethal for the infected individual. However, such virus infections would not be the cause of the immune depression, but its consequence. The effectiveness of condoms and spermaticide substances to reduce the risk of contamination can be
If there is any essence of truth in this hypothesis, then the center of attention should be focused on the prevention’of the immuno-deficiency syndrome which, once acquired, by either of the ways here proposed, would turn the human body into a living Petri dish filled with the optimal cultural medium for elemental and dangerous forms of life. References
5.
6.
I.
8.
9.
Chin .I. Current and future dimensions of the HIV/AIDS pandemic in women and children. Lancti 1990; 336: 221. Center for Disease Control. Mortality attributable to HIV/AIDS United States 1981-1990. MM WR 1990. Moss A R, Baccheai P. The natural history of HIV infection. AIDS 1989; 3: 55. Groopman J E. Salahuddin S Z, Samgdharan M G et al. HTLV-III in saliva of people with AIDS-Related Canplex and healthy homosexual men at risk for AIDS. Science 1984, 226: 441. Holodniy M, Kazenstein D A, Sengupta S et al. Detection and quantification of human immuno-deficiency virus RNA by use of the Polymerase Chain Reaction. J Infect Dis 1991; 163(4): 862. Fenouillet E, Sorensen A M, Lacroix M et al. Early and specific diagnosis of seropositivity to HIV by an enzyme-linked immunoabsorbmt assay. AIDS 19W; 4(11): 1137. Yasumiro Gota, Chi-Ko Yeh, Notkins A L, Prabbakar N S. Detection of proviral sequences in saliva of patients infected with Human Immuno-Deficiency virus type 1. AIDS Research and Human Retrovirus, 1991; 3: 343. Kestem L. Brattegard K, Adjorlolo G et al. Immunological canparison of HIVI, HIV2 in dually-reactive women delivering in Abidjan, Cote d’lvoire. AIDS 1992, 6: 803. Rrettle R P, Len C D. Tbe natural history of HIV and AIDS in women. Editorial. AIDS 1991; 5(11): 1283.
A New Approach to the Etiopathogenesis
of Al DS
J. L. SCAR0 National
University of Jujuy, Department
of Erital (CONICET),
4600 San S de Jujuy, Argentina
Abstract-This hypothesis proposes as an explanation for the origin of the Acquired Immune-Deficiency Syndrome (AIDS), the homosexual transmission of spermatozoons. The male gamete may possess a depressing action on the immuno-competence of the egg aimed to prevent the rejection of the spermatozoon material. The female organism may be able to inactivate this action, an ability that might be absent in the male organism. As a consequence of the loss of its immunological competence, the body is invaded by a variety of microorganisms, among which certain elemental classes of viruses would strive successfully for long periods of time. Their permanence in the depressed organism would enable them to overcome the immune barriers present in normal subjects, becoming thus, transmissible and in some cases even pathogenic for the new host.
Introduction AIDS, the most serious epidemic disease of modem medicine, has caused a global response of scientists in search of means for controlling its expansion (1, 2, 3). However, in spite of the vast amount of information now available, no significant progress has been made in the understanding of the biology of the viruses involved. Researchers now are scrutinizing its molecular details looking for a more meaningful understanding of the behavior of these viruses that prove so peculiar and far removed from other families of these agents. On the other hand, the immunological side of the disease has not yet received the same intense consideration. Problems with the existing theory Two species of AIDS viruses have already clearly been recognized through their genetic differences and
both were found pathogenic, the HIV1 and HIVZ The first is overwhelmingly responsible for AIDS in the United States, whereas the second though more frequently found in Africa, is now expanding to other arcas. Among the obstacles to designing a vaccine is the ability of both classes of viruses to mutate and hide in immune cells. The concept that the transmission of the virus occurs by the transfer of body fluids containing infected blood cells, is compatible with the transmission via blood transfusion and through the use of non sterile syringe needles. However, the infection of male homosexuals, which is the largest group of individuals with high risk of infection with HIV1 and ultimate development of the disease, is only inferential. In this case, it is assumed that the infected cells get access into the circulation through minor lesions of the rectal membrane. This explanation also implies the existence of bleeding areas in the male genital
Date received 30 January 1993 Date accepted 7 April 1993
306
THE ETIOPATHOGENESIS
307
OF AIDS
New hypothesis
explained by this hypothesis as those means prevent the spermatozoon from invading another male organism. The recent observations using the Polymerase Chain Reaction to detect the presence of pro virus sequences in the saliva (Z-8) support the possibility that the salival route may have a significant share in the transmission of the infection. The large number of AIDS cases in Africa as well as in India, which are associated with the presence of the HIV2 virus, could be interpreted as caused originally by the deterioration of the immunologic system, which is due to the severe degree of malnutrition existing in these areas. The development of the disease in this case, in addition to its affecting a large number of children, shows no difference in the proportion of male and female subjects which is in line with the fact that malnutrition affects all ages and both sexes in equal proportion (9).
There are facts that support the possibility that homo-
Conclusion
tract to make possible the mixture of the seminal fluid with traces of blood containing the infected cells. The high incidence of the disease in this group contmdicts the admitted practical absence of transmission through the saliva1 route. It is widely admitted that the virus is not transmitted by this means, and yet there is a far greater probability that the gums should bleed than there is of the existence of bleeding in the male genital or gastrointestinal tracts. Also, the wide occurrence of mouth to mouth kisses adds doubts to the appropriateness of excluding this means as a significant route of the transmission. There is no clear explanation for the continuously expanding gap between the number of infected subjects and the number that develop AIDS. Neither is the notion of the AIDS Related Complex (4) in patients that develop AIDS in the absence of the virus at all clear.
sexual transmission of spermatozoans could play a role in the production of the acquired immunodeficiency syndrome. This hypothesis is in line with the well known fact that the male gamete contains in its head substances capable of inducing a change in the egg membrane that prevent the entrance of a second spermatozoon. This fact gives ground to suggest the presence in the male gamete of other factors or substances capable of causing a temporary immunological paralysis in the egg, aimed at preventing the rejection of the spermatozoon as their materials have obviously different antigenic identities. After fertilization has taken place, female individuals would be able to neutralize or eliminate the immune depressing action contributed by the spermatozoon. This ability would not have developed in the male, who, after repetitive exposures to the mentioned depressing action would end up with the loss of his immunologic competence. The existence of viral forms of life greatly depends on their ability to overcome the biological barriers of the infected subject. Once this barrier deteriorates or disappears, virus families with low virulence and complexity can invade and proliferate in the defenseless organism. The virus at this stage of the disease would mutate actively, turning into more complex forms capable of being transmitted and even to become dangerously pathogenic or even lethal for the infected individual. However, such virus infections would not be the cause of the immune depression, but its consequence. The effectiveness of condoms and spermaticide substances to reduce the risk of contamination can be
If there is any essence of truth in this hypothesis, then the center of attention should be focused on the prevention’of the immuno-deficiency syndrome which, once acquired, by either of the ways here proposed, would turn the human body into a living Petri dish filled with the optimal cultural medium for elemental and dangerous forms of life. References
5.
6.
I.
8.
9.
Chin .I. Current and future dimensions of the HIV/AIDS pandemic in women and children. Lancti 1990; 336: 221. Center for Disease Control. Mortality attributable to HIV/AIDS United States 1981-1990. MM WR 1990. Moss A R, Baccheai P. The natural history of HIV infection. AIDS 1989; 3: 55. Groopman J E. Salahuddin S Z, Samgdharan M G et al. HTLV-III in saliva of people with AIDS-Related Canplex and healthy homosexual men at risk for AIDS. Science 1984, 226: 441. Holodniy M, Kazenstein D A, Sengupta S et al. Detection and quantification of human immuno-deficiency virus RNA by use of the Polymerase Chain Reaction. J Infect Dis 1991; 163(4): 862. Fenouillet E, Sorensen A M, Lacroix M et al. Early and specific diagnosis of seropositivity to HIV by an enzyme-linked immunoabsorbmt assay. AIDS 19W; 4(11): 1137. Yasumiro Gota, Chi-Ko Yeh, Notkins A L, Prabbakar N S. Detection of proviral sequences in saliva of patients infected with Human Immuno-Deficiency virus type 1. AIDS Research and Human Retrovirus, 1991; 3: 343. Kestem L. Brattegard K, Adjorlolo G et al. Immunological canparison of HIVI, HIV2 in dually-reactive women delivering in Abidjan, Cote d’lvoire. AIDS 1992, 6: 803. Rrettle R P, Len C D. Tbe natural history of HIV and AIDS in women. Editorial. AIDS 1991; 5(11): 1283.