Journal of the InterAmerican Medical and Health Assn.
January-April 1992, Vol.1, No.1
IMMUNE IMPAIRMENT AND THE HYPOTHESIS OF THE "ACQUIRED IMMUNE DEFICIENCY CYCLE"Dr. Maurizio Luca Moretti
ABSTRACTBased on the fact that infection, malnutrition, and immunosuppression are well-known causes of immune impairment, their effects in the host are being reviewed. The findings suggest that infection, malnutrition, and immunosuppression can interact as synergistic causes of immune impairment, and could also be components of a cycle capable of inducing immune impairment. Based on these findings, it has been hypothesized that the "Acquired Immune Deficiency Cycle" (AIDC) is a physiological cycle that could be a primary cause of temporary, chronic, or congenital immune impairment.
INTRODUCTION
Various degrees of immune impairment have been found among HIV-seronegative individuals at high risk for the Acquired Immune Deficiency Syndrome (AIDS); namely, HIV-seronegative hemophiliacs (1-13), HIVseronegative homosexual and bisexual males (14-26), HIV-seronegative intravenous drug users (IVDUs) and their infants (22,27-31), and HIV-seronegative heterosexuals of developing countries (32). These findings strongly suggest that the subjects' immune impairment is a result of factor(s) other(s) than Human Immunodeficiency Virus (HIV) infection (33,34) .
Three major adverse factors have been shown to be common among individuals at high risk for AIDS; namely, increased risk of infection (1,3,15,20-22,25,30,32,35-73), increased risk of malnutrition (31-34,72,74-98), and increased risk of immunosuppression (1,7,10,12,18,31-34,38-40,82-89,99-108). This is not surprising since a number of habitual practices by individuals at high risk for AIDS are potential causes of infections (32-34,64-73,84-98,109-133), malnutrition (109-111,134-156), and immunosuppression (1,7,10,12,18,31-34,38-40,82-89,99-108).
Therefore, it is important to realize that infection (35-37,157-211), malnutrition (212-248), and immunosuppression (1,7,10,12,18, 38-40,99-108) are major causes of immune impairment (1,7,10,12,18,24,35-40,99-108,157-248).
When the effects of infection, malnutrition, and immunosuppression are further analyzed, it can be observed that they can interact as synergistic causes of immune impairment.
INFECTION, MALNUTRITION, AND IMMUNOSUPPRESSION AS SYNERGISTIC CAUSES OF IMMUNE IMPAIRMENT
I. INFECTION
Infection can cause both immunosuppression (35-37,157-204) and malnutrition (109-111,134-151). As a result, the induced malnutrition can cause immunosuppression or increase a current immunosuppression (126,127,212-233,235-253). The induced immunosuppression can cause both increased frequency and severity of infection(s), and out-break of opportunistic disease(s) (109,212,254-261) .
II. MALNUTRITION
Malnutrition can cause immunosuppression (126,127,212-233,235-253). As a result, the induced immunosuppression can cause both increased frequency and severity of infection(s) and out break of opportunistic disease(s) (109,212,254-261). The induced infection can cause both immunosuppression (35-37,157-204) and malnutrition (109-111,134-151) .
III. IMMUNOSUPPRESSION
Immunosuppression can cause both increased frequency and severity of infection(s) and out-break of opportunistic disease(s) (109,212,254-261). As a result, the induced infection can cause both immunosuppression (35-37,157-204) and malnutrition (109-111,134-151). It seems reasonable, therefore, to conclude that infection, malnutrition and immunosuppression not only can interact as synergistic causes of immune impairment, but also could be components of a physiological cycle capable of inducing immune impairment in the host. Based on these findings, the following is hypothesized about the "Acquired Immune Deficiency Cycle" (AIDC).
HYPOTHESIS
The Acquired Immune Deficiency Cycle
(Figure I)
AIDC Characteristics
Structure. The Acquired Immune Deficiency Cycle (AIDC) comprises three synergistic components: infection, malnutrition, and immunosuppression.
External Activation. AIDC can be activated through its components by an external activating factor (EAF), specifically a potential cause of infection, malnutrition, or immunosuppression .
Internal Activation. AIDC can be self-activated through its components by an internal activating factor (IAF), specifically an AIDC component currently activated by a condition of infection, malnutrition, or immunosuppression.
Inactivation. AIDC can become inactive when both EAFs and IAFs are neutralized. Then the organism itself, under normal physiological and psychological conditions, should correct the immune impairment caused by AIDC's activation.
Adverse effects. Depending on the frequency and intensity of its activation, AIDC can be a primary cause of a temporary, chronic, or congenital immune impairment in the host.
The following explanation of AIDC's mechanism may offer approaches to better understand how AIDC could be activated through specific activating factors (AFs), which are common among individuals at high risk for AIDS (1,7,10,12,18,31-34,38-40,64-73,82-156). However, it is imperative to consider that AIDC's adverse effects on the immune system would not be limited only to individuals at high risk for AIDS.
I. AIDC's INFECTION COMPONENT ACTIVATION
AIDC could be activated through its infection component by the following AFs, which are common among individuals at high risk for AIDS, because many of their habitual practices are potential causes of infections (32-34,64-73,84-98,109-133). Consequently, individuals at high risk for AIDS are also at increased risk for infections (1,3,15,20-22,25,30,32,35-73). The following illustrate specific examples of potential causes of either symptomatic or asymptomatic infection.
(A) Intravenous drug addiction is a potential cause of infections. These can be caused by the following: (a) The injection of contaminated "street drugs" (84,85,90) into the bloodstream. (b) The use of a contaminated needle or syringe (124,125) .
(B) The sexual practice of anal intercourse is a potential cause of infections. These can be caused by the following: (a) The contact of genital mucosa with intestinal microorganisms contained in fecal material (91-98) (Table I) during this practice. (b) The contact of genital mucosa with a causative microorganism(s) of anorectal sexually transmitted diseases (114-123) (Table II).
(C) Vaginal intercourse, fellatio, or cunnilingus, if at least one partner is at high risk for AIDS, are potential causes of infections. These can be caused by the following: (a) Heterosexual or orogenital contact with a partner who is at high risk for AIDS (1,3,15,20-22,25,30,32,35-73). (b) Heterosexual orogenital transmission of causative microorganisms of sexually transmitted diseases (114-118).
(D) The practice of "anilingus" is a potential cause of infections. These can be caused by contact of oral mucosa with intestinal microorganisms contained in fecal material (91-98) (Table I).
(E) Erotic activity, such as fist fornication (commonly known as "fisting") is a potential cause of infections. This practice consists of receiving into the rectal cavity the insertion of the sexual partner's hand, up to the wrist and even the forearm (126,262). These infections can be caused by intestinal microorganisms contained in one's own fecal material (91-98) (Table I) through abrasion(s) and/or laceration(s) of the anus and/or rectum resulting from this practice (127).
(F) Erotic activity such as the insertion of object(s) into the anus and rectum (128,129), is a potential cause of infection(s) . These are caused by intestinal microorganisms contained in one's own fecal material (91-98) (Table I) through tissue laceration of the anus and/or the rectum resulting from this practice (129,130).
Table I INFECTIONS TRANSMITTED BY CONTACT WITH FECAL MATERIAL Causative organism DISEASE Campylobacter GASTROENTERITIS AND OTHERS (183) Hepatitis A virus HEPATITIS A (178) Shigella SHIGELLOSIS (179) Salmonella Typhi TYPHOID FEVER (180) Entamoeba histolytic AMEBIASIS (181) Cryptosporidia CRYPTOSPORIDIOSIS (182) Giardia lamblia GIARDIASIS (184) Enterobius vermicularis PINWORM INFESTATION (185)
Table II SEXUALLY TRANSMITTED DISEASES Causative organism Sexual contact Disease Neisseria gonorrhoea Heterosexual
Anorectal
OrogenitalGONORRHEA (209)
RECTAL GONORRHEA (209)Treponema pallidum Heterosexual
Anorectal
OrogenitalSYPHILIS (210)
RECTAL SYPHILIS (210)Chlamydia trachomatis Heterosexual
AnorectalLYMPHOGRANULOMA (211)
VENEREUM (211)Herpes simplex virus Heterosexual
AnorectalGENITAL HERPES (212)
ANOGENITAL HERPES (212)Human papilloma virus Heterosexual
AnorectalGENITAL WARTS (213) Gonococci Anal-receptive
intercoursePROCTITIS (214) Human papilloma virus Anal-receptive
intercoursePROCTITIS (215) Herpes simplex virus Anal-receptive
intercoursePROCTITIS (216) Syphilis Anal-receptive
intercoursePROCTITIS (217) Chlamydia trachomatis Anal-receptive
intercoursePROCTITIS (218) (G) Erotic activity such as the use of enemas (klismaphilia, commonly known as "water sports") for erotic or erotic-hygienic purposes before and/or after anal intercourse, (86-89) is a potential cause of infections. Improper insertion of the nozzle, during this practice, can cause laceration of the anus and/or rectal mucosa (131,132), or possible perforation of the rectal wall (228) allowing infections by intestinal microorganisms contained in one's own fecal material (91-98) (Table I).
(H) The use of commercial clotting factors is a potential cause of infections. These are caused by pathogenic microorganism(s) disseminated in the plasma pools used to elaborate commercial clotting factors (112). These pathogenic microorganisms are still undetectable during blood screening due to limitations of current technology (113) .
(I) Pregnancy under adverse conditions such as current infectious disease(s), is a potential cause of vertical transmission of infection(s). Vertical transmission of infections is common among the fetuses of mothers at high risk for AIDS (64,67).
(J) Infections are common among the populations of developing countries (32,68-73,109-111) in which infections and their associated immune impairment (32,35 37,157-211) are main causes of the high mortality rates (263) .
As a consequence of one of the previous AFs, the AIDC's activated infection component could act as an IAF of both immunosuppression (35-37,157-204) and malnutrition (109-111,134-151) AIDC's components. As a result, the induced immunosuppression could act as IAF to cause both increased frequency and severity of infection(s) and out-break of opportunistic disease(s) (109,212,254-261). Thus, the induced malnutrition could act as IAF to cause immunosuppression or increase a current one (126,127,212-233,235-253).
II. AIDC's MALNUTRITION COMPONENT ACTIVATION
AIDC could be activated through its malnutrition component by the following AFs, which are common among individuals at high risk for AIDS, because many potential causes of malnutrition (109-111,134-156) are common among individuals at high risk for AIDS (1,3,15,20-22,25,30,32-81,109-111,152,156, 263-265). Consequently, individuals at high risk for AIDS have increased risk for malnutrition (31-34,72,74-98). The following illustrate some specific examples.
(A) Infection(s) cause malnutrition (109111,134-151) and infections are common among individuals at high risk for AIDS (1,3,15,20 22,25,30,32,35-73).
(B) Diarrheal diseases are causes of malnutrition (153-155) and diarrhea! diseases are common among individuals at high risk for AIDS (32,72,74-81). This is because most of the infections caused by intestinal microorganisms contained in fecal material (91-98) (Table I) also can cause chronic diarrhea, which is a cause of malabsorption and consequentially malnutrition (153-155).
(C) Bleeding, a potential cause of malnutrition, is common among hemophiliacs (152) and homosexual men (rectal bleeding) (156) .
(D) Malnutrition is common among the populations of developing countries (263-265) in which malnutrition and its associated immune impairment (126,127,212-233,235 -253) are main causes of a high mortality rates (263) .
As a consequence of one of the previous AFs, the AIDC's activated malnutrition component could act as an IAF of immunosuppression (126,127,212-233,235-253) AIDC's component. As a result, the induced immunosuppression could act as IAF to cause both increased frequency and severity of infection(s) and out-break of opportunistic disease(s) (109,212,254-261).
III. AIDC's IMMUNOSUPPRESSION COMPONENT ACTIVATION
AIDC could be activated through its immunosuppression component by the following AFs, which are common among individuals at high risk for AIDS, because many of their habitual practices are potential causes of immunosuppression (1,7,10,12,18,31-34,38-40,82-89,99-108). The following illustrate some specific examples.
(A) Injection of "foreign substances" contained in " street drugs" (84,85), or heroin itself (even if 100% pure) (31,82,83) into the bloodstream has immune suppressive effects (31,82-85).
(B) Exposure of rectal mucosa to seminal plasma has immune suppressive effects (18, 37,40,102-108).
(C) Use of an enema with up to four gallons of water for erotic purposes (klismaphilia, commonly known as "water sports" ), or erotic-hygienic purposes before and/or after anal intercourse (86-89) has immune suppressive effects. The immune suppressive effects are caused by an abnormal elimination of antibodies from the intestinal mucosa due to the mechanical action of the water used during the enema.
(D) Use of commercial clotting factors has immune suppressive effects. These are caused by chronic exposure to multiple protein antigens and immune complexes contained in pooled-blood products derived from thousands of donors (1,7,10,12,38,99-101).
(E) Pregnancy during current immune impairment or current drug abusing practice has immune suppressive effects on the fetus (31).
(F) Immunosuppression (31) and its associated immune impairment (1,7,10,12,18, 38-40,99-108) are common among the populations of developing countries (31,32) where these are the predominate causes of high mortality rates (263).
As a consequence of one of the previous AFs, the AIDC's activated immunosuppression component could act as IAF of infection (109,212,254-261) AIDC's component, through both increased frequency and severity of infection(s) and out-break of opportunistic disease(s). As a result, the induced infection could act as a IAF to cause both immunosuppression (35-37,157-204) and malnutrition (109-111,134-151).
PROSPECT
Based on a unanimous consensus of the importance to avoid immune impairment, we are confident that the understanding and control of AIDC's activation could be an invaluable tool in the prevention and treatment of its associated immune impairment. The prevention of AIDC's activation should be achieved through the avoidance of AIDC's AFs, specifically potential causes of infection, malnutrition, and immunosuppression. The treatment of AIDC's associated immune impairment should be achieved through AIDC's inactivation by a multi-disciplinary effort to control the patient's current infection(s), malnutrition, and immunosuppression, thus avoiding their consequential immune impairment. If this could be achieved, the high mortality rate associated with immune impairment, through increased risk of infections, should be expected to decrease dramatically.
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