Medical Hypotheses


Medical Hypotheses (1992) 39, 225-228

Longman Group UK Ltd 1992



Pre-existing Chronic Infraepithelial Trichomonas Invasion with Consecutive Immunodepression Enables Progression of Human Immunodeficiency Virus: A New Concept of Acquired Immunodeficiency Syndrome Pathogenesis


S. KRVAVAC

<>Notice: With correction of printing errors which alter the meaning of a sentences. The correction is not done on time because of the author's war isolation in Sarajevo in the 1992-1995.

Public Health Center Stari Grad, 71000 Sarajevo, Bosnia



Abstract – All three existing species of human trichomonads cause similar immune and histopathological host responses. The elicited crossimmunity causes interspecific competition of trichomonal infections in their typical localizations, which results in very rare simultaneous colonization of the same host by different species. This phenomenon points to the existence of a unique immune disorder or subclinical sensitization, regardless of which trichomonas species is in question. The total percentage of infestations in all three species points to the most widespread parasitosis, i.e. the immunodepression of human beings. Trichomonaemia has a very strong immunodepressive action. All the other agents, including viruses act only as opportunists.

Introduction


The author’s own clinical observations of the phenomena connected with the Trichomonas/man interactions (especially trichomonaemia), the voluminous literature about Trichomonas (T) infections and acquired immunodeficiency syndrome (AIDS), the frequent presence of antitrichomonal antibodies in male homosexuals (1) in contrast to the enigmatic complete absence of T infections reports in AIDS patients, suspicion of the dominant role of viruses in AIDS etiology (2), and finally, a very suggestive rejection of viral AIDS concept (3), have inspired creation of the T/AIDS concept.

 

Today dominates the opinion that Ts are mucous ectoparasites and that there exist 3 human species: T vaginalis, T hominis (intestinalis) and T tenax (oralis). In one report about rectal infestion with morphologically different parasites in a male patient (however without the evidence of eventual homosexuality) the author suggests the existence of a new T species, Trichomonas fecalis (4).

 

Ts appear in two biological forms (or morphophysiological states): flagellary motile trophoziotes and aflagellary motionless pseudocystic form. The former are more frequently the subject of scientific and practical observations, while the latter are rarely reported in literature, although practitioners find them frequently in urogenital, digestive and upper parts of respiratory tract. As the aflagellary T forms have bee found in various secretions of patients affected by totally different diseases, as well as in healthy looking individuals, they are considered to be saprophytes. However, there is clinical, immunological and experimental evidence that all of the T species are evoking the host immune response (5). It imposes a justified question; is it correct to consider the agents which activate the immune apparatus of the host, as saprophytes, as is a case with Ts? Furthermore, is aflagellary form a result of activity of the host immune system which controls invasiveness of parasites by the immune forces? These conclusions result from the fact that the host rapidly produce antiflagellary antibodies, thus causing regression of Ts to their aflagellary pseudocystc forms. In fact, if an agent causes sensitization of the host, then it could not, from the biological point of view, be taken as saprophyte or commensal. Progress in immunology during the last decades obligates us to revise our attitude and requires stricter criteria for separation of parasites and saprophytes.


Hypothesis


The existence of common antigens in all three human species has been proved (6). Besides the immune responses there are similar histopathological responses in experimental animals and in human pathological materials (7). Host reactions vary from one to another T species only quantitatively. From the immunobiological point of view, common antigens together with the consequent crossimmunity, push into the background the existing morphological differences between distinct T species. Protective crossimmunity explains the clinically observed competition between T infections of the distant organs (8,9). The already established infection with a T species in a single organ, in the condition of good host immune status, disables establishing of the infection with some other T species on the remote organ. Therefore, a similar histopathological and immune host responses suggest the idea of a unique infective immune disturbance, disregarding which T species is in question. The incidence of all T species infections varies considerably according to reports from different geographic areas, but the total percentage of infections (including all species) suggests the conclusion that more than one third of the total human population has been infected by some of the T species. That is a reason I believe it is without question the most widespread immunity disorder.

 

During the last 6 decades several reports and opinions on trichomonaemia have appeared  (10-13) but this phenomenon has never been scientifically clarified, nor have its pathological consequences recognized. According to my observations trichomonaemia is not a rare event though it is most frequently transient and short lasting.

 

That is the reason it is out of scientist’s attention (14). After entering the circulation Ts come into close contact with the immune apparatus which results in maximal sensitization and consequently the parasite suppression from circulation. The host pathologic response characteristics depend on the parasite virulence, the innate and acquired host resistance as well as on the function and structure of the affected organs. Mechanism of parasite expulsion, mostly mediated by mucus secretion and which is evolutionarily determined, established most frequently in some organ of the upper respiratory tract (nose, pharynx, larynx). Penetration of trichomonal toxins or even parasites themselves may affect the function and structure of distant organs including central nervous system (CNS) (15). A single report about pathogenic activity of Ts in CNS of experimental animals (16) describes morphological changes which are strikingly similar to those of CNS in AIDS (17). Frequent genital trichomoniasis during pregnancy (up to 25%) enables peripartal infection of fetus or newborn, and especially in case of the premature and transient ruptures of membranes can cause congenital infection or just sensitization. Too intense challenge of the immune apparatus in the early fetal period may cause damage and consequently the insufficiency of the immunity in the newborn. Therefore, Ts may participate in, if not even initiate, pathogenesis of congenital immunodeficiencis or some other diseases (18) characterized by the increased susceptibility to different other infections. The unrecognized Ts may at least participate as a cofactor in pathogenesis of some diseases in adults (19,20).

 

In the cases of prepartal genital trichomoniasis and massive partal damages of genital mucous membranes, parasites may penetrate into circulation (trichomonaemia) and later cause lactoparasitosis (personal unpublished observations). In that way, expulsion of aflagellary Ts may occur through the breast, i.e. milk, which explains vertical mother-to-child transmission of the immunodepressive agents or AIDS. Anatomical characteristics of the female external genitals are responsible for the higher incidence of peripartal transmission of AIDS in girls (21). Genital Ts have the strongest pathogenicity, while the oral have the weakest, but all species obligatorily cause sensitization even when they are localized intraluminaly in hollow organs. It appears that the more caudal localization of parasites results in a higher virulence. It is probably the consequence of biological fact that urogenital and distal parts of digestive tract, as excretory organs, possess higher immunobiological resistance which results in the selection of more virulent Ts. This biological mechanism may rasultin the creation of the rectal and subpreputial T strains, which may explain a close relationship between homosexuality and uncircumcised state of males. (accompanied with poor hygiene) with immunodeficiency.

 

It is well known empirical fact that individuals (including animals) with intensively pigmented skin possess higher mucous resistance. It is also well known that in Subsaharan Africa people have the darkest skin. In some countries of that region trichomoniasis is very widespread, so is heterosexually transmitted AIDS (e.g. Uganda) By those immunobiologically superior hosts, chronic trichomoniasis leads to the selection of T strains with higher immunopathogenicity. Such strains, named as tropical, along with the simultaneous stimulation by other antigens very often cause immunodepression in less pigmented, i.e. less resistant hosts. In the former ones the host-parasite interaction often remains on the level of subclinical sensitization. In other words, the excess of immunogenicity in tropical strains of Ts more intense damage the immune system of less pigmented hosts and widely opens the door for the opportunistic infections, such as human immunodeficiency virus too. The former conclusion is derived from a very well known fact about the existence of an extremely rare and short lasting HIV viraemia, which implicates the ability of the host to neutralize the virus efficiently and rapidly.


The role of secondary sensitizations


Secondary antigenic stimulations of microbial, dietary, environmental and medicamentous origin and even emotional stress (22) and exposure to sunlight (23) can additionally aggravate immunodepression, consequently causing further decrease in mucosal resistance. The penetration of T antigens through the mucous membrane barrier usually cause regional lympha denopathy, which can be observed in genital trichomoniasis (5). Physical, chemical and mechanical (micro)traumas of mucosal membranes enable parasites to penetrate into lymph- and hemo circulation. Homosexual and heterosexual promiscuity, iv drug abuse and their various combinations, as well as the application of the blood products, increase the possibility of mucocutaneous penetration of Ts or antigens only, directly into circulation. Trichomonaemia with the consequent severe immunodepression and immunity exhausting, decreases the resistance to the other microbial agents thus closing the fatal circle.

Immunogenic variability of trichomonads


Similarly to plasmodia and trypanosomes, Ts possess the ability of antigen reconstruction, which enables them to evade the host immune system. Due to a change of antigenic battery of the subepuithelially invaded Ts, the commercial immunodiagnostic tests are not efficient, since they are prepared on the basis of the mucosal strains of parasites. The other reason for diagnostic “blindness” is fixation of blood smears, which prevents differentiation between leucocytes and aflagellary forms of Ts, since they are of similar form and size. T-parasitaemia with a consequent maximal sensitization prevents colonization of Ts at various mucosal mebranes which explains extremely rare trichomoniasis (with flagellary trophozides) in AIDS patients. Aflagellary T forms can be expected in ulcers of mucosal membranes particularly in homosexuals’ rectal mucosa (recipients of sperm).

 

A very important fact in pathogenesis and epidemiology of AIDS is a frequent finding of prostatic thrichomoniasis, more often diagnosed in blacks (up to 70%) than in whites (24).  

 

Ts facilitate the propagation of secondary infections not only by immunity erosion but also as a mechanical vector transmitting various microbial agents on the cell membrane or even within cytoplasm (25). This last phenomenon suggests the possibility that not only T lymphocytes but also unrecognized Ts may be a reservoir for HIV in blood as well as in various secretions, notably in ejaculates. Longlasting subclinical trichomoniasis with the possible HIV hyperparasitosis of Ts, may explain the cases with extremely long subclinical phases of AIDS. After mucosal and vascular phase, the following qualitatively new phase of T/man interaction happens as allergic reaction of sensitized host to eliminated parasites, or to Ts which originate from the exogenous infection with the identical or similar antigen batteries. T superinfections with different antigen batteries is the additional factor of exhausting of immune apparatus, that usually happens by homosexual and heterosexual promiscuity and other non-physiological sexual behaviors. Extreme liberalization of sexual relations and their non-physiological practices leads to accelerated expansion of trichomoniasis and selection of new and highly pathogenic T strains. Figuratively speaking ‘laboratories’ for creating the most pathogenic Ts are today rectal mucosal membranes of white homosexuals and subpreputial sack of black homo/heterosexuals. More sensitive immunodiagnostic tests, which will enable the detection of subephitelially invaded Ts and their geographic variants (26) may accelerate the final solution of trichomonaemia. Furthermore, such tests, with better cultivation methods, will probably show that the significant part of human population is already infested with those protozoes, which have been incorrectly considered as saprophytes at extragenital localizations.

Conclusion


In exposed T/AIDS concept, the role of viruses is not excluded but more light is cast on the nowadays unrecognized role of infraepithelial invasion of Ts in their biologically regressive aflagellary form. The inexplicable total lack of reports about t infections in AIDS patients, though it is a very strong and obligatory immunogenic agent, could be explained by the fact that the immune system of the infected individuals in preclinal phaseis able to suppress parasites into their regressive aflagellary pseudocystic form. The occurrence of flagellary trophozoites in the final AIDS phase may indicate the definitive collapse of the host immune system.


Acknowledgements


I thank Professor Dr H Kulenovic for valuable criticism and Professors I Kostich and J Karaula for friendly linguistic help.


References


  1. Ackers J P, MMillan A, Street D A, Taylor-Robinson D. Trichomonal antibody in male homosexuals. The Lancet 1: 880, 1983.

  2. Balter M. Montagnier pursues the Mycoplasma-AIDS link. Science 251: 271, 1991.

  3. Duesberg p H. Human immunodeficiency virus and AIDS: Correlation but not causation. Proc. Natl Acad Sci 86: 755, 1989.

  4. Cleveland L R. Trichomonas fecalis nov. spec. of man: its ability to grow and multiply indefinitely in faeces diluted with tap water and in frogs and tadpoles. Am J Hyg 8: 232, 1928.

  5. Honigberg B M. Trichomonads of importance in human medicine. P275 in Parasitic Protozoa, Vol 2 (J P Kreier ed) Academic press Inc, New York, 1978.

  6. Teras J. Kazakova I. Ellama M. Comparison on the antigenic properties of Trichomonas vaginalis and trichomonas tenax. Wiad parazytol 15(3-4): 241, 1969.

  7. Teras J. Extraurogenital infections of man by Trichomonadidae. Acta Univ carol Biol (Prague) 39: 459, 1986.

  8. Grollet J. Trichomonas enterovaginalis. Revue Pathol Gen Physiol Clin 54: 475, 1957.

  9. Jirovec O. Petru M. Trichomonas vaginalis and Trichomoniasis. Adv parasitol 6: 117, 1968.

  10. Wagner H, Hees E. Der Kulturelle Nachweis von Trichomonas vaginalis und anderen Trichomonasarten. Zbl. Bakt I Orig 135: 310, 1935.

  11. Coutts W E, Silva-Inzunza E, Tallman B. Genitourinary complications of non-gonococcal urethritis and Trichomoniasis in males. Urol Int 9: 189, 1959.

  12. Korte W, Sanft HH. Pathologie und Klinik der Infektion mit Trichomonas vaginalis beim Menschen. Hippokrates, 47: 103, 1976.

  13. Krvavac Š. and Rustembegović A. Possible correlation between high eruytrocyte sedimentation rate and trichichomonaemia in rheumatic diseases. P274 in Abstracts, 3rd Interscience world Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, Monte Carlo, 1989.

  14. Piekarski G. Introduction. P1 in Trichomonads Parasitic in Humans. (BM Honigberg, ed.) Springer-Verlag, NewYork-Berlin-Heidelberg-London-Paris-Tokyo-Hong Kong, 1990.

  15. Krvavac S. Stojkovic N. Trichomonas species-aflagellary forms in Multiple sclerosis lesions. Abstract S23-25 in Abstracts, Eur Feder Imunol Soc, Xth Meeting, Edinburgh, 1990.

  16. Nicolau S, Lwoff A. L’Action pathogene de trichomonas foetus pur le systeme nerveux central. Ann Inst Pasteur 55: 654, 1935.

  17. Price R W, Brew B, Sidtis J, Roenblum M, Sheck A C, Cleary P. The brain In AIDS: entral nervous system HIV-I infection and AIDS dementia complex. Science 239: 586, 1988.

  18. Krvavac S. Trichomoniasis and cystic fibrosis. Postgrad Med. J. Letters 66: 155, 1990.

  19. Krvavac S. Genitorectal Trichomonas invasion as cofactor in pathogenesis of bechet’s syndrome. Ann Rheum Dis, Letters 49: 423, 1990.

  20. Krvavac S, Starovic T. Immunity mediated genitor-respiratory relocation of trichomonas infections. Abstract S 32-24 in Abstracts, Eur Feder Imunol Soc, Xth Meeting, Edinburgh, 1990.

  21. European Collaborative Study. Mother-to-child transmission of HIV infection. Lancet 11: 1039, 1988.

  22. Ader R. Psychoneuroimmunology. Academic press, New York, 1981.

  23. Hersey P, BradleyM, Hasic E, Haran G, Edwards A, McCarthy W H. Immunological effects of solarium exposure. Lancet 1: 545, 1983.

  24. Weston T E, Nicol C S. Natural history of Trichomonal infection in males. Brit J Ven Dis 39: 251, 1963.

  25. Keith L G, Friberg J, Fullan N, Bayley R, Berger G S. The possible role of Trichomonas vaginalis as a ‘vector’ for the spread of other pathogens. Int J Fert 34: 272, 1986.

  26. Krieger J N. Geographic variations among isolates of Trichomonas vaginalis: demonstration of antigenic heterogeneity by using monoclonal antibodies and the indirect immunofluorescence technique. J Infect Dis 152: 979, 1985.