VIRUSMYTH HOMEPAGE


DESTRUCTION OF NORMAL RESIDENT MICROFLORA AS THE MAIN CAUSE OF AIDS

By Vladimir L. Koliadin

Aug. 1996


Introduction

The main clinical manifestation of AIDS is ultra-high vulnerability of the patients to opportunistic infections (OI) as well as severe and recurrent course of these diseases. These infections are caused by microorganisms which are normally present in organism of healthy individuals and environment, but harmless to otherwise healthy hosts. That is why, almost in the very beginning of AIDS epidemic, this syndrome was unanimously attributed to deficiency of the immune system of AIDS patients. Since then, the "AIDS = immunodeficiency" postulate has never been seriously doubted. Even though mainstream AIDS researchers and AIDS- dissidents disagree violently on what causes this deficiency of the immune system, both sides tacitly agree that just immunodeficiency is responsible for the severe and frequently incurable OI in AIDS patients. A hypothesis presented in this paper (in short -- "destroyed-microflora" hypothesis) challenges this totally shared postulate, and provides quite a different view on both nature of AIDS and its causal factors.

The main points of the "destroyed-microflora" hypothesis

1. Contrary to a widely shared belief, the immune system (T- cell mediated immunity) plays no any significant role in protection from the bacterial and parasitic OI observed in AIDS patients. The main factor which prevents these infections in healthy individuals is normal resident (friendly) microflora -- the harmless and frequently useful microorganisms which populate various body compartments: mucous membranes of inner tract (guts, lungs, respiratory tract, etc.) as well as skin. These microflora occupy ecological niches in organism and prevent these areas from colonization by other species of microorganisms, including species pathogenic for the host macroorganism.

2. The main factor which triggers bacterial and parasitic OI in HIV-positives and AIDS patients is destruction of their normal microflora -- the natural protection against OI. Microflora in AIDS patients is destroyed by unusually prolonged exposure to broad- spectrum antibacterial and antiparasitic antibiotics, and, probably, by exposure to drugs with cytostatic effect (AZT, ddI, etc.). Destruction or severe depletion of the normal microflora makes the ecological niches vacant, and they are being easily colonized by pathogenic species of microorganisms which are normally present in harmless quantities in organism and environment. Otherwise, these microorganisms cannot proliferate effectively because they lose ecological competition with normal resident microflora. Moreover, many species forming the normal microflora are incorporated in vital functions: digestion and utilization of food, production of vitamins. Depletion of the microflora results in depression of these functions and leads to worsening general health and decline of non-specific resistance of the organism.

3. CD4 lymphocytopenia observed in many HIV-positives and almost all AIDS patients as well as concomitant viral infections are of secondary nature: they are caused by severe and permanent psychological stress (caused by intensive propaganda of the "HIV = AIDS = Death" postulate), worsening general health due to bacterial and parasitic OI and toxic medication. Neither CD4-lymphocytopenia itself nor viral infections pose any direct threat to life -- they are only indicators and consequences of worsening general health and concomitant depression of the non-specific resistance of the organism.

4. Epidemic of severe OI named AIDS started in highly promiscuous groups (the gay community and severe drug abusers) in late 1970's because of the popular fashion to use broad-spectrum antibiotics as a permanent prophylaxis against sexually transmissible diseases (STD) frequent in these groups, and partially by frequent treatment of recurrent STD by broad-spectrum antibiotics. Then, with the acceptance of the wrong "AIDS = immunodeficiency" and, later, "HIV = AIDS" postulates, the dubious practice to administer broad-spectrum antibiotics (as permanent prohylaxis against allegedly possible OI) became normal for individuals with non-specific symptoms named pre-AIDS (CD4- lymphocytopenia, lymphoadenopathy, severe diarrhea, weight loss, and CD4-lymphocytopenia), with AIDS diagnosis, or with a positive test for HIV-antibodies. This increased dramatically the number of individuals exposed for unusually long time to broad-spectrum antibiotics, and resulted in rapid growth of incidence of severe and incurable OI due to destruction of normal resident microflora - - the natural defense against OI.

5. The course of events typical to most cases of AIDS -- HIV- seroconversion -> CD4-lymphocytopenia -> severe and recurrent OI (AIDS) -- is not a result of the "HIV = immunodeficiency = OI" mechanism specified by the official viral theory, but a direct consequence of the general belief in the "HIV=AIDS=Death" and "AIDS=immunodeficiency" postulates and clinical strategy based on these postulates. A positive test for HIV-antibodies causes severe and permanent psychological stress and, frequently, is followed by permanent prophylaxis by broad-spectrum antibiotics and toxic medication by drugs with clearcut cytostatic effect (AZT, ddI, ddC, etc.). The permanent severe stress and cytostatic drugs lead to CD4- lymphocytopenia; broad-spectrum antibiotics and, partially, cytostatic drugs destroy normal resident microflora -- the natural protection against OI. Progression of CD4-lymphocytopenia and first signs of OI, in turn, force physicians to intensify therapy by broad-spectrum antibiotics and, frequently, by antiretrovirals. This leads to further destruction of the normal resident microflora and facilitates OI. Thus, a vicious circle takes place: medication normally prescribed with intention to cure complications of AIDS in reality has an opposite effect -- it facilitates further progression of the disease. Naturally, AIDS demonstrates very high mortality -- simply because the individuals are being treated by just the same sort of drugs as those which have caused this condition.

The above described hypothesis seems to explain the basic peculiarities of AIDS: (i) HIV-AIDS correlation, (ii) susceptibility of the patients to OI, (iii) severe course of the disease and extremely high mortality, (iv) emergence and concentration of AIDS in highly promiscuous groups -- male homosexuals and severe drug abusers, (v) rapid and synchronous growth of incidence of AIDS in different high-risk groups, (vi) relatively low progression of health decline in HIV-positives, but rapid progression after detecting CD4-lymphocytopenia or diagnosis of AIDS.

The role of normal resident microflora in health and disease

Even though the role of normal resident microflora in organism is grossly underestimated by mainstream biomedical schools of thought, it is well understood by many authors [1-9]. Various species of microorganisms normally populating human organism form a complex ecological system which is far from being fairly understood yet. To a great extent this lack of understanding is caused by little interest of the mainstream biomedical science to this subject. In brief, the role of microflora may be summarized as follows [1-7].

1. Partially normal resident microflora is formed by various species of microorganisms which are harmless passengers and play no any significant role in body functions directly. On the other hand, these species occupy ecological niches in various areas of the organism (mucous membranes, lungs, gut, skin) and prevent them from colonization by other species of microorganisms, including potentially pathogenic species, due to successful ecological competition with the latter.

2. Another part of normal microflora is formed by microorganisms which are obviously useful for the host macroorganism and directly incorporated in its vital functions. First of all, it is friendly microflora of gut which play immediate role in digestion and utilization of food as well as in production of vitamins.

This symbiosis (mutually useful coexistence) of the host human macroorganism and its normal microflora is a natural result of thousands years of coevolution of homo sapience and microorganisms. It is a direct consequence of the benefits from this symbiosis for the host macroorganism -- harmless nature of these species, their successful competition with other microorganisms pathogenic for the host organism, and their direct incorporation in biochemical functions of the host.

According to the "destroyed-microflora" hypothesis, normal resident microflora (not the immune system as it is totally believed) is the main factor preventing AIDS-associated and other opportunistic bacterial and fungal infections in healthy individuals. Just destruction of the normal resident microflora (not deficiency of the T-lymphocytes) is the factors which makes the individuals highly susceptible to bacterial and parasitic OI.

Is it just the immune system what normally protect from OI?

In the very beginning of the epidemic of AIDS, it was noticed that AIDS patients were extremely susceptible to infections caused by low-grade pathogens that were earlier known to cause OI only in compromised hosts -- mainly in individuals subjected to therapy by drugs with immunosuppressive effect: cancer patients (treated by cytostatic drugs), recipients of transplantants (treated by immunosuppressive drugs). On the other hand, these microorganisms are normally present in small quantities in healthy individuals and environment, but do not cause infection in healthy individuals. This observation, along with depletion of T-lymphocytes in individuals with OI, was explained by protective role of the immune system in otherwise healthy individuals, and susceptibility to OI was attributed to deficiency of the immune system. Since that time, the postulate "AIDS = immunodeficiency" became totally accepted as the ultimate truth.

According to the "destroyed microflora" hypothesis, the above described observation has quite different explanation which does not rest on the "AIDS = .immunodeficiency" postulate. The central point of the hypothesis is that the main factor normally protecting from bacterial and parasitic OI is the normal resident microflora, not the immune system as it is widely believed. In individuals with OI, these microflora are being seriously depleted or destroyed by prolonged exposure to broad-spectrum antibiotics and, probably, to other drugs -- mainly those with clearcut cytostatic effect. Do all the categories of individuals susceptible to OI (cancer patients, recipients of transplants, and first patients with AIDS) had been subjected to some factors which might destroy their resident microflora? There at least two such factors.

First, it is extremely prolonged use of broad-spectrum antibiotics. Individuals treated by drugs with immunosuppressive effect (cancer patients, recipients of transplantants, etc.) as well as patients with other forms of immunodeficiency are normally subjected to permanent prophylaxis by broad-spectrum antibiotics (which are well known to destroy normal microflora). As for first AIDS patients, they were mainly highly promiscuous male homosexuals and severe drug abusers who admittedly used broad- spectrum antibiotics as a permanent prophylaxis against sexually transmissible diseases (STD) -- extremely frequent in these groups because of high promiscuity, and many of them had been frequently exposed to broad-spectrum antibiotics while treatment of recurrent STD.

Second factor depleting microflora is drugs with cytostatic effect normally used for anti-cancer therapy, and for deliberate suppression of the immune system in recipients of transplantants. After 1984, with the advent of the "HIV = AIDS" formula, many patients with a positive test for HIV, pre-AIDS symptoms, or AIDS diagnosis became also subjected to exposure to drugs with cytostatic effect (AZT, ddI, ddC, etc.).

Thus, besides compromised T-cells, all the categories of individuals which demonstrate high susceptibility to bacterial and parasitic OI have another common trait -- unusually long-term exposure to factors depleting normal resident microflora (broad- spectrum antibiotics and, partially, drugs with cytostatic effect). As for the deficiency of T-lymphocytes itself, there are no any tangible evidence that T-cells can protect from OI, and that deficiency of T-cells mediated immunity is the prime factor which triggers infections. To the same extent, the observed association between T-cell deficiency and OI is explainable by simultaneous exposure of the individuals to immunosuppressive factors (drugs with cytostatic effect, stress, compromised general health, etc.) and factors which destroy normal microflora (broad-spectrum antibiotics, cytostatic drugs). Moreover, the very detection of immunodeficiency with a great probability results in prescription of long-term prophylaxis by broad-spectrum antibiotics (leading to further destruction of the normal resident microflora and its replacement by conditionally pathogenic flora which cause OI).

Another plausible explanation of the observed association between deficiency of T-cells and high susceptibility to bacterial and parasitic OI is that this immunodeficiency is of secondary nature -- i.e. infections themselves cause reduction of T- lymphocytes counts in peripheral circulation. This assumption fits current biomedical dogmas. For example, T-cell population is known to be depressed in persons with lepromatous leprosy, and degree of this depression is correlated directly with the bacillary load [10]. This correlation cannot be explained by the primary nature of T-cell deficiency -- simply because infection develops first. The primary role of bacterial infection in depletion of T-cells is the most plausible explanation [10].

There are also some other reasons to doubt the direct causal link between immunodeficiency and OI.

1. Bacterial and parasitic opportunistic infections associated with AIDS normally develop in the body compartments which are beyond any direct reach of the immune system: mucous membranes of the gut, lungs, respiratory tract, etc. as well as surface of the skin.

2. AIDS patients demonstrate no any significant increase in susceptibility to usual (non-opportunistic) infections from which the immune system protects, even though pathogenic microorganisms are present in small quantities in environment and organism. It is a sign that the immune system of AIDS patients is still competent enough to tackle with infections.

3. Microorganisms usually proliferate very rapidly unless some factors stifle and limit this process. If just the CD4-lymphocytes were the factor which controls proliferation of the microorganism casing OI, any significant drop in CD4+ cell counts would have resulted in rapid development of OI (provided the microorganisms are normally present in small quantities in the organisms). Nevertheless, many individuals live with low counts of CD4- lymphocytes for long time without any signs of OI. This supports the view that it is not the immune system, but some other factors what control proliferation of these microorganisms.

Prolonged prophylaxis by antibiotics main cause of AIDS

Most HIV-positives and almost all AIDS patients, irrespective to the risk-group they belong to, are subjected to long-term prophylactic treatment by broad spectrum antibacterial and antiparasitary drugs (antibiotics). Because of the total belief in the dubious "AIDS = immunodeficiency" and "HIV = AIDS = Death" formulas, either a positive test for HIV or some symptoms which are considered as pre-AIDS are frequently followed by unprecedented in its intensity and longevity prophylaxis by broad spectrum antibiotics, including cocktails of these drugs. At the same time, just longevity of administering and broad-spectrum of antibiotics are the main factors which determine degree of destruction of normal microflora [3,4,11] There are at least three biological mechanisms which explain the link between prolonged broad-spectrum antibacterial prophylaxis and the main clinical manifestations of AIDS -- severe and incurable OI and rapid decline of general health.

1. Normal resident microflora prevents the ecological niches they populate from colonization by other species of microorganisms. Destruction or severe depletion of the microflora results in otherwise impossible colonization of the freed ecological niches by other species of microorganisms, including conditionally pathogenic ones. This explains the ultra-high susceptibility of AIDS patients to bacterial and parasitic opportunistic infections. A classical and well known model of such a process is the fungal infections, mainly that caused by Candida ( ubiquitous fungi, not sensitive to antibacterial drugs), which frequently follow even relatively short courses of broad-spectrum antibacterial therapy due to depletion of normal resident microflora (sensitive to antibiotics) [11,12].

2. Many species forming normal resident microflora take an active part in vital functions of the host macroorganism -- digestion and utilization of food, production of vitamins [1,3,4]. Long term depletion or destruction of these species by antibiotics naturally result in malfunctions of the subsystems of the organism these microorganisms are involved in, and worsening the general health status. This partially explains the "non-specific illness" observed in AIDS patients.

3. Prolonged use of antibiotics frequently results in emergence of drug-resistant strains of microorganisms -- simply due do classical natural selection of drug resistant mutants under the selective pressure of antibiotics [3,4,13-15]. In organisms whose normal microflora -- the main natural protection against OI -- has been destroyed by antibacterial therapy, these drugs are the only factor which stifles proliferation of conditionally pathogenic microorganisms. Therefore, emergence of drug-resistant strains makes further drug therapy ineffective and leads to incurable and progressive course of infection with frequent lethal outcome.

Natural questions arising in the context of "destroyed- microflora" hypothesis are: Why AIDS is new while antibiotics had been in use at least for three decades before AIDS epidemic had started? Why AIDS-like syndrome has not been observed in multiple clinical studies of antibiotics?

Antibiotics were designed for short-term therapy of conditions caused by proliferation of pathogenic microorganisms. Classical scheme of treatment implies isolation of pathogenic microorganisms which cause the disease, determining to what antibiotics they are sensitive, and administering just these narrow spectrum drugs for therapy. Duration of a traditional course of antibiotics does not normally exceed several weeks; and just such a scheme of treatment by antibiotics is normally tested in clinical trials of these drugs. It is worth noting here that even such short- term therapy relatively frequently results in noticeable destruction of the resident microflora with its typical manifestation -- fungal infections [3,4,11,12].

In contrast with most other categories of individuals treated by antibiotics, AIDS patients and HIV-positives are subjected to unprecedented in its intensity and longevity prophylaxis by antibiotics -- for many months and years. Moreover, powerful broad- spectrum drugs (many of them are relatively new) are normally used, and frequently in combination of several drugs. Wide use of broad- spectrum antibiotics and administering combinations of these drugs for long-term prophylaxis is a relatively new practice; and it became extremely popular only in the AIDS era. The only categories of patients subjected to similar prohylaxis by antibiotics before AIDS epidemic were individuals subjected to therapy by immunosuppressive drugs (e.g. patients with cancer, recipients of organs and tissues) or those with immunodeficiency of other nature. And only these categories demonstrate high incidence of OI (even though these OI are normally attributed to deficiency of their immune system).

Due to total uncritical acceptance of a wrong "HIV = immunodeficiency = AIDS" view, AIDS patients and HIV-positives virtually became subjects of a large-scale experiment on unprecedented long-term administering of broad-spectrum antibiotics. The epidemic of severe OI misleadingly named AIDS is a natural outcome of this "experiment". 6. Some additional arguments in support of the "destroyed- microflora" hypothesis:

- unprecedented long-term prophylaxis by broad-spectrum antibiotics is a factor common to all AIDS patients and many HIV- positives (irrespective to the risk-group); on the other hand such prophylaxis is extremely rare in other categories of patients;

- a positive test for HIV or otherwise nonspecific symptoms called pre-AIDS are frequently, if not always, followed by unprecedented long-term prophylaxis by broad-spectrum antibiotics; this explains why AIDS is highly correlated with and normally preceded by a positive test for HIV or non-specific symptoms named pre-AIDS (lymphoadenopathy, thrush, diarrhea, weight loss);

- the official HIV=AIDS hypothesis fails to explain why male homosexuals are the main targets of AIDS; the attempts to explain this essential epidemiological peculiarity of AIDS via presumably drastic difference in rates of transmission of HIV during anal and vaginal intercourse have no any factual underpinning; at the same time, in 1970's broad-spectrum antibiotics became popular in promiscuous segment of gay community as a long-term prophylactic measure against otherwise frequent sexually transmissible diseases [16]; specific spectrum of sexually transmissible diseases (not treatable well by penicillin or other narrow-spectrum antibiotics) in gays as well as growing availability of broad-spectrum antibiotics are responsible for arising this "fashion" mainly in the gay community, and admittedly, in other groups with extremely high promiscuity (marked also by severe abuse of recreational drugs);

- the official HIV-causes-AIDS hypothesis fails to explain why AIDS is distributed very unevenly over the globe: for example AIDS is extremely rare on the territory of the former Soviet Union (even though incidence of sexually transmissible diseases there is at the same order of rate as in the USA), but AIDS is reported frequent in Africa and Latin America; on the other hand, in the former Soviet Union neither HIV-testing nor prolonged prophylactic use of powerful broad spectrum antibiotics are popular to a noticeable extent; at the same time, according to [3, p.195], "in countries within Africa, Asia, Latin America and elsewhere ... the overuse and abuse of antibiotics ... amounts to a truly frightening crisis";

- among symptoms normally preceding full-blown AIDS, various forms of candidiasis, including thrush, are widely met; on the other hand, infections caused by Candida are frequent in patients subjected even to short-term broad-spectrum antibacterial therapy, and such infections is a reliable sign that normal microflora have been destroyed [1-4,11,12];

- most patients with AIDS suffer from severe diarrhea and weight loss; there is no any visible link between immunodeficiency and diarrhea; at the same time, severe diarrhea is frequent in patients whose normal microflora of the gut have been destroyed by antibiotics [17];

- drug-resistant strains of microorganisms are frequently detected in AIDS patients, and just this drug-resistance is partially responsible for the frequent lethal outcome of opportunistic infection incurable by antibiotics; there is no any visible link between deficiency of the immune system and drug- resistance of microorganisms; on the other hand, drug-resistance is a natural consequence of natural selection of drug-resistant mutants during long-term use of antibiotics [3,4,13-15];

- during the years 1983-1990, when incidence of AIDS was growing rapidly in the USA, this growth was strikingly synchronous in different risk-groups; such epidemiological feature is hardly compatible with infectious nature of AIDS as well as with "multicausal" hypotheses (explaining AIDS in various risk-groups by different non-infectious factors); at least these views need quite an artificial additional postulates: either that rate of individual- to-individual infection is almost equal in various risk groups (infectious hypothesis) or that exposure to various non-infectious causal factors in different risk groups was growing synchronously ("multicausal" theories); in contrast, "destroyed-microflora" hypothesis do not need such artificial assumptions -- because the causal factor (long-term prophylaxis by broad spectrum antibiotics) is common to almost all HIV-positives and AIDS patients irrespective to the risk group they belong to.

Social history of AIDS in the light of the "destroyed- microflora" hypothesis

In late 1970's, long-term (self)administering of broad- spectrum antibiotics became a popular fashion in the gay community (as a prophylactic measure against sexually transmissible diseases), especially in its most promiscuous segment, as well as in some groups of heterosexual population with specific lifestyle marked by high level of promiscuity, heavy abuse of recreational drugs, etc. Availability of new powerful antibiotics contributed much to emergence and growing popularity of such a "fashion". The "fashion" to use broad-spectrum antibiotics for a long time resulted in gradual depletion of the normal resident microflora -- natural defense against bacterial and parasitic OI. In individuals prone to more intensive "prophylaxis" by antibiotics (mainly those with extremely high promiscuity), this process was progressing more rapidly. Naturally, the first cases of severe OI emerged among just these individuals (what made researchers think that an infectious agent causes AIDS). Later, OI became to emerge in other adherents of the "fashion".

The first cases of severe OI were spotted by the CDC in 1979- 1981 and erroneously attributed to immunodeficiency as the primary biological cause. This error had a tragic consequences: the individuals were put under long-term prophylaxis by broad spectrum antibiotics -- just the substances by which their condition had been caused. Naturally, such "prophylaxis" and treatment resulted in further destruction of their normal microflora with concomitant severe and incurable OI and frequent lethal outcome. The wrong "AIDS = death" view was widely accepted. This caused rapid expansion of the dubious practice to administer broad-spectrum antibiotics as a permanent prophylaxis or treatment for individuals with some signs of OI, CD4-lymphocytopenia, or nonspecific symptoms named pre-AIDS --thrush, lymphoadenopathy, diarrhea, weight loss. The growing number of severe and incurable OI, which occurred after some period of such treatment due to destruction of normal microflora, were explained by progression of immunodeficiency and seemed to confirm "AIDS = Death" formula.

With the promulgation of the "HIV=AIDS" formula in 1984 as the ultimately proven scientific fact and expanding the practice of testing for HIV-antibodies, the number of potential victims of the deadly practice to administer broad-spectrum antibiotics as a permanent prophylaxis skyrocketed. Any individual who demonstrated a positive test for HIV antibodies, became a potential target for such prophylaxis. Permanent and severe psychological stress, caused by intensive propaganda of the "HIV=AIDS = death" formula, and toxic medication led to gradual decline of CD4-lymphocytes in individuals with a positive test for HIV. This apparent progression of immunodeficiency forced physicians to intensify prophylaxis by broad spectrum antibiotics, what, in turn, led to further destruction of normal resident microflora and made the individuals devoid of their natural defense against OI. The rapid growth of AIDS incidence in second half of 1980s was a natural consequence of this self-accelerating process. Unfortunately, for most researchers, the visible link between HIV-positiveness and AIDS, rapid growth of incidence of AIDS, and extremely high mortality seems to be an ultimate proof that the officially accepted "HIV = AIDS = Death" postulate is the ultimate truth.*

This work was supported by private donations from Dr. Ingeborg Heinrich (UK). To some extent, some parts of this work were spin-offs of a research on mathematical ecology supported by grant UAD000 from the International Science Foundation. I thank the editorial board of "Continuum" for permanent supply me with issues of the magazine -- the unique information I found there had played an esential role in the birth of the "destroyed microflora" hypothesis.

This article is dedicated to memory of Jody Wells -- the man who contributed much more to victory over the plague of AIDS than thousands and thousands mainstream AIDS researchers

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VIRUSMYTH HOMEPAGE