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Vaccines as an Autism Trigger: A TB Link?

August 11, 2017

by Lawrence Broxmeyer, MD

From NEXUS Magazine, February–March 2015 (vol. 22, no. 2)

Vaccines as an Autism Trigger: A TB Link?
by Lawrence Broxmeyer, MD
© December 2014 – January 2015


[Sidebar Introduction]
While it can’t be said categorically that vaccines trigger autism, it can’t be denied that many vaccines still contain toxic mercury compounds as well as animal and human components which may be contaminated with tuberculosis mycobacteria, with deleterious effects.
At present, the cause of autism and its related spectrum disorders is unknown. Many hypotheses regarding what causes autism have been and will continue to be put forth, but only one will prevail: its true cause. A conversation as to whether vaccines trigger autism cannot be made in a vacuum but, rather, must be weighed against certain epidemiologic, scientific and historic considerations because its complexity is too great.

California Department of Developmental Services, Sacramento, 1999

California, in 1999, had been on high alert for some time. Level-one autism, without any of its “spectrum”, went from almost 5,000 cases in late summer 1993 to an estimated 20,377 cases by December 2002. As California’s Department of Developmental Services stood by incredulously, it witnessed a tripling of California’s autism rate and all but 15 per cent of cases were in children.

California wasn’t alone, but its autism rates had become the fastest-growing group in that state’s developmental disability system and a number of Bay Area school districts were forced to fill entire classes with youths with different forms of autism.

But even in the midst of California’s mini-epidemic, its Santa Clara County seemed particularly singled out. The California Department of Social Services’ aid, brokered by the San Andreas Regional Center, staggered to its breaking point, and its forecast for autism in Santa Clara wasn’t good.

What was behind this epidemic? A major clue, overlooked from a critical standpoint, was contained in the timeline of the department’s own 1999 autism report1 which concluded that the disease had increased dramatically between 1987 and 1998. What had happened in California in and around 1987 that could have sown the surplus of autism that California now reaped?
Division of Communicable Disease Control, Sacramento, California, 1999

While autism exploded in California, there was also, beginning in 1987, a major spike in the number of tuberculosis cases reported by the Tuberculosis Control Branch of California’s Division of Communicable Disease Control. There, division head Dr Sarah Royce proclaimed a tuberculosis (TB) epidemic in California. The epidemic peaked in 1992, had the same male preponderance as autism, and took off at precisely the same moment in time.

California’s TB epidemic was claimed to have peaked well before 1999, but this didn’t stop it from continuing to contribute the greatest number of cases to the nation’s total tuberculosis morbidity.2 But, as with autism, the problem was worldwide, and even the World Health Organization, traditionally slow to react, had declared a global tuberculosis emergency six years earlier.3

Among children, brain-seeking central nervous system tuberculosis is common in a disease that kills more children each year than any other, with the potential to cause in survivors a withdrawal from social interaction, among other things, in its devastating wake.4

It had to be more than a coincidence, therefore, that since the 1980s California experienced a dramatic increase in the number of children diagnosed with autism as well.

Santa Clara County, California, March 2006

If California was experiencing autistic tremors, then surely its Santa Clara County was at the epicentre. By 2006, Santa Clara had some of the highest rates for autism in the entire USA. Although this was for unknown reasons, again the question became: why Santa Clara? The answer pointed in a similar direction.

By 2002, it had become apparent that tuberculosis was on the rise in Santa Clara. By 2006, that county had the highest number of new TB cases in California. A news report of 2014 mentioned that Santa Clara now has “more tuberculosis cases than most US states”.5 At the same time, the immigrant share of the population in Santa Clara County, mostly from countries where TB is endemic, is at its highest point since 1870.6

Santa Clara’s Health Department sounded the alarm. Santa Clara now knew that it had two problems on its hands. Its medically trained psychiatrists, doctors, personnel and statisticians just never stopped to think that the two problems might be related.

Centers for Disease Control and Prevention, Atlanta, Georgia, September 2008

Time passed. More information came in. In September 2008, the Centers for Disease Control and Prevention (CDC) published a study7 by lead author, paediatrician and researcher Dr Laura J. Christie of the California Department of Public Health entitled “Diagnostic Challenges of Central Nervous System Tuberculosis”. Christie and colleagues identified 20 cases of unexplained encephalitis referred to the California Encephalitis Project that were indeed tubercular. The team importantly began with this significant statement: “Tuberculosis (TB) of the central nervous system (CNS)” as thought of by physicians “is classically described as meningitis. However, altered mental status, including encephalitis, is within the spectrum of [its] clinical manifestations.”

In most of the 20 cases, the California Encephalitis Project cultured out tuberculous encephalitis, the same tuberculosis considered the least likely cause for encephalitis. Yet there it was. But, as Christie pointed out, as little as 25 per cent of patients with a diagnosis of CNS TB actually cultured out TB, which was a criterion for this particular study. That means that only a quarter of possible cases were confirmed.

Subcommittee on Human Rights and Wellness, Washington, DC, September

[Photo caption]
Congressman Dan Burton, Chairman of the Hearing before the Subcommittee on Human Rights and Wellness, 8 September 2004

The following excerpts are from the transcript of the “Hearing before the Subcommittee on Human Rights and Wellness of the Committee on Government Reform, House of Representatives, One Hundred Eighth Congress, Second Session, September 8, 2004”.8

[The Subcommittee’s Chairman, Congressman Dan Burton (R-Indiana), is thanking Dr Melinda Wharton, Acting Deputy Director of the National Immunization Program, Centers for Disease Control and Prevention, for her opening testimony.]

Mr Burton: Thank you for your testimony. Everybody knows the value of vaccinations. And every time you testify, you tell us how valuable they’ve been. And we already know that.

We’re not here to say that vaccinations aren’t important. They’re very important. They’ve given us the highest quality of life of any civilization in the history of mankind. That isn’t what we’re talking about. We’re talking about why they’re putting mercury in vaccinations and why it’s never been tested since 1929 when Lilly developed it.

[Congressman Burton turns his attention to Dr William Egan, the Acting Director of the Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration (FDA).]

Mr Burton: Has thimerosal ever really been tested? Has thimerosal ever been tested by our health agencies?

Mr Egan: Only in those early tests that you know of that were done by Lilly.

Mr Burton: When was that? That was done in 1929. Let’s follow-up on that. In 1929, they tested this on 27 people that were dying of meningitis. All of those people died of meningitis, so they said there was no correlation between their death and the mercury in the vaccines. That is the only test that’s ever been done on thimerosal that I know of. Can you think of any other?

Mr Egan: No, in people, no. Except for accidental exposures over time.

Mr Burton: So we have mercury that’s being put into people’s bodies in the form of this preservative, and has been since the 1930s, and it’s never been tested by our health agencies. And yet you folks come here and you testify that there’s no conclusive evidence, and the IOM [Institute of Medicine] says, they favor, get this, they don’t say they’re sure, they say they favor rejection of a causal relationship between mercury and autism and other neurological disorders. Nobody ever gives a categorical statement, that no, mercury does not cause this, no, it doesn’t. And that’s because you can’t do it…

Mr Egan: We are diligently working, as we have testified today and previously, toward eliminating thimerosal mercury from vaccines as quickly as can be done. But there are many issues that are involved in doing this. If we were to say tomorrow that all vaccines, for example, all flu vaccines could only be administered in single dose syringes or single dose vials [thus eliminating the need for thimerosal], the capacity to fill those does not exist…

Mr Burton: OK. Now, my grandson got nine shots in one day, seven of which contained mercury. So if he got the very small amount, he’d be getting maybe nine micrograms, right?

Mr Egan: No, much less than that. Because the maximum that we calculate that a child could receive now during the first six months of life is somewhat less than three. A number of these vaccines [have] defined trace as less than one, some of them have considerably less than one.

Mr Burton: But that amount of mercury would not do any neurological damage to anybody?

Mr Egan: Not according to any guideline.

Mr Burton: No, no, no, no. I want you to say yes or no.

Mr Egan: I do not believe so.

Mr Burton: You do not believe so. I didn’t say believe. Can you say to me right now that amount of mercury being injected into a baby will not hurt it?

Mr Egan: It’s impossible to make those categorical statements with 100 percent—

Mr Burton: That’s right. So it is possible that the amount of mercury that’s being injected, even in trace amounts, could damage a child neurologically, right?

Mr Egan: I don’t think it has that capacity, no. We can argue.

Mr Burton: I know, but you don’t think it is, but you can’t say categorically, can you?

Mr Egan: Do I have evidence for every single child, for every possible dose, the answer is no…
As it turns out, the doses of thimerosal referenced in micrograms cited by Egan were small change compared to what is in certain current multidose flu shots.9 The CDC’s 2014–2015 guidelines for eligible child influenza vaccinations advise: “To protect their health, all children 6 months and older should be vaccinated against the flu each year.”10 With some multidose influenza preparations containing as high as 25 micrograms per dose of thimerosal or higher, this can add up to a lot of thimerosal. And on top of this, concurrently, the CDC still insists: “Pregnant? Get a Flu Shot!”11

Congressman Burton had established, as of 2004, that the only study ever done to conclude that thimerosal was not neurotoxic or could not precipitate the first signs and symptoms of autism was done by its manufacturer, Ely Lilly, in 1929—a study in which 22 meningitis patients (not 27, as Congressman Burton mentioned) in an Indianapolis epidemic were treated with thimerosal, all of whom died.

Lilly showcased and funded the study for one reason and one reason only: its scientist Smithburn, the study’s lead author, out of the sheer desperation of having nothing with which to cure his patients, had injected 22 of those patients dying of meningitis with large doses of thimerosal (up to 10 milligrams per kilogram intravenously) with supposedly no significantly grave consequences.12 That is, no grave consequences other than the fact that seven out of 22 of Smithburn’s patients died within one day after receiving the thimerosal. Only one patient made it to day 62 before succumbing—hardly enough of a window to investigate for chronic mercury damage from the thimerosal. Nevertheless, Lilly would next try to turn a lemon into an orange, sponsoring other scientists13 to say that the thimerosal had nothing to do with the deaths of Smithburn’s meningitis patients.

Unknown to either Burton or Egan, there was one other study testing a mercury compound on humans—a sizeable series which also appeared in the same publication, The Journal of the American Medical Association (JAMA), which had published the Lilly study. Hartz14, looking for a cure for his chronic TB patients, concluded that his trial with a mercury compound was “positively injurious and detrimental to one afflicted with tuberculosis”. Of the 14 patients to whom Hartz administered six or more injections (consisting of 1/5 gram or 13-milligram doses every second day), 12 died within from two weeks to six months after their last injection. Hartz was only using a small fraction of what Smithburn had used, yet his results for those on the receiving end of multiple injections of the mercury compound were disastrous. Hartz wrote:15

“This enormous percentage of deaths, namely, 85.7 per cent, among those [TB] patients who received six or more injections [of mercury], can be attributed only to the use of mercury, simply from the fact that the expectation of life in many of the cases chosen was very favorable indeed. In fact, on account of the age of the patients and the chronic arrested type of the disease, they were the kind of patients who live long and have a favorable prognosis.”

Also unknown to the scientists and the congressman present at the hearing was that although the 1929 Lilly investigators purportedly had an epidemic of meningococcal meningitis on their hands, as the epidemic wore on they were considering it as having originated as a mixed infection with an underlying tubercular infection—making the Hartz and Lilly publications have more in common than might at first meet the eye. It was an era when Mycobacterium tuberculosis and Neisseria meningitidis (the meningococcus) were the two most common causative organisms responsible for meningitis.16 And to this day, TB meningitis is in the differential rule-out for meningococcal meningitis.17

In back-to-back studies of the Indianapolis outbreak of 1929, Smithburn, present in the initial investigation, left the second-phase probe to Kempf, Gilman and Zerfas.18 Both publications showed how anti-meningococcal serums were of little or no use for the Indianapolis outbreak—an unexpected finding for a meningococcal meningitis epidemic.

The actual genesis of meningococcal disease was and still is not fully understood. Meningococcus colonises large numbers in the general population harmlessly, with only a very small percentage of individuals having serious illness from it—notably in the limbs and the brain. Front and centre in the follow-up study done by Smithburn’s colleagues was a mysterious “micrococcus” found in both phases of the Indianapolis outbreak. Just prior to Lilly’s publications, a similar micrococcus was uncovered by Sweany19, also published in JAMA, and subsequently by Mellon and Fisher20 in The Journal of Infectious Diseases. But both Sweany and Mellon’s micrococcus proved to be a (pleomorphic) form of cell-wall-deficient (CWD) tuberculosis (see figure 1 for an example of CWD TB). According to Kempf et al.:21

“The fact that the meningococcus could not be recovered from the blood, spinal fluid or nasopharynx does not necessarily mean that it was not there. However, it [the mysterious micrococcus] was readily recovered from the few meningococcic [meningococcal] cases that we have observed during the last few months and during the first and second years of this epidemic. One might expect to find an organism of this nature in traumatic meningitis or as a complication in tuberculosis…”

As he left the congressional hearing, very much on Congressman Dan Burton’s mind, after having grilled the FDA’s Dr William Egan, was that despite promises time and again to remove mercury from vaccines it never seemed to happen.

Figure 1: One of the stealth, viral-like forms of “cell-wall-deficient” atypical tuberculosis colonies that grew from the brain of a child who expired from the disease. Such forms of tuberculosis are extremely difficult to detect and require special stains and culture media not used routinely in today’s laboratories.
(Source: Korsak, T., Acta Tuberc. Pneumol. Belg. 1975; 66[6]:445-469)
Uncommon Valour

“My name is William Thompson. I am a Senior Scientist with the Centers for Disease Control and Prevention, where I have worked since 1998. I regret that my coauthors and I omitted statistically significant information in our 2004 article published in the journal Pediatrics. The omitted data suggested that African American males who received the MMR vaccine before age 36 months were at increased risk for autism. Decisions were made regarding which findings to report after the data were collected, and I believe that the final study protocol was not followed…”22

On 27 August 2014, CDC scientist Dr William Thompson spoke out, admitting that he had co-authored a study23 which purposely cooked the data to avoid showing that African-American infants and toddlers given the MMR (measles, mumps, rubella) vaccine before 36 months of age were at a 340 per cent increased risk for coming down with autism. At the time of the study, and for a decade after, Thompson was silenced—but troubled. This was no average witness; this was a man who knew the intricacies of the study and the original data obtained like the back of his hand.

Obviously, the CDC’s doctored 2004 study was an attempt to clear the MMR vaccine of troublesome implications—an attempt to give the vaccine a clean bill of health. But if the study’s purpose was to examine honestly the possibility of a causal relationship between the MMR vaccine and autism, it failed miserably.

After Thompson came out, the CDC’s Director of Immunization Safety and Thompson’s co-author, Dr Frank DeStefano, defended the study as originally published. But Thompson was already on record. Thompson believed that the removal of some of the study’s subjects because of the lack of a Georgia birth certificate not only went against the original study protocol, but, by reducing the study size by 41 per cent, obscured the strong statistical association between the timing of the MMR vaccination and the appearance of autism in African-American male toddlers. DeStefano was lead investigator in the 2004 paper. Subsequently, DeStefano had a telephone interview with investigative reporter Sharyl Attkisson.24 Here are a few verbatim excerpts from their exchange:

Attkisson: Were you aware of any of his [whistleblower William Thompson’s] concerns of, you know, have you been aware before today of any of his concerns about this?

DeStefano: Uh, uh, yeah, I mean I’ve continued to see, uh, uh, see him for over the past ten years and we’ve interacted fairly frequently, and, uh, uh, no I wasn’t aware of this.

Attkisson: So whoever he raised his concerns to, he didn’t, he didn’t raise it to you or anybody you knew of?

DeStefano: No, I mean the last time I saw him was probably about two months ago, and he didn’t mention anything about this…

[Ms Attkisson turns up the heat, relating to lead author DeStefano, that she thought that leaving out anything in the results of the study, especially through a birth certificate criterion which went against the study’s protocol, didn’t seem appropriate. It was also hiding the true conclusion of the study, which otherwise found a 340 per cent increase in autism in black children given the MMR before 36 months.]

Attkisson: …I still think it would be pretty important to know…

[DeStefano’s reply below apparently was his way of deflecting Attkisson’s probing comment by saying that autism probably developed in the womb before 36 months anyway and that somehow this meant that an MMR vaccination given before 36 months was already too late for the vaccine to cause or precipitate the first signs of autism.]

DeStefano: No, I mean, I think, you know, the other, the other important consideration here is looking at what, what time period we’re talking about. We’re, you know, autism, as you probably are aware, is a condition that really probably has its start while the child is still in the womb. And, you know, it doesn’t, some of the behaviors and such don’t come apparent, become apparent until maybe the child is one, two, three years old. But, uh, uh, what we know about autism that, uh, the, uh, characteristics or behavioral signs do become ava–, you know, apparent by 24 months of age, so. So we had different cut-offs, before 18 months of age, there was no difference in, in any group in terms of, uh, vaccination levels, between the cases and controls. At 24 months of age, when, uh, au—you know—behaviors of autism or some features of autism become apparent, there was no difference between the, uh, cases and controls in any group, it was at 36 months where there was a slight differen—and the difference was, we’re talking about a difference between 93% versus 91%, not a, a big difference. But, so that’s at 36 months. And at 36 months, an exposure around that time period is just not biologically plausible to have a uh, uh, a causal association with autism. I mean autism would’ve already started by then…

Attkisson: Let me just, let me just interrupt, before I lose that thought. So you already made up your mind regardless of what the stats show that if it, certain things show that it didn’t make sense, you wouldn’t, you would try to find out a way to…

DeStefano: No, that’s not what we said. I’m just saying, you know, you interpret, you interpret findings, also, you know, there’s the statistics, then you have to also interpret, bring in things like biological plausibility, how do you interpret these results? So I think we had pretty strong evidence that these results at 36 months were primarily a reflection of requirements to attend early intervention special education programs for the, for the children with autism…

Attkisson: Is there any possibility that it is biologically plausible and you just haven’t, you know, that that’s, the consensus is that it’s not, among you guys, but that it is and you’re overlooking that?

DeStefano: I’m, I’m not aware of any data that would say, you know, that would s-, you know, that would say that, uh, you would have, um, onset of autism after 36 months.
Granted DeStefano’s remark that “autism, as you probably are aware, is a condition that really probably has its start while the child is still in the womb”, which many believe, what did this have to do with a vaccine like MMR exacerbating or bringing on the first signs or symptoms of an autism, perhaps from chronic infection first acquired in the womb—even if the vaccination was given just before 36 months of age? Moreover, now that the real results of the 2004 autism–vaccine study were revealed, why did they show a 340 per cent increase in young black children given the MMR before age 36 months? Autism is certainly not more prevalent in African-American children than in whites. In fact, the rates of autism in black children are considerably less.25

Sir William Osler, co-founder of Johns Hopkins Hospital and frequently described as the Father of Modern Medicine, mentioned that “a quiescent malady” such as congenital syphilis and tuberculosis “may be lighted into activity by vaccination”.26 So, perhaps the differential with the MMR might lie in the racial differential in one of the diseases which Osler mentioned. The CDC’s own statistics, for example, show that the percentage of tuberculosis in blacks is way out of proportion to their percentage in the US population, with TB rates being seven times higher in blacks than in whites.27

The MMR, then, could very well be acting adversely in the fashion described by Osler through statistical evidence alone—but there was much, much more.

Exhibit 1: Known Contents of the MMR Vaccine

Of all the issues of concern regarding a vaccination–autism link, one of the most prominent is, according to Sugarman28, the continued use of thimerosal in certain influenza shots, especially the widely used and economical multidose influenza vials through which many patients can be vaccinated using the same vial of influenza vaccine. Most of the legal battles over vaccines and autism, Sugarman mentions, have alleged that the first signs and symptoms of autism were precipitated by this mercury-containing preservative, which used to be an ingredient in many childhood vaccines and still is found in some of the multidose flu shots used by paediatricians.

Others have argued that the culprit is the measles, mumps and rubella vaccine (MMR) or perhaps MMR in combination with thimerosal. Yet in many other autistic cases, a direct causal link is not there for either. Nevertheless, the thought lingers that these agents as well as other vaccines could, in certain cases, still trigger the first signs and symptoms of autism. In the meantime, the lay term pointing to “toxins” in the vaccines is inadequate.

Whenever one deals with biologicals originating from the cow, the calf, the chicken, the chicken embryo, the swine or from another human in the form of albumen or a foetal cell line—all found in the MMR—one hits upon the potential of such biologicals used in the vaccine bearing or being contaminated by mycobacterial infection. This holds particularly true of a vaccine like MMR, whose components can potentially carry Mycobacterium tuberculosis from human fluids or tissue, Mycobacterium avium from poultry (a subspecies of which is Mycobacterium paratuberculosis) or Mycobacterium bovis from cows or the foetal tissue of cows. And in this case, we are not talking about mere environmental exposure: we are talking about direct injection through vaccination.

To say that the US Department of Health and Human Services’ Food and Drug Administration is aware of this is a stark understatement. One just need download its “Guidance for Industry”29 for viral vaccines—a 50-page paper—each page carefully framed under the heading “Contains Nonbinding Recommendations”. In such a “Guidance for Industry”, the words and warnings for human Mycobacterium tuberculosis as well as mycobacteria from animal sources are scattered throughout.

The MMR vaccine is generally administered to children around the age of one year (12 months), with a second dose before starting school (i.e., at age 4–5).
MMR is front-loaded with such entities as foetal bovine serum (FBS). Foetal bovine serum or foetal calf serum is the blood fraction remaining after the natural coagulation of blood, followed by centrifugation to remove any remaining red blood cells. FBS comes from the blood drawn from a bovine foetus via a closed system of collection at the slaughterhouse.30

This presents a problem.

Johne was the first to report a case of congenital TB in animals, his specimen consisting of the very same bovine foetus.31 Macroscopically though, he noted, the uterus and placenta of the pregnant cow were normal.

Autism has already been linked to be triggered in certain cases by an atypical tuberculosis called paratuberculosis, frequently found in cattle.32 A critical review found that this same form of tuberculosis can infect bovine cow foetuses about nine per cent of the time when the bovine mother has subclinical disease, and an average of 39 per cent of cow foetuses in cases where the expectant cow shows signs of clinical paratubercular disease.33

Industry Turns a Blind Eye

Once the most prevalent infectious disease of cattle in the US, yet today largely ignored and purportedly no longer nearly the problem it once was, bovine TB caused more losses among US farm animals in the early part of the 20th century than all other infectious diseases combined.34

By 1917, the situation had become so grave in hogs and cattle that the Cooperative State–Federal Tuberculosis Eradication Program, administered by the US Department of Agriculture (USDA) and the Animal and Plant Health Inspection Service (APHIS), had to be instituted. For in 1917, it was estimated that 25 per cent of deaths from tuberculosis in adult humans were caused by animal tuberculosis.35

Although it is claimed that in the United States TB “once was” a common disease of farm poultry flocks, cattle, swine and people, this author remains unimpressed with present governmental agency attempts to diagnose both the bacilli and, moreover, their predominant cell-wall-deficient forms.

As another strategy to hide the true incidence of TB, our domestic animals and poultry are often killed young before the onset of tubercular disease becomes obvious.36 Furthermore, most inspection is done visually.

In the meantime, the USDA continues to downplay and ignore the actual incidence of TB not only in cows and their milk (especially with regard to paratuberculosis) but in poultry and eggs. For example, when forced to address the issue of finding paratuberculosis in containers of milk, the USDA initiated a study in 1998, but first used methods like freezing and ultrasound to damage the very mycobacteria being tested for, and then ignored established techniques to isolate mycobacteria related to TB, growing samples on a culture medium which was considered inadequate—and for not nearly a long enough time.37, 38 Not surprisingly, the USDA results in that study were all negative.

MMR vaccine also contains WI-38 human lung fibroblasts. A fibroblast is the most common type of cell found in our connective tissue. Although no study has addressed the possibility of mycobacteria contaminating such fibroblasts, Higuchi et al. in 2002 found that the all too common and dangerous strain of tuberculosis H37Rv can invade and grow in a WI-38 foetal cell line quite efficiently.39

Actually, WI-38 is a human cell culture line composed of fibroblasts which were derived from the lung tissue of a three-month-old white female foetus. It is commercially known as “WI-38 (ATCC® CCL-75™)”. First sequestered by Hayflick and Moorhead40 in the 1960s, WI-38 has been used ever since in the production of many of our vaccines.

Finally, in the MMR we have the chick embryo cell culture used to propagate the mumps and rubella (German measles) viruses.

Although authorities seem totally unconcerned today, Hull41, Trylich42 and Romanenko43 all certainly saw the danger of tuberculosis from tubercular hens getting into embryonated chicken eggs.

Chick embryo cell cultures also consist of hydrolysed gelatin as well as human albumen. Hydrolysed gelatin is the hydrolysed connective tissue from an animal—usually from the skin and bones of an animal, generally a pig. The process involves adding enzymes which break down the proteins. It separates the proteins along hydrogen bonds. Then the foetal calf serum from the blood drawn from a bovine foetus through a closed system at a slaughterhouse is also added.

Against all of this you have the antibiotic neomycin added to the MMR in an attempt to contend with any unknown mycobacterial content in the vaccine—which neomycin by itself is totally unequipped to do.

Almost lost in the package insert of Merck’s popular MMR II vaccine is the admission that no studies have been reported to date of the effect of the measles virus vaccine in the MMR on untreated tuberculous children: “However, individuals with active untreated tuberculosis should not be vaccinated.”44 Although infants and children are “individuals”, so difficult is it to isolate TB in them that some paediatric experts recommend a spinal tap in all children under 12 months of age.45 Yet it is specifically at 12 months of age that mandatory MMR vaccination first cuts in.

The Science of Denial

“They believe that TB is an extinct disease. I don’t know why.”46 So said Mario Raviglione, MD, infectious diseases specialist and Director of the World Health Organization’s Global Tuberculosis Programme about a disease which WHO admits infects a third of the world.

While frontal assaults on thimerosal, the MMR vaccine and the overburdened vaccine schedule have justifiably sprung up, a satisfactory and comprehensive explanation as to why and how vaccines might trigger autism has not.

In a 2013 interview, Mel Spigelman, MD, President and CEO of the TB Alliance, a nonprofit TB drug research group based in New York, said of tuberculosis: “It’s still in the US, we just don’t recognize it.”47 Perhaps this is because we just don’t want to recognise it—in ourselves, in our livestock, in the products from our livestock, and in the biologicals used in our vaccine manufacture. But it won’t let us not recognise it.

Meanwhile, we have with tuberculosis one of the few diseases that could possibly account for the soaring rate of autism—a disease which is not only the most common cause of infectious death in children48 but, according to WHO, in their child-bearing mothers aged 15–44, one million of whom die from it each year49; a disease which is extremely neurotropic (nerve-seeking) and remains, worldwide, the most common type of central nervous system infection, particularly among children50; and a disease in which 20–25 per cent of such children can manifest mental retardation as well as other anomalies often associated with neurodevelopmental disorders and the autistic spectrum.51

By 2007, Rzhetsky, in a proof-of-concept biostatistical analysis of 1.5 million patient records, had found significant genetic overlap in victims of autism and those with TB.52

No one who has done a serious study of the literature, old and new, can doubt for a second that the incidence and transfer of maternal tuberculosis, even when there are no maternal symptoms and the disease is latent, are being grossly underestimated. This has been duly noted in recent publications, but more in depth in the past writings and solid research of Charles C. Norris, Pennsylvania physician, gynaecologist, obstetrician and medical investigator. Norris wrote:53

“Pregnancy is prone to light up a latent or chronic tuberculosis, and thus produce a condition in which a bacillemia [blood-borne infection] is likely to be present. Secondary infection and metastasis [by TB] occur in the placenta in the same manner in which they affect other portions of the body.”

“Baumgarten’s theory…has done much to show that congenital tuberculosis may occur, and that tubercle bacilli may remain latent in the child for quite prolonged periods. It has been shown that the tubercle bacillus may remain latent for some time. Under such circumstances congenital tuberculosis is probably mistaken for, and classified as, a postnatal infection [of childhood].”

“Undoubtedly the strong uterine contractions incident to labor constitute a most important factor in the transmission of tubercle bacilli at the end of pregnancy. Organisms that, prior to the onset of labor, were lodged in the placenta or in the intervillous spaces, may, as the result of these contractions, be forced into the fetal circulation. Schlimpert, Schmorl and Geipel, Warthin and Cowie, Dardeleben, and others are very insistent on this point.”

Thus, throughout the first half of the 20th century, the method of choice for an expectant mother with proven TB—if it was found—was early termination of pregnancy.54

Others, like Norris, also saw the possibility of maternal– foetal transfer of even non-symptomatic TB as not uncommon.55-59 Dr Henry William Welch, often called the Dean of American Medicine and a colleague of Osler at Johns Hopkins, was already on record as saying that the mere inability to pick up TB in the foetus or newborn wasn’t an argument against frequent transmission to them.60 There were just too many factors involved, such as the hostile, low-oxygen environment of foetal blood, which could tame even the most virulent TB bacilli into dormant forms for some time, making diagnosis difficult to impossible. The history of associating what we presently call “autism” with tuberculosis is an old one, going back to John Langdon Down, a subset of whose young patients clearly were the first cases of “autism” on record. Such associations persist.61-63

While a blanket statement that vaccinations cause autism cannot be supported, the assertion that certain vaccines can aggravate and precipitate the first signs of an autism originating from chronic disease cannot be denied. A vaccine or group of vaccinations could trigger autism simply by inadvertently introducing, through their human, animal and poultry components, mycobacterial elements into the mother, foetus or young child. Mixed tubercular infection in man with human and fowl TB isn’t a new discovery: Tsukamura and Mizuno64 found it rather commonly in their 1981 study. Once introduced, one tubercular form can potentiate and make more virulent an existing tubercular infection.

Another way in which vaccine components can trigger autism was laid out by Hartz in his JAMA probe regarding how mercury compounds like thimerosal activate and make much worse an existing tubercular infection.

Finally, in vaccinations there are adjuvant oils or lipids, many of which do not have to be reported, used to increase a vaccine’s potency. Such oils or lipids are cholesterol precursors, becoming cholesterol in the body.65 Such a cholesterol surge is a big boost for any dormant systemic tuberculosis already in the body, whose very ability to maintain infection is linked to its ability to acquire and utilise cholesterol. So crucial is this unique ability of TB to use cholesterol in the body for both carbon and energy sources that if it were not for its ability to consume cholesterol, tuberculosis, unlike other pathogens, would be unable to resist eradication through cytokine attack and the attempts of certain activated white blood cells called macrophages to starve it of essential nutrients.66

In comparative and simpler terms, one might look at an injection of certain vaccine oil or lipid adjuvants, squalene among them, whether inside or outside of a vaccination, as lighting up chronic foci of tuberculosis like a Christmas tree; or, in the words of Sir William Osler, chronic tuberculosis “may be lighted into activity by vaccination”—for a few reasons, key to why vaccines, in certain cases, can trigger what a child’s parents clearly see as the first signs of autism in their toddler.
About the Author:
Pennsylvania internist and medical researcher Lawrence Broxmeyer, MD, was on the staff at NY affiliates of Downstate, Cornell and NYU for 14 years. He was the originator and lead author of a novel way to kill AIDS mycobacteria (J. Infectious Diseases 2002; 186[8]:1155-60). His ideas on phagotherapy are still in use today. He contributed a chapter to the textbook Patho-Biotechnology (Landes Bioscience, 2008). His peer-reviewed articles are on PubMed. He is the author of several books including AIDS: What the Discoverers of HIV Have Never Admitted (new edition, July 2014; see review in 20/01) and Autism: An Ancient Foe Becomes a Modern Scourge (2012). He has had several articles published in NEXUS: “Ebola…or African Strains of Tuberculosis” (22/01); “Influenza and the TB Connection” (19/01-02); and “The Untold Truth About Cancer” (17/01-02).
Dr Broxmeyer can be contacted by email at nyinstituteofmedicalresearch@ For more information, visit

Endnotes accompanying the article “Vaccines as an Autism Trigger: A TB Link?”
by Lawrence Broxmeyer, MD
Article published in NEXUS Magazine, February–March 2015 (vol. 22, no. 2)
California Department of Developmental Services, Sacramento, 1999
1. Developmental Services System. Changes in the Population of Persons with Autism and Pervasive Developmental Disorders in California’s Developmental Services System: 1987 through 1998,

Division of Communicable Disease Control, Richmond, California, 1999
2. Ussery, X.T., Valway, S.E., McKenna, M., et al. Epidemiology of Tuberculosis among Children in the United States. Pediatric Infectious Disease Journal 1996; 15:697-704
3. Dolin, P.J., Raviglione, M.C., Kochi, A. Global Tuberculosis Incidence and Mortality during 1990–2000. Bull. of the World Health Organization 1994; 72:213-20
4. Subramanian, P. Extrapulmonary Tuberculosis. In Walsh & Hoyt’s Clinical Neuro-Opthalmology, Vol. 3. Edited by Neil R. Miller, MD and Nancy Newman, MD. Philadelphia: Lippincott, Williams & Wilkins, 2005, p. 2690

Santa Clara County, California, March 2006
5. Bay City News Service. Santa Clara County has more tuberculosis cases than most U.S. states,
6. Center for Immigration Integration. University of Southern California,

Centers for Disease Control and Prevention, Atlanta, Georgia, September 2008
7. Christie, L. J., Loeffler, A. M., Honamand, S., Flood, J. M., Baxter, R., Jacobson, S., Alexander, R., Glaser, C.A. Diagnostic Challenges of Central Nervous System Tuberculosis. Emerg. Infec. Dis. 2008 Sep; 14(9):1473-75

Subcommittee on Human Rights and Wellness, Washington, DC, September 2004
8. Hearing before the Subcommittee on Human Rights and Wellness of the Committee on Government Reform, House of Representatives. One Hundred Eighth Congress. Second session. September 8, 2004. Serial No. 108-262. U.S. Government Printing Office. Washington, DC, 2005,; video of Hearing available at
9. Centers for Disease Control and Prevention (CDC). Influenza Vaccines – United States, 2014–15 Influenza Season,
10. CDC. Children, the Flu, and the Flu Vaccine,
11. CDC. Pregnant? Get a Flu Shot!,
12. Smithburn, K.C., Kempf, G.F., Zerfas, I.G., Gilman, L.H. Meningococcic Meningitis: a clinical study of one hundred and forty-four epidemic cases. Journal of the American Medical Association (JAMA) 1930; 95(11):776-780
13. Powell, H.M. and Jamieson, W.A. Merthiolate as a germicide. Am. J. Hyg. 1931; 13:296-310
14. Hartz, H. J. Ultimate Results in the Treatment of Pulmonary Tuberculosis with Mercury Succinimid. JAMA 1910 Sep; 55(11):915-18
15. Hartz, ibid., p. 917
16. Tauber, M.G., Sande, M.A. The impact of penicillin on the treatment of meningitis. JAMA 1984; 251:1877-80
17. Ramachandran, T.S. Tuberculous Meningitis Differential Diagnoses. Medscape,
18. Kempf, G.F., Gilman, L.H., Zerfas, L.G. Meningococcic meningitis and epidemic meningo-encephalopathy: reports of one hundred and twenty-two additional cases in the Indianapolis epidemic and of sixty-eight cases of an epidemic meningo-encephalopathy. Arch. Neur. Psych. 1933; 29(3):433-453
19. Sweany, H.C. Mutation forms of the tubercle bacillus. JAMA 1926; 87(15):1206-1211
20. Mellon, R.R., Fisher, L.W. New studies on the filterability of pure cultures of the tubercle group of microorganisms. J. Infect. Dis. 1932; 51:117-128
21. Kempf, op. cit., p. 450

Uncommon Valour
22. Statement of William W. Thompson, PhD, regarding the 2004 article examining the possibility of a relationship between MMR vaccine and autism,
23. DeStefano, F.I., Bhasin, T.K., Thompson, W.W., Yeargin-Allsopp, M., Boyle, C. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan Atlanta. Pediatrics 2004 Feb; 113(2):259-66
24. Audio of Sharyl Attkisson telephone interview with CDC’s Dr. Frank DeStefano about his questioned MMR-autism study, August 26, 2014,
25. Child Trends DataBank. Figure 2. Percentage of Children Ages 3-17 with Autism Spectrum Disorders (ASD), by Race/Hispanic Origin, 2007 and 2011/12,
26. Duke, W.D. Multiple Infections – A study of the relation of one infection to another. JAMA 1918 Nov 23; 71(21):1703-1706
27. CDC Factsheet. Tuberculosis In Blacks,

Exhibit 1: Known Contents of the MMR Vaccine
28. Sugarman, S.D. Cases in vaccine court—legal battles over vaccines and autism. N. Engl. J. Med. 2007; 357(13):1275-77
29. U.S. Department of Health and Human Services Food and Drug Administration (FDA). Guidance for Industry. Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications. Center for Biologics Evaluation and Research. Rockville, MD, February 2010 (50 pp.),
30. Jochems, C. et al. The Use of Fetal Bovine Serum: Ethical or Scientific Problem?. Altern. Lab Anim. 2002 Mar-Apr; 30(2):219-227
31. Norris, Charles C. Gynecological and Obstetrical Tuberculosis, New York & London: D. Appleton & Co., 1923, p. 58: Johne, H.A. Deutsche Zeitschr. f. Thiermed. (Leipzig) 23:207; also Forts. d. Med. 1885; 3:108
32. Dow, C.T. Mycobacterium paratuberculosis and autism: is this a trigger?. Med. Hypotheses 2011 Dec; 77(6):977-81. Epub 2011 Sep 7
33. Whittington, R.J., Windsor, P.A. In utero infection of cattle with Mycobacterium avium subsp. paratuberculosis: a critical review and meta-analysis. Vet J. 2009 Jan; 179(1):60-9. Epub 2007 Oct 24

Industry Turns a Blind Eye
34. USDA Factsheet: Bovine Tuberculosis. Animal and Plant Health Inspection Service, Maryland, August 2002
35. Youmans, G.P. Tuberculosis. Philadelphia: W.B. Saunders Co., 1979
36. Mutalib, A.A., Riddell, C. Epizootiology and Pathology of Avian Tuberculosis in Chickens in Saskachewan. Can. Vet. J. 1988 Oct; 29(10):840-842
37. Stabel, J.R., Steadham, E.M., Boilin, C.A. Heat Inactivation of Mycobacterium paratuberculosis in Raw Milk: Are Current Pasteurization Conditions Effective?. Applied and Environmental Microbiology 1997; 63:4975-77
38. Greger, M. Paratuberculosis and Crohn’s Disease: Got Milk? USDA Farce? section. January 2001,
39. Higuchi, K., Harada, N., Yamada, H., Kobayashi, K., Takeda, M. The invasion of Mycobacterium tuberculosis into non-phagocytic cells. Kekkaku 2000 Nov; 75(11):649-59
40. Hayflick, L., Moorhead, P.S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 1962; 25:585-621
41. Hull, T.G. Diseases Transmitted from Animals to Man. Springfield, Illinois: Charles G. Thomas Publisher, 1947, 3rd ed.
42. Trylich, C. Some Thoughts on Tuberculosis of Domestic Animals Particularly as Relating to Meat Inspection. Canadian Journal of Comparative Medicine 1957 Apr; 21(4):121-133
43. Romanenko, V.F., Diachenko, A.M., Kravchenko, N.A., Mikitin, O.O. Experimental findings on the role of chicken eggs in the epidemiology of tuberculosis. Probl. Tuberk. 2001; 6:40-1
44. Package Insert. M-M-R® II (Measles, Mumps, and Rubella Virus Vaccine Live). Merck & Co., Inc., Whitehouse Station, NJ 08889. Revised June 2014,
45. Rock, R.B., Olin, M., Baker, C.A., Moliter, T.W., Peterson, P.K. Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects. Clinical Microbiology Reviews 2008 Apr; 21(2):243-261

The Science of Denial
46. Abrams, L. This is the infectious disease you should be worried about. October 24, 2014,
47. Reuters. Los Angeles health officials concerned about TB outbreak on skid row. February 22, 2013,
48. Walia, R., Hoskyns, W. Tuberculous meningitis in children: problem to be addressed effectively with thorough contact tracing. Eur. J. Pediatr. 2000 Jul; 159(7):535-38
49. WHO. TB Is Single Biggest Killer Of Young Women. Press Release, Geneva, Switzerland. WHO/40, 26 May 1998
50. Waecker, N.J. Jr, Connor, J.D. Central nervous system tuberculosis in children: a review of 30 cases. Pediatr. Infect. Dis. J. 1990; 9:539-543
51. Garg, P.K. Tuberculosis of the central nervous system. Postgraduate Med. J. 1999; 75:133-40
52. Rzhetsky, A., Wajngurt, D., Park, N., Zheng, T. Probing Genetic Overlap among Complex Human Phenotypes. Proceedings of the National Academy of Sciences 2007 Jul 10; 104(28):11694-99
53. Norris, Charles C., Gynecological and Obstetrical Tuberculosis, New York & London: D. Appleton & Co., 1923, pp. 46, 56, 54
54. Kobrinsky, S. Pregnancy and Tuberculosis. Canad. M.A.J. 1948 Nov; 59:462-64
55. Warthin, A.S., Cowie, D.M. A Contribution in the Causuitry of Placental and Congenital Tuberculosis. J. Infectious Diseases 1904; 1:140-169
56. Weber, F.P. Congenital tuberculosis. Br. J. Children’s Dis. 1916; 13:321,359
57. Dorozhkova, I.R., Deshkekina, M.F., Ereneeva, A.S., Zemskova, Z.S., Ilyiash, N.I, Zhukova, E.K. Congenital Tuberculosis. Probl. Tuberk. 1972; 50(10):80-83
58. Insanov, A.B., Gadzhiev, F.S. Comparative Analysis of the Results of Spinal Fluid Microbiological Study in Children and Adults Who Suffered from Tuberculous Meningitis. Probl. Tuberk. 1996; 5:25-28
59. Adhikari, M., Pillay, T., Pillay, D.G. Tuberculosis in the Newborn: An Emerging Problem. Pediatr. Infect. Dis. 1997; 16:1108–12
60. Welch, W.H. Papers and Addresses, Vol. 2: Bacteriology. Baltimore: Johns Hopkins University Press, 1920
61. Schoeman, C.J., Herbst, I., Nienkemper, D.C. The Effect of Tuberculous Meningitis on the Cognitive and Motor Development of Children. South African Medical Journal 1997 Jan; 87(1):70-72
62. Gourion, D., Pélissolo, A., Orain-Pélissolo, S., Lepine, J.P. Neonatal Tuberculous Meningitis in a Patient with Asperger’s Syndrome. Journal of Autism and Developmental Disorders 2003 Oct; 33(5):559-60
63. Broxmeyer, L. Autism: An Ancient Foe Becomes a Modern Scourge – The Return of a Stealth Pathogen. North Charleston, SC: CreateSpace, 2012 (159 pp.)
64. Tsukamura M., Mizuno, S. Occurrence of Mycobacterium tuberculosis and strains of the Mycobacterium avium–M. intracellulare complex together in the sputum of patients with pulmonary tuberculosis. Tubercle 1981; 62:43-46
65. Carlson, B.C., Jansson, A.M., Larsson, A. The Endogenous Adjuvant Squalene Can Induce a Chronic T-Cell-Mediated Arthritis in Rats. American Journal of Pathology 2000 Jun; 156(6):2057-65
66. Pandey, A.K., Sassetti, CM. Mycobacterial Persistence Requires the Utilization of Host Cholesterol. PNAS 2008 Mar 18; 105(11):4376-80

Cancer and the Science of Denial -with Breast Cancer/Long Island Breast Cancer

August 11, 2017

By Dr. Lawrence Broxmeyer MD

Broxmeyer L. Cancer and the Science of Denial. J Tumor Med Prev 2017;1(3):1-26


View this document on Scribd

Lawrence  Broxmeyer, MD

Submitted: May 24, 2017  Published: July 14, 2017

The word ‘cancer’ is of Latin derivation and means crab. By the turn of the 20th Century organized medicine had come to the conclusion that it was not a matter of whether infectious disease caused cancer, but which one. Then, in 1910, certain American medical powers did a 180-degree rotation –abruptly deciding that cancer was not caused by a microbe. This flew in the face of over two hundred years of research in which a cancer germ had been discovered and rediscovered. Of all the infectious possibilities for cancer, unquestionably the one class of microbes that has been long recognized to most consistently mimic and imitate ‘cancer’ at both clinical and tissue levels were the mycobacteria of the family Actinomycetales of which tuberculosis and leprosy are premier examples. The association of TB with carcinoma was initially described about 200 years ago by Bayle who considered the lung malignancy ‘cavitation cancereuse’ to merely be one of the various types of tuberculosis. Ever since, almost as if in reflex to the obvious –the potential association between TB and subsequent development of cancer has drawn active investigation.

1. Falagas ME, Kouranos VD, Athanassa Z, Kopterides P (2010) Tuberculosis and malignancy. Q J M 103(7): 461-487.
2. Yu YH, Liao CC, Hsu WH, Chen HJ, Liao WC, et al. (2011) Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study. J Thorac Oncol 6(1): 32-37.
3. Zhang S, Guang-ling Z, Yan-sheng T (2009) Detection of Mycobacterium tuberculosis L-form infection in tissues of lung carcinoma. Chin J Public Health 25: 1317-1318.
4. Chauhan A, Madiraju MV, Fol M, Lofton H, Maloney E, et al. (2006) Mycobacterium tuberculosis Cells Growing in Macrophages Are Filamentous and Deficient in FtsZ Rings. J Bacteriol 188(5): 1856-1865.
5. World Health Organization, Global Tuberculosis Report (2016) Geneva: World Health Organization, USA.
6. Yang B, Tian Y, Cui X, Zhang W, Ma Y, et al. (2013) Detection of Mycobacterium tuberculosis L-forms and MPB64 in breast cancer tissues. The Journal of Practical Medicine 29(15): 2552-2555.
7. KJ Ryanand, CG Ray (2004) Sherris Medical Microbiology, 4th (edn), McGraw-Hill, USA.
8. Guliang H, Tefu L (1999) Mycobacterium tuberculosis L-forms. Microbial Ecology in Health and Disease 10: 129-133.
9. Kakkar S, Kapila K, Singh MK, Verma K (2000) Tuberculosis of the breast. A cytomorphologic study. Acta Cytol 44(3): 292-296.
10. Puneet, Satyendra KT, Ragini R, Sanjay Singh, Guptav SK, et al. (2005) Breast Tuberculosis: Still Common In India. The Internet Journal of Tropical Medicine 2(2).
11. Vagholkar K, Gopinathan I, Pandey S, Maurya I (2014) Tuberculosis of the Breast (Case Report and Review of Literature). The Internet Journal of Surgery 31(1).
12. Liu Y, Lin TF (1996) Studies on morphology and electron-micrographic analysis of M tuberculosis filamentous L-forms. Chinese J Micro Boil Immunobiol 16(Suppl 2): 49.
13. Dai YH, Lin TF, Huang GL (1996) A serial study on mycobacteria L-forms. Zhongguo Fanglao Zazhi 45-46.
14. Shleeva MO, Salina EG, Kaprel’iants AS (2010) Dormant form of Mycobacterium tuberculosis. Mikrobiologiia 79(1): 3-15.
15. Marcova N, Slavchev G, Michailova L (2012) Unique biological properties of Mycobacterium tuberculosis L-form variants: impact for survival under stress. Int Microbiol 15(2): 61-68.
16. Warthin AS (1899) The Coexistence of Carcinoma and Tuberculosis of the Mammary Gland. Am J M Sci 118: 25-35.
17. Rosen PP (1979) Multinucleated mammary stromal giant cells-a benign lesion that simulates invasive carcinoma. Cancer 44(4): 1305-1308.
18. Hektoen L (1898) The fate of the giant cells in healing tuberculous tissue, as observed in a case of healing tuberculous meningitis. J Exp Med 3(1): 21-52.
19. Iakimenko LN (1976) Changes in the Mitotic Regime of a Cell Culture under the Influence of Sensitins. Biull Eksp Biol Med 81(2): 237-239.
20. Golubchik IS, Iakimenko LN, Lazovskaya AL (1972) Effect of Tuberculin on the Mitotic Regime in Cell Cultures. Biull Eksp Biol Med 73(5): 105-107.
21. Rao VV, Gupta EV, Thomas IM (1990) Chromosome Damage in Untreated Tuberculosis Patients. Tubercle 71(3): 169-172.
22. Much H, Uber Die Granuläre, Nach Ziehl Nicht Färbbare Form des Tuberkulosevirus. Beit Z Klin Tuberk 8th (edn), 85(1907): 85-97.
23. Kahn MC (1929) The Developmental Cycle of the Tubercle Bacillus as Revealed by Single Cell Cultures. Am Rev Tuberc 20(1929): 150.
24. Ribbert H (1894) Beitrage zur Histogenese des Carcinoms. Arch Pathol. Anat U Physiol Virchow’s 135: 433-469.
25. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, et al. (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science 266(5192): 1865-1869.
26. Huang YQ, Li JJ, Kaplan MH, Poiesz B, Katabira E, et al. (1995) Human herpesvirus-like nucleic acid in various forms of Kaposi’s sarcoma. Lancet 345(8952): 759-761.
27. Floto RA, Sarkar S, Perlstein EO, Kampmann B, Schreiber SL, et al. (2007) Small Molecule Enhancers of Rapamycin-Induced TOR Inhibition Promote Autophagy, Reduce Toxicity in Huntington’s Disease Models and Enhance Killing of Mycobacteria by Macrophages. Autophagy 3(6): 620-622.
28. Jang WS, Kim S, Podder B, Jyoti A, Nam KW, et al. (2015) Anti-Mycobacterial Activity of Tamoxifen against Drug-Resistant and Intra-Macrophage Mycobacterium tuberculosis. J Microbiol Biotechnol 25(6): 946-950.
29. Ertem E, Yüce K, Karakartal G, Onal O, Yüce G (1990) The antituberculous effect of bleomycin. J Antimicrob Chemother 26(6): 862-863.
30. Gajadeera C, Willby MJ, Green KD, Shaul P, Fridman M, et al. (2015) Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG. J Antibiot (Tokyo) 68(3): 153-157.
31. Forbes L, Ebsworth-Mojica K, Di Done L, Li S-G, Freundlich JS, et al. (2015) A High Throughput Screening Assay for Anti-Mycobacterial Small Molecules Based on Adenylate Kinase Release as a Reporter of Cell Lysis. PLoS One 10(6): e0129234.
32. Subramanyam CSV, Ahuja JM, Sapra ML (1975) Miliary tuberculosis simulating acute myeloid leukemia- review of literature and report of a case. Ind J Tub 22(4): 136-141.
33. Ananthan S, Faaleolea ER, Goldman RC, Hobrath JV, Kwong CD, et al. (2009) High throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv. Tuberculosis (Edinb) 89(5): 334-353.
34. Greenstein RJ, Su L, Shahidi A, Brown WD, Clifford A, et al. (2014) Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and Vitamins A and D: clinical implications. Int J Infect Dis 26: 37-43.
35. Zhang L, Zheng Y, Callahan B, Belfort M, Liu Y (2011) Cisplatin Inhibits Protein Splicing, Suggesting Inteins as Therapeutic Targets in Mycobacteria. J Biol Chem 286(2): 1277-1282.
36. Batista AA, Back DF, Lang ES, Ellena J, Lemos S, et al. (2010) Palladium (II) complexes with thiosemicarbazones. Syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity. J Braz Chem Soc 21(7): 1177-1186.
37. Datta M, Via LE, Kamoun WS, Liu C, Chen W, et al. (2015) Antivascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc Natl Acad Sci U S A 112(6): 1827-1832.
38. Lamb R, Ozsvari B, Lisanti CL, Tanowitz HB, Howell A, et al. (2015) Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease. Onco target 6(7): 4569-4584.
39. Watt B, Rayner A, Harris G (1996) Comparative activity of azithromycin against clinical isolates of mycobacteria. J Antimicrob Chemother 38(3): 539-542.
40. Walker NF, Clark SO, Oni T, Andreu N, Tezera L, et al. (2012) Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases. Am J Respir Crit Care Med 185(9): 989-997.
41. Pang H, Li G, Wan L, Jiang Y, Liu H, et al. (2015) In vitro drug susceptibility of 40 international reference rapidly growing mycobacteria to 20 antimicrobial agents. Int J Clin Exp Med 8(9): 15423-15431.
42. Shu X, Gao YT, Linet MS, Brinton LA, Gao RN, et al. (1987) Chloramphenicol use and childhood leukemia in Shanghai. Lancet 2(8565): 934-937.
43. Yuan ZR, Shi Y (2008) Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells. Cancer Res 68(12): 4875-4881.
44. Smith RM, Joslyn DA, Gruhzit 0M, McLean IW, Penner MA, et al. (1948)Chloromycetin: biological studies. J Bacteriol 55: 425.
45. Youmans GP, Youmans AS, Osborne RR (1948) Tuberculostatic action of Chloromycetin in vitro and in vivo. Proc. Soc. Exp Biol & Med 67: 426.
46. Rattan R, Ali Fehmi R, Munkarah A (2012) Metformin: an emerging new therapeutic option for targeting cancer stem cells and metastasis. J Oncol 2012: 928127.
47. Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K (2009) Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 69(19): 7507-7511.
48. Singhal A, Jie L, Kumar P, Hong GS, Leow MK, et al. (2014) Metformin as adjunct antituberculosis therapy. Sci Transl Med 6(263): 263ra159.
49. Esumi H, Lu J, Kurashima Y, Hanaoka T (2004) Antitumor activity of pyrviniumpamoate, 6-(dimethylamino)-2-[2-(2,5-dimethyl-1-phenyl-1H-pyrrol 3-yl)ethenyl]-1-methyl-quinolinium pamoate salt, showing preferential cytotoxicity during glucose starvation. Cancer Sci 95(8):685-690.
50. Lougheed KEA, Taylor DL, Osborne SA, Bryans JS, Buxton RS (2009) New Anti tuberculosis agents amongst known drugs Tuberculosis (Edinb) 89(5): 364-370.
51. Maitra A, Bates S, Kolvekar T, Devarajan PV, Guzman JD, et al. (2015) Repurposing -a ray of hope in tackling extensively drug resistance in tuberculosis. Int J Infect Dse 32: 50-55.
52. Livingston (1972) Virginia Wuerthele-Caspe. Cancer: a new breakthrough, Nash Publishing, Los Angeles, USA.
53. Ewing J (1919) Neoplastic diseases. 2nd (edn), WB Saunders, Philadelphia, USA, p. 1027.
54. Rusch HP (1985) The beginnings of cancer research centers in the United States. J Natl Cancer Inst 74(2): 391-403.
55. Hunter D (1978) The diseases of occupation. 6th (edn), Little Brown and Company, Boston, UK.
56. Fraenkel E, Much H (1910) Uber die Hodgkinsche Krankheit (Lymphomatosis granulomatosa), insbesondere derenAtiologie. Z Hyg 67: 159-200.
57. L’Esperance E (1931) Studies in Hodgkin’s disease. Annal Surg 93(1): 162-168.
58. Livingston V, Allen RM (1948) Presence of consistently recurring invasive mycobacterial forms in tumor cells. Microscop Soc Bull 2: 5-18.
59. Sweany HC (1926) Mutation forms of the tubercle bacillus. JAMA 87(15): 1206-1211.
60. Beinhauer LG, Mellon RR (1938) Pathogenesis of non-caseating epithelioid tuberculosis of hypoderm and lymph glands. Arch Dermatol Syph 37: 451-460.
61. Mellon RR, Fisher LW (1932) New studies on the filterability of pure cultures of the tubercle group of microorganisms. J Infect Dis 51(1):117-128.
62. Livingston V, Alexander-Jackson EA (1950) Cultural properties and pathogenicity of certain microorganisms observed from various proliferative and neoplastic diseases (published under Virginia Wuerthele-Caspe). Am J Med Sci 220: 636-648.
63. Boesch M (1960) The long search for the truth about cancer. GP Putnam’s Sons, New York, USA.
64. Glover T, Scott M (1926) A study of the Rous chicken sarcoma No.1. Can Lancet Practitioner 66(2): 49-62.
65. Goodman LS, Gilman A (1975) The pharmacologic basis of therapeutics. 5th (edn), MacMillan, New York, USA.
66. Skirvin JA, Relias V, Koeller J (1996) Long term sequelae of cancer chemotherapy. Highlights Oncol Practice 14(2): 26-34.
67. Pukkala E, Kyyronen P (2002) Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population based case-control study. Int J Cancer 100(3): 337-341.
68. Mankiewicz E (1965) Bacteriophages that lyse Mycobacteria andCorynebacteria and show cytopathogenic effect on tissue cultures of renal cells of Cercopithecus aethiops. Can Med Assn J 92: 31-33.
69. Dubos R (1987) The White Plague: Tuberculosis. New Brunswick, NJ: Man & Society; Rutgers University Press, USA, A Journal of History of Science 78: 615-616.
70. Aaronson JD (1926) Spontaneous tuberculosis in salt water fish. J Infect Dis 39(4): 315-320.
71. Wuerthele-Caspe VE, Alexander-Jackson E, Smith LW (1971) Some aspects of the microbiology of cancer. J Am Woman’s Med Assoc 8: 7.
72. Alexander-Jackson EA (1954) A specific type of microorganism isolated from animal and human cancer. Growth 18(1): 37-51.
73. Inoue S, Singer M (1970) Experiments on a spontaneously originated visceral tumor in the Newt Trituruspyrrhogaster. Annal NY AcadSci174(2): 729-764.
74. Lwoff A (1962) Biologic order. Karl Taylor Compton Lectures, Cambridge MA: The MIT Press, USA.
75. Klieneberger-Nobel E (1949) Origin, development and significance of L-forms in bacterial cultures. J Gen Microbiol 3: 434-442.
76. Rogers AD (1953) Erwin Frink Smith: a story of North American plant pathology. Philadelphia: American Philosophical Society 152(9): 879.
77. Seibert FB (1968) Pebbles on the Hill of a Scientist. In: Florence B (ed.), Seibert publisher, St. Petersburg, USA.
78. Cantwell A (1990) The cancer microbe. Aries Rising Press, USA.
79. Mattman LH (1993) Cell wall deficient forms-stealth pathogens. 2nd (edn), Boca Raton (ed.), CRC Press, USA.
80. Schneider B (1994) Specific binding of Bacillus Calmette-Guerinin urothelial tumor cells. In- vitro World J Urol 12(6): 337-344.
81. Rosenberg SA, Barry JM (1992) The transformed cell/unlocking the mysteries of cancer. GP Putnam’s Sons, New York, USA.
82. Devados PO, Klegerman ME, Groves MJ (1993) Phagocytosis of Mycobacterium bovis BCG organisms by murine S180 sarcoma cells. Cytobios 74(296): 49-58.
83. Moss RW (1997) The independent consumer’s guide to non-toxic treatment and prevention. Cancer therapy. Equinox Press, New York, USA.
84. Martin W (1997) Medical heroes and heretics. Old Greenwich, The Devin Adair Company, Connecticut, USA.
85. Acevedo H, Pardo M, Campbell-Acevedo E, Domingue GJ (1987) Human choriogonadotropin–like material in bacteria of different species: electron microscopy and immunocytochemical studies with monoclonal and polyclonal antibodies. J Gen Microbiol 133(3): 783-791.
86. (1990) Congress of the United States Office of Technology Assessment. Unconventional Cancer Treatments US Govt Printing Office, Washington, USA.
87. Glover TJ (1930) The bacteriology of cancer. Canada Lancet Mar 74(3): 92-111.
88. Mazet G (1941) Etude Bacteriologique sur la Maladie d’ Hodgkin. Montpellier Med, pp. 1-6.
89. Wuerthele-Caspe V (1949) Mycobacterial forms observed in tumors. J Am Med Womens Assoc 4: 135-141.
90. Alexander-Jackson E (1976) Progenitor Cryptocides, The Specific Pleomorphic Microorganism Isolated From Cancer. J Int Acad Metab 5: 31-39.
91. Alexander-Jackson E (1978) Microscopic and Submicroscopic Phases of P Cryptocides from Fresh Lymphocytic leukemia. J Int Acad Metab 1: 9-18.
92. Diller I, Diller W (1965) Intracellular acid-fast organisms isolated from malignant tissues. Trans Am Micr Soc 84: 138-148.
93. Diller I, Donnelly A, Fisher M (1967) Isolation of pleomorphic, acid- fast organisms from several strains of mice. Cancer Res 27(8): 1402-1408.
94. Seibert F, Feldmann F, Davis R, Richmond I (1970) Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods. Ann N Y Acad Sci 174: 690-728.
95. Wang A, Xie J (1998) Infection of mycobacterium tuberculosis in lung cancer. Zhongguo Fei Ai ZaZhi 1(2): 92-94.
96. Xie J, Anchao W, Xiazhi Z (1999) Isolation of acid fast bacillus L- forms from carcinoma of Lung. Acta Academiae Medicinae Bengbu 24: 145-146.
97. Song LY, Yan WS, Zhao T (2002) Detection of in lung cancer tissue by indirect in situ nested PCR. Di Yi Jun Yi Da XueXueBao 22(11): 992-993.
98. Yesong WXQ, Lifa X (2004) A case report on pneumoconio tuberculosis complicated with lung cancer and Mycobacterium tuberculosis- L form infection. Chin J Industrial Med.
99. Zhang S, Guang-ling Z, Yan-sheng T (2009) Detection of Mycobacterium tuberculosis L forms infection in tissues of lung carcinoma. Chin J Public Health 25: 1317-1318.
100. Sheng TY, Kun CX, Tong H, Guang LH, Wei Z, et al. (2009) Study on the relationship between Mycobacterium tuberculosis L infection and lung cancer. Tumor 29(11): 1085-1089.
101. Tian Y, Hao T, Cao B, Zhang W, Ma Y, et al. (2015) Clinical End-Points Associated with Mycobacterium tuberculosis and Lung Cancer: Implications into Host-Pathogen Interaction and Coevolution. Bio Med Research Intern p. 9.
102. Alexander-Jackson E (1970) Ultraviolet spectrogramic microscope studies of Rous sarcoma virus cultured in cell-free medium. Ann N Y Acad Sci 174(2): 765-781.
103. Shinde SR, Chandawarkar RY, Deshmukh SP (1995) Tuberculosis of the breast masquerading as carcinoma: A study of 100 patients. World J Surg 19(3): 379-381.
104. Deng B, Huang W, Tan QY, Fan XQ, Jiang YG, et al. (2011) Breast cancer anti-estrogen resistance protein 1 (BCAR1/p130cas) in pulmonary disease tissue and serum. Mol Diagn Ther 15(1): 31-40.
105. Hatwal Deepa, Suri Vijay, Mishra Jai P, Joshi Chitra (2011) Tubercular mastitis is common in garhwal region of uttarakhand: clinico pathological features of 14 cases. Journal of Clinical and Diagnostic 5(8):1569-1573.
106. Lay G, Poquet Y, Salek-Peyron P, Puissegur MP, Botanch C, et al. (2007) Langhans giant cells from M tuberculosis-induced human granulomas cannot mediate mycobacterial uptake. J Pathol 211(1): 76-85.
107. Weiss MG, Sommerfeld J, Uplekar MW (2008) Social and cultural dimensions of gender and tuberculosis. Int J Tuberc Lung Dis 12(7):829-830.
108. Holmes CB, Hausler H, Nunn P (1998) A review of sex differences in the epidemiology of tuberculosis. Int J Tuberc Lung Dis 2(2): 96-104.
109. Tsuyuguchi K, Suzuki K, Matsumoto H, Tanaka E, Amitani R, et al. (2001) Effect of estrogen on Mycobacterium avium complex pulmonary infection in mice. Clin Exp Immunol 123(3): 428-434.
110. Havlik JA, Horsburgh CR, Metchock B, Williams PP, Fann SA, et al. (1992) Disseminated Mycobacterium avium complex infection: clinical identification and epidemiologic trends. J Infect Dis 165(3):577-580.
111. Tanaka E, Amitani R, Niimi A, Suzuki K, Murayama T, et al. (1997) Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium complex pulmonary disease. Am J Respir Crit Care Med 155(6): 2041-2046.
112. Prince DS, Peterson DD, Steiner RM, Gottlieb JE, Scott R, et al. (1989) Infection with Mycobacterium avium complex in patients without predisposing conditions. N Engl J Med 321(13): 863-868.
113. Reich JM, Johnson RE (1991) Mycobacterium avium complex pulmonary disease. Am Rev Respir Dis 143(6): 1381-1385.
114. Howlader N, Noone AM, Krapcho M (2012) SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). National Cancer Institute, Bethesda.
115. Philley JV, Kannan A, Griffith DE, Devine MS, Benwill JL, et al. (2017) Exosome secretome and mediated signaling in breast cancer patients with nontuberculous mycobacterial disease. Oncotarget 8(11): 18070-18081.
116. Cassidy PM, Hedberg K, Saulson A, Nelley Mc E, Winthrop KL (2009) Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis 49(12): e124-e129.
117. Franson JC, Friend M (1999) Field manual of wildlife diseases, Geological Survey, Washington DC, USA.
118. Miller RE, Fowler ME (2012) Fowler’s Zoo and Wild Animal Medicine Current Therapy, Volume 7. Elsevier Health Sciences, p. 688.
119. Phillips MS, von Reyn CF (2001) Nosocomial Infections Due to Nontuberculous Mycobacteria. Clin Infect Dis 33(8): 1363-1374.
120. Nason EN (1898) The Influence of Locality on the Prevalence of Malignant Disease. Br Med J 1(1941): 679-681.
121. Jones L (1899) The Influence of Locality on the Prevalence of Cancer. Br Med J 1(1996): 812-813.
122. Mason H (1902) A Possible Predisposing Cause of Cancer. Br Med J 1(2142): 139-141.
123. Miller BA, Gloeckler Ries LA, Hankey BF (1993) SEER cancer statistics review, 1973-1990. Bethesda, MD: National Institutes of Health.
124. Kulldorff M, Feuer EJ, Miller BA, Freedman LS (1997) Breast cancer clusters in Northeastern United States: a geographic analysis. Am J Epidemiol 146(2): 161-170.
125. Jenks S (1994) Researchers to comb Long Island for potential cancer factors. J Natl Cancer Inst 86: 88-95.
126. Lewis-Michi EL, Melius JM, Kallenbach LR (1996) Breast cancer risk and residence near industry or traffic in Nassau and Suffolk counties, Long Island, New York. Arch Environ Health 51: 255-265.
127. Wittenberg C (1994) Long Island breast cancer studies move forward. J Natl Cancer Inst 86: 1501-1503.
128. Jacquez GM, Greiling DA (2003) Local clustering in breast, lung and colorectal cancer in Long Island, New York. Int J Health Geogr 2(1): 3.
129. Gammon MD, Neugut AI, Santella RM, Teitelbaum SL, Britton JA, et al. (2002) The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer. Breast Cancer Res Treat 74(3): 235-254.
130. Davidson A (1999) Oxford Companion to Food. Oxford: Oxford University Press, India, p. 593.
131. Zeng Y, Du J, Pu X, Yang J, Yang T, et al. (2015) Coevolution between Cancer Activities and Food Structure of Human Being from Southwest China. Bio Med Res Int 2015:497934.
132. (2009) Long Island Duck Farm History and Ecosystem Restoration Opportunities Report. US Army Corps of Engineers, New York District. Suffolk County, NY, pp. 1-20.
133. Davids HW, Cosulich WF (1968) Water Pollution from Duck Farms and Recent Developments in Treatment. 1968. Paper presented at the June 10, 1968 meeting of the New York Water Pollution Control Association, Montauk, NY, p. 9.
134. Partridge MS, Smith WG, Rutz DA (1992) Pest and Pesticide Use Assessment for Poultry Production Systems in New York State for 1998. Pesticide Management Education Program, Cornell University, USA.
135. World Health Organization (2008) Guidelines for Drinking water Quality, Incorporating 1st and 2nd Addenda, Volume 1, Recommendations. 3rd (edn), WHO, Geneva, Switzerland.
136. Fenwick A (2006) Waterborne Diseases-Could they be Consigned to History? Science 313: 1077-1081.
137. George I, Crop P, Servais P (2001) Use of β-D-Galactosidase and β-D-Glucuronidase Activities for Quantitative Detection of Total and Faecal Coliforms in Wastewater. Can J Microbiol 47(7): 670-675.
138. Shivaprasad HL, Palmieri C (2012) Pathology of mycobacteriosis in birds. Vet Clin North Am Exot Anim Pract 15(1): 41-55.
139. Song XH, Chen HX, Zhou WS, Wang JB, Liu MF, et al. (2016) Complete Genome Sequence of Mycobacterium avium, Isolated from Commercial Domestic Pekin Ducks (Anas platyrhynchos domestica), Determined Using PacBio Single-Molecule Real-Time Technology. Genome Announc 4(5).
140. (2003) Proceedings the U.S. EPA’s Research on Microorganisms in Drinking Water Workshop August 5-7, Cincinnati, Ohio.
141. Kids Count Data Center-a project of the Annie E. Casey Foundation, Maryland, United States.
142. Rosenzweig DY (1979) Pulmonary mycobacteria infections due to Mycobacterium avium complex. Clinical features and course in 100 consecutive patients. Chest 75: 115.
143. Wolinsky E (1979) Nontuberculous mycobacteria and associated diseases. Am Rev Respir Dis 119(1): 107-159.
144. Rosenzweig DY (1980) A typical mycobacteriosis. Clin Chest Med 1: 273-284.
145. Dlugovitzky D, Luchesi S (1995) Circulating immune complexes in patients with advanced tuberculosis and their association with autoantibodies and reduced CD4+ lymphocytes. Braz J Med Biol Res 28(3): 331-335.
146. Lamoureux G, Davignon L (1987) Is prior mycobacterial infection a common predisposing factor to AIDS in Haitians and Africans? Ann Inst Pasteur Immunol 138(4): 521-529.
147. Hirsch CS, Toossi Z (1999) Apoptosis and T-cell hyporesponsiveness in pulmonary tuberculosis. J Infect Dis 179(4): 945-953.
148. Chaouchi N, Arvanitakis L, Auffredou, Blanchard DA, Vazquez, et al. (1995) Characterization of transforming growth factor-B1 induced apoptosis in normal human B cells and lymphoma B cell lines. Oncogene 11(8): 1615-1622.
149. McDonald I, Wang H (1996) Transforming growth factor B1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines. Blood 87: 1147-1154.
150. Fratazzi C, Arbeit RD, Carini C, Balcewicz-Sablinska MK, Keane J, et al. (1999) Macrophage apoptosis in mycobacterial infections. J Leukoc Biol 66(5): 763-764.
151. Molloy A, Laochumroonvorapong P, Kaplan G (1994) Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guerin. J Exp Med 180(4): 1499-1509.
152. Hirsch CS, Toossi Z, Johnson JL, Luzze H, Ntambi L, et al. (2001) Augmentation of apoptosis and interferon-γ production at sites of active Mycobacterium tuberculosis infection in human tuberculosis. J of Infectious Dis 183(5): 779-788.
153. Bermudez LE, Parker A, Petrofsky M (1999) Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour necrosis factor TNF and Fas and involves the activation of caspases. Clin Exp Immunol 116(1): 94-99.
154. Edition of the Drinking Water Standards and Health Advisories (2012) Environmental Protection Agency, Office of Water, Washington, US, pp. 1-12.
155. Shin GA, Lee J, Freeman R, Cangelosi GA (2008) Inactivation of mycobacterium avium by UV irradiation. Appl Environ Microbiol 74(22): 7067-7069.
156. Pedley S, Bartram J, Cotruvo JA, Alfred D, Gareth Rb (2004) Pathogenic
mycobacteria in water: a guide to public health consequences, monitoring and management. World Health Organization, London pp. 144-168.
157. Nalbandian A, Yan BS, Pichugin A, Bronson RT, Kramnik I (2009) Lung carcinogenesis induced by chronic tuberculosis infection: the experimental model and genetic control. Oncogene 28(17): 1928-1938.
158. Da Silva AL, Bresciani MJ, Karnopp TE, Weber AF, Ellwanger JH, et al. (2015) DNA damage and cellular abnormalities in tuberculosis, lung cancer and chronic obstructive pulmonary disease. Multidiscip Respir Med, pp. 10-38.
159. Daley CL, Iseman M (2012) Mycobacterium avium complex and lung cancer: chicken or egg? Both? J Thorac Oncol 7(9): 1329-1330.
160. Lande L, Peterson DD, Gogoi R, Daum G, Stampler K, et al. (2012) Association between Pulmonary Mycobacterium Avium Complex Infection and Lung Cancer. J Thorac Oncol 7(9): 1345-1351.
161. Hosoda C, Hagiwara E, Shinohara T, Baba T, Nishihira R, et al. (2014) Clinical characteristics of pulmonary Mycobacterium avium complex infection complicated with lung cancer. Kekkaku 89(8): 691-695.
162. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, et al. (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175(4): 367-416.
163. Bender F (1956) Primary pulmonary carcinoma associated with active pulmonary tuberculosis. Dis Chest 30(2): 207-216.
164. Moll A (1949) “Der Bronchialkrebs,” Medizinische Klinik. 44: 916.
165. Woodruff CE, Sen-Gupta N, Wallace S, Chapman PT, Martineau PC (1952) Anatomic Relationships between Bronchogenic Carcinoma and Calcified Nodulesin the Lung. Am Rev Tuberc 66(2): 151-160.
167. Sunnetcioglu A, Sunnetcioglu M, Binici I, Baran AI, Karahocagil MK, et al. (2015) Comparative analysis of pulmonary and extrapulmonary tuberculosis of 411 cases. Ann Clin Microbiol Antimicrob, pp. 14-34.
168. Ates Guler S, Bozkus F, Inci MF, Kokoglu OF, Ucmak H, et al. (2015) Evaluation of pulmonary and extrapulmonary tuberculosis in immunocompetent adults: a retrospective case series analysis. Med Princ Pract 24(1): 75-79.
169. Rasolofo Razanamparany V, Ménard D, Aurégan G, Gicquel B, Chanteau S (2002) Extrapulmonary and pulmonary tuberculosis in Antananarivo (madagascar): high clustering rate in female patients. J Clin Microbiol 40(11): 3964-3969.
170. Sreeramareddy CT, Panduru KV, Verma SC, Joshi HS, Bates MN (2008)
Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study. BMC Infect Dis p. 8.
171. Cooper A (1829) Diseases of the Breast-Part 1. S. McDowall Publisher, London, P. 73.
172. Audebert F, Schneidewind A, Hartmann P, Kullmann F, Schölmerich J (2006) Lymph node tuberculosis as primary manifestation of Hodgkin’s disease. Med Klin (Munich) 101(6): 500-504.
173. Centkowski P, Sawczuk-Chabin J, Prochorec M, Warzocha K (2005) Hodgkin’s lymphoma and tuberculosis coexistence in cervical lymph nodes. Leuk Lymphoma 46(3): 471-475.
174. Lamden K, Watson JM, Knerer G, Ryan MJ, Jenkins PA (1996) Opportunist mycobacteria in England and Wales: 1982 to 1984. Commun Dis Rep CDR Rev 6(11): 147-51.
175. Meissner G, Anz W (1977) Sources of Mycobacterium avium complex infection resulting in human disease. Am Rev Respir Dis 116(6):1057-1064.
176. Schaad UB, Votteler TP, McCracken GH, Nelson JD (1979) Management of atypical mycobacterial lymphadenitis in childhood: a review basedon 380 cases. J Pediatr 95(3): 356-360.
177. White MP, Bangash H, Goel K, Jenkins PA (1986) Nontuberculous mycobacterial lymphadenitis. Arch Dis Child 61(4): 368-371.
178. Felini M, Johnson E, Preacely N, Sarda V, Ndetan H, et al. (2011) Apilot Case-Cohort Study of Liver and Pancreatic Cancers in Poultry Workers. Ann Epidemiol 21(10): 755-766.
179. Johnson ES, Zhou Y, Lillian Yau C, Prabhakar D, Ndetan H, et al. (2010) Mortality from malignant diseases-update of the Baltimore union poultry cohort. Cancer Causes Control 21(2): 215-221.
180. Duesberg PH (1987) Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res 47(5): 1199-1220.
181. Demochowski L, Grey CE (1957) Subcellular Structures of Possible Viral Origin in Some Mammalian Tumors. Ann NY Acad Sci, pp. 559-615.
182. Miller JM, Miller LD, Olson C, Gillette KG (1969) Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst 43(6): 1297-1305.
183. Seibert FB, Yeomans F, Baker JA, Davis RL, Diller IC (1972) Bacteria in
Tumors. Trans of the NY Acad of Sci June 34(6): 504-533.
184. Buehring GC, Shen HM, Jensen HM, Choi KY, Sun D, et al. (2014) Bovine leukemia virus DNA in human breast tissue. Emerg Infect Dis 20(5): 772-782.
185. Buehring GC, Shen HM, Jensen HM, Jin DL, Hudes M, et al. (2015) Exposure to Bovine Leukemia Virus is Associated with Breast Cancer: A Case-Control Study. PLoS One 10(9): e0134304.
186. Lysenko AP, Broxmeyer L, Vlasenko VV, Krasochko PA, Lemish AP, et al. (2016) Further Evidence for Cancer as a Cell-Wall-Deficient Mycobacterial Disease. J Mol Path Epidemol 1(1): 1-12.
187. Bittner JJ (1936) Some possible effects of nursing on the mammary gland tumor incidence of mice. Science 84(2172): 162.
188. Chauveau A. Transmission of virulent diseases by the ingestion of virulent principles in the digestive tract. Gaz de Paris p. 45.
189. Klebs E (1870) On the history of tuberculosis. Virchows Arch F path Anat, p. 291.
190. Gerlach AC (1870) On the inoculability of tuberculosis and theperilla, and on the transferability of the latter by feeding. Virchows Arch F path Anat 11: 297.
191. Pfeiffer DU (1994) The role of a wildlife reservoir in the epidemiology of bovine tuberculosis. New Zealand.
192. Dameshek W, Gunz (1965) Leukemia. Am J Med Sci 249: 115.
193. Latarjet R, Duplan JF (1962) Experiment and Discussion on Leukemogenesis by Cell-Free Extracts of Radiation-Induced Leukemia in Mice. Int J Rad Biol 5(4): 339-344.
194. Dobrindt U, Reidl J (2000) Pathogenicity islands and phage conversion: evolutionary aspects of bacterial pathogenesis. Int J Med Microbiol 290: 519-527.
195. Landman OE, Burchard WK, Angelety LH (1962) Lysogeny and bacteriophage adsorption in stable and reverting L-forms of Salmonella paratyphi B and Escherichia coli. Bacteriol Proc, p. 53.
196. Nelson EL, Pickett MJ (1951) The Recovery of L Forms of Brucella and their Relation to Brucella Phage. J Infect Dis 89(3): 226-232.
197. Kruegar AP, Cohn T, Smith PN, McGuire CD (1948) Observations on the effect of penicillin on the reaction between phage and staphylococc. J Gen Physiol 31: 477-488.
198. Takahashi S (1979) L phase growth of Mycobacteria. Cell wall deficient form of Mycobacteria. Kekkaku 54: 63-70.
199. Broxmeyer L, Sosnowska D, Miltner E, Chacón O, Wagner D, et al. (2002) Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J Infect Dis 186(8): 1155-1160.
200. Halsted WS (1912) W.W. Duke to Halsted. In: William Stewart Halsted papers, Series I. The Alan Mason Chesney Medical Archives of the Johns Hopkins Medical Institutions, Baltimore, USA.

CWD Tuberculosis Found in Spongiform Disease Formerly Attributed to Prions: Its Implication towards Mad Cow Disease, Scrapie and Alzheimer’s

May 9, 2017


Journal of MPE Molecular Pathological Epidemiology 2017 Vol. 3 No. 3: 3

Lysenko AP PhD,
Broxmeyer L MD,
Vlasenko VV PhD,
Krasochko PA PhD,
Lemish AP and
Krasnikova EL


The TSE’S or transmissible spongiform encephalopathies, include bovine spongiform encephalopathy (also called BSE or “mad cow disease”), Creutzfeldt– Jakob disease (CJD) in humans, and “scrapie” in sheep or goats (caprine spongiform encephalopathy).  They remain a mystery, their cause still hotly debated. Current mad cow diagnosis lies solely in the detection of late appearing “prions”, an acronym for hypothesized, geneless, misfolded proteins, somehow claimed to cause the disease. Yet laboratory preparations of prions contain other things, which could include unidentified bacteria or viruses. And the only real evidence that prion originator Stanley Prusiner had in his original paper that the disease agent behind “Scrapie” in sheep and goats was devoid of DNA or RNA– was based upon the fact that he couldn’t find any. Furthermore, the rigors of prion purification alone, might, in and of themselves, have killed any causative microorganism and Heino Dringer, who did pioneer work on their nature, candidly predicts “it will turn out that the prion concept is wrong.” Roels and Walravens as well as Hartly traced Mad Cow to Mycobacterium bovis. Moreover, epidemiologic maps of the origins and peak incidence of Mad Cow in the UK, suggestively match those of England’s areas of highest bovine tuberculosis, the Southwest. The neurotaxic potential of bovine tuberculosis has for some time been well known. By 1911 Alois Alzheimer called attention to “a characteristic condition of the cortical tissue which Fischer referred to as ‘spongy cortical wasting” in Alzheimer’s disease (AD). But behind AD, Fischer suspected a microbe called Streptothrix which was constantly being mistaken and confused for tuberculosis. Our present investigation of the TSEs clearly shows cell-wall-deficient (CWD) tubercular mycobacteria present, verified by molecular analysis, ELISA, PCR and microscopy to cause spongiform encephalopathy.

Keywords: Prions; Scrapie; The Spongiform Encephalopathies; Alzheimer’s disease; The etiology of Alzheimer’s Disease; Mycobacterium tuberculosis Complex

Received: April 05, 2017; Accepted: April 27, 2017; Published: April 29, 2017



1   Curto M, Reali C, Palmieri G, Scintu F, Schivo ML, et al. (2004) Inhibition of Cytokines Expression in Human Microglia Infected with Virulent  and  Nonvirulent  Mycobacteria.  Neurochem  Internat  44: 381-392.

2    Broxmeyer  L,  Sosnowska  D,  Miltner  E,  Chacón  O,  Wagner  D,  et al. (2002) Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J Infect Dis 186: 1155-1160.

3    Randall PJ, Hsu NJ, Lang D, Cooper S, Sebesho B, et al. (2014) Neurons are host cells for Mycobacterium tuberculosis. Infect Immun 82: 1880-1890.

4    Manuelidis  EE,  Manuelidis  L  (1989)  Suggested  Links  Between Different Types of Dementias: Creutzfeldt-Jakob disease, Alzheimer disease, and Retroviral CNS Infections. Alzheimer Dis Assoc Disord 3: 100-109.

5    Stockman S (1911) The habits of British ticks found on sheep and cattle. J Comp Pathol 24: 229-37.

6    Fischer O (1911) The spongious loss of the bones, a special process of destruction of the cerebral cortex. Z ges Neurol Psychiat 7: 1-33.

7   Babes V, Levaditi C (1897) On the Actinomycotic Shape of the Tuberculosis Bacilli (Sur la Forme Actinomycosique du Bacilli de la Tuberculosis). Arch of Med Exp et D’anat 9: 1041-1048.

8    Dunkin GW (1936) Paratuberculosis of Cattle and Sheep. Section of Comparative Medicine. Proc R Soc Med 30: 83-90

9    Chauveau A: Transmission of virulent diseases by the ingestion of virulent principles in the digestive tract. Gaz de Paris: p 45.

10  Klebs E (1870) On the history of tuberculosis. Virchows Arch F path Anat :p 291

11  Gerlach  AC  (1870)  On  the  inoculability  of  tuberculosis  and  the perilla, and on the transferability of the latter by feeding. Virchows Arch F path Anat 11: 297.

12  Pfeiffer DU (1994) The role of a wildlife reservoir in the epidemiology of bovine tuberculosis. Massey University, Dept of Veterinary Clinical Sciences, New Zealand.

13 Bourne J, Donnelly C (2001) An epidemiological investigation into bovine tuberculosis third report of the Independent Scientific Group on Cattle TB.

14  Francis  J  (1947)  Bovine  Tuberculosis:  Including  a  Contrast  with Human Tuberculosis. Staples Press Limited, London: p 220.

15  Taubes G (1986) The game of the name is fame. But is it science? Discover 7: 28-52.

16 Hadlow WJ, Prusiner SB, Kennedy RC, Race RE (1980) Brain tissue from persons dying of Creutzfeldt-Jacob disease causes scrapie-like encephalopathy in goats. Ann Neurol 8: 628-631.

17  Griffith JS (1967) Self-replication and scrapie. Nature 215: 1043-4.

18  Prusiner SB (1995) The  prion  diseases. Sci Am 272: 48-51.

19  Pethe K, Bifani P, Drobecq H, Sergheraert C, Debrie AS, et al. (2002) Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc Natl Acad Sci USA 2002 99: 10759-10764.

20  Tsubuki S, Takako Y (2003) Dutch,    Flemish,    Italian    and Arctic mutations of App and resistance of Abeta to physiologically relevant proteolytic degradation. Lancet 361: 1957-1958.

21  Lasmézas  CI,  Deslys  JP  (1997)  Transmission  of  the  BSE  agent to mice in the absence of detectable abnormal prion protein. Science 275: 402-405.

22  Baker  CA, Martin D, Manuelidis L (2002) Microglia from  Creutzfeld– Jakob disease-infected brains are   infectious and   show specific mRNA activation profiles. J Virol 76: 10905-10915.

23  Botsios S, Manuelidis L (2016) CJD and Scrapie Require Agent- Associated  Nucleic  Acids  for  Infection.  J  Cell  Biochem  117: 1947-1958.

24  Abalos P, Retamal P (2004) Tuberculosis: a re-emerging zoonosis? Rev Sci Tech 23: 583-94.

25  O’Reilly LM, Daborn CJ (1995) The epidemiology of Mycobacterium bovis infections in animals and man: a review. Tuber Lung Dis 76: 1-46.

26  Grange JM (2001) Mycobacterium bovis infection in human beings. Tuberculosis 81: 71-77

27  Mattman LH (2001) Cell Wall Deficient Forms: Stealth Pathogens.CRC Press 3 (416).

28  Xalabarder C (1958) Electron microscopy of tubercle bacilli. Excerpta Medica. Sec XV Chest Dis 11: 467-473.

29  Xalabarder C (1963) The Nature of So-Called Atypical Mycobacteria. Neumol Cir Torax 24: 259-74.

30  Csillag A (1964) The mycococcus form of mycobacteria. Journ of Gen Microbio 34: 341-352

31  Shleeva  MO,  Salina  EG,  Kaprel’iants  AS  (2010)  Dormant  form  of Mycobacterium tuberculosis. Mikrobiologiia 79: 3-15

32  Zhang Y, Yang Y, Woods A, Cotter RJ, Sun Z (2001) Resuscitation of dormant Mycobacterium tuberculosis by phospholipids or specific peptides. Biochem Biophys Res Commun 284: 542-547.

33 Marcova N, Slavchev G, Michailova L (2012) Unique biological properties of Mycobacterium tuberculosis L-form variants: impact for survival under stress. Int. Microbiol 15: 61-68.

34  Shleeva MO, Mukamolova GV, Telkov MV, Berezinskaia TL, Syroeshkin AV et al. (2003) Formation of nonculturable Mycobacterium tuberculosis and their regeneration. Mikrobiologiia 72: 76-83.

35  Prusiner SB (2014) Madness and Memory: The Discovery of Prions – A New Biologic Principle of Disease. Yale University Press.

36  Hass G, Huntington R (1943) Amyloid. III The properties of amyloid deposits occurring in several species under diverse conditions. Arch Pathol 35: 226.

37 Schwartz P (1972) Amyloid degeneration and tuberculosis in the aged. Gerontologia 18: 321-362.

38 Delgado WA (1997) Amyloid deposits in labial salivary glands identified by electron microscopy. J Oral Pathol Med 26: 51-52.

39  de Beer FC, Nel AE (1984) Serum amyloid A protein and C-reactive protein levels in pulmonary tuberculosis: relationship to amyloidosis. Thorax 39: 196–200.

40  Tomiyama T, Satoshi A (1994) Rifampicin prevents the aggregation and neurotoxicity of amyloid B protein in vitro. Biochem Biophys Res Commun 204: 76-83.

41  Chauhan A, Madiraju MV, Fol M, Lofton H, Maloney E, et al. (2006) Mycobacterium  tuberculosis  Cells  Growing  in  Macrophages  Are Filamentous and Deficient in FtsZ Rings. J. Bacteriol 188: 1856-1865.

42 Markova N, Michailova L, Kussovski V, Jourdanova M (2008) Formation of Persisting Cell Wall Deficient Forms of Mycobacterium bovis BCG during Interaction with Peritoneal Macrophages in Guinea Pigs. Electronic Journal of Biology 4: 1-10

43 Thacore H, Willett HP (1966) The formation of spheroplasts of Mycobacterium tuberculosis in tissue culture cells. Am Rev Respir Dis 93: 786-796.

44 Lysenko AP, Vlasenko AP, Broxmeyer L (2014) Phenomenon of variability of mycobacteria and its use for detection of a tuberculosis infection.

45 Lysenko AP, Vlasenko VV, Broxmeyer L, Lemish AP, Novik TP, et al. (2014) The tuberculin skin test: how safe is safe?  The tuberculins contain unknown forms capable of reverting to cell-wall-deficient mycobacteria. Clinical and Experimental Medical Sciences 2: 55-73.

46  Lysenko  AP,  Broxmeyer  L,  Vlasenko  V,  Krasochko  PA,  Lemish  AP, et al. (2016) Further evidence for Cancer as Cell-wall-deficient Mycobacterial Disease. J Mol Pathol Epidemiol 1: 1-12.

47  Lysenko AP, Vlasenko VV, Lemish AP (2014) Detection of mycobacteria in tis- sues by means of the differentiating  immunoperoxidase staining. Tuberculos i bolezni legkhih. 10: 55-58.

48  Harry EJ (2001) Bacterial cell division: regulating Z-ring formation. Mol Microbiol 40: 795-803.

49  Errington J, Daniel RA, Scheffers DJ (2003) Cytokinesis in bacteria. Microbio Mol Biol Rev 67: 52-65.

50  Xalabarder C (1970) L-forms of chronic mycobacteria and nephritis. Publ Inst Antituberc(Barcelona) Supple 7:7-83.

51 Seidel B, Thomzig A, Buschmann A, Groschup MH, Peters R, et al. (2007) Scrapie agent (strain 263K) can transmit disease via the oral route after persistence in soil over years. PLoS One 2: e435.

52  Ghodbane R, Mba Medie F, Lepidi H, Nappez C, Drancourt M (2014) Long-term survival of tuberculosis complex mycobacteria in soil. Microbiology 160: 496-501.

53  Insanov AB, Gadzhiev FS (1996) Comparative Analysis of the Results of Spinal Fluid Microbiological Study in Children and Adults Who Suffered from Tuberculous Meningitis. Probl tuberk. 5: 25–28.

54  Slavchev  G,  Michailova  L,  Markova  N  (2013)  Stress-induced L-forms of M. bovis: challenge to survivability. New Microbiologica 36: 157-166.

55  Calmette A, Valtis J, Lacomme A (1928) New experimental research on tuberculous ultravirus. CR Acad Sci 186: 1778-1781.

56  Xiao X, Miravalle L, Yuan J, McGeehan J, Dong Z, et al. (2009) Failure to Detect the Presence of Prions in the Uterine and Gestational Tissues from a Gravida with Creutzfeldt – Jakob disease. Am J Pathol 174: 1602-1608.

57  Brieger EM (1949) The Host Parasite Relationship in Tuberculous Infection. Tubercle 30: 242-253.

58 Brieger EM, Glauert AM (1952) A Phase-Contrast Study of Reproduction in Mycelial Strains of Avian Tubercle Bacilli. J Gen Microbiol 7: 287-294.

59  Prusiner SB (2004) Development of the Prion Concept. Prion Biology and Diseases, Cold Spring Harbor Laboratory Press: pp 89-141.

60  Pattison IH (1988) Fifty years with scrapie: a personal reminiscence. Vet Rec 123: 661-666.

61  Pattison IH, Jones KM (1967) The possible nature of the transmissible agent of scrapie. Vet Rec 80: 7.

62  Gerston KF, Blumberg L, Tshabalala VA, Murray J (2004) Viability of mycobacteria in formalin-fixed lungs. Hum pathol 35: 571-575.

63  Vinnie DS, Mary R (2002) Does formaldehyde kill Myco tuberculosis? Tech Bull Histopath 2: 37-38.

64  Alzheimer A, Forstl H, Levy R (1991) On Certain Peculiar Diseases of Old Age. History of Psychiatry 2: 71-101.

65  Goedert M (2015) Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aß, tau and α-synuclein. Science 349: 1255555.

66 Schwab C, Hosokawa M, McGeer PL (2004) Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol 188: 52-64

67 Mawanda F, Wallace R (2013) Can infections cause Alzheimer’s disease? Epidemiol Rev 35: 161-80.

68  Alteri CJ, Xicahténcati-Cortes J, Hess S, Caballero-Olin G, Girón JA,et al. (2007) Mycobacterium Tuberculosis Produces Pili during Human Infection. Proc Natl Acad Sci USA 104: 5145-5150.

69 Jordal PB, Dueholm MS, Larsen P, Petersen SV, Enghild JJ, et al. (2009)  Widespread  abundance  of  functional  bacterial  amyloid in mycolata and other gram-positive bacteria. Appl Environ Microbiol 75: 4101-4110.


Review Article: Are the Infectious Roots of Alzheimer’s Buried Deep in the Past?

February 26, 2017

Dr. Lawrence Broxmeyer, MD

LINK-OUT TO REVIEW ARTICLE -51778-ipjpe-3-s2-2

Citation: Broxmeyer L. Are the Infectious Roots
of Alzheimer’s Buried Deep in the Past? J Mol
Path Epidemol. 2017, 3:2.

Received: January 13, 2017; Accepted: February 20, 2017; Published: February 22,

© Under License of Creative Commons Attribution 3.0 License


Recent literature shows a controversial new push to tie microorganisms to Alzheimer’s disease (AD). Study after study, in which scientists have injected human Alzheimer-diseased brain tissue into mice and other laboratory animals that later developed the disease have left little doubt that Alzheimer’s disease (AD) arises from an infectious process. By 2013 Mawanda and Wallace’s “Can Infections Cause Alzheimer’s Disease” struck down some of the commonly entertained pathogens for AD such as herpes simplex virus type 1, Chlamydia pneumoniae, and several types of spirochetes. Instead they pointed to two prime suspects for Alzheimer’s amyloid-beta deposition: “especially chronic infections like tuberculosis and leprosy.” To be sure, it was German neuropathologist Oskar Fischer of the Prague school of Neuropathology, Alzheimer’s great rival, who was the first to suggest that infection might be causative for Alzheimer’s. Fischer’s credentials: he was the co-discoverer of Alzheimer’s disease. His suspected germ was the Streptothrix, today classified as an Actinomycetes, a rare central nervous system pathogen which at the time was so constantly and consistently mistaken for tuberculosis that Choppen-Jones suggested that TB be called tuberculomycosis. And Just ten years before Oskar Fischer found Actinomycosis-like forms in Alzheimer’s cerebral plaque, Babèş and immunologist Levaditi reported in “On the Actinomycotic Shape of the Tuberculous Bacilli” that Fischer’s typical Actinomyces-like clusters [Drüsen] with clubs appeared in the tissue of rabbits inoculated with tubercle bacilli beneath the dura mater of their brains. Investigators who supported and subsequenly followed up on Fischer’s Alzheimer’s germ are also discussed.

Keywords: Alzheimer’s disease, Infectious Cause of Alzheimer’s Disease, Oskar Fischer, Alois Alzheimer, Neurodegenerative Disease, Neurotuberculosis


  1. Itzhaki RF, Lathe R, Balin BJ, Ball MJ, Bearer EL, Braak H et al. Microbes and Alzheimer’s Disease. J Alzheimers Dis. 2016;51(4):979-84.
  2. Mawanda F, Wallace R. Can infections cause Alzheimer’s disease? Epidemiol Rev. 2013; 35:161-80.
  3. Itzhaki RF, Lin WR, Shang D, Wilcock GK, Faragher B, Jamieson GA. Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet. 1997 Jan 25;349(9047):241-44.
  4. Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M et al. American College of Medical Genetics and the National Society of Genetic Counselors. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011; 13(6): 597-605.
  5. Mayeux R, Sanders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT et al. Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer’s disease. NEJM. 1998; 338(8):506-511.
  6. Riviere GR, Riviere KH, Smith KS. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol. 2002;17(2):113–118.
  7. Goedert M. Oskar Fischer and the study of dementia. Brain. 2009 Apr; 132(4): 1102–1111.
  8. De Beer FC, Nel AE, Gie RP, Donald PR, Strachan AF. Serum amyloid A protein and C-reactive protein levels in pulmonary tuberculosis: relationship to amyloidosis. Thorax. 1984; 39(3):196–200.
  9. Looi LM, Jayalakshim P, Lim KJ, Rajagopalen K. An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients. Ann Acad Med Singapore. 1988; 17(4):573–578.
  10. Looi LM. The pattern of amyloidosis in Malaysia. Malays J Pathol. 1994; 16(1):11–13.
  11. Röcken C, Radun D, Glasbrenner B, Malfertheiner P, Roessner A. Generalized AA-amyloidosis in a 58-year-old Caucasian woman with an 18-month history of gastrointestinal tuberculosis. Virchows Arch. 1999; 434(1):95–100.
  12. Wangel AG, Wegelius O, Dyrting AE. A family study of leprosy: subcutaneous amyloid deposits and humoral immune responses. Int J Lepr Other Mycobact Dis. 1982; 50(1):47–55.
  13. Tank SJ, Chima RS, Shah V, et al. Renal amyloidosis following tuberculosis. Indian J Pediatr. 2000; 67(9):679–681.
  14. Urban BA, Fishman EK, Goldman SM,  Scott WW Jr, Jones B, Humphrey RL et al. CT evaluation of amyloidosis: spectrum of disease. Radiographics.1993; 13(6):1295–1308.
  15. Alzheimer A. “Uber Eigenartige Krankheitsfalle des Spateren Alters,” Zeit fur die Ges    Neur und Psych 1911; 4: 356–85.
  16. Barlow T. Tuberculous Meningitis in A System of Medicine by Many Writers, edited by Thomas Clifford Allbutt, New York:The Macmillan Company. 1899; 7:466–91.
  17. Ranke O. Beitrage zur Lehre von der Meningitis tuberculoa. Edited by Franz Nissl and Alois Alzheimer. Histologische und Histopathologische Arbeiten uber die Grosshirnrinde. Jena, Germany. Verlag Von Gustave Fischer. 1908; 252–347
  18. Alzheimer A, Forstl H, Levy R. An English translation of Alzheimer’s 1911 paper Uber Age), Hist of Psychia 1991. 2:71–101.
  19. Spielmeyer W. Alzheimer’s Lebenswenk. Zeit fur die Ges Neur und Psych. 1916; 22: 1–44.
  20. Dunn N, Mullee M, Perry VH, Holmes C. Association between Dementia and Infectious Disease: Evidence from a Case-Control Study. Alz Dis & Assoc Disord. April–June 2005. 19: 2: 91–4.
  21. Nee IE, Lipppa CF. Alzheimer’s Disease in Twenty-Two Twin Pairs—Thirteen-Year Follow-Up: Hormonal, Infectious, and Traumatic Factors.  Dement and Geriat Cognit Disord 1999; 10: 148–51.
  22. Alteri CJ, Xicahténcati-Cortes J, Hess S, Caballero-Olin G, Giron JA, Friedman RL. Mycobacterium Tuberculosis Produces Pili during Human Infection. Proc of the Nat Acad of Sci. 2007; 104:12:5145–50.
  23. Tukel C, Wilson RP, Nishimori JH, Pezeshki M, Chromy BA, Baumler AJ. Responses to Amyloids of Microbial and Host Origin Are Mediated through Toll-Like Receptor 2 Cell Host and Microbe. Cell Host Microb. July, 2009; 6: 45–53.
  24. Kidd M. Paired Helical Filaments in Electron Microscopy of Alzheimer’s Disease, Nature. 1963; 197: 192–93.
  25. Fischer O. Miliare Nekrosen Mit Drusigen Wucherungen der Neurofibrillen, eine Regelmassige Veranderung der Hirnrinde bei Seniler Demenz (Miliary Necrosis with Nodular Proliferation of the Neurofibrils: A Common Change of the Cerebral Cortex in Senile Dementia). Monatsschr f Psychiat Neurol 1907; 22: 361-372.
  26. Leonard JM, des Prez RM. Tuberculous Meningitis. Infect Dis Clin of Nor Amer Dec, 1990; 4: 4: 769–87.
  27. Chantemesse A, Ėtude Sur la Méningite Tuberculeuse de L’adulte: Les Formes Anormales en Particulier. These de Med de Paris. 1884.
  28. Blocq P, Babes V, Marinesco G. Atlas der Pathologischen Histologie des Nervensystems.  Berlin: Hirschwald, 1892.
  29. Vera HD, Rettger LF. Morphological Variation of the Tubercle Bacillus and Certain Recently Isolated Soil Acid Fasts, with Emphasis on Filterability. Journ of Bact June, 1940; 39:6: 659–87.
  30. Babes V, Levaditi C. On the Actinomycotic Shape of the Tuberculosis Bacilli (Sur la Forme Actinomycosique du Bacilli de la Tuberculosis). Arch. of Med. Exp. et D’anat. 1897; 9:6:1041-8.
  31. Blocq P, Marinescu G. Sur les Lesions et la Pathogenie de L’epilepsie Dite Essentielle, Sem Med 1892; 12:445–6.
  32. Giulianz D, Vaca K, Corpuz M. Brain Glia Release Factors with Opposing Actions upon Neuronal Survival, Journ of Neurosci 1993; 13: 29–37.
  33. Curto M, Reali C, Palmieri G, Scintu F, Schivo ML, Sogos V et al., Inhibition of Cytokines Expression in Human Microglia Infected with Virulent and Nonvirulent Mycobacteria. Neurochem Internat 2004; 44: 381–92.
  34. Rock RB, Gekker G, Hu S, Sheng WS, Cheeran M, Lokensgard JR et al. Role of Microglia in Central Nervous System Infections. Clin Microb Rev. 2004; 17: 942–64.
  35. Peterson PK, Gekker G, Hu S, Sheng WS, Anderson WR, Ulevitch RJ et al. CD14 Receptor-Mediated Uptake of Nonopsonized Mycobacterium Tuberculosis by Human Microglia, Infect and Immun. April, 1995; 63:4:1598–602.
  36. Green JA, Elkington PT, Pennington CJ, Roncaroli F, Dholakia S, Moores RC et al. Mycobacterium Tuberculosis Upregulates Microglial Matrix Metalloproteinase-1 and -3 Expression and Secretion via NF-kappaB- and Activator Protein-1-Dependent Monocyte Networks. Journ of Immunol June, 2010;184:11: 6492–503.
  37. Beltan E, Horgen L, Rastogi N. Secretion of Cytokines by Human Macrophages upon Infection by Pathogenic and Nonpathogenic Mycobacteria, Microbio and Pathol. 2000; 28: 313–8.
  38. Fischer O. Die Presbyophrene Demenz, Deren Anatomische Grundlage und Klinische Abgrenzung, Z. Ges. Neurol. Psychiat 1910. 3: 371–471.
  39. Marinesco G, Etude Anatomique et Clinique des Plaques Dites Seniles, 1er semestre Encephale. Paris. 1912; 105–132.
  40. Harbitz F, Grondahl NB, Actinomycosis in Norway: Studies in the Etiology, Modes of Infection, and Treatment, Amer J of Med Sci 1911; 142:386–95.
  41. Woodhead GS. Bacteria and Their Products. London and New York: Walter Scott, Ltd./Charles Scribner’s Sons.1895; 258
  42. Cope VZ. Actinomycosis: The Actinomyces and Some Common Errors about the Actinomyces and Actinomycosis. Postgrad Med. 1952; 28: 572–4.
  43. Bolton CF, Ashenhurst EM, Review Article: Actinomycosis of the Brain. Can Med Assoc Journ April, 1964; 90: 922–8.
  44. Ponfick E, Die Actinomykose des Menschen, Eine Neue Infectionskrankheit auf Vergleichend-Pathologischer und Experimenteller Grundlage Geschildert. Berlin: A. Hirschwald, 1882.
  45. Harz B. Actinomyces Bovis, ein Neuer Schimmel in den Geweben des Rindes: Deutsche Zeitschr. f. their. Med. und Vergl. Path. Zweites Supplementheft. 1870;125
  46. Corper HJ. Complement-Fixation in Tuberculosis. The J of Infect Dis September 1916; 19:3:315–21.
  47. Maurer K, Maurer U. Alzheimer’s disease: The Life of a Physician and the Career of a Disease Chichester, West Sussex: Columbia University Press. 2003.
  48. Bielschowsky M. Die Silberimpragnation der Achsenzylinder. Centralbl 1902; 21:578–84.
  49. Bielschowsky M. Die Silberimpragnation der Neurofibrillen. Centralbl 1903; 22: 997–1006.
  50. Perusini G. Uber Klinisch und Histologish Eigenartige Psychische Erkrankungen des Spateren Lebensalters, in Histologische und Histopathologische Arbeiten, edited by F. Nissl and A. Alzheimer. Jena, Germany: Verlag G. Fischer. 1909; 297–351.
  51. Darzins E. The Bacteriology of Tuberculosis. University of Minnesota Press. 1958; 488:187.
  52. Schneider A, Arau´jo GW, Trajkovic K, Herrmann MM, Merkler D, Mandelkow E et al. Hyperphosphorylation and Aggregation of Tau in Experimental Autoimmune Encephalomyelitis. The J of Biolog Chem Dec, 2004; 279;53: 55833–39.
  53. Harris JE, Fernandez-Vilaseca M, Elkington PTG, Horncastle DE, Graeber MB, Friedland JS et al. IFN Synergizes with IL-1to Up-Regulate MMP-9 Secretion in a Cellular Model of Central Nervous System Tuberculosis, The FASEB J Feb, 2007; 21: 356–65.
  54. Kusebauch U, Ortega C, Ollodart A, Rogers RS, Sherman DR, Moritz RL et al., Mycobacterium Tuberculosis Supports Protein Tyrosine Phosphorylation, Proc of the Nat Acad of Sci June, 2014; 111:25: 9265–70.
  55. Chow K, Ng D, Stokes R, Johnson P. Protein Tyrosine Phosphorylation in Mycobacterium Tuberculosis, FEMS Microbi Letters  December, 1994; 124:2: 203–7.
  56. Shapiro IP, Masliah E, Saitoh T. Altered Protein Tyrosine Phosphorylation in Alzheimer’s disease. J of Neurochem April, 1991; 56:4: 1154–62.
  57. Wang X.-X., Tan M.-S., Yu J.-T., Tan L. Matrix Metalloproteinases and Their Multiple Roles in Alzheimer’s Disease, BioMed Res Internat 2014,
  58. Lubarsch O. Zur Kenntnis der auf die Samenblaschen Amyloidablagerungen, Virch Arch Path Anat 1930; 274:139–145.
  59. Southard EE, Anatomical Findings in Senile Dementia: A Diagnostic Study Bearing Especially on the Group of Cerebral Atrophies. Amer J of Insan April, 1910; 66:4:673–708:701, 706.
  60. Southard EE, Solomon HC. Neurosypilis: Modern Systematic Diagnosis and Treatment—Presented in One Hundred and Thirty-Seven Case Histories 1917; Boston: W. M. Leonard. 496 pp.
  61. Southard EE. Nondementia Nonpraecox: Note on the Advantages to Mental Hygiene of Extirpating a Term in History of Psychiatry, Classic Text No. 72. Los Angeles, London, New Delhi: Sage Publications 2007; 18:4: 483–502.
  62. Southard EE, Jarrett MC. The Kingdom of Evils: Psychiatric Social Work Presented in One Hundred Case Histories Together with a Classification of Social Divisions of Evil. New York: Macmillan 1922; 298–9.
  63. Kraepelin E. Memoirs. Berlin and New York: Springer-Verlag. 1987; 270:136.
  64. Clouston TS, Unsoundness of Mind New York: E. F. Dutton and Co., 1911.
  65. Clouston TS. Illustrations of Phthisical Insanity. J of Ment Sci 1864; 50:220-229: 226.
  66. Clouston TS. Clinical Lectures on Mental Disease. London: J. & A. Churchill, 1883; 210.
  67. Sethi NK, Sethi PK, Torgovnick J, Arsura E. Central Nervous System Tuberculosis Masquerading as Primary Dementia: A Case Report, Neurologia i Neurochirurgia Polska. September-October 2011; 45:5:510–513.
  68. Carpenter EG. Determinate Factors in the Cause of Insanity, Jour of the Amer Med Assoc 1903 Jan 24; 60:4:240–44.
  69. Winslow F. On Obscure Diseases of the Brain and Disorders of the Mind: Their Incipient Symptoms, Pathology, Diagnosis, Treatment, and Prophylaxis. London: John Churchill Publishers. April 1860; 790 pp.
  70. Claisse P and Abrami A. Un Cas de Méningite Tuberculeus Terrninee par Guerison. Bull. et mém. soc. méd. d. hop. de Par.1905; 22:390–403.
  71. Marta M, Pomponi M. Il Ruolo di Perusini Nella Definizione del Morbo di Alzheimer, Kos. 1992; 77: 39–41.
  72. Braun B, Stadlober-Degwerth M, Kluemann H. Alzheimer–Perusini Disease: The One-Hundredth Anniversary of Gaetano Perusini’s Publication. Nervenarzt March 2011; 82:3: 363–66.
  73. Papavoine, LN Propositions Sur Les Tubercules Considérés Spécialement Chez le Enfans. Paris. 1830; 86:231.
  74. Rindfleisch R. Der Miliare Tuberkel. Virchow’s Arch. 1862; 24:571.
  75. Osler W, McCrae T. Modern Medicine: Its Theory and Practice, vol. V: Diseases of the Nervous System, 2nd edition. Philadelphia and New York: Lea & Febiger. 1915; 319.
  76. Guarnieri G. Note Istologiche Sulla Meningite Tubercolare.  Arch. Per le Scien. Med., Torino, 7th ed., 1883 1: 59–70.
  77. Hektoen L. The Vascular Changes of Tuberculous Meningitis, Especially with Tuberculous Endarteritis, J of Exper Med 1896; 1:112-163.
  78. Schwartz P. Amyloidosis—Cause and Manifestation of Senile Deterioration. Springfield, Illinois: Charles C Thomas. 1970; 363.
  79. Schwartz P. Amyloid Degeneration and Tuberculosis in the Aged. Gerontologia 1972; 18:5: 321–62.
  80. Hass GM, Huntington R. Amyloid 111: The Properties of Amyloid Deposits Occurring in Several Species under Diverse Conditions. Arch of Path 1943; 35: 226–41.
  81. Alzheimer A. Uber Eine Eigenartige Erkrankung des Zentralen Nervensystems Mit Bulbaen Symptomen und Schmerzhaften Spastischen Krampfzustanden der Extremitaen, Zeit fur die Gesamte Neurolog und Psychiat. 1916. 33: 45–59.
  82. Maurer K, Volk K, Gerbaldo S. Auguste D and Alzheimer’s disease, The Lancet May 1997; 349: 9064:1546–49.
  83. Jelliffe SE. Proceedings: National Association for the Study and Prevention of Tuberculosis, The Med News January-June, 1905; 86:1150 .
  84. Gerstenbrand F, Jellinger K, Maida E, Pilz A, Sandhofer F, and Weissenbacher G, Symptomatology of the Most Severe Form of Tuberculous Meningitis. J of Neurol 1980; 222:3:191–204.
  85. Kelynack TN. Tuberculosis in Infancy and Childhood. London: Bailliere, Tindall, and Cox. 1908.
  86. Rao VV, Gupta EV, Thomas IM. Chromosome Damage in Untreated Tuberculosis Patients. Tubercle September, 1990; 71:3:169-72.
  87. Wuerthele-Caspe V, Alexander-Jackson E, Gregory M, Smith LW, Diller IC, Mankowski Z. Intracellular Acid-Fast Microorganism: Isolated from Two Cases of Hepatolenticular Degeneration, J of the Amer Med Wom Assoc 1956 11:4:120–9.
  88. Jancovic J, Tolosa E. Parkinson’s Disease and Movement Disorders. Baltimore: Williams & Wilkins 1998; 205-16.
  89. Burn CG, Unidentified Gram-Positive Bacillus Associated with Meningo-Encephalitis, Proc of the Soc for Exper Biol and Med 1934; 31:1095.
  90. Livingston V, A Specific Type of Organism Cultivated from Malignancy: Bacterial and Proposed Classification. Ann of the New York Acad of Sci 1970; 174: 636–54.
  91. Bandelier B, Roepke O, Lehrbuch der Spezifischen Diagnostic und Therapie der Tuberkulose: fur arzte und Studierende Wurzburg: Curt Kabitzsch. 1911.
  92. Bandelier B, Roepke O. A Clinical System of Tuberculosis, translated from the Second German Edition by G. Band and Bertram Hunt, MD. New York: William Wood and Company. 1913.
  93. Nature Editorial, Forthcoming Books. March 13, 1913, Nature 91: 44.
  94. Millar BC, Moore JE, Emerging Issues in Infective Endocarditis, Emerg Infect Dis June, 2004; 10:6: 1110–6.
  95. Liu A, Nicol E, Hu Y, Coates A. Tuberculous Endocarditis, Internat J of Cardiol August, 2013; 167:3: 640–5.
  96. Gordon BL, Ocular Tuberculosis, Its Relation to General Tuberculosis—Ophthalmologic Reviews, edited by Francis Heed Adler. 1944; 541–56.
  97. Sands IJ, Senile and Presenile Psychosis, Neur Bulletin October 1918; 1:10: 377–385.

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage Delivered by a Nonvirulent Mycobacterium: A Model for Phage Therapy of Intracellular Bacterial Pathogens

January 12, 2017
Lawrence Broxmeyer, Danuta Sosnowska, Elizabeth Miltner, Ofelia Chacon, Dirk Wagner, Jeffery McGarvey, Raul G. Barletta, and Luiz E. Bermudez

Killing of Mycobacterium avium and Mycobacterium tuberculosis by a Mycobacteriophage

The Journal of Infectious Diseases


Mycobacterium avium causes disseminated infection in patients with acquired immune deficieny syndrome. Mycobacterium tuberculosis is a pathogen associated with the deaths of millions of people worldwide annually. Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. The present study describes a system using Mycobacterium smegmatis, an avirulent mycobacterium, to deliver the lytic phage TM4 where both M. avium and M. tuberculosis reside within macrophages. These results showed that treatment of M. avium–infected, as well as M. tuberculosis –infected, RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4, resulted in a significant time and titer  dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fuses with the M. avium vacuole in macrophages. These results suggest a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.

1. Bloom B. Tuberculosis: pathogenesis, protection and control. Washington,DC: American Society for Microbiology Press, 1995.
2. Surveillance TWIGP. Anti-tuberculosis drug resistance in the world. Geneva:World Health Organization Global Tuberculosis Programme, 1997.
3. Inderlied CB, Kemper CA, Bermudez LE. The Mycobacterium avium complex. Clin Microbiol Rev 1993; 6:266–310.
4. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853–60.
5. Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus–associated opportunistic infections in the United
States in the era of highly active antiretroviral therapy. Clin Infect Dis 2000 ; 30(Suppl 1):S5–14.
6. Falkinham JO 3rd. Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 1996; 9:177–215.
7. Guthertz LS, Damsker B, Bottone EJ, Ford EG, Midura TF, Janda JM. Mycobacterium avium and Mycobacterium intracellulare infections in patients with and without AIDS. J Infect Dis 1989; 160:1037–41.
8. Heifets L. Susceptibility testing of Mycobacterium avium complex isolates. Antimicrob Agents Chemother 1996; 40:1759–67.
9. Horsburgh CR Jr. Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324:1332–8.
10. Chaisson RE, Benson CA, Dube MP, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease: a randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med 1994; 121:905–11.
11. Young LS, Wiviott L, Wu M, Kolonoski P, Bolan R, Inderlied CB. Azithromycin for treatment of Mycobacterium avium–intracellulare complex infection in patients with AIDS. Lancet 1991; 338:1107–9.
12. Bermudez LE, Kolonoski P, Young LS. Roxithromycin alone and in combination with either ethambutol or levofloxacin for disseminated Mycobacterium avium infections in beige mice. Antimicrob Agents Chemother 1996; 40:1033–5.
13. Dube MP, Sattler FR, Torriani FJ, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis 1997; 176:1225–32.
14. Holzman D. Phage as antibacterial tool. Genetic Engineering News 1998; 18:11–16.
15. Ford ME, Stenstrom C, Hendrix RW, Hatfull GF. Mycobacteriophage TM4: genome structure and gene expression. Tuber Lung Dis 1998; 79:63–73.
16. Foley-Thomas EM, Whipple DL, Bermudez LE, Barletta RG. Phage infection,transfection and transformation of Mycobacterium avium complex and Mycobacterium paratuberculosis. Microbiology 1995; 141:1173–81.
17. Bermudez LE, Parker A, Goodman JR. Growth within macrophages increases the efficiency of Mycobacterium avium in invading other macrophages by a complement receptor–independent pathway. Infect Immun 1997; 65:1916–25.
18. Jacobs WR Jr, Kalpana GV, Cirillo JD, et al. Genetic systems for mycobacteria. Methods Enzymol 1991; 204:537–55.
19. Black CM, Bermudez LE, Young LS, Remington JS. Coinfection of macrophages modulates interferon gamma and tumor necrosis factor–induced activation against intracellular pathogens. J Exp Med 1990; 172:977–80.
20. Hafner R, Inderlied CB, Peterson DM, et al. Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection. J Infect Dis 1999; 180:438–47.
21. Sula L, Sulova J, Stolcpartova M. Therapy of experimental tuberculosis in guinea pigs with mycobacterial phages DS-6A, GR-21 T, My-327. Czech Med 1981; 4:209–14.
22. Rastogi N, Labrousse V. Extracellular and intracellular activities of clarithromycin used alone and in association with ethambutol and rifampin against Mycobacterium avium complex. Antimicrob Agents Chemother 1991; 35:462–70.
23. Bermudez LE, Young LS. New drugs for the therapy of mycobacterial infections. Curr Opinion Infect Dis 1995; 8:428–38.
24. Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, et al. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 1994; 263:678–81.
25. Clemens DL, Horwitz MA. Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 1995
; 181:257–70.
26. de Chastellier C, Lang T, Thilo L. Phagocytic processing of the macrophage endoparasite, Mycobacterium avium, in comparison to phagosomes which contain Bacillus subtilis or latex beads. Eur J Cell Biol 1995; 68:167–82.
27. Gomes MS, Paul S, Moreira AL, Appelberg R, Rabinovitch M, Kaplan G. Survival of Mycobacterium avium and Mycobacterium tuberculosis in acidified vacuoles of murine macrophages. Infect Immun 1999; 67:3199–206.


January 8, 2017



Broxmeyer L. Questioning the Zika
Virus. J Mol Path Epidemol. 2017, 1:1.

© Under License of Creative Commons Attribution 3.0 License


A growing body of health officials in Brazil are doubting that the Zika “virus” is responsible for the rise in birth defects in parts of that country. Zika, along with yellow fever, has been tossed into the family Flaviviruses; the Latin “flavus” meaning yellow. But unlike yellow fever, the vast majority of Zika’s symptoms for the last 70 years have been mild to non-existent. Despite disseminations by the lay and scientific press, there are serious questions whether Zika causes microcephaly at all. If by March, 2016 the Brazilian Ministry of Health reported 2,197 suspected cases of microcephaly, only 11.48% of these were Zika-positive. Zika is widespread throughout Brazil and South and Central America, yet the bulk of microcephaly cases are confined to the costal tip of Northeastern Brazil. Furthermore, despite extensive testing, no known mosquito-borne arbovirus or any other virus has to this point been proven to cause Brazilian microcephaly.

While Zika was being portrayed as “the most alarming health crisis to hit Brazil in decades”, tuberculosis and its related mycobacteria were quietly gaining a stranglehold and building an ecologic niche in the very Northeastern region being hit by epidemic microcephaly. Why was this important? With NE Brazilian microcephaly/Zika we are probably dealing with a mosquito-fueled environmental zoonosis – a disease that can be transmitted from animals to humans – such as primates, and to a lesser extent birds (Mycobacterium avium), and rodents (Mycobacterium microti), all mentioned in the Zika literature. Add to this the penchant of Brazilians to illegally capture and keep mycobacterial-laden wild monkies and exotic birds as pets or for revenue,and  you have a potential zoonotic time-bomb ready to explode once the proper vectors presents themselves. Three mosquito vectors have been steadily populating Northeastern Brazil: namely Culex quinquefasciatus, the Aedes aegypti and the Aedes albopictus – all of which have the capacity to transmit viral-like forms of the mycobacteria associated with HIV and through direct laboratory investigation with microcephaly. Perhaps it is time to rethink what’s really behind Brazilian Microcephaly and other symptomatology from the “Zika” agent.

KEYWORDS: The Zika virus; microcephaly; Aedes aegypti; Flaws in Zika diagnostics; Mycobacterium tuberculosis; Rhesus monkey; Brazil; CWD mycobacteria; Yellow fever; Flaviviruses; Systemic lupus erythmatosus; SLE; Neurtralization tests.

Received: October 07, 2016; Accepted: November 16, 2016; Published January 02, 2017


  1. Dick, G.W.A., Kitchen, S.F. and Haddow, A.J. (1952) Communications: Zika Virus—Isolations and Serological Specificity. Transactions of the Royal Society of Tropical Medicine and Hygiene, 46, 509-520.
  2. Bresalier, M, Mazumdar, P (ed.), Kroker, K (ed.) & Keelan, J (ed.) 2008, Neutralizing Flu: ‘Immunological devices’ and the making of a virus disease. in Crafting Immunity: Working Histories of Clinical Immunology. Ashgate, London, pp. 107-144.
  3. F.J. Fenner and R.V. Blanden, ‘History of Viral Immunology’, in A.L. Notkins (ed.), Viral Immunology and Immunopathology, New York, London: Academic Press, 1975, pp. 1–25 at pp.13–14.
  4. Van Helvoort T., “History of virus research in the 20th century: the problem of conceptual continuity”, History of Science 1994; 32(2):185-235
  5. Castets M, Boisvert H, Grumbach F, Brunel M, Rist N. Tuberculosis bacilli of the African type: preliminary note. Rev Tuberc Pneumol (Paris). 1968 Mar; 32(2):179-84.
  6. Broxmeyer, L, Kanjhan, R. (2016) Does Zika Really Have the Capacity to Affect the Nervous System and Cause Microcephaly or Intracranial Calcifications? Modern Research in Inflammation, 5, 20-30.
  7. Musso D, Nilles EJ, Cao-Lormeau VM. Rapid spread of emerging Zika virus in the Pacific area. Clin Microbiol Infect 2014;20:O595-6.
  8. MacNamara FN. Zika virus: a report on three cases of human infection during an epidemic of jaundice in Nigeria. Trans R Soc Trop Med Hyg 1954; 48: 139-45.
  9. Fagbami AH. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State. J Hyg (Lond) 1979; 83: 213-9.
  10.  Moore DL, Causey OR, Carey DE, et al. Arthropod-borne viral infections of man in Nigeria, 1964-1970. Ann Trop Med Parasitol 1975; 69: 49-64.
  11. Olson JG, Ksiazek TG, Suhandiman, Triwibowo. Zika virus, a cause of fever in Central Java, Indonesia. Trans R Soc Trop Med Hyg 1981; 75: 389-93.
  12. Simpson DI. Zika virus infection in man. Trans R Soc Trop Med Hyg 1964; 58: 335-8.
  13. Zika virus: clinical evaluation and disease. Atlanta: Centers for Disease Control and Prevention
  14. Duffy MR, Chen T-H, Hancock WT, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 2009; 360: 2536-43.
  15. Petersen LR, Jamieson DJ, Powers AM, and Honein MA. Zika Virus. N Engl J Med 2016; 374:1552-1563 April 21, 2016.
  16. Yamada S, Pobutsky A. Micronesian Migrant Health Issues in Hawaii: Part 1    Californian Journal of Health Promotion 2009, Volume 7, Issue 2, 16-31.
  17. Opening of Third STOP Tuberculosis in the Pacific. Monday, 31 July 2006. Press Release: Secretariat of the Pacific Community (SPC) Scoop Independent News.
  18. O’Hara CJ, Groopman JE. The ultrastructural and immunohistochemical demonstration of viral particles in lymph nodes from human immunodeficiency virus-related and nonhuman immunodeficiency virus-related lymphadenopathy syndromes. Hum Pathol. 1988; 19(5): 545–549.
  19. Nambuya A, Sewankambo N. Tuberculosis lymphadenitis associated with human immunodeficiency virus (HIV) in Uganda. J Clin Pathol. 1988; 41: 93–96.
  20. Voetberg A, Lucas SB. Tuberculosis or persistent generalized lymphadenopathy in HIV disease. Lancet. 1991; 337: 56–57.
  21. Bader JP. Reproduction of RNA humor viruses. Comprehensive Virol. 1975; 4: 253.
  22. Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jääskeläinen AJ et al. Brief Repot: Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities. N Engl J Med. 2016 Jun 2; 374(22):2142-51.
  23. Biedler JL et al. (1973) Morphology and growth, tumorgenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Research 33: 2643-2652
  24. Helson L et al. (1975) Human neuroblastoma in nude mice. Cancer Research 35: 2594-2599]
  25. Miller JM, Miller LD, Olson C, Gillette KG. Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst. 1969;43:1297–1305
  26. Alexander-Jackson, E. Microscopic and Submicroscopic Phases of P. Cryptocides from Fresh Lymphocytic leukemia. J Int Acad Metab 1978. 1:2:9-18
  27. Klieneberger-Nobel E. Origin, development and signifincance of L-forms in bacterial cultures. J Gen Microbiol 1949; 3: 434–442.
  28. Seibert FB, Feldman RL. Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods. Ann NY Acad Sci. 1970; 174(2): 690–728.
  29. Mattman L. Cell Wall Deficient Forms—Stealth Pathogens. Boca Raton: CRC Press; 1993.
  30. Randall PJ, Hsu N-J, Lang D, et al. Neurons Are Host Cells for Mycobacterium tuberculosis. Appleton JA, ed. Infection and Immunity. 2014; 82(5):1880-1890
  31. FDA. Fact Sheet for Health Care Providers: Interpreting Zika Virus RNA Qualitative Real-Time RT-PCR Test Results. April 28th, 2016.
  32. Butler D. Zika and birth defects: what we know and what we don’t – Experts fear a major epidemic of Zika-linked birth defects, but can’t yet be sure. Nature. 21 March 2016.
  33. Good RC. Simian Tuberculosis: Immunological Aspects. Annals of the New York Acad of Sciences. September 1968. 154: 200-213.
  34. Johnson PDR, Azuolas J, Lavender CJ, Wishart E, Stinear TP, Hayman JA, et al. Mycobacterium ulcerans in mosquitoes captured during outbreak of Buruli ulcer, southeastern Australia. Emerg Infect Dis. 2007 Nov. Available from
  35. Lavender CJ, Fyfe JAM, Azuolas J, Brown K, Evans RN, Ray LR, et al. (2011) Risk of Buruli Ulcer and Detection of Mycobacterium ulcerans in Mosquitoes in Southeastern Australia. PLoS Negl Trop Dis 5(9): e1305. doi:10.1371/journal.pntd.0001305.
  36. Banerjee, R., Banerjee, B.D., Chaudhury, S. and Hati, A.K. (1991) Transmission of Viable Mycobacterium leprae by Aedes aegypti from Lepromatous Leprosy Patients to the Skin of Mice through Intermittent Feeding. Tropical and Geographical Medicine, 42, 97-99.
  37. Narayanan, E., Manja, K.S., Kirchheimer, W.F. and Balasubrahmanyan, M. (1972) Occurrence of Mycobacterium leprae in Arthropods. Leprosy Review, 43, 194-198.
  38. Narayanan, E., Sreevatsa, Kirchheimer, W.F. and Bedi, B.M. (1977) Transfer of Leprosy Bacilli from Patients to Mouse Footpads by Aedes egypti. Leprosy Review, 49, 181-186.
  39. Narayanan, E., Sreevatsa, Raj, A.D., Kirchheimer, W.F. and Bedi, B.M. (1978) Persistence and Distribution of Mycobacterium leprae in Aedes egypti and Culex fatigans Experimentally Fed on Leprosy Patients. Leprosy in India, 50, 26-37.
  40. Golyshevskaya, V.I. (1991) The Role of Coccoid Ultrafine Forms of Mycobacteria in the Transmission of the Mycobacterial Infection. Pneumoftiziologia, 40, 11-13.
  41. Silva-Krott IM, Brock K, Junge RE. “Determination of the Presence of Mycobacterium avium on Guam as Precursor to Reintroduction of Indigenous Bird Species, Pacific Conservation Biology 4 (1998): 227–31.
  42. Smith M. WHO Raises Yellow Fever Warnings Urban outbreak in Angola might go global. MedPage.
  43. Manson P. Tropical Diseases. A Manual of the Diseases of Warm Climates. 1st edition. London: Cassell & Co.; 1898. p. 127.
  44. Lindenbach, BD et al. (2007). “Flaviviridae: The Viruses and Their Replication”. In Knipe, D. M.; P. M. Howley. Fields Virology (5th Ed.). Philadelphia, PA: Lippincott Williams & Wilkins. p. 1101
  45. Rivers TM. Filterable Viruses a Critical Review. From the Hospital of the Rockefeller Institute, New York Received for publication January 31, 1927 Journal of Bacteriology, Vol. XIV, No. 4; 217-257:220.
  46. Finlay C. The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever. Yale J Biol Med. 1937 Jul; 9(6): 589–604.
  47. Eckstein, Gustav. Noguchi. New York: Harper & Brothers, 1931 419pp
  48. Reed W. et al. The etiology of yellow fever. An additional note. J Amer Med Assoc. 1901; 36:431–440.
  49. Yellow fever. A compilation of various publications. Results of the work of Maj. Walter Reed, Medical Corps, United States Army, and the Yellow Fever Commission. 61st Congress, 3rd session. Senate Doc No 822. Washington: Government Printing Office; 1911.
  50. Del Regato, JA. James Carroll: a biography. Ann Diagn Pathol. 1998 Oct; 2(5):335-49.
  51. Kendall, AI. Observations Upon the Filterability of Bacteria, Including a Filterable Organism Obtained From Cases of Influenza. Science. August 7, 1931 74:1910.
  52. Krotz D. First Detailed Microscopy Evidence of Bacteria at the Lower Size Limit of Life. Berkeley Lab. February 27, 2015.
  53. Sternberg ML. George Miller Sternberg, A Biography. American Medical Association. Chicago. 1920. 331pp: p.118.
  54. Elliott CA. A clinical study of yellow fever: observations made in Guayaquil, Ecuador in 1918. Arch Intern Med (Chic). 1920;25(2):174-205
  55. Noguchi, H.: Etiology of Yellow Fever. J. Exper. M. 29:547, 1919; 30:1, 87, 401, 1919.
  56. Noguchi H. Etiology of yellow fever: II. Transmission experiments on yellow fever. J Exp Med. 1919; 29:565–584.
  57.  Noguchi H. Etiology of yellow fever: V. Properties of blood serum of yellow fever patients in relation to Leptospira icteroides. J Exp Med. 1919; 30:9–12.
  58. Stokes A, Bauer JH, Hudson N. The transmission of yellow fever to macacus rhesus: preliminary note. JAMA. 1928; 90(4):253-254.
  59. Mattman LH. Cell Wall Deficient Forms. CRC Press. Cleveland. 1974. 411 pp.
  60. Inada R, Ido Y, Hoki R, Kaneko R, and Ito H. The etiology, mode of infection, and specific therapy of Weil’s disease (Spirochaetosis Icterohaemorrhagica). J. Exp. Med., 23, 377-402. 1916.
  61. Hudson NP. Communication – Adrian stokes and yellow fever research: A tribute. Transactions of the Royal Society of Tropical Medicine and Hygiene.  60:2:170-174. 1966
  62. Letter from Noguchi to Simon Flexner, 1928 Noguchi’s papers. Record Group 450  N689 of the Rockefeller University Archives.;query=;brand=default;;doc.view=contents#aspace_ref36_m4i
  63. Extracts from letter of Hideyo Noguchi, Accra, March 9th, 1928 to Dr. Simon Flexner.;query=;brand=default;;doc.view=contents#aspace_ref36_m4i
  64. Received in NYC, NY Western Union Cablegram from Hideyo Noguchi to Dr. Simon Flexner March 16th, 1918 4/HN45C LCO  RUS  50.
  65. Noguchi to Russell of Rockefeller Institute  (Letter)  Accra  March 25, 1928.;query=;brand=default;;doc.view=contents#aspace_ref36_m4i
  66. Ekstein G. Hideyo Noguchi. Medical Bulletin College of Medicine University of Cincinnati, April, 1929. 5:3:15-17
  67. Jacob NJ, Henein SS. Nontuberculous Mycobacterial infection of the CNS in Patients with AIDS. Southern Medical Journal. Vol. 86 No. 6, 1993
  68. Bishburg E et al. Central Nervous System Tuberculosis with the Acquired Immunodeficiency Syndrome and Its Related Complex. Annals of Internal Medicine, 105: pp. 210-13.
  69. Lambertucci JR, Rayes AM, Nunes F, Landazuri-palacios EJ and Nobre V.  Fever of Undetermined Origin in Patients with the Acquired Immunodeficiency Syndrome in Brazil: Report on 55 Cases. Rev. Inst. Med. trop. S. Paulo Vol.41 N.1 São Paulo Jan./Feb. 1999
  70. Thomson, A. (1894) Microcephaly and Infantile Hemiplegia in the Journal of Anatomy and Physiology, Normal and Pathological, Human and Comparative. Humphray, G.M., Turner, W. and McKendrick, J.G., Eds., Vol. 28, Charles Griffin and Company, London, 419-444.
  71. Gluecksohn-Waelsch, S. (1957) The Effect of Maternal Immunization against Organ Tissues on Embryonic Differentiation in the Mouse. Journal of Embryology and Experimental Morphology, 5, 83-89.
  72. Warthin, A. S., and Cowie, D. M. A Contribution in the Casuistry of Placental and Congenital Tuberculosis. Journ. Inf. Dis., 1 (1904): 140.
  73. Rao, V. V., Gupta, E. V., and Thomas, I. M. Chromosome Damage in Untreated Tuberculosis Patients. Tubercle. 71, no. 3 (September 1990): 169–72.
  74. Lakimenko, L. N. Changes in the Mitotic Regime of a Cell Culture under the Influence of Sensitins. Biull Eksp Biol Med., 81, no. 2 (February 1976): 237–39.
  75. Golubchik, I. S., Lakimenko, L. N., and Lazovskaia, A. L. Effect of Tuberculin on the Mitotic Regime in Cell Cultures Biull Eksp Biol Med., 73, no. 5 (May 1972): 105–7.
  76. Nogales-Ortiz, F., and Tarancon, I. The Pathology of Female Genital Tuberculosis. Obstet. Gynecol., 53 (1979): 422-428.
  77. Favoretto S, Araujo D, Oliveira D, Duarte N, Mesquita F et al. First detection of Zika virus in neotropical primates in Brazil: a possible new reservoir. bioRxiv Apr 20, 2016  pp 1-3.
  78. Macdonald, David (Editor) (1985). Primates. All the World’s Animals. Torstar Books. pp. 1-50.
  79. Duarte-Quiroga, A; Estrada, A (2003). “Primates as pets in Mexico City: an assessment of the species involved, source of origin, and general aspects of treatment”. Am J Primatol 61: 53–60.
  80. Valderrama X, Robinson JG, Attygalle AB, Eisner T. (2000). “Seasonal Anointment with Millipedes in a Wild Primate: A Chemical Defense against Insects?” Journal of Chemical Ecology 26 (12): 2781–2790
  81. Michel AL, Huchzermeyer HF (1998) The zoonotic importance of Mycobacterium tuberculosis: Transmission from human to monkey. Journal of the South African Veterinary Association 69:64–65
  82.  Alfonso R, Romero RE, Diaz A, Calderon MN, Urdaneta G, Arce J, et al. (2004) Isolation and identification of mycobacteria in New World primates maintained in captivity. Veterinary Microbiology 98:285–295
  83. Capuano SV, Croix DA, Pawar S, Zinovik A, Myers A, Lin PL, et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection. Infection and Immunity. 2003; 71:5831–5844
  84. Une, Y. and Mori, T., “Tuberculosis as a zoonosis from a veterinary perspective”, Comp. Immunol. Microb. 2007 Sep; 30(5-6):415-425,
  85. Okia NO, George PV, Tukei PM, Kafuko GW, Lule M, Sekyalo E, et al. Arbovirus survey in wild birds in Uganda. East Afr Med J. 1971; 48(12):725–31. PMID: 5148604
  86. Spinage CA. African Ecology – Benchmarks and Historical Perspectives. Springer Science & Business Media. Jan 28, 2012 1562pp:  p.1124
  87. Garmany, Jeff (2011). Situating Fortaleza: Urban space and uneven development in northeastern Brazil Cities (Elsevier) 28 (1): 45–52
  88. Ranking das maiores regiões metropolitanas do Brasil. 10/12/2010
  89. NatureServe. InfoNatura: birds, mammals, and amphibians of Latin América (Web application). 32nd edition. Arlington, Virginia. NatureServe. 2010.
  90. Marini MA, Garcia FI: Bird conservation in Brazil. Conservation Biology 2005, 19(3):665–671
  91. Alves RRN, Lima JRF, Araújo HF: The live bird trade in Brazil and its conservation implications: an overview. Bird Conservation International 2012.
  92. Alves RRN, Nogueira E, Araujo H, Brooks S: Bird-keeping in the Caatinga, NE Brazil. Hum Ecol 2010, 38(1):147–156.
  93. Gama TF, Sassi R: Aspectos do comércio Ilegal de Pássaros Silvestres na Cidade de João Pessoa, Paraíba, Brasil. Gaia Scientia 2008, 2(2):1–20.
  94. Silva JMC, Souza MA, Bieber AGD, Carlos CJ. Aves da Caatinga: Status, uso do habitat e sensitividade. In: Ecologia e Conservação da Caatinga. 1st Edition. Edited by Leal IR, Tabarelli M, Silva JMC. Recife, Brasil. Universitária da UFPE; 2003:237–274
  95. Fernandes-Ferreira H, Mendonça SV, Albano C, Ferreira FS, Alves RRN: Hunting, use and conservation of birds in Northeast Brazil. Biodivers Conserv. 2012, 21: 221-244.
  96. Dhama, K., Mahendran, M., Tiwari, R., Dayal Singh, S., Kumar, D., Singh, S., & Sawant, P. M. (2011). Tuberculosis in Birds: Insights into the Mycobacterium avium Infections. Veterinary Medicine International, 2011, 712369.
  97. Marx, F. (2011) Tuberculosis in the Region of the Americas – Regional Report 2011: Epidemiology, Control and Financing. Pan-American Health Organization, Regional Office of the World Health Organization. Washington DC, 53pp
  98. Starke JR, Jacobs RF, Jereb J. Review: Resurgence of tuberculosis in children. J  Pediatr. 1992 Jun; 120(6):839-55
  99. Melo, A.S.O., Malinger, G., Ximenes, R., Szejnfeld, P.O., Sampaio, S.A. and Bispo de Filippis, A.M. (2016) Zika Virus Intrauterine Infection Causes Fetal Brain Abnormality and Microcephaly: Tip of the Iceberg? Ultrasound in Obstetrics & Gynecology, 47, 6-7.
  100. Anga G, Barnabas R, Kaminiel O, Tefuarani Vince NJ, Ripa P, Riddell M and Duke T. The aetiology, clinical presentations and outcome of febrile encephalopathy in children in Papua New Guinea. Annals of Tropical Paediatrics 2010, Jun 21. 30(2): 109-18.
  101. Zika Virus in Papua New Guinea. Centers for Disease Control and Prevention (CDC); National Center for Emerging and Zoonotic Infectious Diseases (NCEZID); Division of Global Migration and Quarantine (DGMQ). Last updated: April 29, 2016
  102. There is no outbreak of Zika virus in PNG. Press release: PORT MORESBY (POST COURIER) March 21, 2016]
  103. Eccles, G. Papua New Guinea’s Tuberculosis Pandemic. March 28, 2016 The Diplomat
  104. Koch R., “Die Ätiologie der Tuberkulose” (“The Aetiology of Tuberculosis”), Mitteilungen aus dem Kaiserlichen Gesundheitsamte 1884; 2:1-88.
  105. Zika travel information. Atlanta: Centers for Disease Control and Prevention, January 2016
  106. Gourinat AC, O’Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis 2015; 21:84-86.
  107. Korhonen EM, Huhtamo E, Smura T, Kallio-Kokko H, Raassina M, Vapalahti O. Zika virus infection in a traveller returning from the Maldives, June 2015. Euro Surveill 2016; 21.
  108. Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis 2015; 21:359-361.
  109. Foy BD, Kobylinski KC, Chilson Foy JL, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis 2011; 17:880-882.
  110. McCarthy M. Zika virus was transmitted by sexual contact in Texas, health officials report. BMJ 2016; 352: i720-i720.
  111. Venturi G, Zammarchi L, Fortuna C, et al. An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014. Euro Surveill 2016;21.
  112. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission — continental United States, 2016. MMWR Morb Mortal Wkly Rep 2016; 65:215-216.
  113. Zika virus infection: global update on epidemiology and potentially associated clinical manifestations. Wkly Epidemiol Rec 2016;91:73-81.
  114. Lauritsen J. Has Provincetown Become Protease Town? [Internet]. Available from:
  115. Hellyer TJ, Desjardin LE, Teixeira L, Perkins MD, Cave MD, Eisenach KD. Detection of Viable Mycobacterium tuberculosis by Reverse Transcriptase-Strand Displacement Amplification of mRNA. Clin. Microbiol. March 1999. 37:3:518-523.
  116. Cáceres M. Birth of the Zika Industry. The Vaccine Reaction. May 16, 2016.
  117. Centers for Disease Control and Prevention. CDC Concludes Zika Causes Microcephaly and Other Birth Apr. 13, 2016.
  118. Centers for Disease Control and Prevention (CDC). Zika Virus. Clinical evaluation and disease. April 19, 2016
  119. Kasper DL, Braunwald E, Hauser S, Longo D, Jameson JL et al. Harrison’s Principles of Internal Medicine 16th Edition (July 23, 2004), McGraw-Hill Professional. 2607 p.
  120. Klase ZA, Khakhina S, Schneider ADB, Callahan MV, Glasspool-Malone J, Malone R (2016) Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome. PLoS Negl Trop Dis 10(8).
  121. Schlossberg D. Clinical Infectious Disease. Cambridge University Press. Apr 23, 2015. 1508pp p.481
  122. Cantwell AR Jr, Kelso DW, Jones JE. Histologic observations of coccoid forms suggestive of cell wall deficient bacteria in cutaneous and systemic lupus erythematosus. Int J Dermatol. 1982 Nov; 21(9):526-37.
  123. Doria A, Canova M, Tonon M, Zen M, Rampudda E, Bassi N,et al. Infections as triggers and complications of systemic lupus erythematosus. Autoimmun Rev 2008; 8:24-8.
  124. Ghosh K, Patwardhan M, Pradhan V. Mycobacterium tuberculosis infection precipitates SLE in patients from endemic areas. Rheumatol Int 2009; 29:1047-50.
  125. Purice S, Mitu S, Popescu T, Guran M, Vintilă M, Suţă G. The relationship between systemic lupus erythematosus and tuberculosis. Med Interne 1982; 20:191-6
  126. Prabu VNN, Agrawal S. Systemic lupus erythematosus and tuberculosis: A review of complex interactions of complicated diseases. Journal of Postgraduate Medicine 56, Num. 3, 2010, pp. 244-250.
  127. Zika Virus RNA Qualitative Real-Time RT-PCR. Focus Diagnostics, Inc. For use under an Emergency Use Authorization only Instructions for Use.
  128. R. Nowell, “Comparative Mosquito Collection Data from the Southern Mariana Islands (Diptera: Culicidae),” Proceedings of the California Mosquito and Vector Control Association 48 (1980): 112–6.
  129. Flexner, S. Simon Flexner Papers, 1891-1946. Noguchi to Flexner Aug. 11, 1924. Rockefeller Archive Center.
  130. Mlakar, J., Korva, M., Tul, N., et al. (2016) Brief Report: Zika Virus Associated with Microcephaly. New England Journal of Medicine, 374, 951-958.
  131. Rubin, E.J., Greene, M.F. and Baden, L.R. (2016) Editorial: Zika Virus and Microcephaly. New England Journal of Medicine, 374, 984-985.]
  132. The Pan American Health Organization/World Health Organization (PAHO/WHO). Epidemiological Update. Zika virus infection. 16 October 2015.























Further Evidence for Cancer as a Cell-Wall-Deficient Mycobacterial Disease

December 5, 2016

A.P. Lysenko PhD, L. Broxmeyer MD, V.V. Vlasenko PhD, P.A. Krasochko PhD, A.P.Lemish PhD, and E.A. Krasnikova

Further Evidence for Cancer as a Cell-Wall-Deficient Mycobacterial Disease.pdf

Corresponding author:
Lawrence Broxmeyer, M.D

© Under License of Creative Commons Attribution 3.0 License


Received: October 07, 2016; Accepted: November 03, 2016; Published: November
14, 2016



In 2014, Buehring reported that Bovine Leukemic Virus (BLV), a common oncogenic retrovirus of cattle, was present in some humans, primarily localized to the breast epithelium  ―  the  very  cell  type  from  which  most  breast  malignancies  arise.  By 2015, there appeared data (Buehring, 2015) supporting that as many as 37% of human breast cancer cases could be attributable to BLV exposure. But if recent estimates suggest over 83% of U.S. dairy operations are currently positive for BLV, they also show that approximately 68% are positive for cell-wall-deficient Mycobacterium avium subspecies paratuberculosis (MAP). Although tubercular lung infection has been said to cause 11 times the incidence of lung cancer as normal control subjects, it is its cell-wall-deficient (CWD) forms (also called L-forms) that have recently repeatedly been found through genetic analysis and appropriate stains in such cancer tissue ― suggesting that CWD tuberculosis or atypical tuberculosis “is likely to be involved in the occurrence or development of lung carcinoma”. A similar relationship between tubercular L-forms and the genesis of the very breast cancer addressed in the aforementioned BLV viral trials. This is not a coincidence. L-forms (CWD forms) predominate and are crucial to the survival of mycobacteria in vivo and they have been documented by fluorescence microscopy in all intracellular macrophage-grown M. tuberculosis observed. From its origin, the very concept of the “BLV leukemic virus” has been on shaky, unstable ground. In 1969, veterinarians Janice and Lyle Miller from the University of Wisconsin-Madison spotted C-shaped “virus-like” particles in cattle lymphosarcoma insisting that these were similar to other C-type viruses “regarded as the cause of leukemia in other species.” But by 1978, scientists at Downstate reported atypical mycobacterial forms, including its preferred filterable virus-sized “L” or cell-wall-deficient (CWD) forms in not only leukemia but all other malignancies ― all having, as their common denominator the continuous presence of mycobacterial C-shaped forms.

Tracing back to techniques similar to Miller and Millers original BLV study we found in the very lyophilized antigens present in commercial kits for the diagnosis of BLV (AgBLV), these very same CWD (cell-wall-deficient) mycobacteria and mycobacterial DNA in all BLV samples ― which when introduced into guinea pigs stimulated the same antibody as occurred when mycobacteria-infected internal organ homogenates themselves were injected into other guinea pigs. It is therefore assumed that the Bovine Leukemic Virus (BLV) is being mistaken for viral-like forms of cell-wall-deficient (CWD) atypical tubercular mycobacteria. Since latent tubercular infection, as well as the administration of BCG and tuberculin also results in persistent CWD forms, their possible role in carcinogenesis is also considered.

KEYWORDS: Cancer; Mycobacterium tuberculosis; Bovine Leukemic Virus; BLV; Mycobacteriophages



1   Rous PA (1911) Sarcoma of the fowl transmissible by an agent separable from the tumour cells. J Exp Med 13: 397-411.

2    Bittner JJ (1936) Some possible effects of nursing on the mammary gland tumour incidence of mice. Science 84: 162.

3    Van Helvoort T (1994) History of virus research in the 20th century: the problem of conceptual continuity. History of Science 32: 185-235.

4    Livingston V (1972) Cancer: A New Breakthrough. Nash Publishing p: 269.

5  Livingston V (1970) Specific type of organism cultured from malignancy: bacteriology and proposed classification.  Ann NY Acad Sci 174: 636-654.

6    Duran-Reynals F (1950) Neoplastic infection and cancer. Am J Med 8: 440-511.

7    Glover T, Scott MA (1926) Study of the Rous chicken sarcoma no 1. Canada Lancet Pract 66: 49-62.

8    Diller I (1970) Experiments with mammalian tumor isolates. Ann NY Acad Sci 174: 655-674.

9    Miller JM, Miller LD, Olson C, Gillette KG (1969) Virus-like particles in phytohemagglutinin-stimulated lymphocyte cultures with reference to bovine lymphosarcoma. J Natl Cancer Inst 43: 1297-1305

10 Miller JM (1974) Animal model of human disease. Malignant lymphoma. Am J Pathol 75: 417-420.

11  Sorensen DK, Dutta SK, Hammer RF, Larson VL, Perman V, et al. (1970) Bovine lymphocytic leukemia: studies of etiology, pathogenesis and mode of transmission. Progress Report no. 10 to the U.S. Atomic Energy Commission, 1969-1970 p: 38

12  Alexander-Jackson EA (1954) specific type of microorganism isolated from animal and human cancer: bacteriology of the organism. Growth 18: 37-51.

13  Klieneberger-Nobel E (1949) Origin, development and significance of L-forms in bacterial cultures. J Gen Microbiol 3: 434-442.

14  Mattman LH (2000) Cell wall deficient forms: stealth pathogens. CRC Press.

15  Kashala O, Marlink R, Ilunga M, Diese M, Gormus B, et al. ( 1994) Infection with human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic viruses among leprosy patients and contacts: correlation between HIV-1 cross-reactivity and antibodies to lipoarabinomannan. J Infect Dis 169: 296-304.

16  Glover T (1930) The bacteriology of cancer. Canada Lancet Pract 75: 92-111.

17  Mazet G (1941) Etude Bacteriologique sur la Maladie d’ Hodgkin. Montpellier Med pp: 1-6.

18  Livingston V, Allen R (1948) Presence of consistently recurring invasive myco- bacterial forms in tumor cells. Microscop Soc Bull 2: 5-18.

19  Wuerthele-Caspe V (1949) Mycobacterial forms observed in tumors. J Am Med. Womens Assoc 4: 135-141.

20  Alexander-Jackson  E  (1976)  Progenitor  Cryptocides,  The  Specific Pleomorphic Microorganism Isolated From Cancer. J Int Acad Metab 5: 31-39.

21  Alexander-Jackson E (1978) Microscopic and Submicroscopic Phases of P. Cryptocides from Fresh Lymphocytic leukemia. J Int Acad Metab 1: 9-18.

22  Diller I, Diller W (1965) Intracellular acid-fast organisms isolated from malignant tissues. Trans Am Micr Soc 84: 138-148.

23  Diller I, Donnelly A, Fisher M (1967) Isolation of pleomorphic, acid- fast organisms from several strains of mice. Cancer Res 27: 1402-1408.

24 Seibert F, Feldmann F, Davis R, Richmond I (1970) Morphological, biological, and immunological studies on isolates from tumors and leukemic bloods. Ann N Y Acad Sci 174: 690-728.

25  Wang A, Xie J (1998) Infection of mycobacterium tuberculosis in lung cancer. Zhongguo Fei Ai Za Zhi 1: 92-94.

26  Guliang  H,  Tefu  L  (1999)  Mycobacterium  tuberculosis  L-forms. Microb Ecol Health Dis 10: 129-133.

27  Xie J, Anchao W, Xiazhi Z (1999) Isolation of acid fast bacillus L- forms from carcinoma of Lung. Acta Academiae Medicinae Bengbu 24: 145-146.

28 Song LY, Yan WS, Zhao T (2002) Detection of Mycobacterium tuberculosis in lung cancer tissue by indirect in situ nested PCR. Di Yi Jun Yi Da Xue Xue Bao 22: 992-993.

29 Yesong WXQ , Lifa X (2004)   A case report on pneumoconiotu- berculosis complicated with lung cancer and   Mycobacterium tuberculosis- L form infection. Chin J Industrial Med.

30 Zhang  S,  Guang-ling  Z,  Yan-sheng  T  (2009)  Detection  of Mycobacterium tuberculosis L forms infection in tissues of lung carcinoma. Chin J Public Health 25: 1317-1318.

31 Yang B, Tian Y, Cui X, Zhang W, Ma Y et al. Detection of Mycobacterium tuberculosis L-forms and MPB64 in breast cancer tissues The Journal of Practical Medicine. 2013; 29(15) p2552-2555.

32  Sheng TY, Kun CX, Tong H, Guang LH, Wei Z, et al. (2009) Study on the relationship between Mycobacterium tuberculosis L infection and lung cancer. Tumor 29: 1085-1089.

33  Tian Y, Hao T, Cao B, Zhang W, Ma Y, et al. (2015) Clinical End-Points Associated with Mycobacterium tuberculosis and Lung Cancer: Implications into Host- Pathogen Interaction and    Coevolution. Bio Med Research Intern p: 9.

34 Alexander-Jackson E (1970) Ultraviolet spectrogramic microscope studies of Rous sarcoma virus cultured in cell-free medium. Ann N Y Acad Sci 174: 765-781.

35  Van der Maaten M, Miller J (1976) Replication of bovine leukemia virus in monolayer cell cultures. Bibl Haemat 43: 360-362.

36  Lysenko  AP,  Drogun  AG,  Shurinova  (1998)  Studies  of  influence atypical mycobacterial  infection on AGID results with sera of cattle infected BLV (in Russian). Vet. nauka – proizvodstvu 33: 56-54.

37  ShivRaj L, Patil SA, Girdhar A, Sengupta U, Desikan KV, et al. (1988) Antibodies to HIV-1 in sera from patients with mycobacterial infections. Int J Leprosy 56: 546-551.

38 Lysenko AP, Vlasenko AP, Broxmeyer L (2014) Phenomenon of variability of mycobacteria and its use for detection of a tuberculosis infection.

39 Lysenko AP, Vlasenko VV, Broxmeyer L, Lemish AP, Novik TP, et al. (2014) The tuberculin skin test: how safe is safe?  The tuberculins contain unknown forms capable of reverting to cell-wall deficient mycobacteria. Clin Exp Med Sci 2: 55-73.

40  Lysenko AP, Vlasenko VV, Lemish AP (2014) Detection of mycobacteria in tissues by means of the differentiating immunoperoxidase staining. Tuberculos i bolezni legkhih 10: 55-58.

41  Duesberg PH (1987)  Retroviruses  as carcinogens and pathogens: expectations and reality. Cancer Res 47: 1199-220.

42  Demochowski L, Grey CE (1957) Subcellular Structures of Possible Viral Origin in Some Mammalian Tumors. Ann NY Acad Sci : pp 559-615

43 Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685.

44  Dameshek W and Gunz (1965) Leukemia. Am J Med Sci 249: 115.

45 Seibert  FB,  Feldmann  PM,  Davis  RL,  Richmond  IS  (1970) Morphological, Biological, and Immunological Studies on Isolates from Tumors and Leukemic Bloods. Ann NY Acad Sci 174: 690-728.

46 Mankiewicz E (1965) Bacteriophages that lyse mycobacteria and corynebacteria, and show cytopathogenic effect on tissue cultures of renal cells of cercopithecus aethiops: a preliminary communication. Can Med Assoc J 92: 31-33.

47  Seibert FB (1968) Pebbles on the hill of a scientist. St Petersburg Printing Company 1: 162.

48 Dobrindt U, Reidl J (2000) Pathogenicity islands and phage conversion: evolutionary aspects of bacterial pathogenesis. Int J Med Microbiol 290: 519-27.

49 Landman OE, Burchard WK, Angelety LH (1962) Lysogeny and bacteriophage adsorption in stable and reverting L-forms of Salmonella paratyphi B and Escherichia coli. Bacteriol Proc p: 53.

50  Falagas ME, Kouranos VD, Athanassa Z, Kopterides P (2010) Review ―Tuberculosis and malignancy. Q J Med 103: 461-487.

51  Nelson EL, Pickett MJ (1951) The Recovery of L Forms of Brucella and their Relation to Brucella Phage. J Infect Dis 89: 226-32.

52  Kruegar AP, Cohn T, Smith PN, McGuire CD (1948) J Gen Physiol 31: 477-488.

53 Takahashi S (1979) L phase growth of Mycobacteria. 1. Cell wall deficient form of Mycobacteria. Kekkaku 54: 63-70.

54  Broxmeyer L, Sosnowska  D,  Miltner E, Chacón O, Wagner D, et al. (2002) Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. J Infect Dis 186: 1155-60.

55 Devadoss PO, Klegerman ME, Groves MJ (1993) Phagocytosis of Mycobacterium bovis BCG organisms by murine S180 sarcoma cells. Cytobios 74: 49-58.

56 Marcova N, Michailova L, Kussovsski V, Jordanova M (2008) Formation of persisting Cell Wall Deficient Forms M. bovis BCG during interaction with peritoneal macrophages in guinea pigs. Electronic J. of Biology 4: 1-10.

57  Chauhan A, Madiraju MV, Fol M, Lofton H, Maloney E, et al. (2006) Mycobacterium tuberculosis Cells Growing in Macrophages Are Filamentous and Deficient in FtsZ Rings. J Bacteriol 188: 1856-1865

58  Wagner PL, Waldor MK (2002) Bacteriophage Control of Bacterial Virulence. Infect Immun 70: 3985-3993.





October 9, 2016





Recent literature shows a controversial new push to tie microorganisms to Alzheimer’s disease (AD) ― which despite the protests of some, is badly needed. Indeed there is a good chance that Alzheimer’s is caused by a microbe. Study after study, in which scientists have injected human Alzheimer-diseased brain tissue into mice and other laboratory animals that later developed the disease have left little doubt that Alzheimer’s arises from an infectious process. So the proper focus of the present debate regarding AD should not be ‘is there an infectious process or processes behind Alzheimer’s?’…….. but rather ‘which one?’ Clearly, whatever the infectious cause behind Alzheimer’s is, it must be a disease that is statistically widespread in the world today and that was also prevalent at the time of Dr. Alzheimer. Presently, in America alone, more than 5 million people, to varying degrees, have lost their memory or cognition to this challenging disease.

Specifically mentioned to this point as possible causes have been: [1] herpes simplex virus type 1 (HSV-I), [2] Chlamydia pneumoniae, and [3] several types of spirochetes. Also mentioned is [4] fungal infection in the AD brain as well.

Mawanda and Wallace’s review (2013) gave seven annotated references as to why Herpes Simplex virus type 1 (HSV-1) “remains questionable” as a cause for Alzheimer’s; nine studies referenced as to why there was “no evidence to suggest an association between Chlamydia pneumoniae infection and AD pathogenesis”; and six “rigorous studies which found no evidence to suggest that spirochetal B. Burgdorferi, is “causally linked to AD” Wallace also mentioned that although Riviere et al. found oral spirochetal Treponema, including T. denticola, T. pectinovorum, T. vincentii, T. amylovorum, T. maltophilum, T. medium, and T. socranskii in a significantly higher proportion of postmortem brain specimens from AD cases than controls. These results have, however, according to Mawanda and Wallace’s review, not been replicated.

As for fungal forms found in the Alzheimer’s brain, this is nothing new. Oskar Fischer, the co-discoverer of Alzheimer’s disease, saw such forms in 1907. But Fischer knew that they were related to Streptothrix, a germ with both bacterial and fungal properties often confused with tuberculosis. The disease actinomycosis was at one time referred to interchangeably with its older bacterial name, the “Streptotriches” (the plural form of Streptothrix). Fischer used such older nomenclature in describing certain forms he saw under his microscope. Furthermore, regarding the thick, black, club-shaped “Drüsen” in Oskar Fischer’s 1907 drawing of senile plaque ― at the time, it was widely acknowledged that such drüsen could result from either infection with Streptothrix, now known as actinomycosis (aktinomycesdruse), a rare disease in humans, or tuberculosis, a disease that by 1882, as Alzheimer prepared to leave for Berlin for his medical education, was understood to be far and away the leading cause of infectious death in Europe. And just ten years before Oskar Fischer found Actinomycosis-like Streptothrix in Alzheimer’s cerebral plaque, Babèş and immunologist Levaditi reported in “On the Actinomycotic Shape of the Tuberculous Bacilli” that typical Actinomyces-like clusters [Drüsen] with clubs appeared in the tissue of rabbits inoculated with tubercle bacilli beneath the dura mater of their brains. Once introduced into the brain this way, reported Babes, TB bacilli not only branched out like the Actinomycosis such as Streptothrix, but they developed rosettes that were identical to the “drüsen” that Oskar Fischer spotted in Alzheimer’s plaque.

What Mawanda and Wallace did maintain however was the emerging evidence that supported an infectious pathogen and two prime suspects for Amyloid beta deposition to the extent that it was going on in Alzheimer’s. This book discusses one of them.

Available on Amazon: Alzheimer’s Disease – How Its Bacterial Cause Was Found And Then Discarded

Introductory YouTube Video: click here

Introductory chapter article is on: