Study Finds Bacteria in Milk Linked to Rheumatoid Arthritis
A strain of bacteria commonly found in milk and beef may be a trigger for developing rheumatoid arthritis in people who are genetically at risk, according to a new study from the University of Central Florida.
A team of UCF College of Medicine researchers has discovered a link between rheumatoid arthritis and Mycobacterium avium subspecies paratuberculosis, known as MAP, a bacteria found in about half the cows in the United States. The bacteria can be spread to humans through the consumption of infected milk, beef and produce fertilized by cow manure.
The UCF researchers are the first to report this connection between MAP and rheumatoid arthritis in a study published in the Frontiers in Cellular and Infection Microbiology journal this week. The study, funded in part by a $500,000 grant from the Florida Legislative, was a collaboration between Saleh Naser, UCF infectious disease specialist, Dr. Shazia Bég, rheumatologist at UCF’s physician practice, and Robert Sharp, a biomedical sciences doctoral candidate at the medical school.
Naser had previously discovered a connection between MAP and Crohn’s disease and is involved in the first ever phase III-FDA approved clinical trial to treat Crohn’s patients with antibiotics. Crohn’s and rheumatoid arthritis share the same genetic predispositions and both are often treated using the same types of immunosuppressive drugs. Those similarities led the team to investigate whether MAP could also be linked to rheumatoid arthritis.
“Here you have two inflammatory diseases, one affects the intestine and the other affects the joints, and both share the same genetic defect and treated with the same drugs. Do they have a common trigger? That was the question we raised and set out to investigate,” Naser said.
For the study, Bég recruited 100 of her patients who volunteered clinical samples for testing. Seventy-eight percent of the patients with rheumatoid arthritis were found to have a mutation in the PTPN2/22 gene, the same genetic mutation found in Crohn’s patients, and 40 percent of that number tested positive for MAP.
“We believe that individuals born with this genetic mutation and who are later exposed to MAP through consuming contaminated milk or meat from infected cattle are at a higher risk of developing rheumatoid arthritis,” Naser said.
About 1.3 million adults in the U.S. have rheumatoid arthritis – an autoimmune and inflammatory disease that causes the immune system to attack a person’s joints, muscles, bones and organs. Patients suffer from pain and deformities mostly in the hands and feet. It can occur at any age but the most common onset is between 40 and 60 years old and is three times more prevalent in women.
Although case studies have reported that some RA patients suffer from Crohn’s disease and vice versa, the researchers say a national study needs to investigate the incidence of the two diseases in the same patients.
“We don’t know the cause of rheumatoid arthritis, so we’re excited that we have found this association,” Bég said. “But there is still a long way to go. We need to find out why MAP is more predominant in these patients – whether it’s present because they have RA, or whether it caused RA in these patients. If we find that out, then we can target treatment toward the MAP bacteria.”
The team is conducting further studies to confirm findings and plan to study patients from different geographical and ethnic backgrounds.
“Understanding the role of MAP in rheumatoid arthritis means the disease could be treated more effectively,” Naser said. “Ultimately, we may be able to administer a combined treatment to target both inflammation and bacterial infection.”
Naser holds a Ph.D in Medical Microbiology from New Mexico State University. He joined UCF in 1995. He has been investigating Crohn’s disease and other auto-immune diseases for more than 30 years. He has published more than 100 peer-reviewed articles and has presented his work at numerous conferences. He has several patents including a licensed DNA technology for detecting MAP.
Bég, a board-certified rheumatologist, has been with UCF since 2011 after completing her fellowship in rheumatology at Baylor College of Medicine in Houston. In addition to practicing medicine at UCF Health, she is a full-time faculty member at the college. Her research and clinical interests include conditions such as rheumatoid arthritis, psoriatic arthritis, lupus and osteoporosis.
Lyme/MSIDS patients need to take note of this study as RA is often undiagnosed tick-borne infections – including Mycoplasma. The genetic issue as well as consuming infected animal products should be a concern to us all; however, being infected with TBI’s is right up there on the list.
And previously to that, Dr. Brown way back in the 40’s and 50’s believed that RA was caused by mycoplasmas and used tetracycline rather than prednisone, the drug of choice. He eventually modified his treatment which included Minocycline and brought over 10,000 patients into remission. (This demonstrates the importance of dealing with the infection)
https://madisonarealymesupportgroup.com/2015/08/12/connecting-dots-mycoplasma/ This link also shows Nicholson’s discovery that 90% of evaluated ALS patients had Mycoplasma. 100% of ALS patients with Gulf War Syndrome had Mycoplasma and nearly all of those were specifically the weaponized M. fermentans incognitos.One of the hallmark symptoms of Mycoplasma is fatigue. And the bad news for us is that Nicholson’s experience has found Mycoplasma to be the number one Lyme coinfection, and similar to other coinfections in that it can be supposedly cleared for years only to reappear when conditions are right.
One other note is that immunosuppressive drugs for folks that have TBI’s are going to worsen their condition, so TBI’s must be ruled out before the administration of them, which is going to be tricky business as the tests for all of these pathogens is abysmal. I highly recommend having patients fill out the Horowitz questionnaire along with testing and for doctors to make a clinical diagnosis not based on testing only: https://madisonarealymesupportgroup.files.wordpress.com/2016/01/symptomlist.pdf
This study also shows the dire need for medical professionals to be properly trained regarding TBI’s or they run the risk of putting patients on immunosuppressive drugs to their demise. So far the education in med school on Tick borne infections is antiquated and brief, considering Lyme is the #1 vector borne disease in the U.S. No one has accurate numbers on coinfections. If you know of doctors who are willing to be trained in this area, please send them this: https://madisonarealymesupportgroup.com/2017/06/20/help-doctors-get-educated-on-lyme-and-tick-borne-illness/Dr. Betty Maloney, President, Partnership for Tick-borne Diseases Education created LymeCME.info a website built specifically for the purpose of offering accredited, evidence-based continuing medical education (CME) modules on Lyme and other tick-borne diseases (TBD) for doctors and other healthcare professionals. Doctors will like the convenience of on-demand learning that’s available on PC and mobile devices. The modules I developed for LymeCME provide a concise review of the evidence, highlighting points that are especially relevant to patient care. And, they’re free!
It fits. Mycoplasma and ureaplasma are the smallest of all bacteria. They are obligate intracellular microbes — which means they must live inside cells of a host to survive. They typically infect linings of the body — linings of lungs, intestines, joints, and the urinary tract. Different species of mycoplasma and ureaplasma prefer certain areas of the body, but any species of these microbes can be found in different places the body. The most common species found in the urinary and reproductive tract are Ureaplasma urealyticum and Mycoplasma hominis. These microbes typically spread sexually, but they can be acquired by other routes. Mycoplasma pneumoniae, a frequent cause of respiratory infections, can also be found in the urinary tract.Mycoplasma and ureaplasma are notoriously difficult to culture.”
But back to Mycobacterium…..Dr. Horowitz is finding that Mycobacterium drugs are working for his treatment resistant patients: https://madisonarealymesupportgroup.com/2016/10/09/mycobacterium-drugs-for-ld/ The case study has based on a woman with Borrelia burgdorferi, Borrelia hermsii, possible prior exposure to tularemia, exposure to Mycoplasma pneumonia, multiple viruses, fibromyalgia, and rheumatoid arthritis. Under Dr. Horowitz’s care she improved from 30% to 50%, but with the addition of Dapsone had a sudden fourfold increase in tularemia titers as well as Bartonella titers turning positive.While making continuous progress the patient had ongoing joint pain which interfered with sleep as well as ongoing severe blood-filled blisters, oral/genital ulcerations, and increased granulomas. While a rheumatologist wanted to put her on an immunosuppressive, she and Dr. Horowitz chose to try 500mg (based on body weight) of PZA twice a day combined with rifampin and minocycline. Her liver was monitored every two weeks and was helped with alpha lipoid acid 600mg and milk thistle 250mg.Two months later she reported up to 80% of normal functioning…
The fact that the addition of a mycobacterium drug that gave this woman 80% of normal functioning is something that needs to be noted. It also leads to the conclusion that her prior diagnosis of RA is probably infectious in nature and improved with microbials.
Now if that isn’t a success story, I don’t know what is. So something is going on here with Mycobacterium or a mycobacterium-like pathogen. This needs to be hunted to ground.
Since the beginning of our species we have been at war. It’s a continuous, neverending fight against the smallest of adversaries: armies of pathogens and parasites. As we have developed new ways to survive and stop them, they have evolved ever more complex and ingenious methods to thwart our efforts.
Humans have faced numerous attempts to challenge our dominance on planet Earth and from the Black Death to the Spanish flu, we have weathered them all. However, since the start of the 21st century, with its trend towards global interconnectedness, these onslaughts are ever-increasing. In the past 17 years we have battled Sars, the Ebola virus, Mers, and more recently the mysterious mosquito-borne Zika virus. These diseases seeming to appear from nowhere and rapidly ravage our populations. One commonality is that they almost always originate in animals before jumping across to people, and few parasites are as good at jumping between animals and people as the tick.
Ticks could be best described as the used syringes of the natural world due to their promiscuous feeding habits. Most ticks go through three stages in their lives and feed on a different host at each stage, whilst simultaneously collecting hitchhiking microbes in their blood meals. Ticks also have one of the widest distributions of any vector on Earth – they can be found on every continent, including frigid Antarctica. This combination of ubiquity and a bad habit for accumulating pathogenic microbes make ticks some of the most dangerous vectors on the planet.
So why ticks? And why now?
Partly, it’s because ticks have been understudied for so long that only recently have we begun to realise just how much they affect our health. It took until 1975 for the infamous Lyme disease even to be formally described, and today the list of microbes found within ticks grows ever larger every year as numerous new species are discovered.
Changing ecosystems are also forcing ticks into closer contact with humans. Perhaps the most immediate changes are being driven by land clearing, which is forcing wildlife into closer contact with humans; with wildlife come ticks and the diseases they carry. Climate change has also been implicated: as the climate gets warmer, some ticks are expanding their ranges into places where cool winter temperatures previously limited their distribution. Geographical boundaries are also being eroded as rapid transport links environments which were previously isolated from one another. This presents easy opportunity for ticks to cross borders and spread to new habitats they may not have previously occupied.
In short, our manipulation of the environment has set the stage for a tick-driven health crisis.
Ticks can carry an extremely wide array of human pathogens, including bacteria, viruses, and protozoa. Within the long list of human ailments caused by ticks, several dangerous diseases stand out.
While the recognition of Lyme disease has led to a greater study of the bacteria which cause it and more frequent testing for patients, it has been a double-edged sword, as its notoriety has overshadowed equally important diseases like tick-borne rickettsiosis (TBR). TBR is caused by a number of different bacteria distributed across the globe. Unfortunately, TBR often presents with signs and symptoms similar to Lyme disease, such as rashes, joint and muscle pain, and fatigue. Although deaths are rare when TBR is treated with antibiotics like doxycycline, when the disease is incorrectly diagnosed or adequate medical infrastructure is lacking, mortalities can still occur.
Babesiosis is an emerging tick-borne disease caused by a protozoan called Babesia, a species related to the microbe which causes malaria. The disease is rarely tested for by doctors and the global levels of human infection are unknown, although some researchers believe that they may be much higher than present rates of diagnosis indicate. Infections can be highly variable, with about a quarter of infected adults showing no signs of the disease, while others will die from the infection. In truth the disease is still poorly understood in humans, which is compounded by the fact that several species of Babesia cause the disease and the signs and symptoms can be wide-ranging and often include fever, fatigue, anaemia, and nausea – all common features of other illnesses.
Crimean-Congo haemorrhagic fever (CCHF) is perhaps the most terrifying disease spread by ticks, as there are no treatments available, and mortality rates can be as high as 40% in infected humans. To put it into perspective, that mortality rate is similar to untreated cases of Ebola or the bubonic plague. The World Health Organisation views CCHF virus as having a high chance of causing human disease epidemics and has accordingly directed considerable funding towards finding a treatment, although to date none have been developed. The wide distribution of tick vectors capable of spreading the disease coupled with the ability of common domestic animals such as sheep and cattle to maintain the CCHF virus in their blood at high levels means the potential for CCHF to expand into new regions like Europe is highly probable.
While only discovered in 2009, SFTS virus (severe fever with thrombocytopenia syndrome) has sparked widespread fear through much of Asia, especially in Japan where 57 people have died of the disease since 2013. Signs of the disease can range in severity from relatively mild, like fever and diarrhoea, to severe, which can include multiple organ failure. The fact that the epidemiology of the disease is so poorly known makes predicting and controlling its spread difficult. It is also known to be carried by at least two cosmopolitan tick species which are spread throughout the world from the UK, to the US, and even Australia. That might sounds bad enough, but things are even worse: although the disease typically gets to humans via a tick, from there it can spread to other humans or their pets and back again into ticks who feed on infected hosts.
Ticks are ubiquitous, dangerous, and are coming into ever greater contact with us. We must recognise that the next public health crisis may come from our backyards rather than a remote equatorial jungle in Africa or Asia.
I’m thankful the article points out that other pathogens are involved. For those with Lyme as well as these other pathogens (which is common), they typically have more severe cases and require longer and more extensive treatment.
The Cabal still denies ticks transmit Bart; however, many feel otherwise. This is why all the research in the world put out by the Cabal will never touch Bart. It doesn’t fit the narrative. The fly in the ointment is similar to sexual transmission for Lyme, the organisms have been found but there isn’t conclusive proof of transmission. Many of these pathogens are fastidious and hard to study in a lab. All case studies are ignored.
I’m always fascinated that Bartonella and Mycoplasma are rarely mentioned in regards to coinfections by mainstream news – as according to experts Dr. Nicholson and Dr. Breitshwerdt, they are probably the TOP coinfections with Lyme.
Epstein-Barr Virus: A Key Player in Chronic Illness
by Dr. Bill Rawls
So, you’re experiencing symptoms of tiredness, achiness, sore throat, and possibly swollen lymph nodes and low-grade fever that just won’t go away.
You’ve Googled your symptoms, and mononucleosis pops up as a likely possibility. But if you’re well beyond college age, mononucleosis isn’t very common.
Chronic fatigue syndrome, fibromyalgia, and even Lyme disease are other possibilities you might have entertained, especially if you have symptoms beyond those mentioned above. But then you came across something called reactivated Epstein-Barr virus, which fits your symptoms to a tee.
If you are aware that Epstein-Barr virus (EBV) is the cause of mononucleosis, you may be wondering: What’s the difference between chronic reactivated EBV and mononucleosis? And beyond that, what makes chronic reactivated EBV chronic — and how does it play into other chronic illnesses?
To find out, read on to learn more about this complex and convoluted microbe called Epstein-Barr virus and what can make it a long-term troublemaker.
Almost Everyone Has EBV
Let’s start with the fact that EBV is much more common than you might imagine: >95% of world’s population has been infected with it.
Another interesting fact is that it’s a herpes-type virus. Yep, you read that right: EBV is a close relative of genital herpes. Known technically as Human Herpesvirus 4 (HHV-4), it’s #4 on the list of nine different herpes-type viruses that can infect humans.
Herpesviruses are composed of strands of DNA inside an envelope. After initial infection, they stay dormant in tissues indefinitely, but can reactivate if immune system functions become depressed.
In other words, if you’ve ever been infected with a herpesvirus like EBV, you will always carry it in your tissues.
EBV Can Spread Like Wildfire
The majority of people become infected with EBV as infants or young children. The virus spreads primarily by oral route via saliva. To enter the body, it infects mucous membranes lining the mouth, throat, and stomach. From there, the virus infects B cells, the type of white blood cell that produces antibodies. It also infects T cells and natural killer cells, but to a lesser extent. Infected white blood cells transport EBV throughout the body.
In this active phase, called the lytic phase, the virus takes over the machinery of infected cells to generate new viruses. This is when people are most symptomatic and contagious.
The virus spreads remarkably easily, especially in children. It is most typically spread by people who are infectious, but don’t know it — daycare workers, babysitters, grandmothers with big wet kisses. Following that, infected children rapidly pass it along to other children.
Which is a really good thing — because if you get it as an infant or young child (remember to thank your grandmother), you typically don’t get very sick at all. In fact, it’s unlikely that you would even remember the infection.
It’s only if you don’t get EBV at a young age and then get exposed later in life when your immune system is suppressed that you’re at risk for developing the form of EBV called mononucleosis.
Known as kissing disease, infectious mononucleosis (IM) is spread by intimate contact with someone shedding the virus. It typically occurs in young adults who haven’t been exposed early in life. It usually catches the person off guard when immune system functions are depressed, such as during the stress of high school or college.
Compared to EBV occurring in childhood, IM is much more severe: Common symptoms include sore throat, fever, severe fatigue, and swollen lymph nodes. It can drag on for months and be quite debilitating.25
Whether the initial encounter with EBV occurs as an innocuous infection as a child or as debilitating mononucleosis as a young adult, the host’s immune system eventually gains ground and the infection is contained.
The virus, however, is not eradicated. It persists inside memory B cells, a type of white blood cell that retains “memory” of an infection for future reference — except in this case, the cells are sabotaged into storing the actual virus. Memory B cells infected with EBV accumulate in lymphoid tissue and nerve tissue, and stay there for a lifetime.
This dormant state is referred to as the latent phase.9, 6, 12, 23Traditionally, people in the latent phase weren’t considered noninfectious. But with all the daycare workers, teachers, grandmas, and college students actively shedding the virus without knowing it, it’s become clear that someone can be very infectious without being ill. In fact, recent evidence supports that people often actively shed virus from tonsillar tissues without having significant symptoms.23
Either way, whether EBV is completely dormant or infectious without symptoms, the virus generally doesn’t cause any significant problems as long as immune system functions are robust. You can carry it for a whole lifetime and not know it — as most people do.
However, allow the immune system to become disrupted — by stress, poor diet, and other key factors I’ll explore below — and EBV can reactivate, causing symptoms similar to the mononucleosis, but much worse.4
Reactivated EBV Can Become Chronic
Chronic reactivated EBV is like mononucleosis from hell.
Symptoms of reactivated EBV include severe chronic fatigue, chronic achiness, chronic sore throat and irritation of mucous membranes, swollen lymph nodes, and a range of debilitating neurological symptoms. Symptoms can wax and wane for years. Severe cases can include evidence of liver dysfunction, immune suppression, and anemia.1
The most plausible explanation for why chronic reactivated EBV is so severe and unrelenting is that it’s not just EBV that’s at play.
This is where things get both interesting and complicated.
People often carry other herpesviruses in addition to EBV. The list includes Herpes simplex types 1 and 2 (oral and genital herpes), varicella-zoster virus (causing both chickenpox and shingles), cytomegalovirus (CMV), HHV-6 types a and b, HHV-7, and HHV-8.
Though they are all related, each of these viruses infects the body in a different way — therefore they cause slightly different symptom profiles. In important ways, they are all are remarkably common:
They stay dormant in tissues and can be reactivated just like EBV.
If disruption of a person’s immune functions allows reactivation of multiple herpesviruses at once, symptoms can be severe and highly variable.
But that isn’t the end of the story.
Many people with chronic Lyme disease, fibromyalgia, and chronic fatigue syndrome are found to have reactivation of EBV, along with other herpesviruses and a list of other microbes including Mycoplasma, Bartonella, Chlamydia, and new microbes added to the list every day.
This strongly suggests that reactivation of EBV is likely not EBV alone.
The Connections Between EBV and Chronic Illnesses Are Many
Scientists are just beginning to explore the link between chronic EBV and other chronic illnesses, but one of the most well-researched is EBV’s relationship with multiple sclerosis (MS). Many studies have defined a variety of different mechanisms by which the virus could initiate and perpetuate MS — not enough to define EBV as the sole cause of MS, but highly suggestive that it does play a role in the illness.10
Similarly, studies have shown high viral loads of active EBV in a high proportion of patients with a variety of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, and autoimmune thyroiditis.14 Again, a strong link, but not enough to suggest absolute cause of EBV alone.
And that’s not the end of the multi-microbe connections.
Recent evidence has suggested that EBV and HHV-6a might together play a role in MS.29 MS has also been linked to a variety of different microbes including, but not limited to, Chlamydia pneumoniae,35, 37 Mycoplasma sp., Spherula insularis, and paramyxovirus.14, 36
Autoimmune diseases have also been linked to a variety of microbes, including EBV, but also additional herpesviruses; other viruses including Parvovirus; a protozoan called Toxoplasmosis; and bacteria including Mycoplasma, Yersinia, and others commonly associated with chronic Lyme disease.14
They infect white blood cells and are carried throughout the body, especially to areas of inflammation.
They can persist in a dormant state.
They are master manipulators of the immune system.
They can exist in healthy people without causing illness.
They are present in all populations of the world.
The deeper you dig, the more connections you find between chronic illnesses and stealth microbes. But after a while, you begin to appreciate that it’s not as much the microbes causing problems as it is disruption of the host’s immune functions that allows those microbes to flourish.
In other words, a person could be harboring a variety of stealth microbes — EBV, CMV, HHV-7, Borrelia, Bartonella, Mycoplasma, Chlamydia, and others — and not be ill as long as their immune system functions are robust.
Let immune system functions falter, however, and like a pot boiling over on the stove, the microbes erupt and cause illness.
Chronic Immune Dysfunction Is Triggered by the Perfect Storm
My experience taught me that the microbes are always there — I had likely harbored mine since childhood. It’s not until a perfect storm of factors comes together to disrupt immune functions that a person becomes ill. For me, that perfect storm was caused primarily by years of chronic sleep deprivation associated with every-other-night obstetrics on-call-duty and eating a poor diet on the run, but there were other minor stress factors as well.
As I shifted my practice toward caring for individuals with chronic illness, I began to see similar patterns in my patients — not necessarily the same stress factors that I had experienced, but stress factors that disrupt immune functions just the same. I began cataloging them and, interestingly, I reached a limit of just 7 categories of stress factors that are associated with chronic illness.
As astounding as it may sound, I came to the conclusion that the causes of all chronic illnesses can be traced back to these 7 factors that I came to call System Disruptors. I’ve been testing this theory for more than 10 years and always find it to be reliable. I’ve also discovered solid scientific support for my theory.
The 7 System Disruptors are:
1. Poor diet. We live in a world saturated with artificially manipulated foods. Regular consumption of these foods disrupts all systems of the body.
2. Toxins. The modern world is saturated with artificial toxins. Toxins disrupt all healing systems of the body.
3. Emotional stress. Continually running from the proverbial tiger inhibits digestion, suppresses immune function, disrupts sleep, and sets the stage for chronic illness.
4. Physical stress. Cumulative trauma, excessive heat or cold causes damage to the body, but living a sedentary life can be just as harmful.
5. Oxidative stress. Every cell in the body is continually generating free radicals as a byproduct of energy production. Free radicals damage internal components of cells. Inflammation is also a type of free radical damage.
6. Artificial radiation. Normal background radiation from the sun, solar system, and the earth itself are now amplified sources of radiation that saturate the modern world.
7. Microbes. The effects from this system disruptor set the stage for chronic illness.
For every patient with chronic illness, I can always trace back to a perfect storm of factors that came together to cause the person’s illness. What type of chronic illness they ended up with depends on three factors:
The person’s genetics — which determines risk, but not whether an illness will occur
The variety of different low-grade stealth pathogens the person has collected through life
How System Disruptors contribute to immune dysfunction, which allows low grade pathogens with stealthy characteristics to flourish and upset the balance of the microbiome and homeostasis in the body
Diagnosing and Treating Chronic EBV Isn’t Black and White
To help identify chronic EBV, start by trying to rule out infectious mononucleosis. By definition, IM is an acute infection with EBV alone, and there are antiviral agents (such as acyclovir, ganciclovir, and vidarabine) that work extremely well for IM and other acute infections of herpes-type viruses, so it’s worth doing testing to define IM over reactivated EBV.
Testing for IM looks for antibodies to the virus; the presence of different types of antibodies can distinguish between IM and reactivated EBV. But testing for IM isn’t always straight-forward — mononucleosis-like syndromes can also occur with other herpesviruses (CMV, HHV-6), other viruses (typically adenoviruses), and a protozoan called Toxoplasma gondii.26 In other words, many different viruses can cause viral syndromes similar to EBV.
If you have all the symptoms of chronic reactivated EBV, then the likelihood of EBV being present is quite high, along with other microbes.
As for treating chronic reactivated EBV, because there are antiviral agents that work well for IM, you might expect that chronic EBV would also respond to antivirals.
Unfortunately, antivirals don’t work for chronic EBV.
Scientists have sorted out the technical reason for this. Antiviral agents work by blocking DNA polymerase, an enzyme the virus uses to replicate inside cells. Latent or chronic EBV infection, however, does not require DNA polymerase for the virus to replicate — therefore, current antiviral agents are ineffective against chronic EBV infection.1
Other conventional therapies, including steroid therapy (prednisone) and immunosuppressive drugs, have been used to treat chronic EBV infection, but success has been limited.1These therapies can inhibit the destructive processes of a disrupted immune function, but they have no capacity to restore normal immune function.
Lots of researchers are also looking at vaccines against EBV. The problem is that characteristics of the virus vary greatly across different geographical areas, making it difficult to create a single vaccine.8
Other methods of eradicating EBV being contemplated by conventional medical science include: B-cell depletion with monoclonal antibodies (targeting EBV-infected B cells with immunoglobulins) and new types of antiviral drugs.11, 16, 20
Focusing all efforts on eradicating EBV, however, is short-sighted. The bottom line: The underlying problem is chronic immune dysfunction, and you will not start getting well until normal immune system functions are restored.
There’s A More Practical Approach to Regaining Wellness
Remember, EBV doesn’t cause problems unless immune system functions have been disrupted.1, 14, 20, 23 Therefore, any solution must address restoring normal immune system functions in order to suppress whatever microbes may be present and flourishing.
First and foremost is minimizing the 7 System Disruptors. Following an optimal diet and making some lifestyle modifications to promote a healing environment in the body is essential for overcoming chronic EBV or any other chronic illness.
Modern herbal therapy should be the cornerstone of any restorative approach. Herbal extracts have incredible abilities, including:
Reducing destructive inflammation
Enhancing natural killer cells and other aspects of the immune system necessary to control microbes like EBV
Balancing hormone systems in the body that have been disrupted by chronic illness
Suppressing stealth microbes directly to restore balance in the microbiome
While many herbs have been found to suppress EBV, EBV is rarely found in isolation — chronic immune dysfunction always allows a variety of low-grade stealth pathogens to flourish. Therefore, a comprehensive regimen of herbal extracts is necessary.
Some effective herbal extracts for restoring immune function, balancing the microbiome, and suppressing viruses such as EBV include:
Generally most people will respond to restorative solutions alone. Drug therapy is only necessary if severe or extreme illness is not responding to the restorative therapies. It is, however, important to maintain an ongoing working relationship with your medical provider during your entire recovery.
Ultimately, all of this is great news for those with chronic reactivated EBV: It means the power to take back control of your health and feel better is in your hands. By learning how to limit the System Disruptors in your life, you’ll start to strengthen your immune function so you can live in harmony with microbes like EBV.
The Sleeping Giant – Tips to Treat Reactivation of Epstein-Barr Virus
Jill C. Carnahan, MD
Did you know, you probably have virus lurking in the shadows? It’s called the Epstein-Barr virus (EBV) and an estimated 90 percent of us have it. Fortunately, for most of us it lies dormant, like a sleeping giant. Only when something triggers a reactivation of EBV does this virus rear its ugly head.
Epstein-Barr virus is part of the herpes family and also known as human herpesvirus 4. Usually passed through saliva, EBV is the cause of infectious mononucleosis – also known as “mono” or “kissing disease.” Typically, teenagers come down with this condition and first notice there’s a problem when they experience extreme fatigue. Interestingly, extreme fatigue can also cause a reactivation of Epstein-Barr virus.
Though there are many conditions where EBV is the cause or a trigger, extreme fatigue is a unifying symptom that occurs in most cases. Symptoms of an active Epstein-Barr virus, include:
Autoimmune conditions are caused when an overactive immune system begins attacking healthy tissue. We are learning more and more, what often sets off the immune system response in the first place can be a variety of infections, including EBV.
CD8+T cells are types of white blood cells your body uses to keep the EBV virus in check. When there’s an impairment or a deficiency of these cells, the EBV virus is free to run rampant. The amount of CD8+T cells you have can be negatively impacted by age, estrogen levels, and vitamin D deficiency, certain medications and treatments, and poor immune system function. This is important because autoimmunity is on the rise and we need a better understanding of its underlying causes.
So, what can be done to treat Epstein-Barr? If it’s so common, surely there’s a simple explanation or cure? Actually, the best way to tackle Epstein-Barr is similar to how we deal with an imbalance of gut microbes – manipulate the environment so balance is restored. The most important thing I find is to support the natural immunity and decrease exposures to environmental toxins and other infections. Let’s take a closer look.
Treating the Epstein Barr Virus
There is no known cure for the Epstein-Barr virus, and therefore treatments should focus on returning the creature back to it’s sleeping or dormant state. So, in order to treat EBV the approach needs to focus on getting the virus back in check, not killing it. This means manipulating the condition of your body – the environment where the Epstein-Barr virus lives.
When I discover a patient of mine has Epstein-Barr virus, here are the things I consider:
Clean diet and proper nutrition – This reduces inflammation and immune system burden. We eliminate gluten, dairy, allergens, and start a plant-based Paleo diet. Sugar is one of the most powerful immunosuppressives so that must be eliminated at all costs.
Heal the gut – Healing the gut is a priority for anyone dealing with EBV. Toxins can leak through damaged gastrointestinal lining and cause the immune system to overreact. This process is also known as endotoxemia, driven by LPS.
Eliminate any infections – Check for any coexisting infections and work to treat these. I often think of it as “infectious burden” and work to decrease the load on the immune system.
Reduce toxic burden – We are bombarded by tens of thousands of chemicals everyday, find out how to Reduce Your Daily Toxin Exposure. It is critical also to decrease total toxic load by eliminating any toxic exposures.
Optimize detox pathways – This includes supporting the liver, kidneys, and colon and may be supported by various nutritional supplements and other homeopathic drainage remedies.
Improving sleep habits – This is essential because so many repairing and detoxification processes occur during the deepest stages of sleep. I advise no less than 8 hours per night or as much sleep as required to wake up refreshed without an alarm clock.
Reduce stress – Stress is a major cause of immune system dysfunction, it could even be what awakened your EBV in the first place. You must work to reduce stress – your health depends on it. Try prayer, meditation or spending time in nature. Self care must be a priority.
Herbal supplements – Herbs such as Ashwagandha, licorice, St. John’s wort, lemon balm, ginseng, and holy basil may be used for immune system support and for their antiviral and adaptogenic properties.
Supplements – I use these for suppressing EBV reactivation
Monolauren: 1800 mg twice daily
Olive Leaf: 1000-1500 mg twice daily
L-Lysine: 1000-1500 mg twice daily
Cat’s Claw tincture: 30-60 drops twice daily
When viruses diminish due to these treatments it isn’t because any of these things attack the virus, but instead they help put your body in a state that isn’t ideal for the virus to reproduce. Hopefully, this strengthens your immune system and returns this typically harmless virus back to it’s benign state.
Other more extreme therapies have have been tried in a few cases, with some success and include:
Antiviral medication, Acyclovir or valcyclovir
Immune cell therapy when used in a person after a transplant.
Though I prefer to offer solutions to health conditions, I want to briefly touch on some treatments of EBV are not effective because there’s a lot of misunderstanding surrounding this virus. In general, the follow treatments only temporarily stop symptoms and only in some people:
Antiviral therapy such as ganciclovir and vidarabine.
Immunosuppressive agents such as cyclosporine and corticosteroids.
Immunomodulatory therapy such as interferon alpha and interferon gamma.
Cytotoxic chemotherapy such as anthracyclines, etoposide, cyclophosphamide, vincristine, and prednisone.
Infusions of cytotoxic T and lymphokine-activated lymphocytes.
This isn’t to suggest that your doctor shouldn’t temporarily recommend some of these, however, none of these are by any means a cure for Epstein-Barr virus and you should proceed with extreme caution.
Find a Functional Medicine Doctor with Experience in Epstein-Barr Treatments
The science surrounding the Epstein-Barr virus is developing daily. If you think you might have a condition due to EBV, it’s important to find a doctor who’s experienced in conditions related to the reactivation of this virus. If you need help finding a functional medicine doctor, I’ve made a helpful guide to get you started – How to Choose a Good Integrative and Functional Medicine Doctor.
The Epstein-Barr virus is a significant condition I wish more people knew about – Share this article to spread awareness of this sleeping giant.
Being in Wisconsin, an epicenter for Lyme, our LLMD is also who we take our children to – just in case, God forbid, they should become infected. Our LLMD believes, as Dr. Rawls, that immunoconfusion, or a perfect storm of events overwhelming the immune system, is behind many chronic diseases. Retraining the immune system to recognize friend vs foe is behind LDA/LDI treatment and can often help many chronic conditions. It certainly has helped my daughter, who is also hypothyroid, hypoglycemic, and suffers from severe endometriosis. EBV nearly destroyed her liver.
I can attest to having to learn the importance of diet, hormones, stress, environmental toxins, and microbes. It is crucial to find a practitioner(s) who is versed in this approach to tease out your imbalances through proper testing and clinical diagnosis. As with Lyme, much testing isn’t helpful and requires an experienced eye and listening ear to help you uncover your personal pitfalls. Most doctors are not trained in hormone therapy and with the chemically laden environment we live in, this is most unfortunate as many suffer from serious hormonal imbalances and mineral/vitamin deficiencies. Doctors are taught to fear hormones when they are naturally occurring substances in the body that often need supplementing due to environmental factors. I’m of course advocating for bioidential hormones – as close to nature as possible; however, for those of you suffering with endometriosis that makes your life unbearable, please read this unique approach which gave my daughter her life back: https://www.theendocure.com/
REFERENCES For Dr. Rawl’s article:
1. Cohen J. Optimal Treatment for Chronic Active Epstein-Barr Virus Disease. Pediatr Transplant. 2009 Jun; 13(4): 393–396.
2. Joo E et al. An Adult Case of Chronic Active Epstein-Barr Virus Infection with Interstitial Pneumonitis. Korean J Intern Med. 2011 Dec; 26(4): 466–469.
3. Kang M, Kief E. Epstein–Barr virus latent genes. Exp Mol Med. 2015 Jan; 47(1): e131.
4. Jha H, Pei Y, Robertson E. Epstein–Barr Virus: Diseases Linked to Infection and Transformation. Front Microbiol. 2016; 7: 1602.
5. Tsao S et al. The role of Epstein–Barr virus in epithelial malignancies. J Pathol. 2015 Jan; 235(2): 323–333.
6. Paschale M and Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J Virol. 2012 Feb 12; 1(1): 31–43.
7. Shen Y et al. Understanding the interplay between host immunity and Epstein-Barr virus in NPC patients. Emerg Microbes Infect. 2015 Mar; 4(3): e20.
8. Tzellos S and Farrell P. Epstein-Barr Virus Sequence Variation—Biology and Disease. Pathogens. 2012 Dec; 1(2): 156–175.
9. Iizasa H et al. Epstein-Barr Virus (EBV)-associated Gastric Carcinoma. Viruses. 2012 Dec; 4(12): 3420–3439.
10. Lassmann H et al. Epstein–Barr virus in the multiple sclerosis brain: a controversial issue—report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain. 2011 Sep; 134(9): 2772–2786.
11. Pender M and Burrows S. Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clin Transl Immunology. 2014 Oct; 3(10): e27.
12. Stanfield B and Luftig M. Recent advances in understanding Epstein-Barr virus. Version 1. F1000Res. 2017; 6: 386.
13. Gru A et al. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment. Curr Hematol Malig Rep. 2015 Dec; 10(4): 456–467.
14. Lossius A et al. Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation. Viruses. 2012 Dec; 4(12): 3701–3730.
15. Rowe M, Fitzsimmons L, and Bell A. Epstein-Barr virus and Burkitt lymphoma. Chin J Cancer. 2014 Dec; 33(12): 609–619.
16. Martorelli D et al. Exploiting the Interplay between Innate and Adaptive Immunity to Improve Immunotherapeutic Strategies for Epstein-Barr-Virus-Driven Disorders. Clin Dev Immunol. 2012; 2012: 931952.
17. Houldcroft C and Kellam P. Host genetics of Epstein–Barr virus infection, latency and disease. Rev Med Virol. 2015 Mar; 25(2): 71–84.
18. Draborg AH, Duus K, and Houen G. Epstein-Barr Virus in Systemic Autoimmune Diseases. Clin Dev Immunol. 2013; 2013: 535738.
19. Rac J et al. Telomerase Activity Impacts on Epstein-Barr Virus Infection of AGS Cells. PLoS One. 2015; 10(4): e0123645.
20. Pender M. The Essential Role of Epstein-Barr Virus in the Pathogenesis of Multiple Sclerosis. Neuroscientist. 2011 Aug; 17(4): 351–367.
21. Dittfeld A et al. A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders. Cent Eur J Immunol. 2016; 41(3): 297–301.
22. Chen XZ et al. Epstein–Barr Virus Infection and Gastric Cancer
A Systematic Review. Medicine (Baltimore). 2015 May; 94(20): e792.
23. David A. Thorley-Lawson. EBV Persistence—Introducing the Virus. Curr Top Microbiol Immunol. 2015; 390(Pt 1): 151–209.
24. Iwakiri D. Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis. Cancers (Basel). 2014 Sep; 6(3): 1615–1630.
25. Dunmire SK, Hogquist KA, and Balfour HH. Infectious Mononucleosis. Curr Top Microbiol Immunol. 2015; 390: 211–240.
26. Krupka JA et al. Infectious mononucleosis-like syndrome with high lymphocytosis and positive IgM EBV and CMV antibodies in a three-year-old girl. Cent Eur J Immunol. 2017;42(2):210-212.
27. Collin V, Flamand L. HHV-6A/B Integration and the Pathogenesis Associated with the Reactivation of Chromosomally Integrated HHV-6A/B. Viruses. 2017 Jun 26;9(7).
28. Warren-Gash C et al. Association between human herpesvirus infections and dementia or mild cognitive impairment: a systematic review protocol. BMJ Open. 2017 Jun 23;7(6):e016522.
29. Fierz W. Multiple sclerosis: an example of pathogenic viral interaction? Virol J. 2017 Feb 28;14(1):42.
30.Enquist LW, Leib DA. Intrinsic and Innate Defenses of Neurons: Détente with the Herpesviruses. J Virol. 2016 Dec 16;91(1).
31. Hutt-Fletcher LM. The Long and Complicated Relationship between Epstein-Barr Virus and Epithelial Cells. J Virol. 2016 Dec 16;91(1).
32. Siddiquey MN et al. Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma. Cancer Sci. 2014 Jun;105(6):713-22.
33. Cekanaviciute E et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017 Sep 11. pii: 201711235.
34. Berer K et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Sep 11. pii: 201711233.
35. Ivanova MV et al. Role of Chlamydia in Multiple Sclerosis. Bull Exp Biol Med. 2015 Sep;159(5):646-8.
36. Libbey JE, Cusick MF, Fujinami RS. Role of pathogens in multiple sclerosis. Int Rev Immunol. 2014 Jul-Aug;33(4):266-83.
37. Sriram S et al. Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis. J Infect Dis. 2005 Oct 1;192(7):1219-28. Epub 2005 Sep 2.
38. Buhner S. Herbal Antivirals, Natural Remedies for Emerging & Resistant Viral Infections. Storey Publishing. Copyright 2013.
The following article supports the use of myofascial therapy, “a manipulation technique that is both internal and external to the pelvic floor (focusing specifically on abdominal, pelvic, and hip girdle muscles and other tissue).”
INTERSTITIAL CYSTITIS: THE ROLE OF MYOFASCIAL THERAPY
February 11, 2016 In Women’s Health
Rosia Parrish, Jennifer Pilon, Daeyon JooRi Jun, Kris Somol, ND
The American Urological Association defines Interstitial Cystitis (IC)/Pelvic Bladder Syndrome as an unpleasant sensation perceived to be related to the urinary bladder that is associated with lower urinary tract symptoms greater than 6 weeks’ duration, in the absence of infection or other identifiable causes.1 The condition is 5 to 10 times more common in women than in men. In the absence of clear diagnostic criteria, this condition is underdiagnosed, with an estimated prevalence of 3 to 8 million women in the United States.2
The treatment of IC is a clinical challenge. As a diagnosis of exclusion without a clear etiology, first-line treatment strategies for IC are varied and tend to focus on food-trigger avoidance, stress reduction, and bladder retraining. However, these therapies remain ineffective for some patients, warranting implementation of second-line therapies. These include pelvic floor physical therapy, amitriptyline, antihistamines, and intravesical drug combinations.3
The question of whether myofascial physical therapy (MPT) is an effective treatment for IC is a particularly relevant question for naturopathic doctors, many of whom are trained in and practice a variety of hands-on myofascial therapies. When choosing from among these second-line treatments, naturopathic philosophy would suggest that manual physical therapy would be more effective than conventional treatments in treating the cause of the condition, particularly in cases where somatic abnormalities of the pelvic floor are contributing to the syndrome. The goal of this literature review is to investigate the following clinical question: In female patients with a diagnosis of interstitial cystitis, does the use of myofascial physical therapy decrease symptoms of urinary urgency, urinary frequency, and pelvic pain when compared with conventional treatments?
A search of PubMed and Embase was performed, including combinations of the following terms (designated medical subject headings and other relevant terms): physiotherapy, interstitial cystitis, therapeutics, complementary therapies, physical therapy modalities, alternative medicine, massage, pelvic floor rehabilitation, electrostimulation, and physiatrics. The original searches were done without limiting them to randomized controlled trials (RCTs), in order to accurately assess the current state of the research and identify possible directions for other searches. Combinations of the terms interstitial cystitis, physical therapy modalities, therapeutics, and massage revealed studies that were the most relevant to our clinical question. In the final analysis, only English language RCTs conducted within the last 10 years that were available as free, full-text articles through Bastyr University were considered for review. Complete detail of searches and results is shown in Table 1 (Please see link above for Table 1).
There were 3 English-language RCTs that fulfilled our final search criteria. Of note, there were no studies that directly compared MPT with conventional drug treatments for IC. One particular study was ultimately chosen for review because it was most relevant to the clinical question being asked and to the scenarios which we would be likely to encounter in naturopathic practice.4 This study was performed solely on women (as opposed to other studies which included both women and men with painful bladder syndrome), who had not experienced relief with at least 1 course of conventional first-line management for IC. This is relevant to the fact that almost all patients experiencing IC symptoms are female. Additionally, it is consistent with how many patients seek out naturopathic medicine after experiencing a lack of success with conventional treatments. In a primary care practice, adult women may present with IC within a wide range of ages. This clinical reality is reflected in the study, which included women aged 18-77. Finally, the outcomes measured in this study not only included specific frequency of symptoms, but also a global, subjective measure of improvement as determined by the patient. This contributed to our choice of study, since including this outcome may better reflect changes in quality of life post-treatment than symptom-based questionnaires alone.
The study chosen for review4 sought to answer whether females aged 18-77 with a clinical diagnosis of IC or painful bladder syndrome (PBS), using a standardized myofascial physical therapy protocol (MPT) as compared to a standardized Western global therapeutic massage (GTM) program, show improvement of overall symptom picture and/or specific symptoms of pain, frequency, urgency, and sexual function. Participants were recruited from July of 2008 through May of 2009 across 11 academic clinical centers across North America, and the study lasted 12 weeks. Physical therapists (PTs) providing the MPT were trained in a standardized protocol to minimize variability between therapists. The protocol was not described in the paper chosen, but has been described in detail in a feasibility study conducted by the same authors.5
There were 2 arms of the study: MPT and GTM. MPT is a manipulation technique that is both internal and external to the pelvic floor (focusing specifically on abdominal, pelvic, and hip girdle muscles and other tissue). GTM, in contrast, is a full-body therapeutic massage. Those patients in the GTM treatment group had a series of 10 one-hour massages.
The inclusion criteria included clinical diagnosis of IC/PBS, average recorded ratings for bladder pain, frequency, and urgency of at least 3/10, and present for a minimum of 3 months and a maximum of 3 years. Furthermore, pelvic floor tenderness on vaginal examination, identified by the study’s physician and confirmed by a PT, was required for study inclusion. There were no significant differences in demographics between the MPT and the GTM groups at baseline. Demographic factors assessed were age, ethnicity, education level, employment status, and annual family income; demographic factors were listed in the feasibility study cited in this article.5 Of note, no other specific prognostic factors relating to their clinical diagnosis were assessed, including smoking. Most of the patients were Caucasian, and the exclusion of women without pelvic pain on vaginal examination eliminated a significant number of IC sufferers for whom this treatment might be beneficial. For this reason, the results are difficult to generalize to the population at large.
Patient assignment to treatment groups was randomized. Physical examiners and nurses collecting data were blinded to treatment assignment, but there was no indication of whether investigators were blinded from the process of randomization. Outcome assessors and all study coordinators were also blinded to the group allocation. Randomization process occurred via a pre-specified sequence distributed in a series of sealed envelopes to receive MPT or GTM. Patients were analyzed in the groups to which they were randomized; there was no crossover between the groups. Even though the patients were not told outright what group they were assigned to, given the differences between MPT and GTM, it is likely that they were aware of the group to which they were assigned.
Outcomes were measured with the 7-point Global Response Assessment (GRA) scale, the O’Leary Sant IC Symptom and Problem Index, a 24-hour urinary voiding diary, the 2000 Female Sexual Functioning Index, and the 12-Item Short-Form Health Survey.
Of the 81 patients recruited, 78 (96%) were able to complete the full 12-week duration of the study (including initial follow-up at the completion of treatment phase at 12 weeks, and additional follow-up for 3 months after the 12-week follow-up). Of these 78 participants, 72 (92%) completed at least 7 of the 10 treatments that were assigned to them during the 12 weeks: In the MPT group 55% completed all 10 treatments, and in the GTM group 38% of the GTM group finished 100% of their 10 treatments. The 3 who withdrew from the study had received <5 treatments. During the follow-up phase of the study, the retention rate was smaller, with 77% of the MPT, and 67% of the GTM, participating. Because many of the study’s subjects did not participate in the final follow-up session, it is difficult to draw conclusions about durability of treatment.
The primary outcome of this study was that 59% of the MPT group, compared to 26% in the GTM group, reported moderate or marked improvement (p=0.0012) on the GRA scale. Within the GTM group, 43% reported no change in symptoms, compared to only 18% of the MPT group reporting no change. Both treatment groups reported improved symptoms via the O’Leary Sant IC Symptom and Problem Index of pain, urgency, frequency; there were also reported improvements in quality of life as well. No statistical significance was noted among these secondary symptom outcomes of the study. The Mantel-Haenszel test was employed to take into account the need to control variability at the 11 sites. The Number-Needed-to-Treat to determine 30% effect was 88, and only 81 were recruited; however, this study was still significantly powered.
Adverse events (AE) were also reported. Bladder or pelvic pain was the most commonly reported AE, reported in 14% of the participants. There was no statistical significance in the number of AEs reported by each treatment group. The authors conjectured that the AEs reported, especially that of pain, in part had to do with the intermittent nature of the disorder and was not necessarily related to treatment intervention. Other AEs reported were infection (reported by 12% of the patients), constitutional symptoms like fever (11%), and digestive symptoms (10%).
The age range of subjects in the study (18-77) and the duration of their symptoms (3 months to 3 years) are similar to patients who would potentially be seen in naturopathic medical clinics. It is feasible for naturopathic physicians to determine pelvic floor tenderness during a vaginal exam and to discern suitable candidates for this treatment option. It would also be feasible to refer patients to physical therapists for co-management. However, determining the optimal elements of an effective MPT regimen and finding PTs who can deliver effective pelvic floor MPT might be an obstacle.
The study reviewed here answered the question of whether the use of MPT can improve symptoms associated with IC, including but not limited to urinary urgency, urinary frequency, and pelvic pain. However, the paper did not compare the effects of MPT to conventional treatments, such as food-trigger avoidance, bladder retraining methods, or pain medications. In fact, the study did not disclose whether subjects were concurrently using any other treatment modalities while participating in the study, potentially biasing the results.
Further questions raised by the literature review process and the results of this paper include whether the results of the study can be generalized to the IC patient population at large. For example, it is questionable whether MPT would also be beneficial to patients who do not demonstrate pelvic tenderness on examination. This also points to the currently inadequate understanding we have about the relationship between somatic abnormalities and IC. Another aspect of whether the study could be generalizable centers around the fact that study participants were primarily Caucasian.
A future study examining the durability of subjects’ improvement with this therapy would make the results more clinically meaningful. Due to the loss to follow-up at 3 months post-treatment, the question of how long the beneficial effects of MPT last, remains. It would be very exciting, indeed, to investigate whether the effects are long-lasting and could potentially be a cure of sorts to the unending suffering experienced by patients with interstitial cystitis.
Finally, developing an effective training program for physical therapists and other providers would be critical so that this therapy would become accessible to a large number of patients.
CONCLUDING COMMENTS The evidence from the study reveals that MTP is indeed beneficial for improving symptoms of IC, suggesting that physical therapy is an important modality to consider in a treatment plan for a patient suffering from the disease. It adds credibility to the idea that there are specific pelvic somatic abnormalities involved with IC, as the study showed the treatment effect was not merely due to general therapeutic touch.
The process of finding a robust paper to review to answer our question yielded only 1 study that fit the aforementioned criteria. This points to the lack of research available on myofascial physical therapies to treat IC.
However, even with the limited evidence, considering the strength of the paper reviewed and the fact that no serious adverse events were reported, MPT can be considered a safe and potentially effective therapy for IC that could be recommended and provided to patients. The question as to whether it is more effective than other first- and second-line treatments still remains and requires further research.
Early in my career practicing Ob/Gyn, I became aware of a subset of patients who suffered from a condition called interstitial cystitis (IC), sometimes referred to as painful bladder syndrome.
People with interstitial cystitis feel like they have a bladder infection that never goes away. It doesn’t respond to antibiotics, and urine cultures are typically negative. Because these patients are often treated repeatedly with antibiotics, however, they frequently end up having chronic urinary tract infections with antibiotic-resistant bacteria induced by taking antibiotics. The condition occurs more often in women than men at a 5:1 ratio.
Interstitial cystitis is considered idiopathic — cause unknown. It is notoriously difficult to treat. I developed a special compassion for these people because no other physicians wanted to see them. For years, I searched for solutions, but my efforts were focused primarily on relieving symptoms — gains were minimal and short-lasting.
Symptoms of Interstitial Cystitis
Urinary frequency & urgency
Bladder pain with full bladder
Pain in perineum & urethra
Chronic pelvic pain
Vulvar/vaginal pain (female)
Pain in testicles (male)
The Lyme Connection
Interestingly, with my professional interests now focused on chronic Lyme disease, I’m starting to hear from chronic Lyme patients who suffer from bladder pain and symptoms consistent with IC. I’m also hearing from men with chronic Lyme who have bladder symptoms and chronic prostatitis (chronic infection of the prostate gland).
And, interestingly, remembering back to patients from the past, sufferers of IC frequently had chronic pain in other areas of the body. Many of them also had fatigue and symptoms common to fibromyalgia and chronic Lyme disease.
This makes me believe there has to be a microbial connection. Borrelia, the microbe commonly associated with Lyme disease, could be a culprit. However, I would lay odds on mycoplasma and a closely related bacterium called ureaplasma. About 75% of chronic Lyme disease sufferers have been found to harbor at least one species of mycoplasma.
It fits. Mycoplasma and ureaplasma are the smallest of all bacteria. They are obligate intracellular microbes — which means they must live inside cells of a host to survive. They typically infect linings of the body — linings of lungs, intestines, joints, and the urinary tract.
Different species of mycoplasma and ureaplasma prefer certain areas of the body, but any species of these microbes can be found in different places the body. The most common species found in the urinary and reproductive tract are Ureaplasma urealyticum and Mycoplasma hominis. These microbes typically spread sexually, but they can be acquired by other routes. Mycoplasma pneumoniae, a frequent cause of respiratory infections, can also be found in the urinary tract.
Mycoplasma and ureaplasma are notoriously difficult to culture. Twenty-five years ago, when I first started practicing medicine, routine testing for mycoplasma and ureaplasma was not available. That’s starting to change — DNA testing has become more reliable, and providers are testing for these microbes more routinely.
And they are finding them — not just in symptomatic patients, but also commonly in people with no symptoms.
That makes things complicated — mycoplasma and ureaplasma are commonly found in the urinary tracts of people who don’t have symptoms. It turns out that it’s actually a very common microbe. Some experts have even defined it as a normal flora. This is why many experts discount the connection between mycoplasma/ureaplasma and bladder problems.
It presents the same kind of conundrum found in chronic Lyme disease — why do some people with these microbes develop symptoms and others do not?
What I didn’t know 25 years ago that I learned from understanding chronic Lyme disease is that the immune system is the key. If people have robust immune function, they can harbor these microbes and not have symptoms. People become chronically ill only when a perfect storm of factors comes together to disrupt immune function, which allows the microbes to flourish.
Therefore the solution must go beyond killing or suppressing microbes — you must restore immune system functions to optimal levels to overcome this illness.
Overcoming Mycoplasma and Ureaplasma
Mycoplasma and ureaplasma respond poorly to synthetic antibiotics for the same reason that other microbes associated with chronic Lyme disease respond poorly to antibiotics — they live inside cells, grow very slowly, and occur in low concentrations in tissues. In addition, mycoplasma and ureaplasma do not have a typical cell wall and other characteristics common to bacteria.
To control them, you must suppress them for a very long time and boost immune function at the same time. If you try to do it with synthetic antibiotics, normal flora are disrupted long before the targeted microbes are eradicated.
Herbs provide a more practical solution. Herbs suppress these types of microbes, but do not disrupt normal flora, so they can be used for extended periods of time (months to years) without concern. Herbs also reduce inflammation and boost immune functions — especially natural killer cells important for eliminating cells infected with microbes.
My favorite herb for mycoplasma and ureaplasma in the urinary tract is anamu (Physalis angulata) because it is concentrated in the intestines and urinary tract. The dose I recommend is 1200 mg (2 – 600 mg capsules) twice daily. It is well tolerated with only noticeable side effect being a mild odor to urine and stool. The herb comes from South America, but is readily available from many manufacturers online.
Mullaca (Physalis angulata), another South American herb, is also good for mycoplasma species. It can be taken as a complement to amamu. It can be found online as a loose powder (add to smoothies or make your own capsules) or tincture, as well.
Stephen Buhner, in his book defining therapy for mycoplasma, recommends Chinese skullcap, Isatis, Houttuynia, Sida acuta, and Cordyceps for a primary herbal protocol. I consider Cordyceps and Chinese skullcap to be part of a core protocol for chronic Lyme in general.
Individuals are reporting symptomatic relief of IC symptoms with use of essential oils rubbed into the pubic area several times a day. I have been recommending a formula of tea tree oil and frankincense oil mixed 1:4 in a carrier oil, such as jojoba or grapeseed oil. Recently, I’ve also been recommending adding cannabidiol oil (CBD) from hemp (get a product with 1500 mg CBD per fluid oz.). So far, people are reporting positive benefits.
The recovery protocol for overcoming mycoplasma and ureaplasma in the urinary tract mirrors recovery from chronic Lyme disease or any other condition associated with chronic immune dysfunction. Focusing on a specific microbe alone is not enough; immune system function must be restored. Primary antimicrobial herbs and immune modulating herbs, complemented by cultivation of a healing environment within the body, are your best allies in the fight against interstitial cystitis and Lyme disease.
Dr. Rawls is a physician who overcame Lyme disease through natural herbal therapy. You can learn more about Lyme disease and recovery in Dr. Rawls’ new best selling book, Unlocking Lyme. You can also learn about Dr. Rawls’ personal journey in overcoming Lyme disease and fibromyalgia in his popular blog post, My Chronic Lyme Journey.
Wonderful article. Thank you Dr. Rawls for explaining a particularly troubling issue that Lyme/MSIDS patients can suffer from.
“….90% of evaluated ALS patients had Mycoplasma. 100% of ALS patients with Gulf War Syndrome had Mycoplasma and nearly all of those were specifically the weaponized M. fermentans incognitus. *One of the hallmark symptoms of Mycoplasma is fatigue* And the bad news for us is that Nicholson’s experience has found Mycoplasma to be the number one Lyme coinfection, and similar to other coinfections can be supposedly cleared for years only to reappear when conditions are right.”
The evidence from the study reveals that MTP (Myofascial Therapy) is indeed beneficial for improving symptoms of IC, suggesting that physical therapy is an important modality to consider in a treatment plan for a patient suffering from the disease. It adds credibility to the idea that there are specific pelvic somatic abnormalities involved with IC, as the study showed the treatment effect was not merely due to general therapeutic touch.
As we head into the Maine outdoors this summer, the all-too-familiar warnings about how to avoid ticks reverberate in many of our heads.
Stay on the trail. Steer clear of wooded and brushy areas where ticks congregate.
But while most of us take pains to dodge the eight-legged pests, Chuck Lubelczyk heads straight for them.
As a field biologist at the Maine Medical Center Research Institute’s Lyme and Vector-Borne Disease Laboratory, he studies the spread of diseases carried by ticks, as well as by mosquitoes. That means venturing out into the fields, forests and coastlines of Maine to collect the bugs and evaluate where they pose the most risk to humans.
On a recent June day, Lubelczyk trudged into the greenery of the Wells Reserve, a 2,250-acre spread in York County headquartered at a restored saltwater farm. He partnered with researchers from the Biodiversity Research Institute in Portland to collect ticks from creatures less often associated with them: birds.
The team, assisted by several interns, set up wide nets to ensnare the birds as they flew through the area. They then delicately extricated them, tucked the birds into breathable collection bags, and toted them to a shady picnic table for easier handling. Using tweezers, the team plucked off each tick — typically feasting around the birds’ eyes, bills, and throats — and preserved the bugs for later testing at the lab.
Lubelczyk held up a vial containing at least 50 tiny nymphal deer ticks swirling in a preservative solution. They’d been tweezed off a single bird, a towhee, that morning.
Once free of ticks, the birds were then safely released to continue on their way.
While mice, chipmunks and deer get most of the attention as hosts for ticks, “Not a lot of people talk about the bird issue,” he said. “They’re understudied in a big way, I think. They do have a real role to play.”
Ticks are an annoyance to birds, but they don’t transmit disease to them or slowly and lethally drain them of blood, as researchers have seen among moose calves in Maine. But birds facilitate the spread of ticks, picking them up in Maryland, Connecticut and other eastern states as they fly north in the spring, Lubelczyk explained.
“As they’re migrating, they’re either dropping the ticks off as they fly or when they land. They’re kind of seeding them along migration patterns.”
By tracking the birds and the ticks they carry, researchers hope to predict where Lyme and other tick-borne diseases are most likely to accelerate. Lyme is now present in every county in the state, after hitting a record of 1,488 cases in 2016, but ticks are just getting established in areas such as Aroostook and Washington counties, Lubelczyk said.
Along with Lyme, Lubelczyk tested the ticks for other two other emerging diseases, anaplasmosis and the rare but potentially devastating Powassan virus. Powassan, carried by both the deer tick and the groundhog or woodchuck tick, recently sickened two people in midcoast Maine, following the death in 2013 of a Rockland-area woman.
A recent survey Lubelczyk led found the virus in ticks crawling around southern Maine, Augusta and on Swan’s Island in Hancock County.
In the modest Scarborough lab, medical entomologist Rebecca Robich furthered the findings of that survey. Clad in a white coat and blue gloves, she cloned a tiny band of the Powassan virus’ inactivated RNA, using a sample derived from the ticks that tested positive in the survey. Robich began the work, designed to confirm the earlier test results, last winter.
She expects to know conclusively within the next month what percentage of the sampled ticks were infected with Powassan, she said.
“We’re this close to finishing,” Robich said.
Ticks have become so prevalent in Maine that Lubelcyzk and his colleagues are increasingly called upon to educate the public about the health risks the arachnids pose. That includes speaking at community forums, town meetings, garden clubs and even to groups of employees.
“They’re widespread enough now that DOT, CMP, people like that are bumping into them on a regular basis,” he said. “Even people like law enforcement. The warden service, regular police with police dogs, they’re exposed.”
Their outreach also includes plenty of phone calls to the lab, fielded by its small staff of four, not counting summer interns.
“If somebody calls, we never really turn them down,” he said.
Many people don’t realize that the lab no longer identifies ticks for the public, Lubelczyk said. Now located in Scarborough along with MMC’s medical and psychiatric research centers, the lab formerly operated in South Portland, where it identified a tick’s species for anyone who walked in the door or mailed a sample. The University of Maine Cooperative Extension in Orono has since taken over that service (it does not test ticks for disease).
“It’s very hard to say no to someone when they’re really frantic because they found a tick on themselves, or their child, or even their pet,” he said. “And they’re sitting out in the parking lot.”
So far this season, the lab has fielded numerous calls from worried residents only to discover after viewing a photograph that the tick in question is a dog tick, not a deer tick. Maine is home to 15 species of ticks, and the dog tick is not among those that transmit disease to humans, at least in this region.
Through its outreach work, the lab has also found itself at the center of debates about how to manage ticks. Lubelczyk recalled a town forum on Long Island a couple of years ago that grew tense as residents discussed the use of pesticides.
“As soon as the topic of any kind of spray was brought up, not even by us, by somebody else, the fishing community was dead set against it,” he said. “Understandably, they’re worried about the stock. It really makes that difficult because you start to have divisions in how to control the ticks.”
The lab’s research on the role of birds in spreading tick-borne disease is similarly delicate, because many birds are under threat ecologically, Lubelczyk said.
“No one really cares if you try to target mice. Birds are federally protected in a lot of cases,” he said.
That other biting pest
Educating the public represents a large part of the lab’s mission but only a small part of its budget. Its outreach work is funded largely through small grants from foundations, Lubelczyk said.
Most of its research funding is targeted toward mosquitoes rather than ticks, boosted by the federal government’s initiative to combat the Zika virus, he said. While Zika hasn’t appeared in Maine, warming temperatures due to future climate change could make the state habitable for one of the mosquito species that carries it.
Lubelczyk explained this as he stood in the lab’s testing area, next to a large freezer storing petri dishes packed with frozen mosquitoes. A piece of yellow tape affixed to the door warned, “Not for food.”
While Lyme is far more prevalent, diseases carried by mosquitoes, such as West Nile virus and Eastern Equine Encephalitis, can lead to more acute illness. Both can cause inflammation of the brain and other serious complications.
Funding for tick research is generally less reliable, Lubelczyk said. The recent Powassan survey, for example, was funded by the Maine Outdoor Heritage Fund, which collects money through the sale of instant scratch lottery tickets.
A continuing threat
The lab’s role in helping to prevent tick-borne diseases has only grown as the tick population and the diseases they carry spread. The incidence of Lyme in Maine is among the highest rates in the country, averaging 82.5 cases per 100,000 people between 2013 and 2015.
Anaplasmosis and babesiosis are less common but becoming increasingly worrisome.
Lubelczyk understands the illnesses on both a professional and personal level. He contracted Lyme several years ago, after a deer tick latched onto him while he made a pitstop on the way home from work one steamy July day, he said. He had just changed into shorts and sandals and jumped out of his car for 30 seconds to hang a mosquito trap in Wells, he recalled.
A day and a half later, he spotted the tick bite. After a round of antibiotics, he recovered, Lubelczyk said.
His usual garb for field work includes long sleeves and pants treated with permethrin, along with gaiters over his boots.
“It’s embarrassing,” he said, wincing. “We always talk about wearing appropriate clothing.”
I’m thankful someone is dealing with the bird issue in relation to tick propagation as I believe it will be found to be much more of an issue than previously thought. It would help explain why folks insist they’ve been infected while near trees as birds would drop them onto trees (as well as various rodents). Like deer, birds serve primarily as transits that can spread ticks far and wide.
https://madisonarealymesupportgroup.com/2017/08/14/canadian-tick-expert-climate-change-is-not-behind-lyme-disease/John explains, “The climate change range expansion model is what the authorities have been using to rationalize how they have done nothing for more than thirty years. It’s a huge cover-up scheme that goes back to the 1980’s. The grandiose scheme was a nefarious plot to let doctors off the hook from having to deal with this debilitating disease. I caught onto it very quickly. Most people have been victims of it ever since.” “This climate change ‘theory’ is all part of a well-planned scheme. Even the ticks are smarter than the people who’ve concocted this thing,” he says. “Climate change has nothing to do with tick movement. Blacklegged ticks are ecoadaptive, and tolerate wide temperature fluctuations. On hot summer days, these ticks descend into the cool, moist leaf litter and rehydrate. In winter, they descend into the leaf litter, and are comfortable under an insulating blanket of snow. Ticks have antifreeze-like compounds in their bodies, and can tolerate a wide range of temperatures. For instance, at Kenora, Ontario, the air temperature peaks at 36°C and dips to –44°C, and blacklegged ticks survive successfully.
Also, please note that although there has only been one Zika death in an elderly man with a preexisting health condition in the continental U.S., all the funding is going to it and mosquito research. This is causing untold harm here where Lyme is causing around 400,000 new cases per year. There is no official tally on all the other coinfections that often come with Lyme as they aren’t even reportable in many states but are a crucial detail in understanding the complexity of Lyme/MSIDS. People are often infected with numerous pathogens. https://madisonarealymesupportgroup.com/2017/07/01/one-tick-bite-could-put-you-at-risk-for-at-least-6-different-diseases/
To treat this complex as a one organism/one disease would be folly.
Although the causes of rheumatic diseases have remained relatively unknown, systemic intracellular bacterial infections are commonly found in rheumatic disease patients [1-4]. Because of this, certain infections have been confused with comorbid conditions.
Often patients with rheumatic diseases have co-morbidities, and some authors have concluded that this can include chronic infections. “Infections continue to be a significant cause of morbidity and mortality in patients with rheumatic diseases, and, consequently, early diagnosis and treatment of infection is critical to the successful medical management of these patients” .
A link between certain types of infections and rheumatic diseases has been seen by a number of authors. For example, infections with Mycoplasma species, Borrelia species and other intracellular bacteria have been linked to various forms of rheumatic disease [1-4, 6-13]. In addition, animal models of rheumatic disease have been established by infection with Mycoplasma species [13-15]. In one of these contributions experimental arthritis was induced by a clinical isolate from M. fermentans injected into the joints of rabbits . Outbreaks of rheumatic disease, such as polyarthritis, have been traced to infections by Mycoplasma species . Arthritis in animals caused by Mycoplasma species infections closely resemble the signs and symptoms found in patients with rheumatoid arthritis . In addition, reactive arthritis following M. pneumonia infection has been seen in patients . Mycoplasma infections have also been found in the joints of patients with rheumatic disease [19-21]. In a case-control study the presence of antibodies against Mycoplasma pneumoniae have been statistically correlated to the clinical features of rheumatoid arthritis (p<0.001) . Furthermore, genetic analyses and transmission in animals indicate that arthritis is not directly linked to genetic abnormalities . The pathogenesis of rheumatoid arthritis appears to be linked to immunological features of infection(s) involving host recognition of foreign antigens that mimic host antigens or host antigens that are incorporated into microorganism structures and the presence of localized immune complexes and the influences of environmental conditions .
Standard treatments of chronic infections like mycoplasma often employ long-term antibiotics, such as but not limited to tetracyclines and other antibiotics [23-26]. The U.S. National Institutes of Health sponsored a double-blind, placebocontrolled, long-term clinical trial that showed that the antibiotic minocycline was safe and effective for the treatment of rheumatoid arthritis. The antibiotic-treated patients showed greater improvements in joint swelling and tenderness (p<0.02), and the treatment group also had better improvements in hematocrit, SED rate, platelet counts and rheumatoid factor with no serious toxicity [27, 28]. A 4-year follow-up indicated that the minocycline-treated patients had fewer relapses and less frequent need for immune-suppressive drugs to control their RA (p<0.02) . Although treatment of arthritis with antibiotics was effective and safe, treatment failures can, just as in any treatment for arthritis, be due to therapeutic failures, resistance and/or mutation of the microorganism .
Part of the reason that most rheumatic disease patients do not receive antibiotic treatment may have more to do with the enormous pressure from the marketing and sales of various drugs that do little to address the underlying causes of rheumatic diseases than the effectiveness of various treatments.
In summary, intracellular bacteria are commonly linked to rheumatic diseases, especially rheumatoid arthritis and similar conditions, and these infections can be successfully treated with antibiotics. Treatment often but not always resulted in significant reductions in rheumatic signs and symptoms. Thus chronic infections, such as intracellular bacterial infections, do not appear to be simply co-morbid conditions in rheumatic disease patients. Although there is circumstantial evidence, such as the animal transmission experiments discussed above, that infections like Mycoplasma species may be the cause of rheumatic diseases like rheumatoid arthritis, this has still not been conclusively proven in clinical cases.
1. Ford D (1991) The microbial causes of rheumatoid arthritis. J Rheumatol 18: 1441-1442. Link: https://goo.gl/NfKEJT
2. Krause A, Kamradt T, Burnmester GR (1996) Potential infectious agents in the induction of arthritides. Curr Opin Rheumatol 8: 203-209. Link: https://goo.gl/VNKX6m
8. Schaeverbeke T, Gilroy CB, Bebear C, Dehais J, Taylor-Robinson D, et al. (1996) Mycoplasma fermentans but not M. penetrans detected by PCR in synovium from patients rheumatoid arthritis and other rheumatic disorders. J Clin Pathol 49: 824-828. Link: https://goo.gl/N6h76a
9. Hoffman RW, O’Sullivan FX, Schafermeyer KR, Moore TL, Roussell D, et al. (1997) Mycoplasma infection and rheumatoid arthritis analysis of their relationship using immunoblotting and an ultra-sensitive polymerase chain reaction detection method. Arthritis Rheumatol 40: 1219-1228. Link: https://goo.gl/YKeX8s
10. Haier J, Nasralla M, Franco AR, Nicolson GL (1999) Detection of mycoplasmal infections in blood of patients with rheumatoid arthritis. Rheumatol 1999; 38: 504-509. Link: https://goo.gl/dgh5qA
11. Lünemann JD, Zarmas S, Priem S, Franz, J, Zschenderlein R, et al. (2001) Rapid typing of Borrelia burgdorferr sensu lato species in specimens from patients with different manifestations of Lyme Borreliosis. J Clin Microbiol 39: 1130-1133. Link: https://goo.gl/fDmCLr
12. Ford DK (1979) Yersinia-induced arthritis and Reiter’s syndrome. Ann Rheum Dis 38: 127-128. Link: https://goo.gl/d9xr2M
13. Cole BC, Griffi th MM (1993) Triggering and exacerbation of autoimmune arthritis by the Mycoplasma arthritidis super-antigen MAM. Arthritis Rheumatol 36: 994-1002. Link: https://goo.gl/SXre62
14. Mu HH, Nourian MM, Jiang HH, Justin WT, barry CC, et al. (2014) Mycoplasma super-antigen initiates a TLR4-dependent Th17 cascade that enhances arthritis after blocking B7-1 in Mycoplasma arthritidis-infected mice. Cell Microbiol 16: 896-911. Link: https://goo.gl/TzyHdX
15. Rivera A, Yanez A, Leon TG, Silvia G, Eduardo B, et al. (2002) Experimental arthritis induced by a clinical Mycoplasma fermentans isolate. BMC Musculoskelet Disord. Link: https://goo.gl/EQyzcM
16. Agnello S, Chetta M, Vicari Mancuso R, Manno C, Console A, et al. (2012) Severe outbreaks of polyarthritis in kids caused by Mycoplasma mycoides subspecies. Vet Rec. Link: https://goo.gl/x5mu4j
17. Jansson E, Backman A, Kakkarainen K, Miettinen A, Seniusová B (1983) Mycoplasmas and arthritis. Zeit Rheumatol 42: 315-319. Link: https://goo.gl/AYYBDt
18. Alvarez LB, Ceballos, BI, Alonso JL (2002) Reactive arthritis following a Mycoplasma infection. Med Clin (Barc).
19. Gilroy CB, Keat A, Taylor-Robinson D (2001) The prevalence of Mycoplasma fermentans in patients with infl ammatory arthritides. Rheumatol 40: 1355- 1358. Link: https://goo.gl/t6Vmgv
20. Ataee RA, Golmohammadi R, Alishiri GH, Esmaeili D, JonaidiJ, et al. (2015) Simultaneous detection of M. pneumoniae, M. hominis and M. arthritidis in snovial fl uid of patients with rheumatoid arthritis by multiplex PCR. Arch Iran Med 18: 345-350. Link: https://goo.gl/FQXsh3
21. Ramirez AS, Rosas A, Hernandez-Rerain JA, orengo JC, Saavedra P, et al. (2005) Relationship between rheumatoid arthritis and Mycoplasma pneumonia: a case-control study. Rheumatol 44: 912-914. Link: https://goo.gl/u9yq1Y
22. Ford DK (1969) Current views on the pathogenesis and etiology of rheumatoid arthritis. Canad Med Assoc 101: 147-151. Link: https://goo.gl/w2h9if
23. Nicolson GL, Nasralla M, Nicolson NL (1999) The pathogenesis and treatment of mycoplasma infections. Antimicrob Infect Dis Newsl 17: 81-88. Link: https://goo.gl/fGZz1S
24. Nicolson GL, Nasralla M, Franco AR, A. Robert F, Nancy LN, et al. (2000) Diagnosis and integrative treatment of intracellular bacterial infections in chronic fatigue and fi bromyalgia syndrome, Gulf War illness, rheumatoid arthritis and other chronic illnesses. Clin Pract Alt Med 1: 92-102. Link: https://goo.gl/YsX1mN
25. Baseman JB, Tully JG (1997) Mycoplasmas: sophisticated, reemerging and burdened by their notoriety. Emerg Infect Dis 3: 21-32. Link: https://goo.gl/rbHHgB
26. Couldwell DL, Lewis DA (2015) Mycoplasma genitalium infection: current treatment options, therapeutic failure and resistance-associated mutations. Infect Drug Resist 8: 147-161. Link: https://goo.gl/MxKQu8
27. Tilley BC, Alarcon GS, Heyse SP, David ET, Rosemarie N, et al. (1995) Minocycline in rheumatoid arthritis. A 48-week, double-blind, placebocontrolled trial. MIRA Trial Group. Ann Intern Med 122: 81-89. Link: https://goo.gl/Hbh5jV
28. Pillemer SR, Fowler SE, Tilley BC, Graciela SA, Stephen P, et al. (1997) Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial. MRIA Trial Group. Minocycline in rheumatoid arthritis. Arthritis Rheumatol 40: 419-425. Link: https://goo.gl/s8DXbf
29. O’Dell JR, Paulsen G, Haire CE, Kent B, William P, et al. (1999) Treatment of early sero-positive rheumatoid arthritis with minocycline: four year follow-up of a double-blind, placebo-controlled trial. Arthritis Rheumatol 42: 1691-1695. Link: https://goo.gl/G1jd4i
30. Razin S, Yogev D, Naot Y (1998) Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 62: 1094-1136. Link: https://goo.gl/tZBnMS