Dr. Jay Davidson
Nov. 4, 2018
Dr. Jay Davidson
Nov. 4, 2018
https://www.nature.com/articles/s41598-018-34393-9?fbclid=IwAR3k-zPy2rJu8OuFl3HHqJ0twLPJvQrxiIUALUs0T-BuuJ50_1VQVwcflIQ (Please see comment at end of article)
Kunal Garg, Leena Meriläinen, Ole Franz, Heidi Pirttinen, Marco Quevedo-Diaz, Stephen Croucher & Leona Gilbert
Scientific Reportsvolume 8, Article number: 15932 (2018) https://doi.org/10.1038/s41598-018-34393-9
There is insufficient evidence to support screening of various tick-borne diseases (TBD) related microbes alongside Borrelia in patients suffering from TBD. To evaluate the involvement of multiple microbial immune responses in patients experiencing TBD we utilized enzyme-linked immunosorbent assay. Four hundred and thirty-two human serum samples organized into seven categories followed Centers for Disease Control and Prevention two-tier Lyme disease (LD) diagnosis guidelines and Infectious Disease Society of America guidelines for post-treatment Lyme disease syndrome. All patient categories were tested for their immunoglobulin M (IgM) and G (IgG) responses against 20 microbes associated with TBD. Our findings recognize that microbial infections in patients suffering from TBDs do not follow the one microbe, one disease Germ Theory as 65% of the TBD patients produce immune responses to various microbes. We have established a causal association between TBD patients and TBD associated co-infections and essential opportunistic microbes following Bradford Hill’s criteria. This study indicated an 85% probability that a randomly selected TBD patient will respond to Borrelia and other related TBD microbes rather than to Borrelia alone.
Tick-borne diseases (TBDs) have become a global public health challenge and will affect over 35% of the global population by 20501. The most common tick-borne bacteria are from the Borrelia burgdorferi sensu lato (s.l.) group. However, ticks can also transmit co-infections like Babesia spp.2, Bartonella spp.3, Brucella spp.4,5,6,7,8, Ehrlichia spp.9, Rickettsia spp.10,11, and tick-borne encephalitis virus12,13,14. In Europe and North America, 4–60% of patients with Lyme disease (LD) were co-infected with Babesia, Anaplasma, or Rickettsia11,15,16. Evidence from mouse and human studies indicate that pathogenesis by various tick-borne associated microbes15,16,17 may cause immune dysfunction and alter, enhance the severity, or suppress the course of infection due to the increased microbial burden18,19,20,21,22. As a consequence of extensive exposure to tick-borne infections15,16,17, patients may develop a weakened immune system22,23, and present evidence of opportunistic infections such as Chlamydia spp.24,25,26,27, Coxsackievirus28, Cytomegalovirus29, Epstein-Barr virus27,29, Human parvovirus B1924, and Mycoplasma spp.30,31. In addition to tick-borne co-infections and non-tick-borne opportunistic infections, pleomorphic Borrelia persistent forms may induce distinct immune responses in patients by having different antigenic properties compared to typical spirochetes32,33,34,35. Nonetheless, current LD diagnostic tools do not include Borrelia persistent forms, tick-borne co-infections, and non-tick-borne opportunistic infections.
The two-tier guidelines36,37,38 for diagnosing LD by the Centers for Disease Control and Prevention (CDC) have been challenged due to the omission of co-infections and non-tick-borne opportunistic infections crucial for comprehensive diagnosis and treatment39,40. Emerging diagnostic solutions have demonstrated the usefulness of multiplex assays to test for LD and tick-borne co-infections41,42. However, these new technologies do not address seroprevalence of non-tick-borne opportunistic infections in patients suffering from TBD and they are limited to certain co-infections41,42. Non-tick-borne opportunistic microbes can manifest an array of symptoms24,29 concerning the heart, kidney, musculoskeletal, and the central nervous system as seen in patients with Lyme related carditis43, nephritis44, arthritis45, and neuropathy46, respectively. Therefore, Chlamydia spp., Coxsackievirus, Cytomegalovirus, Epstein-Barr virus, Human parvovirus B19, Mycoplasma spp., and other non-tick-borne opportunistic microbes play an important role in the differential diagnosis of LD24,29. As the current knowledge regarding non-tick-borne opportunistic microbes is limited to their use in differential diagnosis of LD, it is unclear if LD patients can present both tick-borne co-infections and non-tick-borne opportunistic infections simultaneously.
For the first time, we evaluate the involvement of Borrelia spirochetes, Borrelia persistent forms, tick-borne co-infections, and non-tick-borne opportunistic microbes together in patients suffering from different stages of TBD. To highlight the need for multiplex TBD assays in clinical laboratories, we utilized the Bradford Hill’s causal inference criteria47 to elucidate the likelihood and plausibility of TBD patients responding to multiple microbes rather than one microbe. The goal of this study is to advocate screening for various TBD microbes including non-tick-borne opportunistic microbes to decrease the rate of misdiagnosed or undiagnosed48 cases thereby increasing the health-related quality of life for the patients39, and ultimately influencing new treatment protocol for TBDs.
Positive IgM and IgG responses by CDC defined acute, CDC late, CDC negative, PTLDS immunocompromised, and unspecific patients to 20 microbes associated with TBD (Fig. 1) were utilized to evaluate polymicrobial infections (Figs 2–4). Patient categories included CDC acute (n = 43), CDC late (n = 43), CDC negative (n = 46), PTLDS (n = 31), immunocompromised (n = 61), unspecific (n = 31), and healthy (n = 177).
Polymicrobial infections are present at all stages of tick-borne diseases.
Microbes include Borrelia burgdorferi sensu stricto, Borrelia afzelii, Borrelia garinii, Borrelia burgdorferi sensu stricto persistent form, Borrelia afzelii persistent form, Borrelia garinii persistent form, Babesia microti, Bartonella henselae, Brucella abortus, Ehrlichia chaffeensis, Rickettsia akari, Tick-borne encephalitis virus (TBEV), Chlamydia pneumoniae, Chlamydia trachomatis, Coxsackievirus A16 (CVA16), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Mycoplasma pneumoniae, Mycoplasma fermentans, and Human parvovirus B19 (HB19V).
In Fig. 2A, 51% and 65% of patients had IgM and IgG responses to more than one microbe, whereas 9% and 16% of patients had IgM and IgG responses to only one microbe, respectively. Immune responses to Borrelia persistent forms (all three species) for IgM and IgG were 5–10% higher compared to Borrelia spirochetes in all three species (Fig. 2B). Interestingly, the probability that a randomly selected patient will respond to Borrelia persistent forms rather than the Borrelia spirochetes (Fig. S2) is 80% (d = 1.2) for IgM and 68% for IgG (d = 0.7). Figure 2A and B indicated that IgM and IgG responses by patients from different stages of TBDs are not limited to only Borrelia spirochetes.
In Fig. 3 sub-inlets, more than 50% of the patients reacted to only the individual Borrelia strains suggesting that Borrelia antigens are not cross-reactive. If patients were cross-reacting among antigens, a larger percentage of the patients would be seen with the combination of all three species (Fig. S2). These results provide evidence to suggest that the inclusion of different Borrelia species and their morphologies in current LD diagnostic tools will improve its efficiency.
The study outcome indicated that polymicrobial infections existed at all stages of TBD with IgM and IgG responses to several microbes (Fig. 2). Results presented in this study propose that infections in patients suffering from TBDs do not obey the one microbe one disease Germ Theory. Based on these results and substantial literature11,15,16,17,27,49,50,51 on polymicrobial infections in TBD patients, we examined the probability of a causal relationship between TBD patients and polymicrobial infections following Hill’s nine criteria47.
An average effect size of d = 1.5 for IgM and IgG (Fig. 4A) responses is considered very large52. According to common language effect size statistics53, d = 1.5 indicates 85% probability that a randomly selected patient will respond to Borrelia and other TBD microbes rather than to only Borrelia. Reports from countries such as Australia27, Germany49, Netherlands11, Sweden50, the United Kingdom51, the USA15,16, and others indicate that 4% to 60% of patients suffer from LD and other microbes such as Babesia microti and human granulocytic anaplasmosis (HGA). However, previous findings11,15,16,27,49,50,51 are limited to co-infections (i.e., Babesia, Bartonella, Ehrlichia, or Rickettsia species) in patients experiencing a particular stage of LD (such as Erythema migrans). In contrast, a broader spectrum of persistent, co-infections, and opportunistic infections associated with diverse stages of TBD patients have been demonstrated in this study (Fig. 2). From a clinical standpoint, the likelihood for IgM and IgG immune responses by TBD patients to the Borrelia spirochetes versus the Borrelia persistent forms, and responses to just Borrelia versus Borrelia with many other TBD microbes has been quantified for the first time (Fig. S2).
Borrelia pathogenesis could predispose individuals to polymicrobial infections because it can suppress, subvert, or modulate the host’s immune system18,19,20,21,22 to create a niche for colonization by other microbes54. Evidence in animals55 and humans11,15,16,27,49,50,51 frequently indicate co-existence of Borrelia with other TBD associated infections. Interestingly, IgM and IgG immune levels by patients to multiple forms of Borrelia resulted in immune responses to 14 other TBD microbes (Fig. 4B). In contrast, patient responses to either form of Borrelia (spirochetes or persistent forms) resulted in reactions to an average of 8 other TBD microbes (Fig. 4B). Reaction to two forms of Borrelia reflected an increase in disease severity indicating biological gradient for causation as required by Hill’s criteria47.
Multiple microbial infections in TBD patients seem plausible because ticks can carry more than eight different microbes depending on tick species and geography56,57. Moreover, Qiu and colleagues reported the presence of at least 18 bacterial genera shared among three different tick species and up to 127 bacterial genera in Ixodes persulcatus58. Interestingly, research indicates Chlamydia-like organism in Ixodes ricinus ticks and human skin59 that may explain immune responses to Chlamydia spp., seen in this study (Fig. 2). Additionally, prevalence of TBD associated co-infections such as B. abortus, E. chaffeensis, and opportunistic microbes such as C. pneumoniae, C. trachomatis, Cytomegalovirus, Epstein-Barr virus, and M. pneumoniae have been recorded in the general population of Europe and the USA (Table S2). However, true incidence of these microbes is likely to be higher considering underreporting due to asymptomatic infections and differences in diagnostic practices and surveillance systems across Europe and in the USA. More importantly, clinical evidence for multiple microbes has been reported in humans11,15,16,27,49,50,51, and livestock55 to mention the least. Our findings regarding the presence of polymicrobial infections at all stages of TBD further supports the causal relationship between TBD patients and polymicrobial infections (Fig. 2). Various microbial infections in TBD patients have been linked to the reduced health-related quality of life (HRQoL) and increased disease severity39.
An association between multiple infections and TBD patients relates well to other diseases such as periodontal, and respiratory tract diseases. Oral cavities may contain viruses and 500 different bacterial species60. Our findings demonstrate that TBD patients may suffer from multiple bacterial and viral infections (Fig. 4). In respiratory tract diseases, influenza virus can stimulate immunosuppression and predispose patients to bacterial infections causing an increase in disease severity61. Likewise, Borrelia can induce immunosuppression that may predispose patients to other microbial infections causing an increase in disease severity.
Traditionally, positive IgM immune reaction implies an acute infection, and IgG response portrays a dissemination, persistent or memory immunity due to past infections. Depending on when TBD patients seek medical advice, the level of anti-Borrelia antibodies can greatly vary as an Erythema migrans (EM) develops and may present with IgM, IgG, collective IgM/IgG, or IgA62. This study recommends both IgM and IgG in diagnosing TBD (Figs 5 and S4–S6) as unconventional antibody profiles have been portrayed in TBD patients. Presence of long-term IgM and IgG antibodies have been reported in LD patients that were tested by the CDC two-tier system. In 2001, Kalish and colleagues reported anti-Borrelia IgM or IgG persistence in patients that suffered from LD 10–20 years ago63. Similarly, Hilton and co-workers recorded persistent anti-Borrelia IgM response in 97% of late LD patients that were considered cured following an antibiotic treatment64.
Similar events of persistent IgM and IgG antibody reactions were demonstrated in patients treated for Borrelia arthritis and acrodermatitis chronica atrophicans65, chronic cutaneous borreliosis66, and Lyme neuroborreliosis67. A clear phenomenon of immune dysfunction is occurring, which might account for the disparities in LD patient’s antibody profiles and persistence. Borrelia suppresses the immune system by inhibition of antigen-induced lymphocyte proliferation18, reducing Langerhans cells by downregulation of major histocompatibility complex class II molecules on these cells19, stimulating the production of interleukin-10 and anti-inflammatory immunosuppressive cytokine20, and causing disparity in regulation and secretion of cytokines21. Other studies have demonstrated low production or subversion of specific anti-Borrelia antibodies in patients with immune deficiency status22.
In the USA alone, the economic healthcare burden for patients suffering from LD and ongoing symptoms is estimated to be $1.3 billion per year69. Additionally, 83% of all TBD diagnostic tests performed by the commercial laboratories in the USA accounted for only LD70. Globally, the commercial laboratories’ ability to diagnose LD has increased by merely 4% (weighted mean for ELISA sensitivity 62.3%) in the last 20 years71. This study provides evidence regarding polymicrobial infections in patients suffering from different stages of TBDs. Literature analyses and results from this study followed Hill’s criteria indicating a causal association between TBD patients and polymicrobial infections. Also, the study outcomes indicate that patients may not adhere to traditional IgM and IgG responses.
For the first time, Garg et al. show a 85% probability for multiple infections including not only tick-borne pathogens but also opportunistic microbes such as EBV and other viruses.
I’m thankful they included Bartonella as that one is often omitted but definitely a player. I’m also thankful for the mention of viruses as they too are in the mix. The mention of the persister form must be recognized as well as many out there deny its existence.
Key Quote: “Our findings recognize that microbial infections in patients suffering from TBDs do not follow the one microbe, one disease Germ Theory as 65% of the TBD patients produce immune responses to various microbes.”
But there is another important point.
According to this review, 83% of all commercial tests focus only on Lyme (borrelia), despite the fact we are infected with more than one microbe. The review also states it takes 11 different visits to 11 different doctors, utilizing 11 different tests to be properly diagnosed. https://www.news-medical.net/news/20181101/Tick-borne-disease-is-multiple-microbial-in-nature.aspx?
Only 250 spots available, reserve your spot now: https://drjaydavidson.com/parasite-webinar?
When? Thursday, November 1 at 8 pm Central.
Ixodes scapularis ticks harbor a variety of microorganisms, including eukaryotes, bacteria and viruses. Some of these can be transmitted to and cause disease in humans and other vertebrates. Others are not pathogenic, but may impact the ability of the tick to harbor and transmit pathogens. A growing number of studies have examined the influence of bacteria on tick vector competence but the influence of the tick virome remains less clear, despite a surge in the discovery of tick-associated viruses.
In this study, we performed shotgun RNA sequencing on 112 individual adult I. scapularis collected in Wisconsin, USA. We characterized the abundance, prevalence and co-infection rates of viruses, bacteria and eukaryotic microorganisms.
We identified pairs of tick-infecting microorganisms whose observed co-infection rates were higher or lower than would be expected, or whose RNA levels were positively correlated in co-infected ticks. Many of these co-occurrence and correlation relationships involved two bunyaviruses, South Bay virus and blacklegged tick phlebovirus-1. These viruses were also the most prevalent microorganisms in the ticks we sampled, and had the highest average RNA levels.
Evidence of associations between microbes included a positive correlation between RNA levels of South Bay virus and Borrelia burgdorferi, the Lyme disease agent. These findings contribute to the rationale for experimental studies on the impact of viruses on tick biology and vector competence.
**Eukaryotes are protozoans or parasites which includes worms (nematodes/helminths)**
Mainstream medicine has yet to take into account the synergistic effect of all of the pathogens found within a tick upon human suffering. So far they continue to believe this is a one pathogen/one disease/one drug paradigm, hence the mono-therapy of doxycycline as their answer to this 21st century plague.
Until this changes, we are doomed.
https://www.facebook.com/drjaydavidsondetox/videos/2157853841138452/ Video here Approx. 15 Min.
The top link shows Dr. Jay Davidson talking about rat lungworm, hookworm, Strongyloides, and nematodes in the eye. Believe it or not, this particular eye parasite affects 12 million people worldwide.
He also gives a preview of a parasite symptom checklist.
Disciplines such as business and economics often rely on the assumption of rationality when explaining complex human behaviours. However, growing evidence suggests that behaviour may concurrently be influenced by infectious microorganisms. The protozoan Toxoplasma gondii infects an estimated 2 billion people worldwide and has been linked to behavioural alterations in humans and other vertebrates. Here we integrate primary data from college students and business professionals with national-level information on cultural attitudes towards business to test the hypothesis that T. gondii infection influences individual- as well as societal-scale entrepreneurship activities. Using a saliva-based assay, we found that students (n = 1495) who tested IgG positive for T. gondii exposure were 1.4× more likely to major in business and 1.7× more likely to have an emphasis in ‘management and entrepreneurship’ over other business-related emphases. Among professionals attending entrepreneurship events, T. gondii-positive individuals were 1.8× more likely to have started their own business compared with other attendees (n = 197). Finally, after synthesizing and combining country-level databases on T. gondii infection from the past 25 years with the Global Entrepreneurship Monitor of entrepreneurial activity, we found that infection prevalence was a consistent, positive predictor of entrepreneurial activity and intentions at the national scale, regardless of whether previously identified economic covariates were included. Nations with higher infection also had a lower fraction of respondents citing ‘fear of failure’ in inhibiting new business ventures. While correlational, these results highlight the linkage between parasitic infection and complex human behaviours, including those relevant to business, entrepreneurship and economic productivity.
I’ve always been fascinated with parasites. Call me crazy – maybe I have them….
The take home here is that parasites can affect behavior. This is important for Lyme/MSIDS patients to know as a tick’s gut is a literal garbage can full of bizarre and complex creatures that feast on the human body, wreaking all manner of havoc.
In Lyme circles, it won’t take long before you hear patients stating that they aren’t feeling well and then within the same breath, state it’s due to a full-moon.
For a number of reasons, Lyme/MSIDS patients can be coinfected with T. gondii. While food, congenital, blood transfusions, and organ transplants are the common route of transmission, sexual transmission is theorized. Also, people can get it from cleaning a cat’s litterbox and then not washing their hands well. If you go to the following link, you will read of a case of a person with Lyme and Toxoplasmosis: https://madisonarealymesupportgroup.com/2016/05/21/toxoplasmosis/ This article will also reveal T. gondii is responsible for about 1/5 of schizophrenia cases. Women carrying IgG antibodies when giving birth have a greater risk for self-harm. The article also gives testing and treatment options.
And lastly, I’ll never forget this information on how parasites affect human behavior by Dr. Klinghardt, which I found here: http://www.betterhealthguy.com/a-deep-look-beyond-lyme
Parasite patients often express the psyche of the parasites – sticky, clingy, impossible to tolerate – but a wonderful human being is behind all of that.
We are all a composite of many personalities. Chronic infections outnumber our own cells by 10:1. We are 90% “other” and 10% “us”. Our consciousness is a composite of 90% microbes and 10% us.
Our thinking, feeling, creativity, and expression are 90% from the microbes within us. Patients often think, crave, and behave as if they are the parasite.
Our thinking is shaded by the microbes thinking through us. The food choices, behavioral choices, and who we like is the thinking of the microbes within us expressing themselves.
Patients will reject all treatments that affect the issue that requires treating.
Patients will not guide themselves to health when the microbes have taken over.
With this information in mind, it’s quite clear how Lyme/MSIDS is such a complex disease as many are dealing not only with Lyme but other coinfections including parasites which are either directly transmitted by a tick or activated due to a dysfunctional immune system.
This article has a lot of great info regarding parasites: https://madisonarealymesupportgroup.com/2017/10/03/removing-parasites-to-fix-lyme-chronic-illnesses-dr-jay-davidson/
His wife wasn’t home, so he drove himself to the university hospital emergency room near where he lived in Chapel Hill, N.C. As he explained his symptoms at the check-in counter, he began to feel faint, then fell to one knee. An orderly offered a wheelchair. He sat down — and promptly lost consciousness.
When he came to, he was on the floor. He had rolled out of the wheelchair and hit his head. A gaggle of worried-looking medical staff stood over him. They asked if he was on drugs. Did he have heart problems? His blood pressure was extremely low, probably the reason he had passed out. Niegelsky, who was 58, told them that he was healthy and drug-free and had no heart condition.
“I could see the concern on their faces in a way that did not help my confidence level at all,” Niegelsky says.
He felt as if insects were biting every inch of his hands, armpits and groin. A doctor asked if he had any food allergies. The hives and the low blood pressure suggested anaphylaxis, a severe allergic reaction. Again the answer was no, but Niegelsky did recall that he had a very bad allergic reaction a month earlier to a tick bite he got at a concert.
The E.R. doctor ordered two shots of epinephrine, a form of adrenaline that dampens the allergic reaction; the hives and itching began to subside about 25 minutes later. Now the doctor asked Niegelsky what he’d eaten that day. A hamburger for lunch, Niegelsky told him. In his recollection, the doctor’s eyes widened, and he said,
“I think we know what you have” — a condition called mammalian-meat allergy.
Meat allergy was first observed in the 1990s and formally described in 2009, which makes it a relatively recent arrival to the compendium of allergic conditions. Its most curious quality may be that it is seemingly triggered by a tick bite. In America, the culprit, called the lone-star tick — females have a distinctive white splotch on their backs — is common in the warm and humid Southeast, where most cases of meat allergy have been diagnosed. Niegelsky had in fact heard about the allergy from friends. He remembers shaking his head and thinking that it sounded “made up.” He understood now, in a visceral way, how real it was. That bite from a month ago had primed his body for today’s hives and plummeting blood pressure.
Mammalian-meat allergy “really has the potential to revolutionize our understanding of food allergy, because it doesn’t fall under the umbrella of our paradigm,” Dr. Maya R. Jerath, a professor of medicine at Washington University School of Medicine, in St. Louis, told me. “Maybe our paradigm is wrong.”
“Six hours later I was in a hotel, covered in hives, itching like crazy and laughing at myself,” he told me. By then, he thought he knew what was happening: The ticks had made him allergic to those chops.
“This is really allergy in a kit — how to get it and how to lose it,” van Nunen said. “There’s really nothing else like it.”
Mammalian-meat allergy differs from most other food allergies in several important ways. One is the delayed reaction; it’s not uncommon for sufferers to wake up in the middle of the night, hours after a steak dinner, covered with hives and struggling to breathe. By contrast, those with food allergies to peanuts usually develop symptoms within minutes after ingesting the offending food. And whereas in most cases of allergy, the immune system pursues a protein, meat allergy is set off by a sugar.
Another unusual aspect of meat allergy is that it can emerge after a lifetime spent eating meat without problems. In other food allergies, scientists think that children’s immune systems may never learn to tolerate the food in the first place. But in meat allergy, the tick seems to break an already established tolerance, causing the immune system to attack what it previously ignored. One way to understand how the parasite pulls this off is to consider its bite as a kind of inadvertent vaccine. A vaccine teaches an immune system to pursue a pathogen it otherwise wouldn’t by exposing it to weakened versions of that pathogen — an attenuated measles virus, say — or bits and pieces of dead pathogen. Vaccines also often contain a substance called an adjuvant, which is designed to spur the immune system into action.
In similar fashion, when the lone-star tick feeds, alpha-gal leaks from its mouth into the wound, exposing the victim’s immune system to the sugar, prompting the immune system to remember and pursue alpha-gal. But exposure to alpha-gal alone probably doesn’t achieve this feat. Commins, who is at the University of North Carolina, at Chapel Hill, has identified a candidate, an enzyme in the tick’s saliva called dipeptidyl-peptidase that works as an adjuvant. It’s also common in bee and wasp venom. This enzyme, Commins argues, is what tells your immune system to see alpha-gal as the type of threat that warrants the itching and swelling of the allergic response.
Once sensitized, some victims find that they can no longer tolerate beef, pork, lamb — even milk or butter, foodstuffs with only very small amounts of alpha-gal. Several factors can also affect the severity of the allergic reaction, or if there is an allergic reaction at all. Grilled meat is less allergenic than other methods of preparation that preserve more of its fat. Fatty meat leads to more alpha-gal crossing a person’s gut barrier into his or her circulatory system, triggering a stronger immune reaction than leaner cuts. A study of German patients also found that alcohol imbibed with meat can push people toward an allergic reaction, as can exercise; both actions make the gut more permeable, exposing the immune system to more alpha-gal.
As it happens, an immune response to alpha-gal is also what drives, in part, the rejection of tissue transplanted from animals to people.
A recent study by scientists at the National Institutes of Health, which included Commins and Platts-Mills as co-authors, linked allergic sensitization to alpha-gal with a greater risk of arterial plaques, a hallmark of heart disease. It’s unclear whether having alpha-gal antibodies specifically increases your risk of developing plaques or whether some other factor increases a person’s risk of heart disease and sensitization to alpha-gal. But if it turns out that meat allergy pushes people toward cardiac arrest, it would imply that encounters with the lone-star tick contribute to the leading cause of death in the United States.
The big, unanswered question is why meat allergy is on the rise today. Commins estimates that at least 5,000 cases have been diagnosed in the United States, and many more probably remain undiagnosed. In some tick-heavy regions, the prevalence of meat allergy is estimated to be at least 1 percent of the population. Ticks are not new. Neither is the human consumption of meat. Why the sudden problem for so many? One possibility is that the ticks have changed somehow.
The idea is plausible and could nicely explain how an arachnid that has been around for a long time could begin causing a new set of complications. Scientists have long debated where the alpha-gal in the tick originates: Does it come from the blood a tick sucks from other mammals and then regurgitates as it feeds on people, or does it come from the tick itself? Shahid Karim, a vector biologist at the University of Southern Mississippi, in Hattiesburg, told me that the answer might be neither; the sugar probably comes from the microbes that the tick carries within it. So it’s entirely possible, he said, that changes in its microbiome could, by increasing the amount of alpha-gal humans are exposed to in tick bites, make the lone-star tick more likely to induce meat allergy.
What such an account fails to address, however, is why the meat allergy has increased in other parts of the world, like Australia and Europe. (Van Nunen says that in the tick country around Sydney, people are now more likely to carry EpiPens, which contain a shot of adrenaline, for meat allergy than for better-known peanut allergies.) Other tick species are linked with meat allergy in those regions, not the lone-star tick. And it seems very unlikely that the microbiomes of all these ticks on different continents have changed in similar ways at the same time.
“I don’t for the life of me have a unifying hypothesis for why it’s happening everywhere,” Commins told me, although he added that pesticides could be one factor changing tick microbiomes globally.
It may simply be that an increase in the number of ticks has turned a problem once so rare that it went scientifically unnoticed into an observable epidemic.
“I think we’ve got far more tick bites today than people had as recently as 35 years ago,” Platts-Mills told me. He lays the blame for the growing spread of ticks on newly abundant deer.
In Virginia, he thinks new laws requiring dogs to remain on leashes have emboldened deer, which then bring ticks closer to people. People aren’t necessarily venturing deeper into the forests than in the past, he says. More than half the patients he sees with the allergy were bitten on their own lawns.
His leash theory is anecdotal, but it’s certainly true that the current ecological state of Eastern forests is probably encouraging ticks to multiply. After having been cleared in the Colonial era, the forests have partly grown back. Deer and turkey, which the lone-star tick likes to feed on, are abundant again. They thrive in the new-growth forests, now fragmented by roads and suburbs. Large predators are mostly absent. And the rise of tick-borne disease generally has been linked with the decline (or absence) of predators that eat the animals ticks feed on. In Australia, for example, van Nunen points to the eradication of foxes, an introduced species there, as one factor in the increase of ticks and the rise of meat allergy.
We might label this the disturbed ecosystem theory of meat allergy. Forests ecosystems have recovered partially — lots of animal hosts for ticks but not enough predators to keep those hosts in check — and this imbalance has fostered an exponential growth in the number of ticks. In some ways, this is the most probable explanation for the rise of meat allergy. Climate change may be aiding the lone-star tick’s move northward too, Rick Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies, told me. Hundreds of cases of meat allergy have been diagnosed on Long Island in recent years, which wasn’t part of the tick’s range in recent history. The tick has been spotted as far north as Maine.
But what’s happening in the American East can’t account for the full extent of the phenomenon elsewhere in the world. In Northern Europe, ticks are proliferating as forests recover and the climate becomes warmer. But in Spain and Southern Europe, the rising incidence of meat allergy has not been accompanied by an increase in tick numbers, according to José de la Fuente, a professor at the Institute of Game and Wildlife Research in Ciudad Real, Spain. For him, the mystery of meat allergy is captured in one question: If a tick bites two genetically similar people, why might only one develop the meat allergy?
Onyinye Iweala, an assistant professor who works with Scott Commins’s lab at the University of North Carolina, echoes this uncertainty. Why are some people sensitized to alpha-gal — meaning they have allergic antibodies directed at the sugar in their blood stream — but never have an allergic reaction to it? This can happen in all allergies. You can have antibodies to, say, cat dander, yet never wheeze or sneeze around cats. Iweala suspects that sensitization to alpha-gal isn’t new. What’s changing is the proportion of people who, after sensitization, proceed to overt allergy. Something else in the environment, she told me, is likely pushing people toward full-blown meat allergy. Perhaps shifts in the microbes that live within us have somehow made us more easily sensitized by tick bite. As a model of how this might work, Iweala points to intriguing research on the interaction between malaria and the human microbiome that centers on alpha-gal.
OUR DISTANT ANCESTORS once made alpha-gal. Understanding why humans don’t could shed light on the meat-allergy mystery. Like other mammals, South American monkeys produce alpha-gal. Only Old World monkeys and apes (and humans) have lost the ability to make the sugar. Hence scientists deduce that the change most likely happened after New and Old World primates diverged from each other around 40 million years ago. One explanation for the disappearance of alpha-gal is that it was driven by some catastrophe, a deadly infection that afflicted Old World primates, perhaps, and as a result maybe these distant relatives of ours stopped being able to produce the sugar because doing so conferred an evolutionary advantage. The mutation that eliminated alpha-gal could have improved a primate’s ability to fight off an infection by enabling its immune system to more easily distinguish between its own body and some pathogen with alpha-gal.
What could this pathogen have been? In the late 2000s, Miguel Soares, a scientist at the Instituto Gulbenkian de Ciência in Oeiras, Portugal, began to suspect the plasmodium parasite that causes malaria. Because the protozoan is so deadly and has historically been so widespread in warmer climes, geneticists often say that malaria has been the single greatest force shaping the human genome in our recent evolutionary history. The parasite remains a leading cause of death in the developing world. And it’s coated in alpha-gal.
Soares and his colleagues investigated a rural Malian population that was naturally exposed to malaria. As it happens, humans produce some antibodies to alpha-gal all the time. They’re not allergic antibodies like those responsible for Lee Niegelsky’s anaphylactic experience, but antimicrobial ones that give rise to a different, less drastic immune response. Between 1 and 5 percent of all the antibodies circulating in any person, a remarkably large quantity, are directed at alpha-gal, Soares estimates. The target of these antibodies is not the alpha-gal in the steak you may have eaten for dinner but the alpha-gal that leaks into circulation from the microbes dwelling in your gut. There are natural variations in the amount of these antibodies any individual produces; some people make more, some less. Soares wanted to know if this variability influenced the villagers’ susceptibility to malaria.
What was different about those with more alpha-gal antibodies? They had more gut microbes that produced the sugar, Soares speculated. By priming their immune response against alpha-gal, these individuals’ microbiomes probably helped shield them against malaria. Soares showed as much using mice. Rodents colonized by a strain of E. coli found in the human microbiome that contains alpha-gal produced antibodies to the sugar and were protected from malaria. Rodents that harbored an E. coli strain that didn’t produce the sugar, on the other hand, were not protected. (Other scientists later observed a connection between resistance to malaria and the composition of Malian villagers’ microbiomes.) This research highlights one reason we probably have a few pounds of microbes in us: Friendly microbes can help protect us against unfriendly ones.
Soares is currently working on a vaccine to spur the immune system to attack alpha-gal more actively, thereby conferring greater protection against malaria. His findings also raise the prospect, at least theoretically, of an antimalarial probiotic. In the context of meat allergy, his work underscores the fact that our microbes may affect how we respond to alpha-gal from other sources, including, perhaps, tick bites.
How might this work? You can envision antibodies as arrows that have Velcro on the front instead of arrowheads. Depending on their targets, that Velcro sticks only to a particular substance, like alpha-gal or peanut protein. The back end of the arrow displays a signal that tells the immune system what to do. Allergic antibodies, called immunoglobulin-E, or IgE for short, call for an allergic response. But the antibodies that humans typically have in circulation directed at alpha-gal are antimicrobial antibodies like IgM and IgG, not allergic ones.
A question central to the meat-allergy mystery is how, if we’re always exposed to alpha-gal from our gut microbes, and we’re constantly mounting a nonallergic response against it, the lone-star tick prompts what’s called “class switching,” spurring the immune system to pump out allergic antibodies instead of antimicrobial ones?
The microbes we host may, by stimulating the immune system and guiding its response to alpha-gal, make this class switching more or less likely, Onyinye Iweala told me. But scientists don’t yet know how the relationship works. Perhaps if your microbiota have more species that produce alpha-gal, these microbes stimulate your immune system in a way that protects you from allergic sensitization to the sugar when a tick bites. Or maybe the relationship works the other way around: If you host fewer alpha-gal-producing species and your immune system is less exposed to alpha-gal on a daily basis, that relative lack of stimulation might prevent alpha-gal allergy from developing when you’re bitten by a tick. These interactions can be tested — as Iweala is doing — with mice that, like humans, don’t produce alpha-gal.
What scientists do know is that if you treat a baboon with antibiotics, reducing the amount of alpha-gal-producing microbes in its gut, and thus lessening the stimulation they provide, the quantity of alpha-gal antibodies in its bloodstream also declines. This suggests that altering a primate’s gut microbes may change its immune response to alpha-gal. People living in developed countries, where most cases of meat allergy have been diagnosed, have been doing something very similar to themselves. “We keep changing the microbiome with antibiotics and what we eat,” Iweala says. By tweaking the microbes that live inside us, we may have inadvertently changed how our immune system responds to alpha-gal, making us more vulnerable to tick-induced meat allergy. It’s also possible, however, that the microbes that determine the general tone of our immune function have shifted, altering how we respond to all potential allergens, not just alpha-gal.
Since at least the late 20th century, and probably earlier, we’ve been living in the midst of what’s often called the allergy epidemic, an era that has seen an increase in the prevalence and severity of food allergies generally and, before that, a rise in the prevalence of respiratory allergies and asthma. The forces driving this trend may help account for meat allergy as well. A leading explanation holds that we develop more allergies now because our immune systems have become more sensitive to what they encounter, not because they are exposed to more pollens or allergenic foods than in the past. The reason the modern immune system errs this way, the thinking goes, is that it’s not receiving the right kind of education.
The news media have taken to calling this explanation the “hygiene hypothesis,” which is unfortunate and misleading; personal hygiene has little to do with what’s at issue. More accurate terms coined by researchers include the microbial-deprivation hypothesis, the disappearing-microbiota hypothesis and even the “old friends” hypothesis (the implication being that we’ve lost contact with once-ever-present friendly organisms).
Whatever you call it, the idea is that the rising tide of allergic diseases comes from changes to the type and quantity of microbes we encounter in our environment, particularly in our early life, as well as from changes to the microbes that live on and in us. Improved sanitation, antibiotics and the junk-food-ification of our diet, among other factors, may have shifted our microbial communities, giving us an immune system that’s overly jumpy, unable to reliably distinguish friend from foe and prone to diseases of overreaction, like allergies.
Studies on populations that have bucked the increase in allergies support the idea. Nearly 20 years of research on European children who grow up on farms with animals, for example, indicates that they are less likely to have respiratory allergies, asthma and eczema compared with other children in the same rural areas. The abundant microbial stimulation of the farm environment, scientists have proposed, tunes farming children’s immune system in a way that prevents allergic disease. The cowshed has thus become a stand-in for premodern conditions and the immune system that that environment produces — lightly stimulated but less likely to react to allergens — a model of how the human immune system might have worked in a more microbially enriched past.
So here is the question as it relates to meat allergy: If a lone-star tick bit a Bavarian farm-raised child, would she be less likely to develop an allergy to alpha-gal compared with her nonfarming counterparts? Put another way, if the tick bit someone 150 years ago when the whole world was more like a cowshed, would that person be less or more likely to develop a food allergy than someone from modern-day Chapel Hill?
It’s pure speculation at this point, but gradual, intergenerational changes to our microbes may have altered our immunological tenor, shifting it from cool, calm and collected toward restless and irritable and increasing the odds of developing allergy from a tick bite. Today we may encounter more ticks than in times past, but they may also be interacting with an immune system that’s more sensitive to their bites than ever before. “It’s the ‘perfect storm,’ as you would say in America,” Sheryl van Nunen told me.
For Lee Niegelsky, who had eaten hamburgers his entire life, the allergy forced him to constantly scrutinize his diet. You don’t realize how many foods have meat-derived products in them, he told me — especially in the South, where pork fat and bacon are widely used as flavoring — until you have to avoid meat for fear of passing out. Not long ago, for example, he fell ill after eating clam chowder, which he attributes to meat broth that he suspects was in the soup.
The good news is that, provided you’re not bitten by a tick again, sometimes the meat allergy fades on its own. A year after his visit to the emergency room, under Scott Commin’s supervision, Niegelsky began introducing small amounts of lean meat into his diet. The idea is to test the possibility that his allergic alpha-gal antibodies have subsided to the point that his immune system no longer attacks the sugar. It took Niegelsky about a week to muster the courage to take his first bite of pork tenderloin. He waited anxiously for six hours. When nothing happened, he moved on to steak.
“According to Dr. Nicolson, some of the experiments used Mycoplasma while others utilized various “cocktails of microbial agents” such as Mycoplasma, Brucella, and DNA viruses such as Parvovirus B19. This project later become the topic of a book by Dr. Nicolson entitled Project Day Lily.
Dr. Nicolson believes that Mycoplasma fermentans is a naturally occurring microbe. However, some of the strains that exist today have been weaponized. Dr. Nicolson’s research found unusual genes in M. fermentans incognitus that were consistent with a weaponized form of the organism. Weaponzing of an organism is done in an attempt to make a germ more pathogenic, immunosuppressive, resistant to heat and dryness, and to increase its survival rate such that the germ could be used in various types of weapons. Genes which were part of the HIV‐1 envelope gene were found in these Mycoplasma. This means that the infection may not give someone HIV, but that it may result in some of the debilitating symptoms of the HIV disease.”
Regarding the weaponization of tick pathogens: https://www.lymedisease.org/lymepolicywonk-questioning-governments-role-lyme-disease-make-conspiracy-theorist/ (Go here to read excerpts of an interview with a biologist who acknowledged doing biowarfare work on ticks and mosquitoes. He admits every time he has a strange illness his physician says it’s probably a rickettsia – an idiopathic condition that never tests positive but symptoms indicate it.)
‘The interview suggests to me that the reason we have such a large problem with our tick population today may be related to military experiments in the 50s. They were part of a biological warfare effort against the Russians. One goal was to figure out how to get ticks to reproduce quickly and abundantly, as well as how to distribute ticks to targeted areas.”
For a lengthy but informative read on the Lyme-Biowarfare connections: CitizensAlert_Bob13 (Scroll to page 44 to see an executive summary. Please notice the names of Steere, Barbour, Shapiro, Klempner, and Wormser, the first four are affiliated with the CDC Epidemic Intelligence Service (EIS). Wormser, lead author of the fraudulent Lyme treatment guidelines, lectures as an expert on biowarefare agents and treatments). The author of the pdf believes borrelia (Lyme) has been bioweaponized due to (excerpt from pdf footnote):
So you tell me. Could all this lab tweaking have something to do with tick borne illness and allergies?