Aluminium Adjuvants And Adverse Events In Sub-cutaneous Allergy Immunotherapy

Aluminium Adjuvants And Adverse Events In Sub-cutaneous Allergy Immunotherapy

Christopher Exley

Author Affiliations

The Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK

Allergy, Asthma & Clinical Immunology 2014, 10:4  doi:10.1186/1710-1492-10-4

The electronic version of this article is the complete one and can be found online at:http://www.aacijournal.com/content/10/1/4

Received: 21 November 2013
Accepted: 15 January 2014
Published: 20 January 2014

© 2014 Exley; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Sub-cutaneous immunotherapy is an effective treatment for allergy. It works by helping to modify or re-balance an individual’s immune response to allergens and its efficacy is greatly improved by the use of adjuvants, most commonly, aluminium hydroxide. Aluminium salts have been used in allergy therapy for many decades and are assumed to be safe with few established side-effects. This assumption belies their potency as adjuvants and their potential for biological reactivity both at injection sites and elsewhere in the body. There are very few data purporting to the safety of aluminium adjuvants in allergy immunotherapy and particularly so in relation to longer term health effects. There are, if only few, published reports of adverse events following allergy immunotherapy and aluminium adjuvants are the prime suspects in the majority of such incidents. Aluminium adjuvants are clearly capable of initiating unwanted side effects in recipients of immunotherapy and while there is as yet no evidence that such are commonplace it is complacent to consider aluminium salts as harmless constituents of allergy therapies. Future research should establish the safety of the use of aluminium adjuvants in sub-cutaneous allergy immunotherapy.

Keywords:

Aluminium adjuvant; Immunotherapy; Allergy; Adverse events

Review

Aluminium salts are the adjuvant of choice in immunotherapy

Aluminium-based adjuvants are the most commonly used adjuvant in sub-cutaneous allergy immunotherapy (SCIT) [1]. Approximately 75% of all such adjuvant-based therapies include an aluminium salt. In parallel with the use of aluminium-based adjuvants in vaccinations these adjuvants have been in use in allergy immunotherapies for over 80 years [2]. In allergy immunotherapy injections are sub-cutaneous and each injection includes between 0.1 and 1.25 mg of aluminium adjuvant. Allergy-specific immunotherapy can involve as many as 15 injections of aluminium adjuvant in a year and a treatment may be continued for 3 to 5 years or even longer, sometimes for the life-time of a patient [3]. Individuals may receive therapies against several allergens simultaneously and will be subject to parallel courses of such a dosing regimen (Table 1). Aluminium salts are the adjuvant of choice in both vaccinations and allergy immunotherapies because of their efficacy in promoting immune reactions to antigens (preventative therapy) and modifying the immune response to allergens (tolerance therapy) respectively. While the detailed mechanisms of their activities as adjuvants remain to be elucidated [4] their immunopotency is testimony to their biological availability and biological reactivity at injection sites and elsewhere in the body. Contrary to the view of a recent otherwise informed commentary [5] aluminium adjuvants are not ‘harmless salts’! They are far from being benign participants in vaccination and immunotherapy and their reactivity’s have been associated with adverse events in the recipients of such therapies. Adverse reactions to aluminium adjuvants might have been avoided if there had been a requirement to demonstrate the safety of their use in humans. However, no such regulations exist and the amount of aluminium salt which is included as an adjuvant is wholly determined by its immuno-efficacy in tandem with the respective antigen or allergen. Indeed it is an anomaly of many trials of the safety of aluminium-adjuvanted vaccines and immunotherapies that the (essentially toxic) aluminium adjuvant is considered to be the appropriate placebo in such clinical trials [6].

Table 1. Typical dosing regimens used in sub-cutaneous allergy immunotherapy

Adverse events associated with aluminium adjuvants in allergy immunotherapy

The safety of aluminium adjuvants used in vaccination is under increasing scrutiny and one serious disease, a neuromuscular disorder called macrophagic myofasciitis, is attributed to the persistence of aluminium salts at injections sites in muscle [13]. Established links with other more common conditions such as chronic fatigue syndrome [14] and autoimmune disease [15] are burgeoning though the incidences of adverse events remain a very small percentage of any vaccinated population. Herein it is already noted that in allergy immunotherapy not only the absolute number of injections of aluminium adjuvants but also their frequency, for example one a month or more (Table 1), often far exceeds that received through vaccinations. If the safety of aluminium adjuvants used in vaccinations is open to question then the safety of the same adjuvants used more frequently and in greater numbers in allergy immunotherapy must also be in question. While adverse reactions in individuals receiving allergy immunotherapy have been reported in the scientific and medical literature these reports are relatively few and far between [16,17]. Reactions include; foreign body granulomas [18], urticaria [19], sub-cutaneous sarcoidosis [20], progressive circumscribed sclerosis [21], sub-cutaneous nodules [22] and cutaneous-sub-cutaneous pseudolymphoma [23]. The actual incidence of adverse events such as the aforementioned is unknown and while the European Medicines Agency (EMA) lists as many as 32 adverse reactions to immunotherapy ranging from discolouration of the skin to encephalopathy their information cannot be verified as the data were not taken from an openly available peer-reviewed resource [24].

Toxicity of aluminium adjuvants

To appreciate the safety issues which relate to the use of aluminium adjuvants in allergy immunotherapy we need an understanding of what happens to the injected aluminium salt. We need to consider the biological availability of aluminium both at the injection site and, as a consequence of the transport of both dissolved and particulate aluminium, beyond the immediate vicinity of the injection, for example in the lymph nodes. Details of the bioinorganic chemistry of aluminium adjuvants have been reviewed recently [4] and herein it is suffice to summarise such as the biological chemistry of the free aluminium cation, Al3+(aq), which is the principal antagonist in aluminium toxicity [25]. Aluminium adjuvants, as sparingly soluble particulates, can be considered as sources of biologically available Al3+(aq). How then could a sub-cutaneous source of biologically available Al3+(aq) be responsible for adverse events or reactions in allergy immunotherapy?

Aluminium body burden

The, perhaps, simplest scenario would be that aluminium adjuvants contribute directly and significantly to an individual’s body burden of aluminium. The latter has recently been defined as the sum of aluminium atoms associated with the human body at any one moment in time [26]. Under this redefinition each injection of an aluminium adjuvant will contribute up to 1.25 mg of aluminium to the body burden of aluminium at the time of the injection. It is important to recognise that the body burden of aluminium is not evenly distributed throughout the body mass and that aluminium will be found as focal accumulations determined by the form of aluminium at exposure and its route of entry into the body [27]. By way of an example, evidence is beginning to demonstrate that aluminium administered as adjuvant may be phagocytosed as particulates by infiltrating cells and transported to distant and specific sites in the body including the lymph nodes but also into the brain [28]. However, contrary to burgeoning scientific evidence it is common practice by regulatory bodies, such as the European Food Standards Agency (EFSA) [29] or the previously mentioned EMA [24], to apply a safety criterion known as a tolerable weekly intake (TWI) to, almost universally, confirm the innocuous nature of all forms of human exposure to aluminium. This criterion, based wholly on the results of animal studies, assumes that all exposures to aluminium are ‘biochemically equal’ and that the route of exposure and the form of aluminium involved are unimportant. Nothing could be further from the truth where human exposure to aluminium is concerned [26]. A single injection of 1 mg of aluminium adjuvant will add 1 mg of aluminium to the body burden but this mg of aluminium will distribute throughout the body according to myriad different influences beginning with those occurring at the injection site [4]. Multiple injections of aluminium adjuvant over relatively short time periods, for example 15 injections over 12 months as might be common in allergy immunotherapies (Table 1), could result in significant focal accumulations of aluminium at single target sites and thereby present the possibility of aluminium toxicity at such sites. Allergy immunotherapy with aluminium adjuvants will contribute significantly to the aluminium body burden of the recipient and because of the nature of the route of exposure it is highly likely that the fate of a significant proportion of the adjuvant aluminium will be focal accumulations with the potential to exert a form of toxicity.

Aluminium the antigen

A second scenario whereby aluminium adjuvants in allergy immunotherapies might contribute towards adverse reactions to such therapies is related to the known antigenicity of aluminium [30]. It is perhaps less well appreciated that in addition to being an effective adjuvant it has also been shown that aluminium can act as an antigen. Thus, aluminium adjuvants in modifying the body’s immune response to allergens in immunotherapy may additionally sensitise the body to the presence of aluminium. The result is that following injection of an adjuvant-allergen therapy the body develops a memory of the exposure to aluminium. Subsequent multiple injections reinforce this memory and raises the possibility that the body is sensitised to not only the aluminium injected as adjuvant but potentially all body stores of aluminium. The body burden of aluminium becomes an immunological target and one which unfortunately the machinery of immunity is unable to deal with as it might ‘normal’ allergens/antigens. When aluminium the adjuvant is simultaneously aluminium the antigen there is the possibility that a relatively small exposure to aluminium, as might occur following a single injection of aluminium adjuvant in immunotherapy, could instigate a cascade of reactions whereby aluminium throughout the body is recruited to produce a significant immune/inflammatory-like response. The severity of such a response would depend upon both the body burden of aluminium and the location of significant deposits of aluminium. It is not yet clear which form or forms of aluminium are capable of acting as antigens[30]. If Al3+(aq) is the antigen then this could help to explain why the body isn’t (presumably) on continuous immune alert against its everyday burden of aluminium. The concentration of Al3+(aq)in the majority of physiological milieu will be nanomolar [27] and its propensity to act as an antigen will depend upon the kinetic inertia of deposits of aluminium in delivering Al3+(aq) at a rate sufficient to fuel the formation of antibodies against it. Such situations could include sites of injection of aluminium adjuvants, the lymph nodes and known targets of aluminium in the brain including myelin.

Aluminium as a potent adjuvant

Another situation which might help to explain the putative toxicity of aluminium adjuvants in allergy immunotherapies and vaccinations is the outcome of the known potency of aluminium salts as adjuvants. Aluminium salts are not only effective in increasing the antigenicity of the allergens and antigens which are the targets of therapies they are also able to induce antigenicity in substances which would not otherwise act as antigens or allergens [31]. One example of this is to induce allergy to codfish by feeding mice with codfish and aluminium antacids [32]. Within a relatively short period of time the mice are demonstrating allergic responses to codfish alone. The potency of aluminium salts as adjuvants must be carefully considered in the preparation of allergy immunotherapies as any additional components or contaminants of the injections [33] could become antigenic and the target of an immune response both at the injection site and even beyond at other places in the body. The adjuvanticity of aluminium salts may also come into play in inducing antigenicity in constituents of foreign- or self-origin in the vicinity of the injection site. Actually such a mechanism may have a role to play in the efficacy of aluminium adjuvants in immunopotentiation though ideally these effects should not be translated elsewhere in the body where such would be unwanted and potentially toxic.

Aluminium adjuvants in allergy immunotherapy need to be both effective and safe

Aluminium is an effective adjuvant in allergy immunotherapy because of its biological reactivity and that same reactivity means that there must be a number of mechanisms whereby aluminium adjuvants could also result in adverse events. One or more of these mechanisms could be a component of the, as yet non-elucidated, mode of action of aluminium adjuvants in stimulating or modifying immunity and in the majority of recipients of allergy therapies will result in little or limited discomfort. However, the likelihood is that each of these mechanisms will play some role, to a lesser or greater extent, in an individual’s response to the injection of aluminium adjuvant and in some individuals or particular circumstances the biological response to one or repeated injections of aluminium salt will be an adverse event. The difficulty is in predicting which individual or what set of circumstances is likely to instigate a biological cascade leading to toxicity. One probable predisposition would be an unusually high body burden of aluminium. There are many possible reasons why an individual’s body burden of aluminium is high including exposure to aluminium through extended periods of sub-cutaneous immunotherapy. Research is on-going into the best way of establishing by non-invasive means an individual’s body burden of aluminium and at present this is achieved by measuring urinary excretion of aluminium [14,26]. Future research should elaborate upon whether individuals with high body burdens of aluminium are more likely to suffer an adverse reaction to immunotherapy as well as whether individuals receiving extended periods of immunotherapy are more likely to have higher body burdens of aluminium and thereby predisposing themselves to an adverse event in the future.

Conclusions

Aluminium hydroxide is currently the adjuvant of choice in sub-cutaneous allergy immunotherapy. Aluminium adjuvants are used to modify the immune response to a range of allergens and are generally used in multiple injections over extended time periods. Adverse events or reactions to allergy immunotherapy are documented and have been associated with aluminium adjuvants. While the mechanism of action of aluminium adjuvants in immunotherapy (likewise vaccination) has not been fully elucidated it will be allied to the biological reactivity of aluminium at both the injection site and elsewhere in the body. Adverse reactions to aluminium adjuvants may be amplifications of aluminium’s activity as an adjuvant and there may be subsets of individuals who are predisposed to such events. For example, individuals with a high body burden of aluminium, to which allergy immunotherapy will be a contributor, may be more susceptible to adverse events. There are few reliable data purporting to neither the safety nor the toxicity of aluminium adjuvants used in allergy immunotherapy. These gaps in knowledge should be remedied in future clinical trials of new immunotherapies and in records of clinical practice of therapies currently in use.

Competing interests

CE has received reimbursement of travel and accommodation costs incurred through meetings with Allergy Therapeutics, a company which manufacturers immunotherapies which do not use aluminium adjuvants.

Authors’ contributions

CE conceived the idea for the paper and wrote the manuscript.

Authors’ information

CE is Professor of Bioinorganic Chemistry and Leader of the Research group on Aluminium and Silicon.

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Federal Government of the United States Prepares To Track Unvaccinated Adults

Federal Government of the United States Prepares To Track Unvaccinated Adults

Stop Drinking and Driving

By Theresa Wrangham 
NVIC Executive Director

During the National Vaccine Advisory Committee’s (NVAC) February meeting, American adults were put on notice by Big Brother that non-compliance with federal vaccine recommendations will not be tolerated. Public health officials have unveiled a new plan to launch a massive nationwide vaccination promotion campaign involving private business and non-profit organizations to pressure all adults to comply with the adult vaccination schedule approved by the Centers for Disease Control (CDC). [1]

adult-vaccine-schedule_Page_1

NVAC has authored the National Adult Immunization Plan (NAIP) and, once finalized, the plan will be turned over to the Interagency Adult Immunization Task Force (AIFT) to create an implementation plan. Notably, this task force is composed of “vested interest” stakeholders and no consumer representation for those groups concerned with vaccine safety and informed consent.

NVIC has submitted our public comments and recommendations for the NVAC’s draft National Adult Immunization Plan. [2] Your opportunity to submit your comments and concerns about this plan has been extended to March 23rd. We encourage all of our readers to participate in the public comment process and submit comments to the NVAC on the NAIP. Please forward this article to family and friends and encourage them to submit public comments, too.

What you need to know – the nutshell

Healthy-People-2020

The basis of the NAIP rests on Healthy People 2020 Goals, [3] many of which are arbitrary. [4] The key fact the plan seems to lose sight of in using these goals as its foundation is …THEY ARE GOALS. These goals have no legal authority over your healthcare decisions and are being used by government officials to shape public health policy, which in turn is spurring legal mandates to force you to comply with them. [5]

The adult immunization plan also “incentivizes” doctors and other vaccine providers to convert patient data into Electronic Health Record (EHR) formats that can then be shared across state and federal electronic databases to track national vaccine coverage rates and also track and identify who is and is not vaccinated. Many states already have electronic vaccine tracking registries (Immunization Information Systems – IIS) in place, but do not share this information due to laws preventing the sharing of personal medical information and/or limited vaccination data on adults. This is where financial and other types of incentives come in to convince vaccine providers and state legislators to participate in the gathering of this private medical information on all adults.

Big Government is Partnering with Your Employer, Community & Religious Organizations

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The NAIP states that it will take more than providers raising awareness about the adult schedule and encouraging compliance to meet Healthy People 2020 goals. So the NAIP contains objectives that foster partnerships with your employer and your community and religious organizations to make you and all adults get every federally recommended vaccine according to the government-approved schedule.

The NAIP makes it clear that in the future, all American adults will be informed of the recommended adult schedule at every possible opportunity outside the healthcare provider domain. You will be encouraged to comply with the adult schedule not only by your healthcare provider, but also via community-based partnerships to ensure that you have the opportunity to roll up your sleeve at work, school, church and other community gatherings.

NVIC has always supported awareness and access to preventative healthcare options, including access to vaccines for everyone who wants to use them. However, there is a difference between awareness, access, recommendations and mandates. In the past, these types of government vaccine use plans do not just seek to increase awareness and access but also make recommendations that foster vaccine mandates without flexible medical, religious and conscientious belief exemptions that align with the informed consent ethic.

Tracking Vaccination Status Raises Privacy Concerns

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Adults should examine this plan carefully because the U.S. Constitution guarantees American citizens the right to privacy. [6] In that context, it is important to understand that the NAIP objectives include electronically harnessing your personal medical information and that of all adults for the purpose of increasing adult vaccine uptake in the U.S. by tracking your vaccination status, with little regard for your privacy. [7]

There is no language in the plan that provides for consumer privacy protections. This is a glaring omission given the acknowledged and known risks for patient data being hacked (security breaches) by malicious outside entities. [8] The plan does not include provisions for raising consumer awareness of their ability to opt out of electronic tracking and patient data sharing schemes. [9] [10]

Closing Vaccine Safety Research Gaps Not Included in Plan

While the NAIP also supports increased reporting to the federal Vaccine Adverse Event Reporting System (VAERS) and ongoing analysis of claims submitted to the federal Vaccine Injury Compensation Program (VICP), it is hollow support. For this to be meaningful, stronger language is needed to support closing vaccine safety research gaps highlighted by the Institute of Medicine’s (IOM) series of vaccine safety reports 11 to lessen the number of VICP off-the-table compensation claims.

These off-the-table claims are a direct result of the continued expansion of the numbers of government recommended adult (and childhood) vaccines without the accompanying identification of vaccine side effects and injury outcomes to expand the federal Vaccine Injury Table (VIT) that governs the awarding of vaccine injury compensation. Off-the-table adult vaccine injury claims now represent the majority of claims12 filed with the VICP and the compensation process has become highly adversarial and costly.

As NVIC President Barbara Loe Fisher stated at the U.S. Health Freedom Congress last year when pointing out that responses to vaccines and infectious diseases are individual:

We do not all respond the same way to infectious diseases [13] and we do not all respond the same way to pharmaceutical products like vaccines. [14] [15] [16] [17] Public health laws that fail to respect biodiversity and force everyone to be treated the same are unethical and dangerous.

The NAIP fails to acknowledge these facts.

Compliance at the Expense of Bodily Autonomy

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Vaccine mandates are made at a state level and the NAIP is a federal vaccine use promotion plan that is has no legal authority to turn government vaccine use recommendations into vaccine use mandates.

However, much like the recommendations made by NVAC a few years ago for healthcare workers to receive annual flu shots, [18] these recommendations are likely to result in future de facto vaccine mandates for adults, whether through employer requirements, [19] or actual state laws. Given the introduction of legislation [20] this year in many states to remove non-medical vaccine exemptions and restrict medical exemptions for school age children in an effort to force parents to comply with the CDC’s recommended childhood vaccine schedule, there is little doubt that that the NVAC’s latest plan will result in similar actions to force adults to use all federally recommended vaccines.

One only has to read stories posted NVIC’s Cry For Vaccine Freedom Wall by healthcare workers who have refused flu shots and are being fired from their jobs to understand the threat posed by the NAIP. Is your profession next? The short answer is yes.

Make no mistake about this plan’s intent, if “awareness” efforts and “incentivization” of vaccine policy do not increase adult vaccine uptake, the partnering with your employer and other community groups is meant to lower the hammer and force you to comply. The electronic tracking systems that are enthusiastically being embraced by not only the federal government but also state governments and employers, without regard for your privacy, will be used to identify noncompliers.

Informed Consent Freedom at Risk

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If you haven’t read Dr. Suzanne Humphries’ book Dissolving Illusions, [21] you may not realize that history is about to repeat itself. Government enforced vaccination through identification and door-to-door efforts to make everyone comply, like was seen with smallpox vaccination campaigns a century ago, is a real possibility again in America. Only this time it won’t just be about one vaccine – it will be about a lot of vaccines you will be forced to get.

The noose being tightened around the necks of our children is being thrown over the necks of adults as well. The tightening of that noose is growing daily in an attempt to strangle vaccine freedom of choice by eradicating the ethical principle of informed consent.

Adults and their children are being asked to accept a one-size-fits-all vaccine schedule that does not allow for the ability to delay or decline one or more vaccines for religious and conscientious beliefs. This is very dangerous when the medical exemption has been narrowed by government so that almost no health condition qualifies for a medical exemption anymore. Families already personally impacted by vaccine reactions, injuries and deaths will be faced with more loss, including their financial stability if they are forced to be revaccinated.

The human right to protect bodily integrity and autonomy – the core value of the informed consent ethic – is at stake.

This battle is not about an anti- or pro- vaccine position. It is a battle over freedom, values and beliefs. [22] What is at risk is your ability as a parent and individual to decide what medical risks you are willing to accept and vaccination is the forefront of this battle.

For over three decades NVIC has supported informed consent protections in all U.S. vaccine laws and policies, which means that parents and individuals must receive full and accurate information on vaccine risks and benefits and retain the right to make voluntary decisions to accept, delay or decline one or more vaccines without being sanctioned for they decision they make.

What You Can Do Today – Get Involved!

NVIC-People

Your rights are being eroded and vaccine exemptions are under aggressive attack in many states. NVIC will continue to advocate for your freedom as we have done for over 30 years, but this battle will not be won without your voice and action.

Submit your comments on the NAIP by March 23rd to the National Vaccine Advisory Committee and forward this article to your friends and family. (NVIC NOTE 3/20/15: We have become aware that the NVAC’s representative assigned to receive your comments email account is autoresponding that she is out of the office until the 25th. NVIC has contacted the National Vaccine Program Office and has been assured that comments sent by the 23rd are being collected and forwarded to the NVAC for their consideration. Please ignore the autoresponder – your comments are getting through and will be a part of the record. Many thanks to everyone for making us aware of this situation and for sending in comments on the NAIP! Keep sending in those comments!)

Most importantly, register and encourage others to register on NVIC’s Advocacy Portal today and join with other concerned Americans to protect informed consent rights. This resource is free and will keep you informed on legislative actions underway in your state, provide guidance on what action to take, and connect you with your legislators.

There is no time to waste. Please do not wait for someone else to do this…that someone is you and you can make a difference!

References

5 CDC. Vaccines and Immunizations. State Immunization Laws for Healthcare Workers and Patients. Nov. 19, 2014.
7 TEDxTraverseCity 2014. Designing Technology to Restore Privacy. Deborah C. Peel, MD.
9 Health information exchanges introduce patient consent questions. K. Terry. Medical Economics. Jul. 8, 2014
11 National Vaccine Advisory Committee – White Paper on U.S. Vaccine Safety System. Sep. 2011.
12 Report from the Department of Justice. Advisory Commission on Childhood Vaccines (ACCV) Certified Minutes. Pg 8. Sep. 2014.
13 Hill AVS. Genetics and Genomics of Infectious Disease Susceptibility. British Medical Bulletin 1999; 55(2): 401-413.
14 Kinman TG, Vandebriel RJ, Hoebee B. Genetic variation in the response to vaccination. Community Genet 2007; 10(4): 201-217.
15 Lemaire D, Barbosa T, Rihet P. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology. Braz J Med Biol Res 2012; 45(5): 376-385.
16 Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccinations: Evidence and Causality. Evaluating Biological Mechanisms of Adverse Events: Increased Susceptibility. Washington, DC: The National Academies Press 2012.
17 DHHS. Vaccine Injury Compensation Program Data and Statistics. HRSA Updated monthly.
18 University of Minnesota. NVAC approves recommendations on health worker flu vaccination. Lisa Schnirring. CIDRAP News & Perspective. Feb. 8, 2012.
19 NVIC. Forcing Flu Shots on Health Care Workers: Who Is Next?. NVIC eNewsletter. Barbara Loe Fisher. Sep. 29, 2010.
21 Humphries, S. MD. Bystrianyk, R. Dissolving Illusions: Disease, Vaccines, and the Forgotten History. Jul. 27 2013.
22 NVIC. The Vaccine Culture War in America: Are You Ready?. NVIC eNewsletter. Barbara Loe Fisher. Mar. 8, 2015
Tetanus Shot: How Do We Know That It Works?

Tetanus Shot: How Do We Know That It Works?

by Tetyana Obukhanych, PhD

Copyright © 2014 by Tetyana Obukhanych, Ph.D.

All rights reserved.  No part of this article may be reproduced or transmitted by any means, including graphic, electronic, or mechanical, without written permission from the author.

Disclaimer: Scientific information presented in this article is for educational purposes only and does not constitute medical advice on vaccination.

 
The cure for tetanus, a life-threatening and often deadly disease, has been sought from the very inception of the modern field of Immunology.  The original horse anti-serum treatment of tetanus was developed in the late 19th century and introduced into clinical practice at the time when a bio-statistical concept of a randomized placebo-controlled trial (RCT) did not yet exist.  The therapy was infamous for generating a serious adverse reaction called serum sicknessattributed to the intolerance of humans to horse-derived serum.  To make this tetanus therapy usable, it was imperative to substitute the animal origin of anti-serum with the human origin.  But injecting a lethal toxin into human volunteers as substitutes for horses would have been unthinkable.

A practical solution was found in 1924: pre-treating the tetanus toxin with formaldehyde (a fixative chemical) made the toxin lose its ability to cause clinical tetanus symptoms.  The formaldehyde-treated tetanus toxin is called the toxoid.  The tetanus toxoid can be injected into human volunteers to produce a commercial human therapeutic product from their sera called tetanus immunoglobulin (TIG), a modern substitute of the original horse anti-serum.  The tetanus toxoid has also become the vaccine against clinical tetanus.

The tetanus toxin, called tetanospasmin, is produced by numerous C. tetani bacterial strains.  C. tetani normally live in animal intestines, notably in horses, without causing tetanus to their intestinal carriers.  These bacteria require anaerobic (no oxygen) conditions to be active, whereas in the presence of oxygen they turn into resilient but inactive spores, which do not produce the toxin.  It has been recognized that inactive tetanus spores are ubiquitous in the soil. Tetanus can result from the exposure to C. tetani via poorly managed tetanus-prone wounds or cuts, but not from oral ingestion of tetanus spores.  Quite to the contrary, oral exposure to C. tetani has been found to build resistance to tetanus without carrying the risk of disease, as described in the section on Natural Resistance to Tetanus.

Once secreted by C. tetani germinating in a contaminated wound, tetanospasmin diffuses through the tissue’s interstitial fluids or bloodstream.  Upon reaching nerve endings, it is adsorbed by the cell membrane of neurons and transported through nerve trunks into the central nervous system, where it inhibits the release of a neurotransmitter gamma-aminobutyric acid (GABA).  This inhibition can result in various degrees of clinical tetanus symptoms: rigid muscular spasms, such as lockjaw, sardonic smile, and severe convulsions that frequently lead to bone fractures and death due to respiratory compromise.

Curative effects of the anti-serum therapy as well as the preventative effects of the tetanus vaccination are deemed to rely upon an antibody molecule called antitoxin.  But the assumption that such antitoxin was the sole “active” ingredient in the original horse anti-serum has not been borne out experimentally.  Since horses are natural carriers of tetanus spores, their bloodstream could have contained other unrecognized components, which got harnessed in the therapeutic anti-serum.  Natural Resistance to Tetanus discusses other serum entities detected in research animals carrying C. tetani, which better correlated with their protection from clinical tetanus than did serum antitoxin levels.  Nevertheless, the main research effort in the tetanus field remained narrowly focused on antitoxin.

Antitoxin molecules are thought to inactivate the corresponding toxin molecules by virtue of their toxin-binding capacity.  This implies that to accomplish its protective effect, antitoxin must come into close physical proximity with the toxin and combine with it in a way that would prevent or preempt the toxin from binding to nerve endings.  Early research on the properties of a newly discovered antitoxin was done in small-sized research animals, such as guinea pigs.  The tetanus toxin was pre-incubated in a test tube with the animal’s serum containing antitoxin before being injected into another (antitoxin-free) animal, susceptible to tetanus.  Such pre-incubation made the toxin lose its ability to cause tetanus in otherwise susceptible animals—i.e., the toxin was neutralized.

Nevertheless, researchers in the late 19th and early 20th centuries were baffled by a peculiar observation.  Research animals, whose serum contained enough antitoxin to inactivate a certain amount of the toxin in a test tube, would succumb to tetanus when they were injected with the same amount of the toxin. Furthermore, it was noted that the mode of the toxin injection had a different effect on the ability of serum antitoxin to protect the animal.  The presence of antitoxin in the serum of animals afforded some degree of protection against the toxin injected directly into the bloodstream (intravenously).  However, when the toxin was injected into the skin it would be as lethal to animals containing substantial levels of serum antitoxin as to animals virtually free of serum antitoxin.[1]

The observed difference in serum antitoxin’s protective “behavior” was attributed to the toxin’s propensity to bind faster to nerve cells than to serum antitoxin. The pre-incubation of the toxin with antitoxin in a test tube, or the injection of the toxin directly into the bloodstream, where serum antitoxin is found, gives antitoxin a head start in combining with and neutralizing the toxin.  However, a skin or muscle injection of the toxin does not give serum antitoxin such a head start.

Researchers in the 21st century have developed an advanced fluorescent labeling technique to track the uptake of the injected tetanus toxin into neurons. Using this technique, researchers examined the effect of serum antitoxin, which was induced by vaccinating mice with the tetanus toxoid vaccine ahead of time (the same one currently used in humans), on blocking the neuronal uptake and transport of the tetanus toxin fragment C (TTC) to the brain from the site of intramuscular injection.  Vaccinated and non-vaccinated animals showed similar levels of TTC uptake into the brain.  The authors of the study concluded that the “uptake of TTC by nerve terminals from an intramuscular depot is an avid and rapid process and is not blocked by vaccination.”[2] They have further commented that their results appear to be surprising in view of protective effects of immunization with the tetanus toxoid.  Indeed, the medical establishment holds a view that a tetanus shot prevents tetanus, but how do we know this view is correct?

Neonatal tetanus

Neonatal tetanus is common in tropical under-developed countries but is extremely rare in developed countries.  This form of tetanus results from unhygienic obstetric practices, when cutting the umbilical cord is performed with unsterilized devices, potentially contaminating it with tetanus spores.  Adhering to proper obstetric practices removes the risk of neonatal tetanus, but this has not been the standard of birth practices for some indigenous and rural people in the past or even present.

The authors of a neonatal tetanus study performed in the 1960s in New Guinea describe the typical conditions of childbirth among the locals:

The mother cuts the cord 1 inch (2.5 cm) or less from the abdominal wall; it is never tied.  In the past she would always use a sliver of sago bark, but now she uses a steel trade-knife or an old razor blade.  These are not cleaned or sterilized in any way and no dressing is put of the cord.  The child lies after birth on a dirty piece of soft bark, and the cut cord can easily become contaminated by dust from the floor of the hut or my mother’s feces expressed during childbirth, as well as by the knife and her finger.[3]

Not surprisingly, New Guinea had a high rate of neonatal tetanus.  Because improving birth practices seemed to be unachievable in places like New Guinea, subjecting pregnant women to tetanus vaccination was contemplated by public health authorities as a possible solution to neonatal tetanus.

A randomized controlled trial (RCT) assessing the effectiveness of the tetanus vaccine in preventing neonatal tetanus via maternal vaccination was conducted in the 1960s in rural Colombia in a community with high rates of neonatal tetanus.[4] The design of this trial has been recently reviewed by the Cochrane Collaboration for potential biases and limitations and, with minor comments, has been considered of good quality for the purposes of vaccine effectiveness (but not safety) determination.[5] The trial established that a single dose of the tetanus vaccine given before or during pregnancy had a partial effect on preventing neonatal tetanus in the offspring: 43% reduction was observed in the tetanus vaccine group compared to the control group, which instead of the tetanus shot received a flu shot.  A series of two or three tetanus booster shots, given six or more weeks apart before or during pregnancy, reduced neonatal tetanus by 98% in the tetanus vaccine group compared to the flu shot control group.  The duration of the follow up in this trial was less than five years.

In addition to testing the effects of vaccination, this study has also documented a clear relationship between the incidence of neonatal tetanus and the manner in which childbirth was conducted.  No babies delivered in a hospital, by a doctor or a nurse, contracted neonatal tetanus regardless of the mother’s vaccination status.  On the other hand, babies delivered at home by amateur midwives had the highest rate of neonatal tetanus.

Hygienic childbirth appears to be highly effective in preventing neonatal tetanus and makes tetanus vaccination regimen during pregnancy unnecessary for women who give birth under hygienic conditions.  Furthermore, it was estimated in 1989 in Tanzania that 40% of neonatal tetanus cases still occurred in infants born to mothers who were vaccinated during pregnancy,[6] stressing the importance of hygienic birth practices regardless of maternal vaccination status.

Tetanus in adults

Based on the protective effect of maternal vaccination in neonatal tetanus, demonstrated by an RCT and discussed above, we might be tempted to infer that the same vaccine also protects from tetanus acquired by stepping on rusty nails or incurring other tetanus-prone injuries, when administered to children or adults, either routinely or as an emergency measure.  However, due to potential biologic differences in how tetanus is acquired by newborns versus by older children or adults, we should be cautious about reaching such conclusions without first having direct evidence for the vaccine effectiveness in preventing non-neonatal tetanus.

It is generally assumed that the tetanus toxin must first leach into the blood (where it would be intercepted by antitoxin, if it is already there due to timely vaccination) before it reaches nerve endings.  This scenario is plausible in neonatal tetanus, as it appears that the umbilical cord does not have its own nerves.[7] On the other hand, the secretion of the toxin by C. tetani germinating in untended skin cuts or in muscle injuries is more relevant to how children or adults might succumb to tetanus.  In such cases, there could be nerve endings near germinating C. tetani, and the toxin could potentially reach such nerve endings without first going through the blood to be intercepted by vaccine-induced serum antitoxin.  This scenario is consistent with the outcomes of the early experiments in mice, discussed in the beginning.

Although a major disease in tropical under-developed countries, tetanus in the USA has been very rare.  In the past, tetanus occurred primarily in poor segments of the population in southern states and in Mexican migrants in California.  It was swiftly diminishing with each decade prior to the 1950s (in the pre-vaccination era), as inferred from tetanus mortality records and similar case-fatality ratios (about 67-70%) in the early 20th century[8] versus the mid-20thcentury).[9] The tetanus vaccine was introduced in the USA in 1947 without performing any placebo-controlled clinical trials in the segment of the population (children or adults), where it is now routinely used.

The rationale for introducing the tetanus vaccine into the U.S. population, at low overall risk for tetanus anyway, was simply based on its use in the U.S. military personnel during World War II.  According to a post-war report:[10]

a)    the U.S. military personnel received a series of three injections of the tetanus toxoid, routine stimulating injection was administered one year after the initial series, and an emergency stimulating dose was given on the incurrence of wounds, severe burns, or other injuries that might result in tetanus;

b)    throughout the entire WWII period, 12 cases of tetanus have been documented in the U.S. Army;

c)     in World War I there were 70 cases of tetanus among approximately half a million admissions for wounds and injuries, an incidence of 13.4 per 100,000 wounds.  In World War II there were almost three million admissions for wounds and injuries, with a tetanus case rate of 0.44 per 100,000 wounds.

The report leads us to conclude that vaccination has played a role in tetanus reduction in wounded U.S. soldiers during WWII compared to WWI, and that this reduction vouches for the tetanus vaccine effectiveness.  However, there are other factors (e.g. differences in wound care protocols, including the use of antibiotics, higher likelihood of wound contamination with horse manure rich in already active C. tetani in earlier wars, when horses were used by the cavalry,etc.), which should preclude us from uncritically assigning tetanus reduction during WWII to the effects of vaccination.

Severe and even deadly tetanus is known to occur in recently vaccinated people with high levels of serum antitoxin.[11] Although the skeptic might say that no vaccine is effective 100% of the time, the situation with the tetanus vaccine is quite different.  In these cases of vaccine-unpreventable tetanus, vaccination was actually very effective in inducing serum antitoxin, but serum antitoxin did not appear to have helped preventing tetanus in these unfortunate individuals.

The occurrence of tetanus despite the presence of antitoxin in the serum should have raised a red flag regarding the rationale of the tetanus vaccination program.  But such reports were invariably interpreted as an indication that higher than previously thought levels of serum antitoxin must be maintained to protect from tetanus, hence the need for more frequent, if not incessant, boosters.  Then how much higher “than previously thought” do serum levels of antitoxin need to be to ensure protection from tetanus?

Crone & Reder (1992) have documented a curious case of severe tetanus in a 29-year old man with no pre-existing conditions and no history of drug abuse, typical among modern-day tetanus victims in the USA.  In addition to the regular series of tetanus immunization and boosters ten years earlier during his military service, this patient had been hyper-immunized (immunized with the tetanus toxoid to have extremely high serum antitoxin) as a volunteer for the purposes of the commercial TIG production.  He was monitored for the levels of antitoxin in his serum and, as expected, developed extremely high levels of antitoxin after the hyper-immunization procedure.  Nevertheless, he incurred severe tetanus 51 days after the procedure despite clearly documented presence of serum antitoxin prior to the disease.  In fact, upon hospital admission for tetanus treatment his serum antitoxin levels measured about 2,500 times higher than the level deemed protective.  His tetanus was severe and required more than five weeks of hospitalization with life-saving measures.  This case demonstrated that serum antitoxin has failed to prevent severe tetanus even in the amounts 2,500 times higher than what is considered sufficient for tetanus prevention in adults.

The medical establishment chooses to turn a blind eye to the lack of solid scientific evidence to substantiate our faith in the tetanus shot.  It also chooses to ignore the available experimental and clinical evidence that contradicts the assumed but unproven ability of vaccine-induced serum antitoxin to reduce the risk of tetanus in anyone other than maternally-vaccinated neonates, who do not even need this vaccination measure when their umbilical cords are dealt with using sterile techniques.

Ascorbic acid in tetanus treatment

Anti-serum is not the only therapeutic measure tried in tetanus treatment.  Ascorbic acid (Vitamin C) has also been tried.  Early research on ascorbic acid has demonstrated that it too could neutralize the tetanus toxin.[12]

In a clinical study of tetanus treatment conducted in Bangladesh in 1984, the administration of conventional procedures, including the anti-tetanus serum, to patients who contracted tetanus left 74% of them dead in the 1-12 age group and 68% dead in the 13-30 age group.  In contrast, daily co-administration of one gram of ascorbic acid intravenously had cut down this high mortality to 0% in the 1-12 age group, and to 37% in the 13-30 age group.[13] The older patients were treated with the same amount of ascorbic acid without adjustments for their body weight.

Although this was a controlled clinical trial, it is not clear from the description of the trial in the publication by Jahan et al. whether or not the assignment of patients into the ascorbic acid treatment group versus the placebo-control group was randomized and blinded, which are crucial bio-statistical requirements for avoiding various biases.  A more definitive study is deemed necessary before intravenous ascorbic acid can be recommended as the standard of care in tetanus treatment.[14] It is odd that no properly documented RCT on ascorbic acid in tetanus treatment has been attempted since 1984 for the benefit of developing countries, where tetanus has been one of the major deadly diseases.  This is in stark contrast to the millions of philanthropic dollars being poured into sponsoring the tetanus vaccine implementation in the Third world.

Natural resistance to tetanus

In the early 20th century, investigators Drs. Carl Tenbroeck and Johannes Bauer pursued a line of laboratory research, which was much closer to addressing natural resistance to tetanus than the typical laboratory research on antitoxin in their days.  Omitted from immunologic textbooks and the history of immunologic research, their tetanus protection experiments in guinea pigs, together with relevant serological and bacteriological data in humans, nevertheless provide a good explanation for tetanus being a rather rare disease in many countries around the world, except under the conditions of past wars.

In the experience of these tetanus researchers, the injection of dormant tetanus spores could never by itself induce tetanus in research animals.  To induce tetanus experimentally by means of tetanus spores (as opposed to by injecting a ready-made toxin, which never happens under natural circumstances anyway), spores had to be premixed with irritating substances that could prevent rapid healing of the site of spore injection, thereby creating conditions conducive to spore germination.  In the past, researchers used wood splinters, saponin, calcium chloride, or aleuronat (flour made with aleurone) to accomplish this task.

In 1926, already being aware that oral exposure to tetanus spores does not lead to clinical tetanus, Drs. Tenbroeck and Bauer set out to determine whether feeding research animals with tetanus spores could provide protection from tetanus induced by an appropriate laboratory method of spore injection.  In their experiment, several groups of guinea pigs were given food containing distinct strains of C. tetani.  A separate group of animals were used as controls—their diet was free of any C. tetani.  After six months, all groups were injected under the skin with spores premixed with aleuronat.  The groups that were previously exposed to spores orally did not develop any symptoms of tetanus upon such tetanus-prone spore injection, whereas the control group did.  The observed protection was strain-specific, as animals still got tetanus if injected with spores from a mismatched strain—a strain they were not fed with.  But when fed multiple strains, they developed protection from all of them.

Quite striking, the protection from tetanus established via spore feeding did not have anything to do with the levels of antitoxin in the serum of these animals. Instead, the protection correlated with the presence of another type of antibody called agglutinin—so named due to its ability to agglutinate (clump together) C. tetani spores in a test tube.  Just like the observed protection was strain-specific, agglutinins were also strain-specific.  These data are consistent with the role of strain-specific agglutinins, not of antitoxin, in natural protection from tetanus.  The mechanism thereby strain-specific agglutinins have caused, or correlated with, tetanus protection in these animals has remained unexplored.

In the spore-feeding experiment, it was still possible to induce tetanus by overwhelming this natural protection in research animals.  But to accomplish this task, a rather brute force procedure was required.  A large number of purified C. tetani spores were sealed in a glass capsule; the capsule was injected under the skin of research animals and then crushed.  Broken glass pieces were purposefully left under the skin of the poor creatures so that the gory mess was prevented from healing for a long time.  Researchers could succeed in overwhelming natural tetanus defenses with this excessively harsh method, perhaps mimicking a scenario of untended war-inflicted wounds.

How do these experimental data in research animals relate to humans?  In the early 20th century, not only animals but also humans were found to be intestinal carriers of C. tetani without developing tetanus.  About 33% of tested human subjects living around Beijing, China were found to be C. tetani carriers without any prior or current history of tetanus disease.[15] Bauer & Meyer (1926) cite other studies, which have reported around 25% of tested humans being healthy C. tetani carriers in other regions of China, 40% in Germany, 16% in England, and on average 25% in the USA, highest in central California and lowest on the southern coast.  Based on the California study, age, gender, or occupation denoting the proximity to horses did not appear to play a role in the distribution of human C. tetani carriers.

Another study was performed back in the 1920s in San Francisco, CA.[16] About 80% of the examined subjects had various levels of agglutinins to as many as five C. tetani strains at a time, although no antitoxin could be detected in the serum of these subjects.  C. tetani organisms could not be identified in the stool of these subjects either.  It is likely that tetanus spores were in their gut transiently in the past, leaving serological evidence of oral exposure, without germinating into toxin-producing organisms.  It would be important to know the extent of naturally acquired C. tetani spore agglutinins in humans in various parts of the world now, instead of relying on the old data, but similar studies are not likely to be performed anymore.

Regrettably, further research on naturally acquired agglutinins and on exactly how they are involved in the protection from clinical tetanus appears to have been abandoned in favor of more lucrative research on antitoxin and vaccines.  If such research continued, it would have given us clear understanding of natural tetanus defenses we may already have by virtue of our oral exposure to ubiquitous inactive C. tetani spores.

Since the extent of our natural resistance to clinical tetanus is unknown due to the lack of modern studies, all we can be certain of is that preventing dormant tetanus spores from germinating into toxin-producing microorganisms is an extremely important measure in the management of potentially contaminated skin cuts and wounds.  If this crucial stage of control—at the level of preventing spore germination—is missed and the toxin production ensues, the toxin must be neutralized before it manages to reach nerve endings.

Both antitoxin and ascorbic acid exhibit toxin-neutralizing properties in a test tube.  In the body, however, vaccine-induced antitoxin is located in the blood, whereas the toxin might be focally produced in the skin or muscle injury.  This creates an obvious physical impediment for toxin neutralization to happen effectively, if at all, by means of vaccine-induced serum antitoxin.  Furthermore, no placebo-controlled trials have ever been performed to rule out the concern about such an impediment by providing clear empirical evidence for the effectiveness of tetanus shots in children and adults.  Nevertheless, the medical establishment relies upon induction of serum antitoxin and withholds ascorbic acid in tetanus prevention and treatment.

When an old medical procedure of unknown effectiveness, such as the tetanus shot, has been the standard of medical care for a long time, finalizing its effectiveness via a modern rigorous placebo-controlled trial is deemed unethical in human research.  Therefore, our only hope for the advancement of tetanus care is that further investigation of the ascorbic acid therapy is performed and that this therapy becomes available to tetanus patients around the world, if confirmed effective by rigorous bio-statistical standards.

Until then, may the blind faith in the tetanus shot help us!


[1] Tenbroeck, C. & Bauer, J.H. The immunity produced by the growth of tetanus bacilli in the digestive tract. J Exp Med 43, 361-377 (1926).

[2] Fishman, P.S., Matthews, C.C., Parks, D.A., Box, M. & Fairweather, N.F. Immunization does not interfere with uptake and transport by motor neurons of the binding fragment of tetanus toxin. J Neurosci Res 83, 1540-1543 (2006).

[3] Schofield, F.D., Tucker, V.M. & Westbrook, G.R. Neonatal tetanus in New Guinea. Effect of active immunization in pregnancy. Br Med J 2, 785-789 (1961).

[4] Newell, K.W., Dueñas Lehmann, A., LeBlanc, D.R. & Garces Osorio, N. The use of toxoid for the prevention of tetanus neonatorum. Final report of a double-blind controlled field trial. Bull World Health Organ 35, 863-871 (1966).

[5] Demicheli, V., Barale, A. & Rivetti, A. Vaccines for women to prevent neonatal tetanus. Cochrane Database Syst Rev 5:CD002959 (2013).

[6] Maselle, S.Y., Matre, R., Mbise, R. & Hofstad, T. Neonatal tetanus despite protective serum antitoxin concentration. FEMS Microbiol Immunol 3, 171-175 (1991).

[7] Fox, S.B. & Khong, T.Y. Lack of innervation of human umbilical cord. An immunohistological and histochemical study. Placenta 11, 59-62 (1990).

[8] Bauer, J.H. & Meyer, K.F. Human intestinal carriers of tetanus spores in California J Infect Dis 38, 295-305 (1926).

[9] LaForce, F.M., Young, L.S. & Bennett, J.V. Tetanus in the United States (1965-1966): epidemiologic and clinical features. N Engl J Med 280, 569-574 (1969).

[10] Editorial: Tetanus in the United States Army in World War II. N Engl J Med 237, 411-413 (1947).

[11] Abrahamian, F.M., Pollack, C.V., Jr., LoVecchio, F., Nanda, R. & Carlson, R.W. Fatal tetanus in a drug abuser with “protective” antitetanus antibodies. J Emerg Med 18, 189-193 (2000).

Beltran, A. et al. A case of clinical tetanus in a patient with protective antitetanus antibody level. South Med J 100, 83 (2007).

Berger, S.A., Cherubin, C.E., Nelson, S. & Levine, L. Tetanus despite preexisting antitetanus antibody. JAMA 240, 769-770 (1978).

Crone, N.E. & Reder, A.T. Severe tetanus in immunized patients with high anti-tetanus titers. Neurology 42, 761-764 (1992).

Passen, E.L. & Andersen, B.R. Clinical tetanus despite a protective level of toxin-neutralizing antibody. JAMA 255, 1171-1173 (1986).

Pryor, T., Onarecker, C. & Coniglione, T. Elevated antitoxin titers in a man with generalized tetanus. J Fam Pract 44, 299-303 (1997).

[12] Jungeblut, C.W. Inactivation of tetanus toxin by crystalline vitamin C (L-ascorbic acid). J Immunol 33, 203-214 (1937).

[13] Jahan, K., Ahmad, K. & Ali, M.A. Effect of ascorbic acid in the treatment of tetanus. Bangladesh Med Res Counc Bull 10, 24-28 (1984).

[14] Hemilä, H. & Koivula, T. Vitamin C for preventing and treating tetanus. Cochrane Database Syst Rev 2:CD006665 (2008).

[15] Tenbroeck, C. & Bauer, J.H. The tetanus bacillus as an intestinal saprophyte in man. J Exp Med 36, 261-271 (1922).

[16] Coleman, G.E. & Meyer, K.F. Study of tetanus agglutinins and antitoxin in human serums. J Infect Dis 39, 332-336 (1926).


naturalimmunityfundamentals.com

WHO Puts Kenyan Tetanus Vaccine Under Police Guard to Avoid Testing

WHO Puts Kenyan Tetanus Vaccine Under Police Guard to Avoid Testing

Originally published at The Liberty Beacon

If the allegations are true, this is one of the biggest stories of our time. Did the WHO try to sterilize Kenyan women of reproductive age by slipping into tetanus vaccines a hormone with anti-fertility effects and then try to cover it up? 

It has been known for many years that the World Health Organization is one of the most unethical organizations on the planet. They have been committing crimes against humanity for decades. What I am going to describe to you now is, in my opinion, one of their most heinous acts to date.

I am going to demonstrate through evidence, given to The Liberty Beacon in an interview, just how far this organization is prepared to go to cover up the truth, mislead the public and cause deliberate harm to millions of vulnerable girls and women in the developing world.

Brief Background

In October 2014, reports from the Kenyan Catholic Doctors Association sent shock waves around the world. The reports stated that 2-3 million girls and women of childbearing age in Kenya had been vaccinated with tetanus vaccinations containing the anti-fertility hormone HCG, rendering them infertile.

This information was discovered after the vaccines being used in the campaign were sent for testing and came back positive for containing the hormone.

To find out more please read: Catholic Doctors Speak: Tetanus vaccination campaign is all about population control‏

WHO Put Tetanus Vaccinations Under Police Guard To Avoid Testing

Interested to learn the truth about how the Kenyan Catholic Doctors Association became suspicious and what they discovered, I decided to contact obstetrician and gynaecologist Dr. Wahome Ngare.

Ngare

Dr. Ngare is a member of the Kenya Catholic Doctors Association and the Kenya Christian Professionals Forum. He was one of the six representatives of the Catholic Church in the joint committee of experts drawn from the Catholic Church and Ministry of Health appointed to test the tetanus vaccine in Kenya.

On behalf of The Liberty Beacon Project, I asked Dr. Ngare a series of questions. His answers, along with documented evidence that he has supplied, tell of a barbaric series of events that prove just how corrupt the WHO really are.

Note: I have highlighted certain sections of Dr. Ngare’s replies that I believe are of extreme importance.

I asked:

“What made the Kenyan Catholic Doctors Association suspicious that the tetanus vaccines contained the anti-fertility hormone, HCG?”

Dr. Ngare replied:

“The Catholic Church as the name suggests has a foot print worldwide. When WHO conducted its first purported neonatal tetanus eradication vaccination campaigns in South America using a fertility regulating vaccine, the population most affected were Catholics. The Church has a strong institutional memory.

In 1995, WHO come to Kenya through the ministry of health and offered to run a similar campaign. On the backdrop of what had happened in South America and the fact that the campaigns details were identical,

the Catholic Church in Kenya requested the ministry of health to have the vaccine tested before it was administered. The ministry of health agreed with the Church and ordered for the vaccine to be tested before administration. WHO opted to withdraw the vaccine and cancel the campaign instead of submitting it for testing!

In March 2014, we heard of a neonatal tetanus campaign that was started in October the year before. All major health campaigns are usually widely advertised and launched with much pomp and color in public. This particular campaign was very secretive and a majority of Kenyans, including health personnel do not know about it even today! This is what is causing the confusion when the Church states that the tetanus injection used in the vaccination campaign is unsafe but the routine vaccine is safe!

The bacterium that caused tetanus is found in soil. Multiple doses (4-5) of tetanus vaccination confers immunity for a maximum of 10 years after which a booster is needed to maintain immunity. [Note: the efficacy of the tetanus vaccine has been called into question].  Therefore, the only rational way of eradicating neonatal tetanus would be to ensure all pregnant women are given a minimum of two tetanus injections during the pregnancy. This protects the new born child for the first 6 weeks of life before they can be given DPT. A campaign that aims at random women aged 15 – 49, regardless of whether they are pregnant or no, run in only some areas of the county would not eradicate neonatal tetanus!!

However, if the aim was to cause irreversible infertility and one used a fertility regulating vaccine disguised as a tetanus vaccine and claimed to be eradicating neonatal tetanus, one would be spot on!

Given the forgoing, when it become clear the ministry of health was going to have a second round of immunization campaigns in March 2014, the Catholic Church meet with the minister of health and the director of medical services and requested for testing of the vaccine – just as it had done in 1995. The minister of health declined to have the vaccine tested to the shock of the church.

Reports from the field during the actual immunization exercise indicated that there was a special batch of vaccines that was under police guard that was not left under the custody of the vaccination center. This particular vaccine was highly controlled with those nurses administering it required to return each empty vials in exchange for a fresh vial. Further, at the end of the vaccination exercise, this particular batch was ferried away from the vaccination center back to Nairobi. Usually, the extra vaccines after an immunization campaign are left at the participating centers and are used for routine immunization. Why was this batch treated so special?

Given the forgoing, the Catholic Church acquired a single vial from the field, during the March vaccination campaign and tested it for HCG using the Elisa methodology and it tested positive.

In October 2014, the government launched a third immunization camping and again refused the request of the Catholic Church to have the vaccine tested.”

If Dr. Ngare is correct, and there is no reason to disbelieve this honorable doctor, then this proves just how far the WHO is prepared to go in order to cover up the truth and avoid detection. We need to ask ourselves why the WHO would need to put this particular batch of vaccines under police guard, if they had nothing at all to hide, and why they were so opposed to having these vaccines tested.

Shocked and sickened by his answer, I asked:

When the Catholic Doctors Association sent the vaccinations for testing, what did you discover?

Dr. Ngare replied:

“We used the Elisa method to test the vaccines and found them to be positive of HCG. However, the Elisa testing machines were calibrated for testing blood samples and not vaccines. For this reason, the results were disputed by the government. The Kenyan parliament then ordered the Church and Ministry of Health to form a joint committee of experts to re-test this vaccines presented by the Church. I was a member of that committee and we were advised to use high performance liquid chromatography (HPLC) as it was the gold standard in vaccine testing. Even with this method, 3 of the 9 vials collected during the actual vaccination campaigns tested positive for HCG. This conclusively proved that the vaccine used in the March and October 2014 purported tetanus eradication campaigns were actually disguised fertility regulating vaccine and not the ordinarily tetanus vaccine.

This was administered to Kenyan women aged 15 – 49 years without their consent and has the potential of causing irreversible infertility. This is unethical and pure evil”.

Note: Elisa method – Enzyme-linked immunosorbent assay (ELISA), also known as an enzyme immunoassay (EIA), is a biochemical technique used mainly in immunology to detect the presence of an antibody or an antigen in a sample. What is ELISA? Enzyme-linked immunosorbent assay

Dr. Ngare is correct; their actions were both unethical and pure evil, which took me to my next question. I asked him why he believed that the WHO would do such a thing?

He replied:

“WHO and other UN organizations together with eugenic organizations like the IPPF have had a population control agenda aimed at the lower developed countries (LDC) for a long time. Refer to the link below for a document called the NSSM 200 that will help understand more. National Security Study Memorandum 200 (NSSM 200) – April 1974. This is a de-classified secret service document.”

Sure enough, on reading the information supplied by Dr, Ngare, I learned these organizations had been studying ways to lower the population in what they called the “Lower Developed Countries” or LDCs, for decades.

The LDCs targeted in their 1975 document were:

“India, Bangladesh, Pakistan, Nigeria, Mexico, Indonesia, Brazil, The Philippines, Thailand, Egypt, Turkey, Ethiopia, and Colombia.”

I asked Dr. Ngare, How many women in Kenya alone would be have been affected, if the WHO had succeeded with their plans?

“This campaign was run in 16 out of 47 counties in the country. The ministry of health had targeted 2.4 million women in this campaign. Kenya has about 40 million people with the ratio of men to women being roughly 50/50. In other words, 20 million would be girls or women. A target of 2.4 million women works out to about 12% of all girls and women in Kenya in just one campaign!”

I asked him whether or not he had any final comments that he would like to portray to the public.

Dr. Ngare replied:

“1. The reputation of WHO has been called to question many times in the past but there is always inconclusive evidence and a great deal of media sensitization of information that they get away Scot free. The Catholic Church in Kenya has offered the world irrefutable evidence in this case of the Kenyan tetanus eradication campaign demonstrating clearly the forceful but secretive sterilization of a community. How much more damage and proof will the world demand before action is taken?

2. This is not an African problem; this is not a racial problem. It is a problem of good versus evil. Passivity allows evil to thrive and ever flourish. It is time individuals who stand for what is good understood that the only way to defeat evil is to confront it head on and took action in their area of direct influence e.g. at home, the work place and their local communities.

3. This chance must not be squandered. The Catholic Church in Kenya has done its part and will continue to be vigilant. However, we appeal to the people and private organizations of good will from all across the world to come together and supported the Catholic Church in Kenya to fight the excesses of this organization.”

Dr. Ngare is absolutely correct; this is a problem of good versus evil and we should ask ourselves whether or not the WHO has the right to forcibly sterilize millions of women and children without their consent?

Dr. Ngare kindly supplied The Liberty Beacon with a statement from the Kenyan Conference of Catholic Bishops Catholic Health Commission of Kenya, signed by Rt. Rev. Paul Kariuki Njiru.

The statement, written to the people of Kenya outlines the true horrors of what had taken place in chronological order.

The Kenyan Conference of Catholic Bishops ended their statement with these words:

“Both the Ministry of Health and WHO/UNICEF were trusted by the people of Kenya, they have broken this trust and betrayed those who depended on them.

No further vaccination campaigns should be undertaken in this country without an all-inclusive sampling and testing exercise done before, during and after the campaign.”

PDF of Statement

The Liberty Beacon Responds

Outraged by the atrocities outlined in this interview, The Liberty Beacon has promised to assist the Catholic Church of Kenya in any way possible to expose the truth and bring the perpetrators to justice.

Dr. Ngare has agreed to speak to The Liberty Beacon Network, on radio, in an hour long broadcast with myself and Mr. Roger Landry, in a bid to inform the world of the truth and ask for their assistance in this matter.

If you care about human dignity and the people of Kenya and wish to support us in our fight, then please listen to our show.

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

TLB: With the steady increase in infertility in the USA … and America being the most vaccinated society on this planet, has anybody even thought to look at these vaccines for HCG … ???

So we told you the World Health Organization and UNICEF is intentionally sterilizing women of child bearing age in the developing world?

We also told you this has been going on for several decades (or longer), unseen and unchecked and possibly affecting as many as 100,000,000 women in the developing world so far.

You MAY believe us … or not.

But what if TLB could provide proof from one of the very team responsible for the discovery of this evil … Straight from the horses mouth TLB presents a must hear conversation with Dr. Ngare

Please understand the following discussion took place between three countries, USA (TLB), England (Christina England) and Kenya (Dr. Ngare), all many thousands of miles apart, so the sound quality is not perfect, but the message and information is PAINFULLY CLEAR !!!

Please listen …

TLB radio

(click image to hear show)


Article copied from GreenMedInfo.com

Note: While I personally have issues with the Catholic Church (pedophilia to name one), I put this article here because of the first hand account of events. It is not surprising to me that the WHO would have a population control agenda. I will attempt to find some proof of that for you and post it here along with anything else I can find about vaccines, adverse reactions, population control, etc… It’s time we learned the full truth of what’s going on and what’s being done to us and to our children. 

Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel

Pertussis1

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Isaac Srugo*Comments to Author , Daniel Benilevi*, Ralph Madeb*, Sara Shapiro†, Tamy Shohat‡, Eli Somekh§, Yossi Rimmar*, Vladimir Gershtein†, Rosa Gershtein*, Esther Marva¶, and Nitza Lahat†
Author affiliations: *Department of Clinical Microbiology, Bnai Zion Medical Center, Haifa, Israel; †Serology Laboratory, Carmel Medical Center, Haifa, Israel; ‡Israel Center for Disease Control, Tel Aviv, Israel; §Wolfson Medical Center, Tel Aviv, Israel; ¶Public Health Laboratories, Jerusalem, Israel

Suggested citation for this article

Abstract

We tested 46 fully vaccinated children in two day-care centers in Israel who were exposed to a fatal case of pertussis infection. Only two of five children who tested positive for Bordetella pertussis met the World Health Organization’s case definition for pertussis. Vaccinated children may be asymptomatic reservoirs for infection.

Pertussis, an acute disease of the upper respiratory tract caused by the gram-negative bacillus Bordetella pertussis, lasts 6 to 8 weeks and has three clinical stages. The initial (catarrhal) stage resembles a common cold with a mild cough. The second (paroxysmal) stage is characterized by episodes of repetitive coughing during a single expiration, followed by a sudden inspiration that generates the typical “whoop.” The final (convalescent) stage, which lasts 1 to 2 weeks, marks a decrease in the severity and frequency of the cough.

Since the introduction of routine childhood vaccine, pertussis has been considered preventable, and pertussis-associated illness and deaths are uncommon (2). However, vaccine-induced immunity wanes after 5 to 10 years, making the vaccinated host vulnerable to infection (3). This susceptibility has been described in outbreaks of pertussis infection in highly vaccinated populations (36).

A recent study by Yaari et al. showed that infection in a vaccinated person causes milder, nonspecific disease, without the three classical clinical stages(7). Whooping cough is seen in only 6% of such cases; instead, the illness is characterized by a nonspecific, prolonged cough, lasting several weeks to months. Because of these atypical symptoms, pertussis infection is underdiagnosed in adults and adolescents, who may be reservoirs for infection of unvaccinated infants (810). In a study in France, up to 80% of infections in unvaccinated children were acquired from siblings and parents, suggesting that adults and even young siblings play a fundamental role in the transmission of pertussis (11).

We demonstrated B. pertussis infection in fully vaccinated children ages 2-3 years and 5-6 years who had contact with an infected child. We investigated whether younger or recently vaccinated children may be protected from classical clinical illness but remain susceptible to infection and become asymptomatic carriers.

The Study

We examined the family of a 4-month-old infant who died of pertussis in Israel, as well as children at two day-care centers that two siblings had attended during the infant’s illness. The two siblings, ages 2 and 5 years, attended different day-care centers, for ages 2-3 years and 5-6 years, respectively. Both siblings continued to attend the centers despite paroxysmal cough for 4 to 5 weeks. Thirty other children attended the day-care center for the 2- to 3-year-old group. Sixteen other children attended the center for the 5- to 6-year-old group.

Thumbnail of Timeline of pertussis infection in children in two day-care centers, IsraelFigure. Timeline of pertussis infection in children in two day-care centers, Israel

In the infant’s family, a third sibling, age 11 years, also had a paroxysmal cough of 4 to 5 weeks duration. The 35-year-old mother had a 3-month history of persistent cough. An 18-year-old aunt, who took care of the infant and lived in the same house, reported a mild respiratory illness without paroxysmal cough. None of the family members had a whooping episode, cyanosis, or pneumonia (Figure).

All the children in the day-care centers had been immunized in infancy with all four doses of Pasteur diphtheria-tetanus toxoid pertussis (DTP) vaccine, which includes a booster dose at 12 months of age. The Pasteur vaccine contains 1 immunization dose (ID) of purified diphtheria toxoid, 1 ID of purified tetanus toxoid, and >4 IU of B. pertussis. All family members of the infant were also fully vaccinated with four doses of DTP. The infant had received only the first dose of vaccine at 2 months of age.

The five family members of the infant and the 46 children in the two day-care centers were tested for B. pertussis. Two nasopharyngeal specimens were taken with Dacron swabs (Medical Wire, MEDECO, Corsham, UK); one specimen was used for culture and the other for polymerase chain reaction (PCR) testing. The culture specimen was immediately spread on charcoal agar plates (Hy Labs, Rehovot, Israel), which were incubated at 37°C for 14 days. Serum samples were also taken from every study participant for specific testing for immunoglobulin (Ig) M, IgA, and IgG antibodies to B. pertussis by an enzyme immunoassay (EIA) with whole-cell antigens (Panbio, East Brisbane, Australia) (12). Primers for the repeated insertion sequences were used in a semi-nested PCR assay (1314). The upstream primer sequence gATTCAATAggTTgTATgCATggTT and downstream primer AATTgCTggACCAT TCgAgTCgACG were used in the first PCR, which included 5 µL sample DNA, reaction buffer (10 mM Tris-HCl, 50 mM KCl, 1.5 mM MgCl2, 0.1% Triton X-100), 1 µM of each primer, 200 µM deoxynucleotide triphosphate, and 1 U Taq polymerase (Boehringer Mannheim, Germany) in a 25-µL volume (14). Statistical analysis was performed by the two-tailed Fischer’s exact test.

A person with positive PCR results was considered to have B. pertussis colonization of the nasopharynx. A person with positive IgM serum antibodies was considered to have had a recent infection. There were no culture-positive results, and nasopharyngeal aspirates were not available from the infant. Positivity by PCR or IgM did not indicate presence of symptoms.

Information on clinical symptoms was obtained from each person by a detailed questionnaire. The children in the day-care centers were followed clinically for 8 weeks after laboratory testing. All family members had been treated with erythromycin before testing, but no antibiotics were administered to the children in the day-care centers.

Eleven percent of the children in the two day-care centers were PCR positive, indicating nasopharyngeal colonization: 4 (25%) of the 16 5- to 6-year-old and 1 (3%) of the 30 2- to 3-year-old children (p <.05). Nine (55%) 5- to 6-year-old children were positive for serum IgM antibodies, and 4 (25%) were IgA positive. Three (10%) of the 2- to 3-year-old children were IgM positive, and 1 (3%) had IgA antibodies. Nasopharyngeal colonization was found more frequently in the 5- to 6-year-old than in the 2- to 3-year-old children (4/16 vs. 1/30, p <.05). This trend was also constant with IgM and IgA serum antibodies (9/16 vs. 3/30, p <.001 and 4/16 vs. 0/30, p <.01, respectively). In the index family, four of five members were positive by PCR, including all three siblings of the infant and the 18-year-old aunt. The 35-year-old mother, who was treated with erythromycin before testing, was negative by PCR. All five family members, including the mother, had high levels of IgM antibodies, indicating recent infection. The 4-month-old infant was seronegative for all subclasses of Ig antibodies to B. pertussis. No cultures were grown from the three groups.

According to a modified World Health Organization (WHO) case definition, two (11%) of the five children colonized with B. pertussis in the two day-care centers had the typical course of pertussis infection, with 3 weeks of paroxysmal cough (Table) (1). The other three children who were positive by PCR had only a mild, nonspecific cough during follow-up.

Conclusions

The effects of whole-cell pertussis vaccine wane after 5 to 10 years, and infection in a vaccinated person causes nonspecific symptoms (37). Vaccinated adolescents and adults may serve as reservoirs for silent infection and become potential transmitters to unprotected infants (311). The whole-cell vaccine for pertussis is protective only against clinical disease, not against infection (1517). Therefore, even young, recently vaccinated children may serve as reservoirs and potential transmitters of infection.

We used PCR, EIA, and culture to confirm B. pertussis infection in two highly vaccinated groups of children in two day-care centers. Three (10%) of 30 2- to 3-year-old children were seropositive for recent infection; one had nasopharyngeal colonization and a clinical illness that met the modified WHO case definition. In the day-care center for the 5- to 6-year-old group, 9 (55%) of 16 children were IgM positive, 4 (25%) of whom had nasopharyngeal colonization. Of these four children, three had nonspecific cough, and only one met the modified WHO definition for pertussis. None of the children in our study, including those who met the WHO definition, had been examined by a physician before our investigation.

Children who were seropositive and remained both asymptomatic and PCR negative probably had sufficient immunity from vaccines or natural boosters to protect them against persistent colonization and clinical disease. Their seropositivity could not be due to vaccine because the children were tested more than a year after having been vaccinated. Yet not all the children were protected from infection and from colonization with the bacteria. Whether a child who is serologically or PCR positive for pertussis and is clinically asymptomatic is a potential transmitter of infection has not been established. What is certain, however, is that vaccine-induced immunity against infection does not persist throughout adulthood. In France, booster vaccinations have been recommended for adolescents and teenagers (18). We found that immunity does not even persist into early childhood in some cases. We also observed that DPT vaccine does not fully protect children against the level of clinical disease defined by WHO. Our results indicate that children ages 5-6 years and possibly younger, ages 2-3 years, play a role as silent reservoirs in the transmission of pertussis in the community. More studies are needed to find the immunologic basis of protection against infection and colonization and thus an effective way to eradicate pertussis.

Dr. Srugo is a senior lecturer and director of the Clinical Microbiology and Pediatric Infectious Disease unit at the Bnai Zion Medical Center, Haifa, Israel.

References

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  4. Christie CD, Marx ML, Marchant CD, Reising SF. The 1993 epidemic of pertussis in Cincinnati: resurgence of disease in a highly immunized population of children. N Engl J Med. 1994;331:1621. DOIPubMed

  5. Rosenthal S, Strebel P, Cassiday P, Sanden G, Brusuelas K, Wharton M. Pertussis infection in young adults during the 1993 outbreak in Chicago. J Infect Dis. 1995;171:16502.PubMed

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  14. Lichtinghagen R, Diedrich-Glaubitz R, von Horsten B. Identification of Bordetella pertussis in nasopharyngeal swabs using a polymerase chain reaction: evaluation of detection methods. Eur J Clin Chem Clin Biochem. 1994;32:1617.PubMed

  15. Fine PEM, Clarkson JA. The recurrence of whooping cough: possible implications for assessment of vaccine efficacy. Lancet. 1982;l:6669.DOIPubMed

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  17. Minh NNTM, He Q, Edelman K, Olander RM, Viljanen MK, Arvilommi H, Cell-mediated immune response to antigens of Bordetella pertussis and protection against pertussis in schoolchildren. Pediatr Infect Dis J. 1999;18:36670. DOIPubMed

  18. Grimprel E, Baron S, Levy-Bruhl D, Garnier JM, N’jamkepo E, Guiso N, Influence of vaccination coverage on pertussis transmission in France.Lancet. 1999;354:1699700. DOIPubMed

Figure

Table

Suggested citation: Srugo I, Benilevi D, Madeb R, Shaprio S, Shohat T, Somekh E, et al. Pertussis Infection in Fully Vaccinated Children in Day-Care Centers, Israel. Emerg Infect Dis [serial on the Internet]. 2000, Oct [date cited]. Available from http://wwwnc.cdc.gov/eid/article/6/5/00-0512

DOI: 10.3201/eid0605.000512

Table of Contents – Volume 6, Number 5—October 2000

Article copied from CDC.GOV