I am a scientist specialized in mitochondria and genetics, but above all, I am just curious guy who loves learning new things.
Vaccinations are essential for public health… but they can be itchy business
In 10 seconds? Aluminium, a common adjuvant in vaccines, is necessary to stimulate and strengthen the immunological power of vaccination, but may cause unwanted side effects, like long-lasting itching and allergies in children.
What are adjuvants and why are they necessary? An adjuvant is an added ingredient in vaccines that helps to create a stronger immune response in the patient’s body, ensuring that patients will be protected against the germ targeted by the vaccine. Aluminium salts, such as aluminium hydroxide, have been commonly used as adjuvants for the past 70 years, and are present today in Infanrix® and Pentavac®, the two most commonly used DTP (Diphtheria, Tetanus, and Pertussis) vaccines in Europe.
If they have been used for over 70 years they must be safe, right? Similarly to medications, vaccines and their components may cause secondary effects, and recent studies seem to agree that although these effects are rare, they are significant. The most common side effects from aluminium adjuvants are itching granulomas and aluminium contact allergies, but more severe outcomes, such as autoimmune reactions and negative consequences on the central nervous system, have been reported, although these results are highly controversial.
If the most probable side effect is only an itch, then there is no need to worry. Well, did I mention that this itch lasts over 5 years? So, yes, these effects are mostly benign but definitely not the most enjoyable feeling a toddler could experience, without mentioning contact allergies to aluminium. But the biggest problem is that almost half of the families will refuse booster vaccinations if their child suffered from these side effects, leaving the child unprotected from infection.
So, what should we do? Most studies agree that the benefits from vaccination are much higher than the eventual negative consequences, but these side effects show that it is necessary to look for alternative adjuvants with lower consequences, to ensure parents about vaccination safety on their child’s health and, thus, improve vaccination coverage.
Abstract: Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles.
Pub.: 03 Sep '13, Pinned: 05 Sep '17
Abstract: There is increasing awareness of reactions to vaccination that include persistent skin reactions. We present here a retrospective investigation of long-lasting skin reactions and aluminium hypersensitivity in children, based on medical records and questionnaires sent to the parents. In the 10-year period 2003 to 2013 we identified 47 children with persistent skin reactions caused by childhood vaccinations. Most patients had a typical presentation of persisting pruritic subcutaneous nodules. Five children had a complex diagnostic process involving paediatricians, orthopaedics and plastic surgeons. Two patients had skin biopsies performed from their skin lesions, and 2 patients had the nodules surgically removed. Forty-two children had a patch-test performed with 2% aluminium chloride hexahydrate in petrolatum and 39 of them (92%) had a positive reaction. The persistent skin reactions were treated with potent topical corticosteroids and disappeared slowly. Although we advised families to continue vaccination of their children, one-third of parents omitted or postponed further vaccinations.
Pub.: 14 Apr '16, Pinned: 05 Sep '17
Abstract: Vaccines are composed of immunogens, preservatives, adjuvants, antibiotics, and manufacturing by-products. Components of vaccines may rarely elicit adverse reactions in susceptible individuals, thus raising concerns regarding vaccine safety. In this report, we add to the medical literature 3 cases of cutaneous delayed-type hypersensitivity to the vaccine preservative aluminum. We provide a review of major constituents in vaccines that have elicited immediate-type or delayed-type hypersensitivity reactions and describe their clinical manifestations. We include a table of the Food and Drug Administration-approved vaccines, which lists the quantities of major components including ovalbumin (egg protein), gelatin, aluminum, neomycin, 2-phenoxyethanol, thimerosal, and formaldehyde. Our goals were to inform physicians on the variety of hypersensitivity reactions to common vaccines and to provide information on the choice of vaccines in patients with suspected hypersensitivity.
Pub.: 02 Jun '12, Pinned: 05 Sep '17
Abstract: Persistent itching subcutaneous nodules and aluminium (Al) allergy have been described after vaccination with Al-adsorbed vaccines but are considered rare. Little is known about the prognosis. Sixty-four children with itching nodules following vaccination with diphtheria-tetanus-pertussis (DTP) vaccines currently used in Sweden (Infanrix® and Pentavac®) were spontaneously reported to the authors from 1999 and followed for up to 12 years. The median duration of itching was 5 years in the 44 children who were free or almost free from symptoms at the latest follow-up. Typical findings were a long interval between vaccination and onset of symptoms (months or years) and intensified itching during intercurrent infections. Contact allergy to aluminium was demonstrated in 60/63 children (95 %). Neither the incidence nor differences between the two vaccines can be estimated from this study, but vaccine-induced itching nodules are probably more common than hitherto realised. The median interval between onset of symptoms and diagnosis was 8 months in a region where nurses were educated to recognise the condition compared to 2 years in other regions. Booster vaccination with DTP-polio was postponed or declined by 15/40 families in fear for new problems. Out of 25 children who received a booster dose, only two had new itching nodules.Intensely itching subcutaneous nodules (vaccination granulomas) and contact allergy to aluminium may occur after primary vaccination with the two most commonly used DTP vaccines in Europe. The condition is probably underreported. Symptoms may last for at least 4-5 years but eventually seem to subside.
Pub.: 12 Oct '12, Pinned: 05 Sep '17
Abstract: Similarly to other medications, vaccines may be responsible for allergic reactions. Although IgE-mediated allergies to vaccine are extremely rare, they are clearly overdiagnosed. Indeed, accurate diagnosis of vaccine allergy is important not only to prevent serious or even life-threatening reactions, but also to avoid unnecessary vaccine restriction. Systematic approaches have been proposed and, if implemented, will likely reduce the number of children being inappropriately labeled as allergic to vaccine. In diagnosis of vaccine allergy, the patient's history is central although not sufficient. In case of suspicion of an allergy, the child should be referred to an allergist in order to perform a complete allergy workup, based primarily on skin tests and/or specific IgE. Highlighting the most recent literature, this article will address the management of children with a possible allergy to vaccine.
Pub.: 18 Oct '13, Pinned: 05 Sep '17
Abstract: In spite of a common view that aluminum (Al) salts are inert and therefore harmless as vaccine adjuvants or in immunotherapy, the reality is quite different. In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as vaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential impact for triggering autoimmunity. Autoimmune and inflammatory responses affecting the CNS appear to underlie some forms of neurological disease, including developmental disorders. Al has been demonstrated to impact the CNS at every level, including by changing gene expression. These outcomes should raise concerns about the increasing use of Al salts as vaccine adjuvants and for the application as more general immune stimulants.
Pub.: 28 Nov '14, Pinned: 05 Sep '17
Abstract: Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past.
Pub.: 29 Apr '14, Pinned: 05 Sep '17
Abstract: In addition to antigens, vaccines contain small amounts of preservatives, adjuvants, and residual substances from the manufacturing process. Some parents have concerns about the safety of these ingredients, yet no large epidemiological studies have specifically examined associations between health outcomes and vaccine ingredients, other than thimerosal. This study examined the extent to which the Vaccine Safety Datalink (VSD) could be used to study vaccine ingredient safety in children.Children born 2004-2011 were identified in VSD data. Using immunization records, two cohorts were identified: children who were up-to-date and children who were undervaccinated before age 2 years. A database was also created linking vaccine type and manufacturer with ingredient amounts documented in vaccine package inserts. Thirty-four ingredients in two or more infant vaccines were identified. However, only amounts (in mg) for aluminum were consistently documented and commonly contained in infant vaccines. Analyses compared vaccine aluminum exposure across cohorts and determined the statistical power for studying associations between aluminum exposure and hypothetical vaccine adverse events.Among 408,608 children, mean cumulative vaccine aluminum exposure increased from 1.11 to 4.00 mg between ages 92-730 days. Up-to-date children were exposed to 11-26% more aluminum from vaccines than undervaccinated children. Power analyses demonstrated that safety studies of aluminum could detect relative risks ranging from 1.1 to 5.8 for a range of adverse event incidence.The safety of vaccine aluminum exposure can be feasibly studied in the VSD. However, possible biological mechanisms and confounding variables would need to be considered before conducting any studies.
Pub.: 01 Nov '15, Pinned: 05 Sep '17
Abstract: In studies in Gothenburg, Sweden, in the 1990s of an aluminium hydroxide-adsorbed pertussis toxoid vaccine, 745 of ~76 000 vaccinated children developed long-lasting itchy subcutaneous nodules at the vaccination site. Of 495 children with itchy nodules patch tested for aluminium allergy, 376 (76%) were positive.To study the prognosis of the vaccine-induced aluminium allergy.Two hundred and forty-one children with demonstrated aluminium allergy in the previous study were patch tested again 5-9 years after the initial test, with the same procedure as used previously.Contact allergy to aluminium was no longer demonstrable in 186 of the retested 241 children (77%). A negative test result was more common in children who no longer had itching at the vaccination site; it was also related to the age of the child, the time after the first aluminium-adsorbed vaccine dose, and the strength of the reaction in the first test.Patch test reactivity to aluminium seems to disappear or weaken with time.
Pub.: 23 Apr '13, Pinned: 05 Sep '17
Abstract: Allergic reactions to vaccines can be classified as sensitivity to one of the vaccine components, pseudo-allergic reactions, often after hyperimmunization, and exacerbation of atopic symptoms or vasculitis. Pseudo-allergic reactions, some possibly due to hyperimmunization, are probably more common than true allergies. Atopic reactions should not be confused with the "flash" phenomenon, defined as an exacerbation of an allergic reaction due to a reduction in the allergic reactivity threshold following the vaccine injection. BCGitis occurs frequently, and for this reason, guidelines for Bacillus Calmette-Guérin (BCG) have been modified. The vaccine is now reserved for people at risk of exposure to Mycobacterium tuberculosis. This review provides an update on the vaccination modalities for people allergic to eggs, on the assessment that should be performed when a reaction occurs due to tetanus vaccination, on the urticaria after hepatitis vaccination, on an aluminum granuloma, which is more and more frequent in young children, and vasculitis after flu vaccination and BCGitis. The side effects associated with new, recently released vaccines, such as anti-influenza A H1N1 or anti-human papilloma virus (HPV) will also be presented.
Pub.: 15 Dec '12, Pinned: 05 Sep '17
Abstract: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule.Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.
Pub.: 23 Apr '14, Pinned: 05 Sep '17