Perspective: Scientific and ethical concerns pertaining to animal models of autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA).

The autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was first described in 2011. The aluminium containing adjuvants of vaccines were stated to be one of the main causes of the condition. Other disorders associated with ASIA include siliconosis, Gulf war syndrome, sick building syndrome and the macrophagic myositis syndrome. We have recently reviewed ASIA as defined by its authors. We have shown that the definition of ASIA is imprecise and includes all patients with an autoimmune disorder as well as potentially the entire population. Application of the Bradford Hill criteria for causality does not support ASIA as an outcome of exposure to aluminium containing adjuvants in vaccines. The advocates of ASIA highlight animal models as evidence for the existence of the disorder. However, as this review will demonstrate, animal models purporting to support the existence of ASIA have methodological, analytical and ethical flaws which, in our view, refute the existence of the condition. Three publications by the advocates of ASIA were recently retracted from peer-reviewed journals. We call for an immediate moratorium on animal experiments of ASIA until an independent inquiry has been conducted to determine the existence of a clinically relevant syndrome, identifiable as ASIA in humans.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data, pertaining to causation, particularly from patients undergoing allergen-specific immunotherapy (IT). Patients undergoing allergen-specific IT receive 100 to 500 times more injected aluminum over 3 to 5 years, compared with hepatitis B and human papillomavirus vaccine recipients. In a large pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus immunized with the hepatitis B vaccine. Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.

Anaphylaxis management: the essential role of adrenaline (epinephrine) auto-injectors. Should PHARMAC fund them in New Zealand?

Anaphylaxis is an important life-threatening medical emergency. There is extensive evidence supporting the early use of intramuscular adrenaline for first medical responders and for self-initiated treatment, in at-risk individuals. Major patient groups identified as at ongoing risk are children and adults with severe food allergy, patients with venom allergy who have not been desensitised, and those with idiopathic anaphylaxis. Individual anaphylactic events are largely unpredictable. The most effective and safe route of administration for adrenaline is intramuscular, but it is difficult for patients and carers to achieve accurate and timely self-administration using an ampoule, needle, and syringe. The adrenaline auto-injector device which is available in New Zealand (the EpiPen) is not funded by PHARMAC, and thus only available to patients and families who are able to afford the purchase cost. It is difficult to understand the continued unwillingness of PHARMAC to fund an adrenaline auto-injector device to at-risk individuals, given the large body of information supporting its efficacy and use. The Australian model, where authorisation from a relevant specialist is required, could be used.