CLINICAL UPDATE Vaccine components and constituents: responding to consumer concerns Barbara E Eldred, Angela J Dean, Treasure M McGuire and Allan L Nash he World Health Organization states “The two public health ABSTRACT interventions that have had the greatest impact on the world’s • Vaccination remains a vital strategy in the prevention of health are clean water and vaccines”.1 However, rates of T 2,3 infectious disease. vaccination uptake in Australia may be suboptimal. Concern about vaccine safety is a potential barrier to immunisation; and reductions • Commercial vaccine formulations contain a range of additives in vaccination rates have been described after media reporting of or manufacturing residuals, which may contribute to patient adverse effects.4 concerns about vaccine safety. Vaccination safety is a frequent motivation for consumers to • The Medical Journal of Australia ISSN: 0025- Primary health care professionals are well placed to address contact drug information services operating out of the Mater Health 729X 20 February 2006 184 4 170-175 patient concerns about vaccine safety. We describe the key Services©The in Brisbane Medical (personal Journal reflection).of Australia Vaccines 2006 contain constitu- constituents present in vaccines, discuss issues related to ents suchwww.mja.com.au as preservatives, stabilisers, adjuvants and biological safety and acceptability of these constituents, and provide growthClinical media, update which may contribute to consumer concern about a table highlighting constituents of commercially available vaccine safety; specifically: vaccines in Australia. • presence of preservatives; MJA 2006; 184: 170–175 • likelihood of allergic reactions; and • constituents of human or animal origin. Community-based health professionals are in a key position to Preservatives address these concerns by providing accurate information about vaccine constituents and components. However, much of this infor- Thiomersal mation is not readily available. We sought to compile a comprehen- Thiomersal (sodium ethylmercuric thiosalicylate) is an organic com- sive overview of constituents, culture and growth media used in the pound containing ethylmercury that has been widely used as a production of the vaccines available in Australia. vaccine preservative since the 1930s. Concerns have focused on its potential toxicity as a heavy metal, and its role in the claimed link Information retrieval between measles, mumps and rubella (MMR) vaccination and 5 Information was retrieved using the following iterative process: autism. • The Therapeutic Goods Administration (TGA) website was used A recent study assessed whether multiple vaccinations can lead to 6 to ascertain vaccines registered in Australia. mercury accumulation. In full-term infants exposed to vaccines • Manufacturers were contacted to confirm current products. containing thiomersal, mercury concentrations detected in blood • This was compared with the Australian Immunisation Handbook (range, 2.85–20.55 nmol/L) were well below the level thought to be to ensure all products were included. associated with adverse effects. Additionally, ethylmercury appears to • Information about excipients and media was obtained from be eliminated via the gastrointestinal tract soon after exposure registered Product Information. (estimated half-life, 7 days).6 Because the developing fetus and low • Where clarification of constituents was required, manufacturers birthweight babies are more vulnerable to toxic effects of mercury, it were contacted. has been suggested that exposure to vaccines containing thiomersal • Final table sections were submitted to individual manufacturers at time of birth may pose some risk in very low birthweight for review. premature infants.6 To minimise any potential risk, all vaccinations in Information is presented in two tables: childhood vaccines (Box 1) the Australian Standard Vaccination Schedule for children younger and travel vaccines (Box 2). As vaccine manufacture is subject to than 5 years are now thiomersal-free or contain only trace amounts.7 ongoing development and change, information provided in this In 1998, a case series was published describing 12 children with review is current at the time of preparation. pervasive development disorder with gastrointestinal features.8 The report claimed that exposure to MMR vaccination may have been FOR EDITORIAL COMMENT, SEE PAGE 150 linked to emergence of behavioural symptoms. Since then, contro- Education and Information Unit, Mater Pharmacy Services, versy has surrounded the potential association between MMR vaccine Mater Misericordiae Hospital, South Brisbane, QLD. and autism, with thiomersal a suggested culprit. The original claims Barbara E Eldred, BPharm, Drug Information Pharmacist; have been criticised for being based on uncontrolled, anecdotal Angela J Dean, BPharm, PhD, Research Fellow, Kids in Minds Research, associations, and more recently, some of the study authors have Mater Child and Youth Mental Health Service; Treasure M McGuire, 9 BPharm, BSc, PhD, Assistant Director, Practice and Development; and retracted their interpretation associating MMR vaccines with autism. Senior Conjoint Lecturer, School of Pharmacy, University of Queensland; Larger epidemiological studies have also failed to demonstrate an Allan L Nash, BPharm, Drug Information Pharmacist. association between MMR vaccination or use of thiomersal-contain- Reprints will not be available from the authors. Correspondence: ing vaccines and autism.10 Dr T M McGuire, Education and Information Unit, Mater Pharmacy The mercury or thiosalicylate components of thiomersal may Services, Mater Misericordiae Hospital, Raymond Terrace, produce hypersensitivity reactions.11 Reactions are uncommon, even South Brisbane, QLD 4101. [email protected] in those with sensitisation, and serious reactions are rare. 170 MJA • Volume 184 Number 4 • 20 February 2006 1 Childhood vaccines CLINICAL UPDATE Live Biological Generic Vaccine vaccine growth media Cells Other additives Chicken pox (Varicella) Varilrix (GSK) Y Cow, human Human cell culture Neomycin, lactose Varivax — refrigerated Y Gelatine, cow Human and guinea Neomycin, monosodium glutamate (MSD) pig cell culture Diphtheria/ tetanus ADT (CSL); CDT (CSL) N Cow or pig Biological culture Thiomersal, aluminium phosphate or horse* Diphtheria/ tetanus/ pertussis Boostrix (10 years) (GSK) N Cow Biological culture Formaldehyde, phenoxyethanol, aluminium phosphate, aluminium hydroxide Infanrix (GSK) N Cow Biological culture Formaldehyde, phenoxyethanol, aluminium hydroxide Tripacel (Aventis Pasteur) N — Biological culture Phenoxyethanol, aluminium phosphate Diphtheria/ tetanus/ pertussis/ Infanrix Hep B (GSK) N Cow Yeast (hep B), Formaldehyde, phenoxyethanol, hepatitis B biological culture aluminium phosphate and hydroxide Diphtheria/ pertussis/ Infanrix IPV (GSK) N Cow Monkey cell culture, Formaldehyde, neomycin, poliomyelitis/ tetanus biological culture phenoxyethanol, aluminium hydroxide, polymyxin B Diphtheria/ hepatitis B/ Infanrix Penta (GSK) N Cow Yeast (hep B), Formaldehyde, neomycin, pertussis/ poliomyelitis/ tetanus monkey cell culture, phenoxyethanol, aluminium biological culture phosphate and hydroxide, polymyxin B Diphtheria/ Haemophilus Infanrix Hexa (GSK) N Cow Yeast (hep B), Formaldehyde, neomycin, influenzae/ hepatitis B/ monkey cell culture, phenoxyethanol, lactose, pertussis/ poliomyelitis/ tetanus biological culture aluminium phosphate and hydroxide, polymyxin B Diphtheria toxoid Diphtheria Vacc (Adsorbed) N Cow or pig Biological culture Thiomersal, aluminium phosphate (CSL); Diphtheria Vacc or horse* (Adsorbed) (Adult) (CSL) Haemophilus influenzae type B Liquid Pedvax HIB (MSD) N — Biological culture Aluminium hydroxide Haemophilus influenzae type B Comvax (MSD) N — Biological culture, Aluminium hydroxide with hepatitis B yeast Hepatitis B Engerix - B (GSK); Engerix- N Cow Yeast Thiomersal, aluminium hydroxide B (Paediatric) (GSK) H-B Vax II (MSD); H-B Vax II N — Yeast Formaldehyde, aluminium hydroxide, Dialysis (MSD); H-B Vax II potassium thiocyanate (Paed) (MSD) Influenza Fluad (Chiron) N Chicken, egg — Formaldehyde, neomycin, squalene (shark liver oil), kanamycin sulfate Fluarix (GSK) N Cow, egg Hen’s egg cell Formaldehyde, thiomersal, culture gentamicin Fluvax (CSL) N Egg — Neomycin, polymyxin B Influvac (Solvay) N Egg — Gentamicin Thiomersal in batches manufactured before February 2005 Vaxigrip (Aventis Pasteur); N Egg — Formaldehyde, neomycin Vaxigrip Junior (Aventis Pasteur) Measles/ mumps/ rubella M-M-R II (MSD) Y Gelatine, Human cell culture, Neomycin, human serum albumin cow chick embryo cell culture Priorix (GSK) Y Cow, egg — Neomycin, lactose Meningococcal C Meningitec (Wyeth) N Cow (milk) Biological culture, Aluminium phosphate, diphtheria yeast conjugate Menjugate (CSL) N Cow Biological culture Aluminium hydroxide, diphtheria conjugate NeisVac-C (Baxter) N Cow Biological culture Aluminium hydroxide, tetanus conjugate Pneumococcal Pneumovax 23 (MSD) N Rabbit Biological culture Phenol Prevenar (Wyeth) N Cow (milk) Biological culture, Aluminium phosphate, diphtheria yeast conjugate Poliomyelitis Ipol (Aventis Pasteur) N Cow Monkey cell culture Formaldehyde, neomycin, streptomycin, polymixin B Polio Sabin (GSK) Y Cow Human cell culture Neomycin, polymixin B Rubella Meruvax II (MSD) Y Gelatine, cow Human cell culture Neomycin, human serum albumin Tetanus Tet-Tox (CSL) N Cow or pig Biological culture Thiomersal, aluminium phosphate or horse* * These vaccines