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Vaccines and Autism
Author: Amy Guan
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"Focus: Brave New World 18 Harvard Science Review ? fall 2008 By Xin Guan S ince the late eighteenth cen- tury invention of the small- pox vaccine by Edward Jenner, the practice of vaccination has proven the most clinically- effective and cost-effective method of infectious disease prevention. Its significance is evident in the nature of todaynulls public health policies where governments have instituted compul- sory vaccination schedules aimed to reduce the risks of disease infectivity. As a result of these measures, every- one in the United States, Europe, and recently in many developing countries are required by law to receive a series of scheduled vaccines from early infancy until late secondary school years (1). Nonetheless, an epidemiological trend that weakened the side-effect free claim of vaccines began to appear beginning in the late 1970s. The exponential hike in frequency of autistic symptoms paral- lels the rise in vaccine use during the late twentieth century. Many health officials, therefore, suggested that there might be a correlation between the rising distribu- tion of vaccines and the occurrence of autism in young infants (2). Molecular medical miracle or menace? biologists soon pointed out thimerosal nulla mercury-containing vaccine preser - vative -- as a possible causative agent of autism. This series of correlative data soon lead health experts to propose a connection between the use of vaccines and the onset of autism. However, results from multiple scientific studies have negated the hypothesis of vaccine- induced autism. Furthermore, reports and advising from the World Health Organization (WHO) and Centers for Disease Control (CDC) consistently as- sert a lack of causal relationship between the two (2, 3). Thimerosal and its role in vaccines In 1928, a Staphylococcus infection incident killed over half of the patients inoculated with a diphtheria injection that lacked a preservative (5). Small- scale, yet consistent outbreaks of infec- tions from preservative-lacking vaccines prompted pharmaceutical companies to develop a compound capable of inhibit- ing microbial propagation in a vaccine medium. Beginning in the late 1930s, a mercury-based preservative marketed by Eli Lilly and Company as thimerosal VACCINES AND AUTISM credit: Centers for Disease Control vaccines.indd 18 2/9/2009 11:36:05 PM Focus: Brave New World fall 2008 ? Harvard Science Review 19 was introduced in multi-dose vac- cines as an antifungal and antiseptic agent that would prevent microbe growth in stored vaccines (4). Its effects were immediate: the adverse and often lethal effects of bacterial infection from vaccine injections were almost eliminated. Additionally, the chemical properties of thimerosal were unique in that it did not reduce the biological potency of the vaccine. Concerns appeared when studies characterized the effects of thimerosal in pure form. When inhaled or in- gested, thimersal produces symptoms physiologically similar to those of hu- man poisoning targeting the central ner- vous system. When thimerosal degrades in the body, it becomes ethylmercury, a chemical that clears from the blood and brain with a half-life of 18 and 14 days, respectively (5). Importantly, the reports published in the 1990s docu- menting the adverse effects of pure thimerosal degradation were made on methylmercury, which is cleared from the blood and brain at a signifi cantly slower rate than ethylmercury. Despite this obvious defi ciency in the study, the data from these reports is still used, pro- credit: W ikimedia Commons. ducing nulloverly conservativenullrisk as- sessment guides for vaccine safety due to ethical concerns (5). Thimerosal and the Epidemiology of Autism Autism is a neurological spectrum- disorder targeting infants before age three. Many children in? icted with this disorder fail to establish friendships with children the same age, possess lack of interest in sharing, and have diffi culty understanding other people?s emotions. Autism can also delay an individualnulls speech capability: as many as 40% of people with autism never speak (10). Although autism possesses a strong genetic basis, environmental causes have also been proposed, such as childhood vaccines. This began when parents started reporting symptoms of autism in their children around the same time as childnulls routine childhood vaccination. In addition, there were strikingly similar observations regarding movement, physical characteristics, be- havior, and visual coordination between autistic symptoms and the after-effects of mercury poisoning (6). Current Controversy As reported by the WHO and CDC, there is severe lack of scientifi c evidence support- ing a causative role of mercur y-based vaccine additives in autistic develop- ment (2, 3). This con- clusion is supported by the preponderance of technical literature published in presti- gious journals (7). For example, a study established that the risk of autism and other autistic- spectrum disorders does not differ signifi cantly between chil- dren vaccinated with thimerosal- containing vaccines and children vaccinated with thimerosal-free vaccines. In addition, there was no evidence of dose-response association for autism and for other autistic-spectrum disorders (9). Multiple studies have reported similar results (7, 8, 9). A recent study ana- lyzed the epidemiological statistics of a Canadian population to examine the relationship between thimerosal and autism. Between the years 1987 and 1998, immunization schedules in Canada changed due to the thimerosal issue, and as a result, the experimenters were presented with a unique oppor- tunity to determine whether a direct relationship existed. The authors found that the greatest incidences of autism occurred in the late 1990s, past the date in which thimerosal was removed in Canada (11). Despite the lack of causal evidence, thimerosal was removed from most childhood vaccines in 1999 to ensure ethically risk-free public health policy. As stated by the National Academy of Sciences, nullthe effort to remove thimerosal from vaccines was a prudent measure in support of the public health goal to reduce the mercury exposure of Two different diagrams depict- ing the chemical thimerosal, which has been implicated in certain harmful effects when used in vaccines. vaccines.indd 19 2/9/2009 11:36:05 PM Focus: Brave New World 20 Harvard Science Review ? fall 2008 References 1.Centers for Disease Control, National Vaccine Pro- gram Office: Immunization Laws. Published online at URL: http://www.hhs.gov/nvpo/law.htm (2008) 2.Centers for Disease Control, Vaccine Safety: Mer- cury and Vaccines (Thimerosal). Published online at URL: http://www.cdc.gov/vaccinesafety/concerns/ thimerosal.htm. (2008). 3.World Health Organization, Global Advisory Com- mittee on Vaccine Safety: Statement on Thimerosal. Published online at URL: http://www.who.int/vac- cine_safety/topics/thiomersal/statement_jul2006/ en/index.html. (2006). 4.Baker, J.P. et al. Mercury, vaccines, and autism: one controversy, three histories. Am J Public Health 98, 244?53 (2008) 5.Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Thimerosal in vaccines. Published online at http://www.fda.gov/ cber/vaccine/thimerosal.htm. (2008). 6.Offit, PA., Thimerosal and Vaccines ? A Cautionary Tale. NEJM, 357, 1278-1279 (2007). 7.Parker, S.K. et al. Thimerosal-Containing Vaccines and Autistic Spectrum Disorder: A Critical Review of Published Original Data. Pediatrics, 114, 793-804 (2004). 8.Ball, L.K. et al. An Assessment of Thimerosal Use in Childhood Vaccines. Pediatrics, 107, 1147-1154 (2001). 9.Hviid, A. et al. Association Between Thimerosal- Containing Vaccine and Autism. JAMA, 290,1763-1766 (2003). 10.Volkmar F.R. et al. (2005). Pervasive developmen- tal disorders. In BJ Sadock, VA Sadock, eds., Kaplan and Sadock?s Comprehensive Textbook of Psychiatry, 8th ed., vol. 2, pp. 3164?3182. Philadelphia: Lippin- cott Williams and Williams. 11.Fombonne E. et al. Pervasive developmental disorders in Montreal, Quebec, Canada: Prevalence and links with immunizations, Pediatrics, 118, 139- 150 (2006) 12. H Honda et al. No effect of MMR withdrawal on the incidence of autism: a total population study. Journal of Child Psychology and Psychiatry 2005 doi: 10.1111/j.1469-7610.2005.01425.x nullin Guan null2 is a prospective Chemistry or Organismic and Evolutionary Biology concentra- tor in Canaday hall. infants and children as much as pos- sible.null(5) Since that statement, many developed nations including the United States and Canada have limited the use of thimerosal in vaccines (2). Conse- quently, most pharmaceutical compa- nies have limited production of live Measles, Mumps, and Rubella (MMR), oral and inactivated polio, yellow fever, and Bacillus Calmete-Guerin (BCG) vaccines exclusively to single-dose packages because this particular type of vaccine delivery does not require the use of a preservative during storage (2). However, the removal process has also resulted in administrative complica- tions. As per regulation by the WHO, any alteration in ingredient composition of a licensed vaccine requires a new licensing process including a series of preclinical and clinical trials to ensure that the new vaccine is safe and efficient according to regulation listings (3). In addition to regulatory complica- tions, costs involved in the single-dose manufacturing process are substantially higher than preservative-supplemented multi-dose packages (2, 3, 8). More- over, some experts contend that it is more ethical to distribute sufficient amounts of preservative-containing vaccines to developing countries as op- posed to investing capital that ensures the production of less single-dose vials especially given the lack of causative evidence (8). In promoting the use of more expensive single-dose vaccines, governmental agencies are instead needlessly increasing the risk of infec- tion of children in developing countries who do not have access to vaccines. Prospects for the Future The devastating effects effect of autism and the undisputed increase in its incidence present an unquestionably grave issue to the public health commu- nity. Despite the claims supporting a correlative association between vaccine use and autism, no causative connec- tion has been established. If thimerosal causes autism, then its removal from scheduled immunizations should lead to a decrease in autism incidences, which epidemiological studies have not observed (3, 6, 7, 9, 11). Nonethe- less, parents remain skeptical about vaccinesnulland when these parents resist the vaccination of their chil- dren, they increase tremendously risk of the harmful diseases the vaccines are designed to prevent. Public fear of vaccines, however, has compelled decision-makers to remove thimero- sal from vaccines, even if it financial unfavorable, without even the assur- ance that such measures are scientifi- cally dictated or even likely to succeed. The graph charts incidence of autism with usage of the MMR vaccination. credit: (12) vaccines.indd 20 2/9/2009 11:36:06 PM "
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