HÜSEYİN GÜDÜCÜOĞLU, Mustafa BERKTAŞ, Görkem YAMAN

Tiomersal ve otizm

Bulaşıcı hastalıklardan korunma amacıyla geliştirilen aşılar içerdikleri katkı maddeleri açısından yıllarca eleştiri konusu olmuştur. Bir kısmı medya aracılığı ile toplumun çeşitli kesimlerinde, bir kısmı da bilimsel araştırmalara dayanan bu eleştiriler nedeniyle aşıların kullanımında çeşitli sıkıntılar yaşanmaktadır. Tüm bunlara rağmen bulaşıcı hastalıkların önlenmesinde aşılardan daha etkin ve zararsız bir yöntem de henüz geliştirilememiştir. Multidoz aşıların içerisinde, onların kontamine olmasını önlemek amacıyla kullanılan tiomersal, oluşturabileceği yan etkileri açısından bilim çevrelerinde yıllardır mercek altına alınmaktadır. Tiomersal, özellikle çocuklarda oluşturabileceği otizm açısından tartışmalara neden olmuştur. Tiomersal ile otizm arasında ilişki kuran araştırıcıların öncüleri olan Geier ve Geier, 2003 yılından başlayarak günümüze kadar ABD’deki “Aşı Yan Etki Raporlama Sistemi” [Vaccine Adverse Events Reporting System (VAERS)] verilerine dayanarak yayınladıkları yirmiye yakın makalenin hepsinde ısrarla bu ilişkinin varlığını öne sürmüşlerdir. Diğer yandan bir çok araştırıcı tarafından, bu sisteme ait verilerin kullanılması ile yapılacak epidemiyolojik çalışmaların doğru bir sonuca ulaşılabilmesi açısından yetersiz olacağı ve yanlış sonuçlara yol açacağı belirtilmiştir. Nitekim 1999 yılında ABD’de aşılarda koruyucu olarak tiomersal kullanımına son verilmesinden sonra çocuklarda azalması beklenen otizmin azalmadığı ve giderek arttığı yapılan çalışmalarda gösterilmiş ve otizmin farklı nedenlerle oluştuğu sonucuna varılmıştır. Bu derlemede aşıların içerisinde koruyucu olarak kullanılan tiomersal ve içerdiği cıva, oluşturabileceği otizm açısından literatür eşliğinde incelenmiştir.

Thiomersal and autism

Vaccines which were developed for the purpose of protection from infectious diseases, have been criticized in terms of both themselves and their additives. Because of these critism, some of which is based on scientific research and through media in various sectors of society, various problems have been experienced in the use of vaccines. Despite of all these criticisms, more effective and harmless methods than vaccines for the prevention of communicable diseases could not be developed. Thiomersal, used in multidose vaccines in order to prevent contamination, has been taken under the lens for years in terms of its side effects. Thiomersal, especially in children, has caused controversy in terms of autism. Geier and Geier, the leading researchers who relate thiomersal to autism, starting from 2003 until today, have suggested insistently the existence of this relationship in about twenty articles based on the data of the United States Vaccine Adverse Reporting System. On the other hand, by many researchers, it has been stated that the use of epidemiological studies will be inadequate to reach an accurate conclusion and will lead to inaccurate results. Indeed in 1999 after the end of thiomersal use as a preservative in vaccines in the United States, it was showed that autism did not decrease in children and controversially gradually increased and it was concluded that autism occurs as a result of different causes. In this interview, thiomersal (and its ingredient mercury) used as a preservative in vaccines, has been examined in accompaniance of literature in terms of the autism it may cause.

PDF

___

1. Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United Kingdom does not support a causal association, Pediatrics 2004;114(3):584-91. http://dx.doi.org/10.1542/peds.2003-1177-L PMid:15342825
2. Aschner M, Ceccatelli S. Are neuropathological conditions relevant to ethylmercury exposure? Neurotox Res 2010;18(1):59-68. http://dx.doi.org/10.1007/s12640-009-9113-2 PMid:19756911
3. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines, Pediatrics 2001;107(5):1147-54. http://dx.doi.org/10.1542/peds.107.5.1147 PMid:11331700
4. Berman RF, Pessah IN, Mouton PR, Mav D, Harry J. Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice, Toxicol Sci 2008;101(2):294-309. http://dx.doi.org/10.1093/toxsci/kfm265 PMid:17977901
5. Bernard S, Enayati A, Roger H, Binstock T, Redwood L. The role of mercury in the pathogenesis of autism, Mol Psychiatry 2002;(7 Suppl 2):42-3. http://dx.doi.org/10.1038/sj.mp.4001177 PMid:12142947
6. Bigham M, Copes R. Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease, Drug Saf 2005;28(2):89-101. http://dx.doi.org/10.2165/00002018-200528020-00001 PMid:15691220
7. Burbacher TM, Shen DD, Liberato N, Grant KS, Cemichiari E, Clarkson T. Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal, Environ Health Perspect 2005;113(8):1015-21. http://dx.doi.org/10.1289/ehp.7712 PMid:16079072 PMCid:1280342
8. Centers for Disease Control and Prevention (CDC). Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service, Morb Mortal Wkly Rep 1999;48(26):563-5. PMid:10418806
9. Centers for Disease Control and Prevention (CDC).National and state-specific pregnancy rates among adolescents-United States, 1995-1997, Morb Mortal Wkly Rep 2000;49(27):605-11. PMid:10914926
10. Centers for Disease Control and Prevention (CDC). Impact of the 1999 AAP/USPHS joint statement on thimerosal in vaccines on infant hepatitis B vaccination practices, Morb Mortal Wkly Rep 2001;50(6):94-7. PMid:11263794
11. Clements CJ. The evidence for the safety of thiomersal in newborn and infant vaccines, Vaccine 2004;22(15-16):1854-61. http://dx.doi.org/10.1016/j.vaccine.2003.11.017 PMid:15121295
12. Eldred BE, Dean AJ, McGuire TM, Nash AL. Vaccine components and constituents: responding to consumer concerns, Med J Aust 2006;184(4): 170-5. PMid:16489901
13. Faras H, Al Ateeqi N, Tidmarsh L. Autism spectrum disorders, Ann Saudi Med 2010;30(4):295-300. http://dx.doi.org/10.4103/0256-4947.65261 PMid:20622347 PMCid:2931781
14. Folb PI, Bernatowska E, Chen R et al. A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety, Am J Public Health 2004;94(11):1926-31. http://dx.doi.org/10.2105/AJPH.94.11.1926 PMid:15514229 PMCid:1448561
15. Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: Prevalence and links with immunizations, Pediatrics 2006;118(1):39-50. http://dx.doi.org/10.1542/peds.2005-2993 PMid:16818529
16. Geier D, Geier MR. Neurodevelopmental disorders following thimerosal-containing childhood immunizations: a follow-up analysis, Int J Toxicol 2004;23(6):369-76. http://dx.doi.org/10.1080/10915810490902038 PMid:15764492
17. Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood neurodevelopmental disorders, Pediatr Rehabil 2003;6(2):97-102. PMid:14534046
18. Geier DA, Geier MR. A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism, Med Sci Monit 2004;10(3):33-9.
19. Geier DA, Geier MR. A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis, Med Sci Monit 2005; 11(4):160-70.
20. Geier DA, Geier MR. An assessment of downward trends in neurodevelopmental disorders in the United States following removal of thimerosal from childhood vaccines, Med Sci Monit 2006;12(6):231-9.
21. Geier DA, Geier MR. A prospective study of mercury toxicity biomarkers in autistic spectrum disorders, J Toxicol Environ Health A 2007;70(20):1723-30. http://dx.doi.org/10.1080/15287390701457712 PMid:17885929
22. Geier DA, Geier MR. A prospective study of thimerosal-containing Rho(D)-immune globulin administration as a risk factor for autistic disorders, J Matern Fetal Neonatal Med 2007;20(5):385-90. http://dx.doi.org/10.1080/14767050701228057 PMid:17674242
23. Geier DA, Geier MR. A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders, J Toxicol Environ Health A 2007;70(10):837-51. http://dx.doi.org/10.1080/15287390701212141 PMid:17454560
24. Geier DA, Geier MR. Autism spectrum disorder-associated biomarkers for case evaluation and management by clinical geneticists, Expert Rev Mol Diagn 2008;8(6):671-4. http://dx.doi.org/10.1586/14737159.8.6.671 PMid:18999918
25. Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication, Exp Biol Med (Maywood) 2003;228(6):660-4.
26. Geier MR, Geier DA. Mercury in vaccines and potential conflicts of interest, Lancet 2004; 364(9441):1217. http://dx.doi.org/10.1016/S0140-6736(04)17133-X
27. Geier MR, Geier DA. The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity, Med Hypotheses 2005;64(5):946-54. http://dx.doi.org/10.1016/j.mehy.2004.11.018 PMid:15780490
28. Geier DA, Kern JK, Garver CR et al. Biomarkers of environmental toxicity and susceptibility in autism, J Neurol Sci 2009;280(1-2):101-8. http://dx.doi.org/10.1016/j.jns.2008.08.021 PMid:18817931
29. Geier DA, Kern JK, Geier MR. A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity, Acta Neurobiol Exp (Wars) 2009;69(2):189-97.
30. Geier DA, King PG, Sykes LK, Geier MR. A comprehensive review of mercury provoked autism, Indian J Med Res 2008;128(4):383-411. PMid:19106436
31. Geier DA, Sykes LK, Geier MR. A review of thimerosal (merthiolate) and its ethylmercury breakdown product: specific historical considerations regarding safety and effectiveness, J Toxicol Environ Health B Crit Rev 2007;10(8):575-96. http://dx.doi.org/10.1080/10937400701389875 PMid:18049924
32. Heron J, Golding J and ALSPAC Study Team. Thimerosal exposure in infants and developmental disorders: a prospective cohort study in the United kingdom does not support a causal association, Pediatrics 2004; 114(3):577-83. http://dx.doi.org/10.1542/peds.2003-1176-L PMid:15342824
33. Hornig M, Chian D, Lipkin WI. Neurotoxic effects of postnatal thiomersal are mouse strain dependent, Mol Psychiatry 2004;9(9):833-45. http://dx.doi.org/10.1038/sj.mp.4001529 PMid:15184908
34. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism, JAMA 2003;290(13):1763-6.
35. Levy SE, Mandell DS, Schultz RT. Autism, Lancet 2009;374(9701):1627-38. http://dx.doi.org/10.1016/S0140-6736(09)61376-3 PMid:12949291
36. Madsen KM, Lauritsen MB, Pedersen CB et al. Thime-rosal and the occurrence of autism: negative ecological evidence from Danish population-based data, Pediatrics 2003;112(3 Pt1):604-6. http://dx.doi.org/10.1542/peds.112.3.604 PMid:19614825
37. Miller L, Reynolds J. Autism and vaccination-the current evidence, J Spec Pediatr Nurs 2009;14(3): 166-72. http://dx.doi.org/10.1111/j.1744-6155.2009.00194.x PMid:12612255
38. National Advisory Committee on Immunization (NACI). Thimerosal: updated statement. An Advisory Committee Statement (ACS), Can Commun Dis Rep 2007;33(ACS-6):1-13.
39. National Advisory Committee on Immunization (NACI).Statement on thimerosal, Can Commun Dis Rep 2003;29(ACS-1):1-12.
40. Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics 2003;111(3):674-9. http://dx.doi.org/10.1542/peds.111.3.674 PMid:14654615
41. Offit PA, Jew RK. Addressing parents’ concerns: do vaccines contain harmful preservatives, adjuvants, additives, or residuals? Pediatrics 2003;112(6 Pt 1):1394-7. http://dx.doi.org/10.1542/peds.112.6.1394 PMid:18332715 PMCid:2581505
42. Oken E, Bellinger DC. Fish consumption, methyl-mercury and child neurodevelopment, Curr Opin Pediatr 2008;20(2):178-83. http://dx.doi.org/10.1097/MOP.0b013e3282f5614c PMid:15342856
43. Oram RJ, Daum RS, Seal JB, Lauderdale DS. Impact of recommendations to suspend the birth dose of hepatitis B virus vaccine, JAMA 2001; 285(14):1874-9. PMid:15630018
44. Parker SK, Schwartz B, Todd J, Pickering LK. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data, Pediatrics 2004;114(3):793-804. http://dx.doi.org/10.1542/peds.2004-0434 PMid:1420 PMCid:275220
45. Parker S, Todd J, Schwartz B, Pickering L. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data, Pediatrics 2005;115(1):200.
46. Pemberton JR. Retention of mercurial preservatives in desiccated biological products, J Clin Microbiol 1975; 2(6):549-51. PMid:18180424
47. Pichichero ME, Cernichiari E, Lopreiato J, Treanor J.Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study, Lancet 2002;360(9347):1737-41. http://dx.doi.org/10.1016/S0140-6736(02)11682-5 PMid:17898097
48. Schechter R, Grether JK. Continuing increases in autism reported to California’s developmental services system: mercury in retrograde, Arch Gen Psychiatry 2008;65(1):19-24. http://dx.doi.org/10.1001/archgenpsychiatry.2007.1 PMid:15060252
49. Thompson WW, Price C, Goodson B et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years, N Engl J Med 2007;357(13): 1281-92. http://dx.doi.org/10.1056/NEJMoa071434 PMid:11724716
50. Verstraeten T. Thimerosal, the Centers for Disease Control and Prevention, and GlaxoSmithKline, Pediatrics 2004;113(4):932. http://dx.doi.org/10.1542/peds.113.4.932 PMid:14595043
51. Verstraeten T, Baughman AL, Cadwell B et al. Enhancing vaccine safety surveillance: a capture-recapture analysis of intussusception after rotavirus vaccination, Am J Epidemiol 2001;154(11):1006-12. http://dx.doi.org/10.1093/aje/154.11.1006
52. Verstraeten T, Davis RL, DeStefano F et al. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases, Pediatrics 2003;112(5):1039-48. PMid:18482737
53. Yarış E. On soru on yanıt: Biyoyararlanım ve biyoeşdeğerlilik, STED 2004;13(11):426-31. PMid:14519711
54. Young HA, Geier DA, Geier MR. Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink, J Neurol Sci 2008;271(1-2):110-8. http://dx.doi.org/10.1016/j.jns.2008.04.002 PMid:11308401