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不含硫柳汞的疫苗:为何如此必要,为何姗姗来迟?

Vaccines without thiomersal: why so necessary, why so long coming?

作者信息

van't Veen A J

机构信息

Department of Dermatology and Venereology, Erasmus University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.

出版信息

Drugs. 2001;61(5):565-72. doi: 10.2165/00003495-200161050-00002.

Abstract

The inorganic mercurial thiomersal (merthiolate) has been used as an effective preservative in numerous medical and non-medical products since the early 1930s. Both the potential toxicity of thiomersal and sensitisation to thiomersal in relation to the application of thiomersal-containing vaccines and immunoglobulins, especially in children, have been debated in the literature. The very low thiomersal concentrations in pharmacological and biological products are relatively non-toxic, but probably not in utero and during the first 6 months of life. The developing brain of the fetus is most susceptible to thiomersal and, therefore, women of childbearing age, in particular, should not receive thiomersal-containing products. Definitive data of doses at which developmental effects occur are not available. Moreover, revelation of subtle effects of toxicity needs long term observation of children. The ethylmercury radical of the thiomersal molecule appears to be the prominent sensitiser. The prevalence of thiomersal hypersensitivity in mostly selected populations varies up to 18%, but higher figures have been reported. The overall exposure to thiomersal differs considerably between countries. In many cases a positive routine patch test to thiomersal should be considered an accidental finding without or, probably more accurately, with low clinical relevance. In practice, some preventive measures can be taken with respect to thiomersal hypersensitivity. However, with regard to the debate on primary sensitisation during childhood and renewed attention for a reduction of children's exposure to mercury from all sources, the use of thiomersal should preferably be eliminated or at least be reduced. In 1999 the manufacturers of vaccines and immunoglobulins in the US and Europe were approached with this in mind. The potential toxicity in children seems to be of much more concern to them than the hidden sensitising properties of thiomersal. In The Netherlands, unlike many other countries, the exposure to thiomersal from pharmaceutical sources has already been reduced. Replacement of thiomersal in all products should have a high priority in all countries.

摘要

自20世纪30年代初以来,无机汞硫柳汞(硫柳汞)已在众多医疗和非医疗产品中用作有效的防腐剂。硫柳汞的潜在毒性以及与含硫柳汞疫苗和免疫球蛋白应用相关的硫柳汞致敏性,尤其是在儿童中,已在文献中受到讨论。药理和生物制品中硫柳汞浓度极低,相对无毒,但在子宫内和生命的前6个月可能并非如此。胎儿发育中的大脑对硫柳汞最为敏感,因此,育龄妇女尤其不应接受含硫柳汞的产品。目前尚无关于产生发育影响的剂量的确切数据。此外,毒性细微影响的揭示需要对儿童进行长期观察。硫柳汞分子中的乙基汞基团似乎是主要的致敏原。在大多经过挑选的人群中,硫柳汞超敏反应的发生率高达18%,但也有更高数据的报道。各国硫柳汞的总体暴露情况差异很大。在许多情况下,硫柳汞常规斑贴试验呈阳性应被视为偶然发现,无临床相关性或可能更准确地说临床相关性较低。实际上,针对硫柳汞超敏反应可采取一些预防措施。然而,关于儿童期初次致敏的争论以及对减少儿童从所有来源接触汞的重新关注,硫柳汞的使用最好予以消除或至少减少。1999年,美国和欧洲的疫苗及免疫球蛋白制造商正是基于这一考虑而被提及此事。对他们而言,儿童的潜在毒性似乎比硫柳汞的隐性致敏特性更令人担忧。在荷兰,与许多其他国家不同,药品来源的硫柳汞暴露已经减少。在所有国家,所有产品中硫柳汞的替代都应列为高度优先事项。

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