Friday, October 15, 2010

美国儿童疫苗第九章 麻疹,腮腺炎,风疹(MMR)三联疫苗

这个东东,争议最大,幸好偶的博客已经有所介绍。就直接copy & paste了。稍微修改一下以跟文章其他部分格式一致。http://justanotherdad888.blogspot.com/2009/04/mmr.html
MMR是Measles(麻疹),Mumps(流行性腮腺炎,简称腮腺炎),Rubella(风疹)的三联疫苗。
关于麻疹,WHO是这么说的: (http://www.who.int/mediacentre/factsheets/fs286/en/)
• Measles is one of the leading causes of death among young children even though a safe and cost-effective vaccine is available.
• In 2008, there were 164 000 measles deaths globally – nearly 450 deaths every day or 18 deaths every hour.
• More than 95% of measles deaths occur in low-income countries with weak health infrastructures.
• Measles vaccination resulted in a 78% drop in measles deaths between 2000 and 2008 worldwide.
• In 2008, about 83% of the world's children received one dose of measles vaccine by their first birthday through routine health services – up from 72% in 2000.
细节就不讨论了。

腮腺炎比较温和,一般不死人。其主要症状包括(http://en.wikipedia.org/wiki/Mumps):
• Parotid inflammation (or parotitis) in 60–70% of infections and 95% of patients with symptoms. Parotitis causes swelling and local pain, particularly when chewing. It can occur on one side (unilateral) but is more common on both sides (bilateral) in about 90% of cases.
• Fever
• Headache
• Orchitis(睾丸炎), referring to painful inflammation of the testicle. Males past puberty who develop mumps have a 30 percent risk of orchitis.

风疹在儿童基本是自限性疾病,症状较少。https://health.google.com/health/ref/Rubella。 成人可能有:
• Fever
• Headache
• General discomfort (malaise)
• Runny nose before the rash appears
• Rush
• Bruising (rare)
• Inflammation of the eyes (bloodshot eyes)
• Muscle or joint pain
但是如果孕妇(特别是前20周)感染风疹可导致的先天性风疹综合征,可以引起:
• Cataracts
• Congenital heart defects
• Congenital rubella syndrome
• Deafness
• Ear infection (otitis media)
• Encephalitis (rare)
• Mental retardation
• Microcephaly
• Transient arthritis (common in adolescents and adults with rubella)
• Miscarriage or stillbirth may occur.
所以,孕妇最好在怀孕前至少1-3个月完成风疹的疫苗接种。

麻疹疫苗的作用建议看一下这个图就明白了:



1964年measles疫苗在美国拿到license(http://www.babycenter.com/0_the-mmr-vaccine_1567.bc)
当然这个是美国的数据。另外常有人引用的是英国的数据:
http://www.whale.to/vaccines/MeaslesDeathsbyPopulation1901-95.pdf。
不幸的是这个数据不能说明我们要说的问题。看Y轴,分明是麻疹的死亡统计,不是感染统计。很多人引用这个数据说麻疹疫苗无效,因为在疫苗引入之前,麻疹死亡率已经降低了。这个是不对的。这个做多说明营养水平,医疗水平已经提高了,麻疹的死亡率降低了,但是麻疹的感染率却是另外一回事。所以用这个数据来暗示麻疹疫苗无效是不对的。
英国数据没找到,所以还是以美国说事儿。在1964年之前,美国每年有大约50万人感染麻疹,其中4万8千人住院,其中 450人死亡。64年引入疫苗之后,麻疹病例下降了10000倍,平均每年50例。而其中基本是由进入美国的外来人口带进来的。可以说,引入疫苗之后,麻疹已经在美国被基本消灭了。
事实上,强烈反对麻疹疫苗这个网站,http://www.whale.to/m/measlesdeaths1.html,也引用了美国数据:
http://www.whale.to/vaccine/Measles%20Mortality%20in%20the%20United%20States%201971-75%20-%20amended%20graph.pdf。
从图上可以看出,1964年美国引入麻疹疫苗后感染率,死亡率都大幅下降。虽然之前麻疹的感染和死亡率都在下降,但是从1964年开始出现了历史性的转折。到1968年,仅仅4年以后,麻疹感染率和死亡率都下降100倍之多。
但是偶尔还是会有麻疹爆发,比如在1969年到1970年,麻疹再次爆发,即使如此感染率也没有达到1964年的1/5。其中原因之一是有部分拒绝疫苗的人士(因为宗教或者健康原因。。。还有不明原因的)被外来病毒感染引起局部爆发。
另外这个疫苗跟其他任何药物一样并非100%有效。凡是号称包治xxx病的,哪怕是治感冒,都是胡扯。天下没有那个绝对的事。
有部分孩子,即使打了疫苗也不产生抗体,具体原因不太清楚。大约有5-10%的人。所以美国现在要求二次注射。一方面可以提供这些没有产生免疫的孩子二次免疫的机会,另一方面也让产生了免疫的孩子加强免疫。
总结:对于95%以上的正常儿童,麻疹疫苗是有效的。

关于腮腺炎疫苗的有效性,baby center的原话是这么说的,具体数据没找到
The current strain of the mumps vaccine has been used worldwide since being approved in the United States in 1967. Before a vaccine was available, the United States had an average of about 150,000 cases every year. In 2003 the number had dropped to 231 — a 99.9 percent decrease in the number of cases.

wiki上关于风疹是这么说的:Rubella is a disease that occurs worldwide. The virus tends to peak during the spring in countries with temperate climates. Before the vaccine to rubella was introduced in 1969, widespread outbreaks usually occurred every 6-9 years in the United States and 3-5 years in Europe, mostly affecting children in the 5-9 year old age group.[17] Since the introduction of vaccine, occurrences have become rare in those countries with high uptake rates. However, in the UK there remains a large population of men susceptible to rubella who have not been vaccinated. Outbreaks of rubella occurred amongst many young men in the UK in 1993 and in 1996 the infection was transmitted to pregnant women, many of whom were immigrants and were susceptible. Outbreaks still arise, usually in developing countries where the vaccine is not as accessible.[18]
During the epidemic in the US between 1962-1965, Rubella virus infections during pregnancy were estimated to have caused 30,000 still births and 20,000 children to be born impaired or disabled as a result of CRS.[19][20] Universal immunisation producing a high level of herd immunity is important in the control of epidemics of rubella.[21]
简单翻译就是风疹过去在美国是6-9年流行一次,欧洲3-5年一次。引入疫苗之后,感染率已经非常低。只有英国有部分人拒绝疫苗,仍有流行。在美国,1962-1965年之间风疹感染孕妇,导致三万死胎,两万婴儿出生缺陷。
1969年,风疹疫苗在美国获得执照,之后风疹感染率就快速下降,到今天风疹几乎消失。但是没有免疫的外来人口仍然偶尔会有流行。正因为如此,风疹的高危人群现在不再是过去的15岁以下儿童,而是在国外出生的,没有免疫的成人。
这里有个90年代美国风疹的研究,发表于2002年的JAMA杂志 http://jama.ama-assn.org/cgi/content/full/287/4/464
最有说服力的是这个图一



其中CRS是先天性风疹综合征,从1969年才开始有数据。

在美国的一般免疫计划是12到15个月和 4到6岁两次免疫注射(http://www.cdc.gov/vaccines/recs/schedules/downloads/child /2009/09_0-6yrs_schedule_bw.pdf)。

MMR疫苗在美国只有一个产品就是MMR II,是减毒活疫苗(http://www.merck.com/product/usa/pi_circulars/m/mmr_ii/mmr_ii_pi.pdf),由Merck公司生产。由于理论上有影响胎儿的可能,安全起见一般孕前一个月和怀孕前三个月内都不建议使用,其实最好生完再打。当然,如果不小心打了八成也没事,不必为此忧心忡忡。到目前为止没有因为在 怀孕期间打MMR引起畸胎的病例。当然如果您有发现,请及时告诉大家。谢谢先。

MMR的副作用为大家所诟病,也确实由于是活疫苗可能更明显。但是总得来说,还是比较安全的。http://pediatrics.about.com/cs/immunizations/a/mmr_vis_2.htm。绝大多数人都可以安全注射MMR疫苗,但是确实有部分孩子会有副作用,有些甚至是比较严重的副作用,比如耳聋,长期抽搐,昏迷,永久大脑损伤。但是目前看来这些严重副作用的发生率如此之低,以至于研究这个的人都无法确信是疫苗引起了这些严重的副作用。
Most people who get MMR vaccine do not have any problems with it.
Mild Problems
* Fever (up to 1 person out of 6)
* Mild rash (about 1 person out of 20)
* Swelling of glands in the cheeks or neck (rare) If these problems occur, it is usually within 7-12 days after the shot. They occur less often after the second dose.
Moderate Problems
* Seizure (jerking or staring) caused by fever (about 1 out of 3,000 doses)
* Temporary pain and stiffness in the joints, mostly in teenage or adult women (up to 1 out of 4)
* Temporary low platelet count, which can cause a bleeding disorder (about 1 out of 30,000 doses)
Severe Problems (Very Rare)
* Serious allergic reaction (less than 1 out of a million doses)
* Several other severe problems have been known to occur after a child gets MMR vaccine. But this happens so rarely, experts cannot be sure whether they are caused by the vaccine or not. These include:
o Deafness
o Long-term seizures, coma, or lowered consciousness
o Permanent brain damage
关于这些严重的副作用CDC(http://www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm)是这么说 的:“Although several cases of sensorineural deafness have been reported after administration of MMR vaccine, evidence from these case reports (e.g., timing of onset and other features) is inadequate to accept or reject a causal relation between MMR vaccination and sensorineural deafness. Aseptic Meningitis”
引用的文献在这里:
Vuori M, Lahikainen EA, Peltonen T. Perceptive deafness in connection with mumps: a study of 298 servicemen suffering with mumps. Acta Otolaryngol 1962;55:231.
Westmore GA, Pickard BH, Stern H. Isolation of mumps virus from the inner ear after sudden deafness. Br Med J 1979;1:14.
一个是62年的,一个是79年的。
但是我们知道,CRS本身就引起deafness等症状,甚至是其重要的诊断依据。
所以MMR疫苗基本是安全的。

以下情况不应该打MMR疫苗。http://pediatrics.about.com/cs/immunizations/a/mmr_vis.htm。
* People should not get MMR vaccine who have ever had a life-threatening allergic reaction to gelatin, the antibiotic neomycin, or a previous dose of MMR vaccine.
曾经有生命危险的过敏反应,对新霉素,明胶或者鸡蛋等过敏的,不能使用MMR!非常重要!
* People who are moderately or severely ill at the time the shot is scheduled should usually wait until they recover before getting MMR vaccine.
正在生病的,应该等病好了再打。
* Pregnant women should wait to get MMR vaccine until after they have given birth. Women should avoid getting pregnant for 4 weeks after getting MMR vaccine.
女性应该在打MMR一个月后怀孕,或者在生完孩子之后再打。前面我们说过了为啥。
* Some people should check with their doctor about whether they should get MMR vaccine, including anyone who:
o Has HIV/AIDS, or another disease that affects the immune system
o Is being treated with drugs that affect the immune system, such as steroids, for 2 weeks or longer.
o Has any kind of cancer
o Is taking cancer treatment with x-rays or drugs
o Has ever had a low platelet count (a blood disorder)
有严重免疫缺陷,或者使用免疫抑制剂的,肿瘤病人 等
* People who recently had a transfusion or were given other blood products should ask their doctor when they may get MMR vaccine
Ask your doctor or nurse for more information.
最近使用了血制品的,应咨询自己的医生。

自闭症问题,前面已经讨论过了,不再赘述。

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