Aaby Peter, Bhuiya Abbas, Nahar Lutfun, Knudsen Kim, de Francisco Andres, Strong Michael
Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Seruminstitut, Copenhagen, Denmark.
Int J Epidemiol. 2003 Feb;32(1):106-16. doi: 10.1093/ije/dyg005.
To examine whether the reduction in childhood mortality after immunization can be explained by the prevention of measles and its long-term effects.
and Data We re-analysed an existing data set from Matlab, Bangladesh. During 1982-1985, measles immunization was used from 9 months of age in half of the study area, and the other half was used as an unvaccinated control area. A total of 8134 immunized children had been matched by age with 8134 non-immunized children; 578 children died during the follow-up period of 3 years. Using these data, we calculated the vaccine effectiveness against death (VED) controlling for significant factors in a matched analysis. In the absence of measles, there should be no difference in mortality between immunized, uninfected children and non-immunized, uninfected children. We therefore calculated VED after the exclusion of all measles cases in the survival analysis. To assess the long-term effects of measles, we compared survival of unvaccinated children after measles disease with children who had not yet contracted measles.
Prior to immunization and again after 1985, childhood mortality rates were 10% lower in the area that had received immunization. Though measles deaths only constituted 12.4% of the non-accidental deaths, the VED controlling for significant factors was 49% (95% CI: 38-58%). The vaccine was protective against measles death throughout the study, but it also had a marked effect against other causes of death, particularly diarrhoea and oedema. This effect may have been particularly strong in the first 6 months after immunization (VED = 74, 95% CI: 57-84%). The VED was only reduced from 49% to 43% (95% CI: 31-54%) when measles cases were excluded in the survival analysis. Controlling for background factors, mortality among measles cases was increased during the acute phase (0-45 days) (mortality ratio [MR] = 17.35, 95% CI: 11.9-25.3) and in the following 1(1/2) months (MR = 2.35, 95% CI: 0.95-5.84). However, post-measles cases had significantly lower mortality than uninfected, non-immunized children in the following 9 months (MR = 0.40, 95% CI: 0.16, 0.98).
The non-randomized character of the original study and the possibility of uncontrolled confounding between the two areas prevent a precise estimate of the effectiveness of measles vaccine, but it is likely to have been substantial. Though there may have been some underreporting of cases of measles, the prevention of measles infection can only explain a limited part of the observed impact of measles immunization in Bangladesh. Furthermore, mortality may be reduced after the acute phase of measles infection. The observations from Bangladesh are consistent with recent research from Africa suggesting that measles immunization may have non-specific beneficial effects on survival.
探讨免疫接种后儿童死亡率的降低是否可归因于麻疹预防及其长期影响。
我们重新分析了来自孟加拉国马特拉布的现有数据集。在1982 - 1985年期间,研究区域的一半地区从9个月大开始进行麻疹免疫接种,另一半作为未接种疫苗的对照区域。总共8134名接种疫苗的儿童按年龄与8134名未接种疫苗的儿童进行了匹配;在3年的随访期内有578名儿童死亡。利用这些数据,我们在匹配分析中控制显著因素计算了疫苗对死亡的有效性(VED)。在没有麻疹的情况下,接种疫苗且未感染的儿童与未接种疫苗且未感染的儿童之间的死亡率应该没有差异。因此,我们在生存分析中排除所有麻疹病例后计算了VED。为评估麻疹的长期影响,我们比较了患麻疹疾病后未接种疫苗儿童与尚未感染麻疹儿童的生存率。
在免疫接种前以及1985年后,接受免疫接种地区的儿童死亡率又降低了10%。尽管麻疹死亡仅占非意外死亡的12.4%,但控制显著因素后的VED为49%(95%置信区间:38 - 58%)。在整个研究期间,疫苗对麻疹死亡具有保护作用,但对其他死因也有显著影响,尤其是腹泻和水肿。这种影响在免疫接种后的前6个月可能尤为强烈(VED = 74,95%置信区间:57 - 84%)。在生存分析中排除麻疹病例后,VED仅从49%降至43%(95%置信区间:31 - 54%)。控制背景因素后,麻疹病例在急性期(0 - 45天)的死亡率增加(死亡率比[MR] = 17.35,95%置信区间:11.9 - 25.3),在接下来的1.5个月内也增加(MR = 2.35,95%置信区间:0.95 - 5.84)。然而,患麻疹后病例在接下来的9个月内的死亡率显著低于未感染、未接种疫苗的儿童(MR = 0.40,95%置信区间:0.16,0.98)。
原始研究未采用随机分组,且两个区域之间存在未控制的混杂因素,这使得无法精确估计麻疹疫苗的有效性,但疫苗的有效性可能很大。尽管可能存在一些麻疹病例报告不足的情况,但预防麻疹感染只能解释在孟加拉国观察到的麻疹免疫接种影响的有限部分。此外,麻疹感染急性期过后死亡率可能会降低。来自孟加拉国的观察结果与非洲最近的研究一致,表明麻疹免疫接种可能对生存有非特异性的有益影响。