The sequence of vaccinations and increased female mortality after high-titre measles vaccine: Trials from rural Sudan and Kinshasa
The sequence of vaccinations and increased female mortality after high-titre measles vaccine: Trials from rural Sudan and Kinshasa
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DOI：
10.1016/j.vaccine.2006.01.004
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发表时间：
2006-04-05
期刊：
影响因子：
5.5
通讯作者：
Jensen, H
中科院分区：
文献类型：
--
作者：
Aaby, P;Ibrahim, SA;Jensen, H
目的：西非研究假设高滴麻疹疫苗（HTMV）后女性死亡率增加是由于随后接种白喉-破伤风-百日咳（DTP）和灭活脊髓灰质炎疫苗（IPV）。我们在苏丹农村和金沙萨的HTMV研究中检验了这一假设的两个推论；首先，当HTMV后未给予百白破时，HTMV受者的女性死亡率不应过高；其次，只有在HTMV后接受百白破的儿童中才应发现女性死亡率过高。研究：苏丹试验随机选取510名儿童接种埃德蒙顿-萨格勒布（EZ） HTMV、康诺特HTMV或对照疫苗（脑膜炎球菌）。Connaught HTMV组和对照组均在9个月时接种标准麻疹疫苗。在金沙萨的研究中，1023名儿童在6个月大时接受了一剂HTMV，在3(1)/(2)和9(1)/(2)个月大时接受了两剂。研究结果：首先，苏丹试验是为数不多的麻疹疫苗随机研究之一；EZ HTMV组5 ~ 9月龄死亡率低于对照组，死亡率（MR）为0.00 （p = 0.030）。这种效果不是由于预防了麻疹感染。其次，两项研究都提供了证据，证明HTMV本身与低死亡率有关。在比较HTMV组和对照组的综合分析中，HTMV组在5 - 9月龄之间的MR为0.09（0.01-0.71）。在金沙萨，未同时接受百白破的HTMV接种者在6个月至3岁期间的年死亡率仅为1.0%。第三，男女MR与随后的百白破疫苗接种有关。在金沙萨，未进一步接种百白破疫苗的HTMV接种者的男女MR仅为0.40（0.13-1.27）。在苏丹，EZ组的男女死亡率为3.89 (95% CI 1.02-14.83)，男女MR随随访期间可能给予百白咳剂量的增加而增加（趋势，p = 0.043）。第四，在金沙萨，同时接受HTMV和DTP的儿童死亡率高于单独接受HTMV的儿童（MR= 5.38(1.37-21.2)）。结论：麻疹疫苗与非特异性有益效应相关。当不给予百白破时，HTMV本身与低死亡率相关。在HTMV后未接受DTP治疗的儿童中，未发现女性死亡率增加。因此，我们的推论得到了支持，接种疫苗的顺序或组合可能对低收入国家的性别死亡率模式产生影响。(c) 2006 Elsevier Ltd.版权所有。
Objective: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV.Studies: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 3(1)/(2) and 9(1)/(2) months of age.Findings: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR= 5.38 (1.37-21.2)).Conclusions: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries. (c) 2006 Elsevier Ltd. All rights reserved.