Aaby Peter, Ibrahim Salah A, Libman Michael D, Jensen Henrik
Bandim Health Project, Danish Epidemiology Science Centre/Statens Serum Institut, Apartado 861, Bissau, Guinea-Bissau.
Vaccine. 2006 Apr 5;24(15):2764-71. doi: 10.1016/j.vaccine.2006.01.004. Epub 2006 Jan 19.
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.
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 312 and 912 months of age.
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)).
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.
西非的研究推测，高滴度麻疹疫苗（HTMV）接种后女性死亡率上升是由于随后接种的白喉-破伤风-百日咳（DTP）疫苗和灭活脊髓灰质炎疫苗（IPV）。我们在苏丹农村和金沙萨的HTMV研究中对这一假设的两个推论进行了检验；第一，当HTMV接种后不接种DTP时，HTMV接种者中女性不应有额外的死亡率；第二，额外的女性死亡率应仅在HTMV接种后接种DTP的儿童中发现。
苏丹的试验将510名儿童随机分为Edmonston-Zagreb（EZ）HTMV组、康诺特HTMV组或对照疫苗（脑膜炎球菌疫苗）组。康诺特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个月时接种一剂HTMV，或在3、12和9、12个月时接种两剂。
第一，苏丹试验是少数几项麻疹疫苗随机研究之一；EZ HTMV组在5至9个月龄时的死亡率低于对照组，死亡率比（MR）为0.00（p = 0.030）。这种效应并非由于预防麻疹感染。第二，两项研究均提供证据表明HTMV本身与低死亡率相关。在一项将两个HTMV组与对照组进行比较的综合分析中，HTMV组在5至9个月龄时的MR为0.09（0.01 - 0.71）。在金沙萨，未同时接种DTP的HTMV接种者在6个月至3岁之间的年死亡率仅为1.0%。第三，女性与男性的MR与随后的DTP接种有关。在金沙萨，未接种更多剂量DTP的HTMV接种者中，女性与男性的MR仅为0.40（0.13 - 1.27）。在苏丹，EZ组中女性与男性的死亡率比为3.89（95%CI 1.02 - 14.83），且女性与男性的MR随着随访期间可能接种的DTP剂量数增加而升高（趋势，p = 0.043）。第四，在金沙萨，同时接种HTMV和DTP的儿童的死亡率高于仅接种HTMV的儿童（MR = 5.38（1.37 - 21.2））。
麻疹疫苗具有非特异性有益效果。当不与DTP同时接种时，HTMV本身与低死亡率相关。在HTMV接种后未接种DTP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，疫苗接种的顺序或组合可能对低收入国家的性别特异性死亡率模式有影响。
