Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.
Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.
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DOI：
10.1136/bmjopen-2011-000707
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Ravn H
中科院分区：
文献类型：
--
作者：
Aaby P;Benn C;Nielsen J;Lisse IM;Rodrigues A;Ravn H
麻疹疫苗(MV)对死亡率有性别差异的影响，这不能通过预防麻疹感染来解释。作者研究了全细胞白喉-破伤风-百日咳(DTP)疫苗是否具有性别差异和非特异性效应。根据以前的综述和一项新的搜索，在所有研究中评估了DTP对下一次接种前死亡率的影响，其中DTP在MV后给予卡介苗或DTP，并在确定疫苗接种状态后进行前瞻性随访。非洲和亚洲的高死亡率国家。对DTP负面影响的初步观察产生了六个假说，所有可用的研究和两个随机试验都对这些假说进行了检验，以减少接触DTP的时间。研究之间的一致性。在第一项研究中，与卡介苗和MV的有益作用相比，DTP对存活率有负面影响。这一模式在其他六项现有研究中也得到了重复。其次，这两项“自然实验”发现，接种DTP疫苗的儿童死亡率明显高于未接种DTP疫苗的儿童。第三，在所有9个研究中，女性和男性死亡率在DTP治疗后都有所增加；相反，在所有研究中，在BCG和MV治疗后，这一比率都降低了。第四，只有在接种了高效价麻疹疫苗后接种了DTP的儿童中，才发现与高滴度麻疹疫苗相关的女性死亡率增加。第五，在6个关于早期MV的随机试验中，如果在MV后给予DTP，则女性的死亡率增加，但男性的死亡率没有增加。第六，接种DTP疫苗的儿童接受MV后，女孩的死亡率明显下降，但男孩的死亡率没有下降。作者通过在DTP后不久接种活疫苗(MV和BCG)减少了对DTP的暴露，这是最近的疫苗接种。这两项试验都降低了儿童死亡率。这些观察结果与仅仅预防目标疾病的DTP不相容。由于对百日咳具有群体免疫力，DTP与女孩更高的死亡率有关。有必要对DTP进行随机研究，以衡量其对存活率的真正影响。MV对儿童存活率有性别差异的非特异性影响。我们检查了DTP疫苗是否对生存有负面影响，特别是对女孩。我们测试了六个假设，这些假设表明，如果发现属实，DTP可能会对健康造成负面影响。此外，我们进行了两项随机试验，通过在DTP后不久提供活疫苗来减少最近一次接种DTP的时间。所有现有的研究表明，DTP对儿童生存的影响与BCG和MV的作用相反。在两个自然实验中，接种DTP疫苗的儿童死亡率显著高于未接种DTP疫苗的儿童。在所有研究中，接种了DTP疫苗的儿童中，女孩的死亡率高于男孩，而接种了卡介苗和麻疹疫苗的儿童的死亡率则相反。在MV的随机试验中，MV后使用DTP与增加女性死亡率有关，但与男性死亡率无关。减少接触DTP的时间，将其作为最近接种卡介苗或MV的疫苗，可降低儿童死亡率。因为最健康的儿童首先接种疫苗，所以人们会认为DTP与一种益处有关。然而，所有数据都一致表明，DTP与女孩的负面影响有关。不能进行关于DTP对总存活率影响的随机试验。现在有必要进行这样的研究。
Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection. The authors examined whether whole-cell diphtheria–tetanus–pertussis (DTP) vaccine has sex-differential and non-specific effects. Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status. High-mortality countries in Africa and Asia. The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP. Consistency between studies. In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two ‘natural experiments’ found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female–male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality. These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls. Randomised studies of DTP are warranted to measure the true impact on survival. MV has sex-differential non-specific effects for child survival. We examined whether DTP vaccine has negative effects for survival, particularly for girls. We tested six hypotheses suggesting that DTP may have negative health consequences if found to be true. Furthermore, we conducted two randomised trials reducing the time of exposure to DTP as most recent vaccination by providing a live vaccine shortly after DTP. All available studies suggest that the effect of DTP on child survival is opposite of the effects of BCG and MV. In the two natural experiments, DTP-vaccinated children had significantly higher mortality than DTP-unvaccinated children. Among DTP-vaccinated children, girls have higher mortality than boys in all studies, whereas the tendency is the opposite for BCG- and measles-vaccinated children. DTP administered after MV in randomised trials of MV is associated with increased female but not male mortality. Reducing time of exposure to DTP as the most recent vaccination with BCG or MV reduce child mortality. Since the healthiest children are vaccinated first, one would expect DTP to be associated with a benefit. However, all the data suggest consistently that DTP is associated with a negative effect for girls. A randomised trial of the effect of DTP on overall survival could not be conducted. There is a need to conduct such studies now.
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影响因子：
28.2
作者：
AABY, P;BUKH, J;SMITS, AJ
通讯作者：
SMITS, AJ
影响因子：
3.6
作者：
Aaby, P;Lisse, IM;Whittle, H
通讯作者：
Whittle, H
DOI：
10.1016/s0035-9203(96)90275-8
发表时间：
1996-05-01
影响因子：
2.2
作者：
Aaby, P;Samb, B;Whittle, H
通讯作者：
Whittle, H
影响因子：
5.5
作者：
Aaby, P;Ibrahim, SA;Jensen, H
通讯作者：
Jensen, H
影响因子：
5.5
作者：
Aaby, P;Jensen, H;Lisse, I
通讯作者：
Lisse, I