Bandim Health Project, University of Southern Denmark, Copenhagen, Denmark.
Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.
BMJ Glob Health. 2020 Mar 5;5(3):e001873. doi: 10.1136/bmjgh-2019-001873. eCollection 2020.
The BCG vaccine protects non-specifically against other diseases than tuberculosis. Three randomised controlled trials of early BCG in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality. Little is known about the underlying mechanisms. In Guinea-Bissau, prevalent infectious diseases display distinct seasonality. Revisiting the three trials (>6500 infants) comparing early BCG versus no early BCG in low weight infants on all-cause neonatal mortality over 12 consecutive years, we explored the seasonal variation in BCG's effect on mortality. In a subgroup of participants, adaptive and innate cytokine responses were measured 4 weeks after randomisation. Consistently over the course of the three trials and 12 years, the effect of BCG on all-cause neonatal mortality was particularly beneficial when administered in November to January, coincident with peaking malaria infections. During these months, BCG was also associated with stronger proinflammatory responses to heterologous challenge. Recent studies have suggested a protective effect of BCG against malaria. BCG may also ameliorate immune-compromising fatal effects of placental malaria in the newborn.
BCG 疫苗可对结核病以外的其他疾病提供非特异性保护。在几内亚比绍进行的三项 BCG 早期接种随机对照试验发现，全因新生儿死亡率降低了 38%。但关于其潜在机制知之甚少。在几内亚比绍，流行传染病具有明显的季节性。我们重新分析了三项比较低体重婴儿早期接种与不接种 BCG 对全因新生儿死亡率影响的试验（超过 6500 名婴儿），这些试验在连续 12 年中观察了全因新生儿死亡率的季节性变化。在参与者的亚组中，在随机分组后 4 周测量适应性和先天细胞因子反应。在三项试验和 12 年的过程中，BCG 对全因新生儿死亡率的影响始终是有益的，尤其是在 11 月至 1 月接种时，此时疟疾感染达到高峰。在这些月份，BCG 也与针对异源挑战的更强的促炎反应相关。最近的研究表明 BCG 对疟疾具有保护作用。BCG 还可能减轻新生儿胎盘疟疾的免疫抑制致命影响。
