Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Vaccine. 2022 Apr 20;40(18):2580-2587. doi: 10.1016/j.vaccine.2022.03.023. Epub 2022 Mar 25.
Oral rotavirus vaccine efficacy is lower in low- and middle-income countries (LMICs) than in high-income countries. The degree to which antibiotic use impacts rotavirus vaccine immunogenicity in LMICs is unknown. Using data from a multisite prospective birth cohort study of malnutrition and enteric disease, MAL-ED, we examined the effect of early life antibiotic use on the immune response to rotavirus vaccine.
We assessed whether antibiotic use from birth up to 7 days following rotavirus vaccine series completion was associated with rotavirus seropositivity at 7 months of age in Brazil, Peru, and South Africa using a modified Poisson regression. We then used parametric g-computation to estimate the impact of hypothetical interventions that treated all children and alternatively prevented inappropriate antibiotic treatments on seropositivity.
Of 537 children, 178 (33%) received at least one antibiotic course during the exposure window. Probability of seropositivity was 40% higher among children who had at least one course of antibiotics compared with those with no antibiotic exposure (PR: 1.40, 95% CI: 1.04, 1.89). There was no significant difference by the number of antibiotic courses received or total duration of antibiotics. Treating all children with antibiotics would be associated with a 19% (95% CI: 18%, 21%) absolute increase in seropositivity at 7 months. In contrast, removing inappropriate antibiotics would result in a 4% absolute reduction (95% CI: -5%, -2%) in seropositivity.
Early life antibiotic use was associated with increased seropositivity. However, a hypothetical intervention to remove inappropriate antibiotics would have little effect on overall seropositivity. Further investigation into the underlying mechanisms of antibiotic use on the infant gut microbiome and immune response are needed.
口服轮状病毒疫苗在中低收入国家（LMICs）的效果低于高收入国家。抗生素的使用在多大程度上影响 LMICs 中轮状病毒疫苗的免疫原性尚不清楚。利用营养不良和肠道疾病多地点前瞻性队列研究 MAL-ED 的数据，我们研究了生命早期抗生素的使用对轮状病毒疫苗免疫反应的影响。
我们使用修正泊松回归评估了轮状病毒疫苗系列完成后 7 天内从出生到出生后 7 天使用抗生素与巴西、秘鲁和南非 7 个月龄时轮状病毒血清阳性率之间的关系。然后，我们使用参数 g 计算来估计治疗所有儿童和替代预防不适当抗生素治疗的假设干预对血清阳性率的影响。
在 537 名儿童中，178 名（33%）在暴露窗口期至少接受了一次抗生素疗程。与无抗生素暴露的儿童相比，至少接受过一次抗生素疗程的儿童血清阳性率高出 40%（PR：1.40，95%CI：1.04，1.89）。接受抗生素疗程的数量或抗生素总持续时间没有显著差异。治疗所有儿童使用抗生素将与 7 个月时血清阳性率绝对增加 19%（95%CI：18%，21%）相关。相比之下，去除不适当的抗生素将导致血清阳性率绝对降低 4%（95%CI：-5%，-2%）。
生命早期抗生素的使用与血清阳性率增加有关。然而，去除不适当抗生素的假设干预对总体血清阳性率影响不大。需要进一步研究抗生素使用对婴儿肠道微生物组和免疫反应的潜在机制。
