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流感疫苗接种与实验性人类肺炎球菌鼻咽部定植相关的症状。

Symptoms associated with influenza vaccination and experimental human pneumococcal colonisation of the nasopharynx.

机构信息

Royal Liverpool and Broadgreen University Hospital Trust, Prescot Street, Liverpool L7 8XP, UK; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

出版信息

Vaccine. 2020 Feb 28;38(10):2298-2306. doi: 10.1016/j.vaccine.2020.01.070. Epub 2020 Feb 5.

Abstract

BACKGROUND

Nasopharyngeal colonisation by S. pneumoniae is a prerequisite for invasive pneumococcal infections. Influenza co-infection leads to increased susceptibility to secondary pneumonia and mortality during influenza epidemics. Increased bacterial load and impaired immune responses to pneumococcus caused by influenza play a role in this increased susceptibility. Using an Experimental Human Challenge Model and influenza vaccines, we examined symptoms experienced by healthy adults during nasal co-infection with S. pneumoniae and live attenuated influenza virus.

METHODS

Randomised, blinded administration of Live Attenuated Influenza Vaccine (LAIV) or Tetravalent Inactivated Influenza Vaccine (TIV) either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes. Participants completed a symptom questionnaire from the first intervention until 6 days post second intervention.

RESULTS

The timing and type of influenza vaccination and presence of S. pneumoniae in the nasopharynx significantly affected symptom reporting. In the study where influenza vaccination preceded bacterial inoculation: nasal symptoms were less common in the LAIV group than the TIV group (OR 0.57, p < 0.01); with colonisation status only affecting the TIV group where more symptoms were reported by colonised participants compared to non-colonised participants following inoculation (n = 12/23 [52.17%] vs n = 13/38 [34.21%], respectively; p < 0.05). In the study where influenza vaccination followed bacterial inoculation: no difference was seen in the symptoms reported between the LAIV and TIV groups following inoculation and subsequent vaccination; and symptoms were unaffected by colonisation status.

CONCLUSION

Symptoms experienced during live viral vaccination and bacterial co-infection in the nasopharynx are directly affected by the precedence of the pathogen acquisition. Symptoms were directly affected by nasal pneumococcal colonisation but only when TIV was given prior to bacterial exposure.

摘要

背景

肺炎链球菌对鼻咽部的定植是侵袭性肺炎链球菌感染的前提。流感病毒的合并感染会导致流感流行期间继发肺炎和死亡率增加。流感引起的细菌负荷增加和对肺炎链球菌免疫反应受损在这种易感性增加中起作用。本研究使用实验性人体挑战模型和流感疫苗,研究了健康成年人在鼻咽部同时感染肺炎链球菌和减毒活流感病毒时所经历的症状。

方法

随机、双盲给予活流感疫苗(LAIV)或四价灭活流感疫苗(TIV),流感疫苗接种或紧随细菌接种之前,两者间隔 3 天。通过鼻冲洗确定肺炎链球菌的存在和密度。参与者从第一次干预开始到第二次干预后 6 天完成症状问卷。

结果

流感疫苗接种的时间和类型以及鼻咽部肺炎链球菌的存在显著影响症状报告。在流感疫苗接种先于细菌接种的研究中:LAIV 组的鼻症状比 TIV 组少见(OR 0.57,p<0.01);只有在接种后,定植状态才会影响 TIV 组,与未定植组相比,定植组的参与者报告的症状更多(n=12/23[52.17%]比 n=13/38[34.21%],分别;p<0.05)。在流感疫苗接种紧随细菌接种的研究中:接种和随后接种后,LAIV 和 TIV 组报告的症状没有差异;定植状态对症状没有影响。

结论

鼻咽部活病毒疫苗接种和细菌合并感染期间经历的症状直接受到病原体获得的先后顺序的影响。症状直接受到鼻咽部肺炎链球菌定植的影响,但仅在 TIV 接种前暴露于细菌时才会受到影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53f6/7045083/b8e8caa2b1e9/gr1.jpg

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