Vaccines for preventing influenza in healthy adults

 

Abstract

Background

Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.

Objectives

Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010).

Selection criteria

Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data.

Main results

We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barré Syndrome per million vaccinations. The harms evidence base is limited.

Authors' conclusions

Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING:
This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.

 

Plain language summary

Vaccines to prevent influenza in healthy adults

Over 200 viruses cause influenza and influenza-like illness which produce the same symptoms (fever, headache, aches and pains, cough and runny noses). Without laboratory tests, doctors cannot tell the two illnesses apart. Both last for days and rarely lead to death or serious illness. At best, vaccines might be effective against only influenza A and B, which represent about 10% of all circulating viruses. Each year, the World Health Organization recommends which viral strains should be included in vaccinations for the forthcoming season.

Authors of this review assessed all trials that compared vaccinated people with unvaccinated people. The combined results of these trials showed that under ideal conditions (vaccine completely matching circulating viral configuration) 33 healthy adults need to be vaccinated to avoid one set of influenza symptoms. In average conditions (partially matching vaccine) 100 people need to be vaccinated to avoid one set of influenza symptoms. Vaccine use did not affect the number of people hospitalised or working days lost but caused one case of Guillian-Barré syndrome (a major neurological condition leading to paralysis) for every one million vaccinations. Fifteen of the 36 trials were funded by vaccine companies and four had no funding declaration. Our results may be an optimistic estimate because company-sponsored influenza vaccines trials tend to produce results favorable to their products and some of the evidence comes from trials carried out in ideal viral circulation and matching conditions and because the harms evidence base is limited..

 

摘要

背景

成人流行性感冒疫苗

全世界目前有各種不同的流感疫苗,只有北美洲有針對健康的成年人,儘管流感疫苗有許多的臨床試驗,但對於其臨床效益仍有相當多的未知數,因而造成流感疫苗被接受及接種率的負面影響

目標

認定,擷取及評估所有針對成年人流感疫苗的效果(包含效力,及害處)所做的研究

搜尋策略

我們搜尋了考科藍對照試驗註冊資料庫(CENTRAL)(考科藍實證資料庫2005年第四期),其中包含了考科藍急性呼吸感染的試驗註冊;MEDLINE醫學文獻資料庫(1966年1月到2006年1月);EMBASE醫藥學文獻資料庫(1990年到2006年一月);我們有寫信詢問疫苗製造者,及各研究的第一作者或通訊作者.

選擇標準

有加入評估的研究,包括隨機或半隨機的臨床試驗,比較流感疫苗,安慰劑,與無接受治療組對人體的影響;各種活,減毒,死亡病毒疫苗,或他們的部分組成經由各種途徑注入人體,不論其抗原結構如何都加以評估;而列入考量的研究,需要評估16歲到65歲的健康個體接受疫苗能否使其免於周遭的流感病毒感染;如果非隨機性試驗有評估流感疫苗與嚴重傷害的相關性則加以納入

資料收集與分析

由二位評論性作者獨立評估臨床試驗的品質及摘錄資料

主要結論

收納58個報告,其中有38個臨床試驗(含57個子研究)提供關於流感疫苗效力,效益及副作用的資料,人數共66,248人;8個研究為非隨機性試驗,檢驗疫苗與副作用的相關性;2個研究報告疫苗的副作用,其無法納入資料分析;去活性的靜脈注射疫苗可30%有效預防類流感疾病(95%信賴區間17%到41%),當疫苗與流行病株符合且該病株流行率高時,可80%有效預防流感(95%信賴區間56%到91%),當疫苗與流行病株不符合時,有效預防率減到50%(95%信賴區間27%到65%);扣除1968到1969年大流行的研究,疫苗的效益有15%(95%信賴區間9%到22%),效力有73%(95%信賴區間53%到84%),疫苗會有相當程度地影響不用工作的時間，但沒有足夠的證據可以證實疫苗會減少住院或併發症發生率;去活性的疫苗會造成局部發紅痠痛;噴霧型疫苗有較適度的表現,單價全病毒疫苗若符合流行病株,若1968到1969年的大流行再度發生,具有高效力(VE93%,95%信賴區間69到98%)及高效益(VE66&,95%信賴區間51到77%)

作者結論

流感疫苗可有效減少得到流行性感冒的病人數,尤其當疫苗準確預測到流行的病毒株而且該病毒株流行率高時,然而其對於類流感疾病的預防效益較差,對工時減少的影響中等,沒有足夠的證據可評估疫苗對於併發症的影響,全病毒疫苗的表現在大流行時可發揮極致.

翻譯人

本摘要由臺灣大學附設醫院郭耀文翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有足夠的證據證實常規的疫苗接種可以有效預防健康成人得到流行性感冒,流感病毒會造成發燒,頭痛,全身酸痛,咳嗽及流鼻水,症狀可持續數週並併發嚴重疾病甚至死亡,流感病毒容易傳播且新型病株一直出現,世界衛生組織每年都會建議那些病株需要加入在疫苗之中,以因應下一季的感染,在許多國家都提供免費為高危險群病人接種,以預防流感併發症並做為公共衛生的措施,本評論發現接種疫苗最佳可預防80%病人感染流行性感冒(經由實驗室檢查證實,且該疫苗是針對該季流行病株),若疫苗不能針對該季的流行病株,在成人的預防效果降到50%,對於類流感疾病的預防效果也只有30%,這樣並不會減少到醫院就診的病人數,或減少需休假休息的時數,有些疫苗會造成注射部份疼痛及發紅,肌肉痠痛,及其他非常少見的嚴重傷害,如暫時性麻痺