Polysaccharide vaccines for preventing serogroup A meningococcal meningitis

 

Abstract

Background

Randomised controlled trials (RCTs) in the 1970s and early 1980s showed the polysaccharide serogroup A vaccine (SgAV) prevented serogroup A meningococcal meningitis (SGAMM). Subsequent non-RCTs suggested significant variations in the age-specific duration of protection among children.

Objectives

To determine the protective effect, duration of protection, age-specific effects and the effect of booster doses in children of the SgAV against SGAMM.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1950 to May Week 3, 2010) and EMBASE (January 1974 to May 2010).

Selection criteria

We included RCTs. Non-RCTs that addressed outcomes not addressed by the RCTs were then identified and assessed.

Data collection and analysis

We assessed the methodological quality of RCTs and identified and assessed the non-RCTs. Of the 12 eligible RCTs, four were excluded because of high risk of bias. Data were pooled from the trials using the Exact method to assess vaccine efficacy. Of the 15 non-RCTs, only two addressed objectives not answered by the RCT but were assessed to be at high risk of bias.

Main results

Eight out of 12 eligible RCTs were included; 236,760 participants were vaccinated and 243,308 participants were controls. The protective effect of the vaccine in the first year was consistent across RCTs - summary vaccine efficacy 95% (95% CI 87% to 99%). Protection extended to the second and third year after vaccination but the results did not attain statistical significance. The vaccine was protective in Finnish children aged three months to five years. The latter was the only trial to offer booster doses to young children but lacked statistical power. The vaccine was protective in one- to five-year olds in low-income countries but the efficacy in narrower age strata could not be determined.

Authors' conclusions

The  vaccine was strongly protective for the first year in children over five and adults, but its efficacy beyond the first year could not be determined with precision. Children aged one to five years in low-income countries were also protected but the efficacy in this age group could not be determined. While the vaccine was strongly protective among children aged three months to five years in Finland, the efficacy in narrower age strata could not be determined. The sample size was too small to draw conclusions on the effect of booster doses.

 

Plain language summary

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis

Meningococcal meningitis is a brain infection caused by bacteria that commonly live in the back of the throat. The bacteria can cause infection of the blood (septicaemia) and can cross a barrier from the blood to the brain to cause meningitis. Infection can progress very quickly to damage the brain and can be fatal. The polysaccharide vaccine is strongly protective in children over five years and in adults. Whilst the vaccine is also protective in children aged three months to five years, in low-income countries the level of protection in children of this age group is not very clear. This review found there was not enough evidence from trials to answer some important questions about vaccination for meningococcal meningitis.

Meningitis is the most common manifestation of invasive disease caused by Neisseria meningitidis (N. meningitidis). Other clinical manifestations of the infection include septicaemia, conjunctivitis, pericarditis and arthritis. Meningitis and septicaemia can be rapidly fatal if untreated. N. meningitidis is a normal commensal of the throat and may be found in about 10% of a healthy population. Reasons why the bacteria may become invasive to cause disease are not clear. Randomised controlled trials (RCTs) showed that the polysaccharide serogroup A vaccine prevented meningitis caused by the serogroup A strain of meningococci, and the vaccine has since been used effectively to control epidemics. However, observational studies suggested variations in the level and duration of protection, particularly among younger children, thus resulting in different interpretations of the potential value of routine vaccinations. The review was conducted to provide a summary estimate of the efficacy of the vaccine, its effectiveness in children under five years old, and its duration of protection. Results from 8 out of 12 eligible RCTs were included, and showed the vaccine highly protective in the first year after vaccination: the summary estimate of efficacy was 95% (95% confidence interval (CI) 87% to 99%). Although protection extended to the third year after vaccination, the results were not statistically significant. The vaccine was protective in Finnish children aged three months to five years, but the effect of a booster dose in children under two years was not statistically significant. The vaccine was protective in one- to five-year old children in low-income countries but its effectiveness by one or two-year age strata in this age group could not be determined. Two of 15 eligible non-RCTs were included in the analysis, but were at high risk of bias.

 

摘要

背景

預防血清A型流行性腦脊髓膜炎的多聚糖疫苗

二十年前的隨機性試驗顯示多聚糖疫苗可預防血清A型流行性腦脊髓膜炎。然而後續的非隨機性研究卻指出在不同年齡層的幼童中,疫苗的保護效力有很大的差異

目標

本篇綜合評論的目的在於確定血清A型多聚糖疫苗能否有效預防A型流行性腦脊髓膜炎,特定目標包含疫苗在不同年齡層的效果,五歲以下兒童增加劑量的效果為何,及兒童與成人的保護效力時間長短。

搜尋策略

該綜合評論在2004年更新。 在下列資料庫搜尋新的臨床試驗紀錄： Cochrane對照試驗中央註冊資料庫(Cochrane文庫第4期， 2004); MEDLINE (1966年1月到2004年11月第一週);以及EMBASE (1990年1月到2004年9月)。

選擇標準

綜合評論的第一階段包括隨機性試驗。 第二階段包括非隨機性研究，闡述特定的臨床結果，因為這些臨床結果在隨機性試驗中並沒有好的答案

資料收集與分析

一個評論者評估隨機性試驗的方法學品質，另有二個評論者獨立認定並評估非隨機性研究。在十二個合格的隨機性試驗中，有四個試驗由於在評估疫苗效力上有高度的偏見可能,因而被排除,在疫苗施打後第一,二,三年使用確切方法從試驗中擷取整合試驗資料來評估疫苗效力;在15個非隨機性研究中，只有二個研究闡述到在隨機性試驗中沒有回答到的特定目標,但這二個研究也被認定有高度偏見

主要結論

各隨機試驗都一致顯示出在第一年內的疫苗保護效力,總結來說疫苗效力是95% (95%信賴區間為87%到99%)。 疫苗效力可延長到第二及第三年,但結果並不具統計學上的意義，保護延伸到第二和第三學年。疫苗對於從3個月到五歲的芬蘭小孩都具保護效力, 後者也是唯一評估在二歲以下小孩,增加施打劑量有無助益的試驗,但結果並無統計學上的顯著意義;在發展中國中(奈及利亞和蘇丹),疫苗對於一到五歲的小孩具保護力,但無法比較一歲及五歲這二個特定年齡層間的效力有無異同

作者結論

在接種疫苗後第一年，多聚糖血清A型疫苗可有效預防五歲以上的試驗者感染血清A型流行性腦脊髓膜炎,在此年齡層中疫苗的保護效果可展延到一年後,但無法精確評其效力;在發展中國家一歲到五歲的小孩疫苗也具保護效果,但效力無法評估,雖然在發展中國家,疫苗可有效保護三個月到五歲的小孩,但在不同年齡層中的效力卻無法評估,二歲以下的小孩由於人數過少,所以無法評估增加劑量能否帶來的保護效益

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

在發展中國家.疫苗能幫助孩子五歲以上的小孩對抗流行性腦脊髓膜炎,在五歲以下的小孩也具有部份保護效力,流行性腦脊髓膜炎是一種由細菌引起的腦部感染,該細菌通常存活於喉嚨後方,該細菌能造成菌血症,更可能侵犯腦部造成腦膜炎,並快速進展破壞腦部,如果沒有治療的話,甚至造成死亡;多聚糖疫苗可有效保護五歲以上的小孩及成人得到此感染,雖然在發展中國家此疫苗對於三個月到五歲的小孩也有保護效果,但其效力不明,這篇綜合評論發現從現有的臨床試驗中,並沒有足夠的證據可以回答與流行性腦脊髓膜炎疫苗相關的重要問題