Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age

Abstract

Pneumonia, caused by Streptococcus pneumoniae, is a major cause of morbidity and mortality among children in low‐income countries. The effectiveness of pneumococcal conjugate vaccines (PCVs) against invasive pneumococcal disease (IPD), pneumonia, and mortality needs to be evaluated. To update the 2004 review on the efficacy of PCVs in preventing vaccine‐serotypes IPD (VT‐IPD) , X‐ray defined pneumonia among HIV‐1 negative children, and other new outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1990 to Week 4 February 2009); and EMBASE (1974 to March 2009). Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, in children under two with IPD and clinical / radiographic pneumonia as outcomes. Two review authors independently identified studies, extracted data, and evaluated their corresponding risks of bias. Differences were resolved by discussion. Meta‐analysis used the inverse variance method. We identified 11 publications from six RCTs conducted in Africa, US, Philippines and Finland where 57,015 children received PCV; while 56,029 received placebo or another vaccine. Seven publications provided high quality evidence on PCV efficacy against IPD and four provided moderate quality evidence against pneumonia. None of the five trials with all‐cause mortality data were powered to investigate this outcome. Only two trials have data on all‐cause admissions. The main analysis for this review involved HIV‐1 negative children and used the pooled results of random‐effects model, intent‐to‐treat analysis (ITT). Pooled vaccine efficacy (VE) for VT‐IPD was 80% (95% confidence interval (CI) 58% to 90%, P < 0.0001); all serotypes‐IPD, 58% (95% CI 29% to 75%, P = 0.001); World Health Organization X‐ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all‐cause mortality, 11% (95% CI ‐1% to 21%, P = 0.08). Analysis involving HIV‐1 positive children had similar findings. PCV is effective in preventing IPD, X‐ray defined pneumonia, and clinical pneumonia among HIV‐1 negative and HIV‐1 positive children under two years. The impact was greater for VT‐IPD than for all serotypes‐IPD, and for X‐ray defined pneumonia than for clinical pneumonia. An 11% reduction with a 95% CI of ‐1% to 21% and a P = 0.08 is compatible with reduction in all‐cause mortality. 肺炎鏈球菌接合型疫苗在小於兩歲之兒童中對於疫苗型之侵入性肺炎鏈球菌疾病及X光定義之肺炎的預防 在低收入的國家中，由肺炎鏈球菌造成之肺炎是兒童罹病以及死亡的一大主要原因。肺炎鏈球菌接合型疫苗對於侵襲性肺炎鏈球菌感染症，肺炎以及死亡率的減低效力需要被評估。 此研究目的在於更新2004年發表關於肺炎鏈球菌接合型疫苗預防疫苗同型之侵襲性肺炎鏈球菌感染症，X光定義之肺炎在後天性免疫不全病毒陰性之兒童身上的效力，以及其他新的結果。 我們搜尋了考科藍中心登記之控制試驗(The Conchrane Library 2009, issue 1)，其中包含了考科藍急性呼吸感染群的特定登記(Cochrane Acute Respiratory Infections Group's Specialised Register)，MEDLINE(1990 – 2009二月第四周)以及EMBASE(1974 – 2009三月)。 我們搜尋了考科藍中心登記之控制試驗(The Conchrane Library 2009, issue 1)，其中包含了考科藍急性呼吸感染群的特定登記(Cochrane Acute Respiratory Infections Group's Specialised Register)，MEDLINE(1990 – 2009二月第四周)以及EMBASE(1974 – 2009三月)。 兩個回顧作者獨立地找出研究，分析資料以及評估各自對應的偏差風險。如果有不同的結果，則會互相討論做解決。統合分析則使用變異數倒數法。 我們從六個在非洲，美國，菲律賓以及芬蘭進行的隨機對照實驗中找出了十一篇文章，總共包含了57015個兒童接受了肺炎鏈球菌接合型疫苗，而有56029個兒童接受了安慰劑或是其他的疫苗。七篇文章提供了關於肺炎鏈球菌接合型疫苗針對侵入性肺炎鏈球菌疾病的效力的高品質證據。四篇提供了對於肺炎中等程度的證據。五個隨機對照實驗中沒有任何一個有足夠的考驗力能夠研究這個結果。只有兩個隨機對照實驗有關於所有原因住院的資料。 這篇回顧主要分析包含了後天免疫不全病毒陰性的兒童並且使用了隨機效果模型和意圖治療分析法的整合結果。 整合疫苗效力對於疫苗型的侵入性肺炎鏈球菌疾病是80%(95%信賴區間是58% – 90%，p值小於0.0001);所有血清型之侵入性肺炎鏈球菌疾病是58%(95%信賴區間是29%75%，p值等於0.001);世界衛生組織x光定義肺炎是27%(95%信賴區間是15%36%，p值小於0.0001);臨床上之肺炎是6%(95%信賴區間是2%9%，p值等於0.0006);以及所有原因的死亡率是11%(95%信賴區間是 −1%21%，p值等於0.08)。關於後天免疫不全病毒陽性的兒童有類似的結果。 肺炎鏈球菌接合型疫苗能夠有效預防在小於兩歲之後天免疫不全病毒陽性以及陰性兒童的侵入性肺炎鏈球菌疾病, x光定義肺炎，以及臨床上之肺炎。比起所有血清型之侵入性肺炎鏈球菌疾病，疫苗的使用在疫苗型的侵入性肺炎鏈球菌疾病的影響較大。比起臨床上之肺炎，疫苗的使用在x光定義之肺炎的影響較大。11%的下降幅度，在95%信賴區間是 −1%21%，p值等於0.08下，是跟所有原因死亡率下降符合的。 本摘要由臺灣大學附設醫院李孟叡翻譯。 此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。...