肺炎鏈球菌疫苗上市後對台灣孩童與年長者減低侵襲性肺炎鏈球菌疾病風險研究

Post-licensure Vaccine Effectiveness Study of Pneumococcal Vaccines against Invasive Pneumococcal Disease in Children and Older Adults in Taiwan

蘇韋如(Wei-Ju Su)

指導教授 ： 賴美淑

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2018年)

https://doi.org/10.6342/NTU201802180

摘要

研究背景與目的：文獻中較缺乏不同價數（different valences）之結合型肺鏈球菌疫苗（pneumococcal conjugate vaccine, PCV）疫苗上市後保護力（post-licensure vaccine effectiveness）研究，且二十三價多醣體型肺炎鏈球菌疫苗（23-valent pneumococcal polysaccharide vaccine, PPV23）於年長者疫苗保護力之實證，多來自歐洲與美國，亞洲與非洲國家較缺乏。本研究欲瞭解不同價數PCV疫苗陸續上市但尚未納入嬰幼兒常規疫苗接種政策時，5歲以下孩童曾接種十三價PCV（13-valent PCV, PCV13）或未接種PCV13但接種其他價數PCV（7-valent PCV, PCV7或10-valent PCV, PCV10）疫苗，相較於未接種者，分別能減低多少所有血清型侵襲性肺炎鏈球菌感染（all serotypes-IPD）與血清型19A侵襲性肺炎鏈球菌感染（19A-IPD）罹病風險。再者，欲探究PPV23公費接種政策施行於75歲以上年長者，可減低多少侵襲性肺炎鏈球菌感染（IPD）罹病風險。
研究材料與方法：資料來源為衛生福利部疾病管制署法定傳染疾病傳染病監視通報系統的IPD疾病監測（IPD surveillance）與全國性預防接種資訊管理系統（National Immunization Information System, NIIS），以配對病例對照研究法（matched case-control study）探究2007年10月至2013年10間出生的孩童，於2007年10月至2013年12月間，施打PCV與首次罹患IPD的相關性。並另以screening method與indirect cohort (Broome ) method估算75歲以上長者接種PPV23疫苗，於2008年7月至2016年6月間，疫苗施打與罹患IPD的相關性。
研究結果：孩童同一價數PCV13接種、接種不同價數PCV疫苗含PCV13、與接種不同價數PCV疫苗但不含PCV13，比起不接種者，分別減少76%（95% CI: 61–85%）、78%（95% CI: 56–89%）與48%（95% CI: 32–60%）之all serotypes-IPD罹病風險。接種同一價數PCV13或接種不同價數PCV含PCV13，比起未接種者，皆可降低八成多19A-IPD罹病風險。PCV疫苗施打後6個月內可減低八成多all serotypes-IPD罹病風險（VE=81%, 95% CI:69–88%），但施打兩年後，則不到兩成（VE=19%, 95% CI: -21–45%）預防效果。Screening method估算75歲以上年長者接種PPV23疫苗保護力，可分別減少IPD罹病後30天內死亡、all serotypes-IPD與PPV23疫苗涵蓋血清型IPD（PPV23 serotypes-IPD）約32.5%（95% CI: 17.5–44.7）、33.9%（95% CI: 25.2–41.5）與43.4%（95% CI: 34.4–51.2）罹病風險。以Broome method分析，PPV23疫苗接種可減少39.0%（95% CI: 15.5–50.9）PPV23 serotypes-IPD風險，且疫苗施打後5年內與5年後，分別減少44.9% (95% CI: 20.8–61.7)與15.5%（95%: -47.1–51.4）罹病風險。
結論：本研究觀察到孩童PCV疫苗同一價數或不同價數PCV混合接種，都能有效減低IPD罹病風險，但保護力隨疫苗施打後的時間間隔可能會改變。同時，PPV23疫苗對75歲以上年長者有中等程度保護力，其減低罹患PPV23疫苗涵蓋血清型IPD風險的持續時間可能約5年。

關鍵字

疫苗保護力 ； 結合型肺炎鏈球菌疫苗 ； 多醣體型肺炎鏈球菌疫苗 ； 侵襲性肺炎鏈球菌感染

並列摘要

Background and Aims: There are limited evidence describing the post-licensure vaccine effectiveness (VE) of a combination of pneumococcal conjugate vaccines (PCVs) of different valences (7-valent PCV, PCV7/10-valent PCV, PCV10/13-valnt PCV, PCV13) and/or the duration of protection they offer against IPD in children. Additionally, most evidence identified 23-valent pneumococcal polysaccharide vaccine (PPV23) VE against IPD in adults comes from western counties. This study was to evaluate the PCV VE before PCV introduction into routine immunization in children and PPV23 VE in the elderly for whom the public-funded PPV23 program targeted at in Taiwan.
Methods: A matched case-control study using the national IPD surveillance database and the national vaccination registry was applied to select four age-matched, gender-matched and neighborhood-matched controls for each incident IPD case ≦5 years with disease onsets between October 2007 and December 2013. Conditional logistic regression was used to assess VE against all-serotype and serotype 19A IPD (the dominant serotype) in children. Additionally, we investigated PPV23 VE in adults ≧75 years against IPD from July 2008 to June 2016 using the screening method and the indirect cohort (Broome) method.
Results: In children, a similar VE against all-serotype IPD was found between PCV13 (76%; 61–85%) and combined PCV7/PCV10 plus PCV13 (78%; 56–89%). Regarding serotype 19A, a significantly reduced risk was observed for both PCV13 (82%; 63–91%) and combined PCV7/PCV10 plus PCV13 (87%; 61–96%). VE was 81% (69–88%) within 6 months of the last dose of PCV and 19% (95% CI: -21–45%) after 2 years. PPV23 VE estimated with the screening method was 32.5% (95% CI: 17.5–44.7), 33.9% (95% CI: 25.2–41.5) and 43.4% (95% CI: 34.4–51.2) against death within 30 days of IPD onset, all-serotype IPD and PPV23-serotype IPD in adults aged ≧75 years, respectively. VE against PPV23 serotypes by the indirect cohort method was 39.0% ((95% CI: 15.5–50.9) overall, 44.9% (95% CI: 20.8–61.7) within 5 years of vaccination, and 15.5% (95%: -47.1–51.4) after 5 years, respectively.
Conclusions: PCVs are effective against IPD during immunization with either the same or with a mixed series, but protection might be differential over time. Furthermore, PPV23 was estimated to have moderate protection against PPV23-serotype IPD in adults aged 75 years and older and the protection may last for about 5 years.

並列關鍵字

Vaccine Effectiveness ； Pneumococcal Conjugate Vaccine ； Pneumococcal Polysaccharide Vaccine ； Invasive Pneumococcal Disease

參考文獻

1. Backhaus E, Berg S, Andersson R, et al. Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors. BMC Infect Dis. 2016;16:367.

2. Verma R, Khanna P. Pneumococcal conjugate vaccine: a newer vaccine available in India. Human vaccines & immunotherapeutics. 2012;8(9):1317-1320.

3. Pneumococcal vaccines WHO position paper--2012. Releve epidemiologique hebdomadaire / Section d'hygiene du Secretariat de la Societe des Nations = Weekly epidemiological record / Health Section of the Secretariat of the League of Nations. 2012;87(14):129-144.

4. Dinleyici EC, Yargic ZA. Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era. Expert review of vaccines. 2008;7(9):1367-1394.

5. Trucchi C, Paganino C, Ansaldi F. Methodological criticisms in the evaluation of Pneumococcal Conjugate Vaccine effectiveness. J Prev Med Hyg. 2015;56(3):E144-149.