進階搜尋


下載電子全文  
系統識別號 U0026-3108201015083700
論文名稱(中文) 台灣兒童侵襲性肺炎鏈球菌感染症流行病學的變化-疫苗政策的應用
論文名稱(英文) Changing epidemiologic pattern of invasive pneumococcal disease among children in Taiwan: Implications for vaccine program
校院名稱 成功大學
系所名稱(中) 公共衛生研究所
系所名稱(英) Graduate Institute of Public Health
學年度 98
學期 2
出版年 99
研究生(中文) 沈雅慧
研究生(英文) Ya-hui Shen
學號 t8697108
學位類別 碩士
語文別 中文
論文頁數 56頁
口試委員 指導教授-陳國東
口試委員-楊宜青
口試委員-章順仁
口試委員-黃高彬
中文關鍵字 肺炎鏈球菌七價結合型疫苗  侵襲性肺炎鏈球菌症  鼻咽腔帶原  時間序列  全民健康保險研究資料庫 
英文關鍵字 pneumococcal 7-valent conjugate vaccine  invasive pneumococcal disease  nasopharyngeal carriage  time series analysis  National health insurance research database 
學科別分類
中文摘要 引言:
肺炎病例中,有30-50%是肺炎鏈球菌感染所致,此外,肺炎鏈球菌更可引起侵襲性疾病,威脅兒童的生命,主要有肺膿瘍、菌血症、敗血症、腦膜炎、腹膜炎、化膿性關節炎、化膿性骨髓炎、心包膜炎、胰臟炎、溶血性尿毒症等等。過去20年來,大多數常見且傳染力強的疾病,如麻疹,都因疫苗的使用而使該疾病受到控制;相對的,近幾年來,肺炎鏈球菌感染的控制就顯得非常重要。疫苗的研發成為世界潮流,7價結合型疫苗於2000年全面在美國施打後,很多的文獻發表均顯示其在直接和間接上之明顯效果。
方法:
台灣也在2005年10月引進自費施打,利用健保資料庫(1997-2008)擷取五歲以下兒童,因侵襲性肺炎鏈球菌症住院病例,分析疫苗引進後住院病例數變化的情形;及利用北、中、南3家醫學中心,收集2005-2009兒童鼻咽腔帶菌情形來分析台灣五歲以下兒童的帶原比例。並引進時間序列的概念,進一步了解及預測疫苗接種的成效。藉由台灣肺炎鏈球菌鼻咽腔帶菌、侵襲性肺炎鏈球菌感染症的住院率與致死率,來佐證疫苗接種最合理的年齡及劑數之建議和預測的效益。
結果:
根據北、中、南3家醫學中心兒童鼻咽腔帶菌研究,顯示疫苗在2005年引進台灣後,2006年開始,台灣兒童鼻咽腔之帶菌率逐年下降,帶菌年齡的最高峰出現在18-24個月大的兒童,其次是介於2歲到5歲之間。進一步血清分行研究發現6B、14、19F、23F 占大多數,這四種血清型均含在七價疫苗中,而又2006-2009年的觀察,鼻咽腔帶菌的血清型並沒有太大的變化,顯示疫苗使用後之血清型別取代現象尚未出現,疫苗效果還未出現抵銷情況,此亦表示疫苗涵蓋率仍不夠高。健保局資料庫顯示1997-2008年5歲以下侵襲性肺炎鏈球菌感染症的住院病例以小於1歲占的比例最高,死亡率也最高,表示台灣1歲以下嬰兒是肺炎鏈球菌重症的高危險群,疾病致死率高達3%,2008年已降至1.36%。隨著疫苗使用量增加,侵襲性肺炎鏈球菌症感染之月住院率在2006年後呈現平穩狀態。
結論:
根據台灣特殊的流行病學資料,2-4 歲是台灣侵襲性肺炎鏈球菌症感染的好發年齡,在經濟的考量之下,建議可在1歲施打1至2劑的13價結合型疫苗,如此一來,可以降低18-24個月大兒童鼻咽腔的帶菌率(降低傳染的機會),進而降低2-4 歲侵襲性肺炎鏈球菌症感染發生率。此外,流感病童容易有肺炎鏈球菌之感染,流感疫苗接種疫苗有助於降低侵襲性肺炎鏈球菌感染之機會,此兩種疫苗應可同時推廣施打。
英文摘要 Pneumonia is the most common infectious disease among children under 5 years old and elderly over 65 years old. According to the report from WHO, pneumonia is the most common cause of death in children less than 5 years of age. However, 30 to 50% of pneumonia cases resulted from Streptococcus pneumonia infection. Except pneumonia, Streptococcus pneumonia was responsible for meningitis, septicemia, and empyema, which collected into invasive pneumococcal disease (IPD). Antibiotics is not the only way to treat or to eradicate pneumococcal disease. 7-valent pneumococcal conjugate vaccine ( PCV7) has been incorporated into USA vaccination program since 2000. Direct and indirect vaccine effects were published enormously during the past 10 years. PCV7 started to enter Taiwan market since 2005. The aim of this study was to survey the efficacy of PCV7 based on the prevalence of invasive pneumococcal disease before and after the introduction of PCV-7.
The author involved in a big nasopharyngeal carriage survey conducted by 3 major medical centers located at north, central and south Taiwan. Nasopharyngeal carriage rate of children in Taiwan reduced year by year after 2006. The peak carriage rate appeared at the age of 18 to 24 months old, followed by age group between 2 and 5 years. The main serotypes of Streptococcus pneumoniae isolated from cases were 6B, 14, 19F and 23F which were included in PCV7. It showed that the phenomenon of serotype replacement had not presented in observing period from 2006 to 2009. Data from Taiwan Bureau of Health Insurance from 1997 to 2008 revealed hospitalization and mortality rate owing to IPD were high in children less than 12 months of age. The case fatality rate is more than 5% at 1997 and decreased to 1.36% at 2008. The hospitalization rate per 100000 due to IPD analyzing from 1997 to 2008 showed the trend of moving down.
According to the highest carriage rate in children of18-24 months old, the maximum age of PCV7 vaccination in order to get immune before colonization is 1 year old. Increasing coverage rate of PCV7 vaccine should be considered seriously in Taiwan to continue lower down the prevalence of IPD.
論文目次 中文摘要 I
Abstract II
致謝 III
目錄 IV
表目錄 V
圖目錄 VI
第一章 前言 1
第二章 文獻探討 4
第一節 疾病簡介 4
第二節 流行病學 5
第三節 鼻咽腔帶原 7
第四節 肺炎鏈球菌疫苗 8
第三章 材料與方法 11
第一節 台灣健康兒童鼻咽腔肺炎鏈球菌帶原情形 11
第二節 台灣五歲以下兒童侵襲性肺炎鏈球菌症的住院率 13
第四章 結果 16
第一節 台灣健康兒童鼻咽腔帶菌情形 16
第二節 台灣五歲以下兒童侵襲性肺炎鏈球菌症的住院率 19
第五章 討論 23
參考文獻 32
參考文獻 1. Tilghman RC & Finland M. Clinical significance of bacteremia in pneumococcal pneumonia. Arch Intern Med 1937;59: 602.
2. Austrian R & Gold J. Pneumococcal bacteremia with especial reference to bacteremic pneumococcal pneumonia. Ann Intern Med 1964;60: 759–776.
3. Hansman D, Bullen MM. A resistant pneumococcus . Lancet 1967;2:264-5.
4. Mace JW, Janik DS, Sauer RL Quilligan JJ. Penicillin-resistant pneumococcal meningitis in an immunocompromised infant. J Pediatr 1977;91:506-57.
5. Hsueh PR, Teng LJ, Lee LN, et al. Extremely high incidence of macrolide and trimethoprim-sulfamethoxazole resistance among clinical isolates of Streptococcus pneumonia in Taiwan. J Clin Microbiol 1999;37:897-901.
6. Lu CY, Lee PI, Hsueh PR, et al. Penicillin-nonsusceptible Streptococcus pneumoniae infections in children. J Microbil Immuno Infect 1999;32:179-86.
7. Wang CC, Chu ML, Yu CM, et al. Antimicrobial resistance and serotype distribution of invasive Streptococcus pneumoniae strains isolated from children in Taiwan. In: Program and abstract of the 10th Asian Congress of Pediatrics Taipei: The Chinese Taipei Pediatric Association 2000:125.
8. WHO (1994) Programme for control of acute respiratory infections. Sixth programme report. (Geneva, World Health Organization).
9. WHO (1996) Global Programme for Vaccines and Immunization: report of the Meeting of Scientific Group of Experts (SAGE) of the Children"s Vaccine Initiative and the Global Programe for Vaccines and Immunization (Geneva, WHO).
10. WHO (1999) Pneumococcal vaccine. WHO position paper. Weekly Epidemiologic Record 74: 177–184
11. Greenwood B. The epidemiology of pneumococcal infection in children in the developing world. Phil Trans R Soc Lond B 1999; 354: 777–785.
12. Hennerberger PK, Galaid EI, Marr, JS. The descriptive epidemiology of pneumococcal meningitis in New York city. Am J Epidemiol 1983; 117, 484-491.
13. Wong WY, Overturf GD, Powars DR. Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis and vaccination. Clin Infect Dis 1992; 14: 1124-1136.
14. Weber MW. The clinical spectrum of respiratory syncytial virus disease in The Gambia. Pediatr Infect Dis J 1998; 17:224-230.
15. Ghafoor A, Nomani N K, Ishaq Z, et al. Diagnoses of acute respiratory infections in children in Rawalpindi and Islamabad, Pakistan. Rev Infect Dis 1990;12:(Suppl. 8), S907-S914
16. Gilks CE. Acute bacterial infections and HIV disease. Br Med Bull 1998 ;54: 383-393.
17. Nathoo K J, Nkrumah F K, Ndlovu D, et al. Acute lower respiratory tract infection in hospitalized children in Zimbabwe. Ann Trop Paediatr 1993; 13: 253-261.
18. Crewe-Brown H H, Karstaedt A S, Saunders G L, et al. Streptococcus pneumoniae blood culture isolates from patients with and without human immunodeficiency virus infection: alterations in penicillin susceptibilities and in serogroups or serotypes. Clin Infect Dis1997; 25: 1165-1172.
19. Klein JO. The epidemiology of pneumococcal disease in infants and children. Rev Infect Dis 1981;3: 246–253.
20. Mats K. Pneumococcal serotypes and their clinical relevance. Thorax 1998;53:159-62.
21. Hsueh PR, Chen HM, Lu YC, et al. Antimicrobial resistance and serotype distribution of Streptococcus pneumoniae strains in southern Taiwan. J Formos Med Assoc 1996;95:29-36.
22. Wang CC, Luo WT, Yu CM, et al. Extremely high antibiotic resistance from nasopharyngeal isolates of Streptococcus pneumoniae among children in Taiwan. In: Program and abstract of the 10th European congress of Clinical Microbiology and Infectious Disease. Stockholm: European Society of Clinical Microbiology and Infectious Disease. 2000.
23. Chiou CC, Liu YC, Huang TS, et al. Extremely high prevalence of nasopharyngeal carriage of penicillin-resistance Streptococcus pneumoniae among children in Kaohsiung Taiwan. J Clin Microbiol 1998;36:1933-7.
24. CDC. Preventing pneumococcal disease among infants and young children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-9).
25. Henrichsen J. Six newly recognized types of Streptococcus pneumoniae. J Clin Microbiol 1995;33:2759–62.
26. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the advisory committee on immunization practices (ACIP). Morb Morta Wkly Report 1997;46:1-24
27. Robinson KA, Baughman W, Rothrock G, et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995-1998: Opportunities for prevention in the conjugate vaccine era. J Am Med Assoc 2001;285:1929-35.
28. World Health Organization. Weekly Epidemiological Record. 2008;42:373-84.
29. Shi ZY, Enright MC, Wilkinson P, et al. Identification of three major clones of multiply antibiotic-resistant Streptococcus pneumoniae in Taiwanese hospitals by multilocus sequence typing. J Clin Microbiol 1998;36:3514-19.
30. Margaret IP, Donald JL, Raymond WH, et al. Evidence of clonal dissemination of multidrug-resistant Streptococcus pneumoniae in Hong Kong. J Clin Microbiol 1999;37:2834–9.
31. Chen YY, Yao SM, Chou CY, et al. Surveillance of invasive Streptococcus pneumoniae in Taiwan, 2002-2003. J Med Microbiol 2006;55:1109-14.
32. Marchisio P, Esposito S, Schito GC, et al. Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children: Implications for the use of heptavalent pneumococcal conjugate vaccine. Emerg Infec Dis 2002;8:479-84.
33. Taiwan CDC. The epidemiology of Streptococcus pneumoniae in Taiwan. 2002;DOH91-DC-1011.
34. Dagan R, Melamed M, Muallem L, et al. Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine. J Infec Dis 1996;174:1271-8.
35. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the advisory committee on immunization practices (ACIP). Morb Morta Wkly Report 2005;54:893-7.
36. Poehling KA, Talbot TR, Griffin MR, et al. Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. J Am Med Assoc 2006;295:1668-74.
37. Kyaw MH, Lynfield R, Schaffner W, et al. Effect of introduction of pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumonia. N Engl J Med 2006;354:1455-63.
38. Farrell DJ, Klugman KP, and Pichichero M. Increased antimicrobial resistance among nonvaccine serotype of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in United States. Pediatr Infect Dis J 2007;26:123-8.
39. Grijalva CG, Nuorti JP, Arbogast PG, et al. Decline in pneumonia admissions after routine childhood immunization with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet 2007;369:1179-86.
40. Victora CG, Habicht J-P, and Byrce J. Evidence-base public health: moving beyond randomized trials. Am J Public Heath 2004;94:400-5.
41. Lo WT, Wang CC, Yu CM, et al. Rate of nasopharyngeal carriage, antimicrobial resistance and serotype of Streptococcus pneumoniae among children in northern Taiwan. J Microbiol Immunol Infect 2003;36:175-181.
42. Marchisio P, Esposito S, Schito CC, et al. Nasopharyngeal carriage of Streptococcus pneumonia in healthy children: Implications for the use of heptavalent pneumococcal conjugate vaccine. Emer Infect Dis 2002;8:479-86.
43. Lauderdale TL, Lee WY, Cheng MF, et al. High carriage rate of high-level penicillin-resistant Streptococcus pneumoniae in a Taiwan kindergarten associated with a case of pneumococcal meningitis. BMC Infectious Diseases 2005; 5:96-103.
44. Ghaffar F, Barton T, Lozano J, et al. Effect of the 7-Valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Colonization by Streptococcus pneumoniae in the First 2 Years of Life. Clin Infect Dis 2004; 39:930–8.
45. Sleeman K, Daniels L, Gupta S, et al. 3rd Int. Symp. Pneumococcai, Pneumococcal Dis., 2002, session R-10, abstr. No.14.
46. Obaro SK, Adegbola RA, Banya WAS, et al. Carriage of pneumococci after pneumococcal vaccination. Lancet 1996;348:271-2.
47. Dagan R, Muallem M, Melamed R, et al. Reduction of pneumococcal nasopharyngeal carriage in early infancy after immunization with tetravalent pneumococcal vaccines conjugated to either tetanus toxoid or diphtheria toxoid.
48. Mbelle N,. Huebner R, Wasas A, et al. Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine. J Infect Dis 1999; 180:1171–6.
49. Dagan R, Givon-Lavi N, Zamir O, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-Valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis 2002; 185:927–36.
50. O’Brien KL, Millar EV, Zell ER, et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial. J Infect Dis 2007; 196:1211–20.
51. Hicks LA, Harrison LH, Flannery B, et al. Incidence of pneumococcal disease due to Non–pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998–2004. J Infect Dis 2007; 196:1346–54Da
52. Choi EH, Kim SH, Eun BW, et al. Streptococcus pneumonia serotype 19A in children, South Korea. Emer Infect Dis 2008; 14: 275-81.
53. Moore MR, Gertz RE, Woodbury RL, et al. Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005. J Infect Dis 2008; 197:1016 –27.
54. Ongkasuwan J, Valdez TA, Hulten KG, et al. Pneumococcal mastoiditis in children and the emergence of multidrug-resistant serotype 19A isolates. Pediatr 2008;122:35-9.
55. Greenberg D. The Shifting Dynamics of Pneumococcal Invasive Disease after the introduction of the pneumococcal 7-valent conjugated vaccine: Toward the new pneumococcal conjugated vaccines. Clin Infect Dis 2009; 49:213–5.
56. Dagan R. Impact of pneumococcal conjugate vaccine on infections caused by antibiotic-resistant Streptococcus pneumonia. Clin Microbiol Infect 2009; 15 (Suppl. 3): 16–20.
57. Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010;201:32-41.
58. Hsieh YC, Lin PY, Chiu CH, et al. National survey of invasive pneumococcal disease in Taiwan under partial PCV7 vaccination in 2007: Emergence of serotype 19A with high invasive potential. Vaccine 2009;27:5513-8.
59. Eskola J, Takala AK, Kela E, et al. Epidemiology of invasive pneumococcal infections in children in Finland. JAMA 1992;268:3323-7.
60. Dubos F, Marechal I, Husson MO, et al. Decline in pneumococcal meningitis after the introduction of the heptavalent-pneumococcal conjugate vaccine in northern France. Arch Dis Child 2007;92:1009–1012.
61. Tsai CJ, Griffin MR , Nuorti JP, et al. Changing epidemiology of pneumococcal meningitis after the introduction of pneumococcal conjugate vaccine in the United States. Clin Infect Dis 2008; 46:1664–72.
62. Liao WH, Lin SH, Lai CC, et al. Impact of pneumococcal vaccines on invasive disease in Taiwan. Eur J Clin Microbiol Infect Dis 2010;29:489-92.
63. Aguiar SI, Serrano I, Pinto FR, et al. Changes in Streptococcus pneumoniae serotypes causing invasive disease with non-universal vaccination coverage of the seven-valent conjugate vaccine. Clin Microbiol Infect 2008; 14: 835–843.
64. Van Gils EJM, Veenhoven RH, Hak E, et al. Effect of reduced-dose schedules with 7-valent pneumococcal conjugate vaccine on nasopharyngeal pneumococcal carriage in children. JAMA 2009;302:159-67.
65. Hollingsworth TD. Controlling infectious disease outbreaks: Lessons from mathematical modeling. J Public Health Policy 2009;30:328-41.
66. Leino T, Hoti F, Syrjanen R, et al. Clustering of serotypes in a longitudinal study of Streptococcus pneumoniae carriage in three day care centres. BMC Infect Dis 2008;8:173-82.
67. Hoti F, Erasto P, Leino T, et al. Outbreaks of Streptococcus pneumoniae carriage in day care cohorts in Finland-Implications for elimination transmission. BMC Infect Dis 2009;9:102-114.
68. Weycker D, Edelsberg J, Halloran ME, et al. Population-wide benefits of routine vaccination of children against influenza. Vaccine 2005;23:1284-93.
69. Reichert TA, Sugaya N, Fedson D, et al. The Japanese experience with vaccinating schoolchildren against influenza. N Eng J Med 2001;344:889-96.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2011-09-02起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2011-09-02起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw