肺炎鏈球菌疾病與疫苗 肺炎鏈球菌疾病與疫苗 2008 年 6 月

什麼是肺炎鏈球菌疾病? 90 肺炎鏈球菌疾病是由《肺炎鏈球菌》所引起的連串疾病。 超過 種型號 超過 種型號 90 Invasive pneumococcal disease is the leading cause of meningitis in children under 5 years and kills one in ten times. Pneumococcal disease can range in severity; on the mild side, it is the leading cause of ear infections and can often cause sinusitis. It is a leading cause of bacterial pneumonia. Invasive pneumococcal disease can cause meningitis and bacteraemia, a life-threatening emergency. In Australia in 2002, pneumococcal disease caused 761 cases of infection and 10 deaths in children under the age of five years. 1 in 4 of the survivors will have long-term disability including hearing impairment, spasticity and learning difficulties. In young children, invasive pneumococcal disease occurs at least 28 times more often than the better-known meningococcal group C disease In children under 5 years old, 81% of the cases of invasive pneumococcal disease occur in children who have no identifiable risk factors. A child with pneumococcal disease can progress from symptom-free to death rapidly.  The symptoms are easily mistaken for a common cold. 

兒童及長者如何感染肺炎鏈球菌疾病? 健康成年人及兒童的鼻腔及咽喉均可帶菌。 小孩透過噴嚏及咳嗽飛沬互相傳染。 幼兒缺乏肺炎鏈球菌抗體，較成年人易受感染。 很多兒童會成為帶菌者，但並非全部會發病。 6-24月齡以至幼稚園學生都是高危人族。 長者體弱及免疫失調，亦容易患病。 The pneumococcal bug is carried usually harmlessly in the nose and throat of healthy adults and children. Most children will become carriers but not all will become sick. Pneumococcal disease is usually spread through air born droplets. So in an enclosed or confined area, such as a childcare centre, an infected child coughing and sneezing can easily pass on the disease to other children. Children are more susceptible to pneumococcal disease as they lack the antibodies to fight the bacteria

香港幼兒的帶菌情況 香港幼兒帶菌率高達19.4%。一項由招瑞生醫生負責，於1999年至2000年間在79間托兒所內進行的研究結果顯示，在1,978名兩歲至六歲的幼童中，383名幼童鼻腔中帶有肺炎鏈球菌。 帶菌率在幼兒群中更為普遍。 年歳 帶菌率(%) 2-6 19.4 2-3 28.8 4 32.6 5 20.1 6 15.2

鼻腔帶菌 肺炎 腹膜炎 腦膜炎 空氣飛沫 吸入 局部散播 中耳炎 鼻竇炎 入侵性 肺腔蓄膿 心包蓄膿 菌血症 關節炎/骨髓炎 非入侵性 Bogaert D., R. de Groot, and P. W. Hermans. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. The Lancet Infectious Diseases 3 (Mar 2004): 144-54.

肺炎鏈球菌疾病有多嚴重 估計每年個案 入侵性 腦膜炎 菌血症 發病率 肺炎 非入侵性 中耳炎 五歲以下兒童： 70 700 疾病嚴重程度 Adapted from: American Academy of Pediatrics. Pediatrics. 2000;106:367-376 & MMWR. 1997;46:1-24 中耳炎 肺炎 菌血症 腦膜炎 估計每年個案 五歲以下兒童： >40000 1-2歲 1300 需入院 700 發病率 疾病嚴重程度 入侵性 非入侵性 70 The cases of disease resulting from the pneumococcus range from 1400 cases of invasive bacterial meningitis per year to the most prevalent 5-7 million cases of noninvasive otitis media.

肺炎鏈球菌疾病的發病率 ★ 二歲以下最高危 全球每年因此病死亡約 1,600,000 人 約 70-100 萬為5歲下幼童 香港每十萬名五歲以下兒童： 腦膜炎: 1 名 菌血症: 20 名 肺炎: 100 名 ★ 二歲以下最高危 Hong Kong Journal of Pediatric (New Series) 2001: 6: 127 – 132 Dr. K C Kwong, Princess Margaret Hospital

肺炎鏈球菌經鼻腔帶菌比率 成人 幼童 托兒所 小學 初中 帶菌率(%) 有孩子家庭 無孩子家庭 10 20 30 40 50 60 60% 35% 25% 有孩子家庭 無孩子家庭 29% 6% 成人 幼童 57

怎樣治療肺炎鏈球菌疾病? 抗生素: 主要治療方法 難題: 診斷困難 時間緊迫 抗生素抗藥性問題嚴重 抗生素: 主要治療方法 難題: 診斷困難 時間緊迫 抗生素抗藥性問題嚴重 Meningitis and septicaemia can develop very quickly – children can go from the flu-like symptoms listed earlier to ICU. If pneumococcal disease is diagnosed early on, it can be treated with antibiotics. However, the bacteria is becoming more resistant to antibiotics making it difficult to treat and resulting in longer hospital time for the individual involved

肺炎鏈球菌腦膜炎的徵狀 徵狀與普通感冒相似，而且發病時不一定出現所有徵狀。 昏厥 發燒 嘔吐 易發怒 怕強光 渴睡、混亂及失去知覺 尖聲痛哭 肌肉或關節痛 頭痛 頸部僵硬 (幼兒並不常見) 腦囟鼓出 徵狀與普通感冒相似，而且發病時不一定出現所有徵狀。 Pneumococcal meningitis can present with the following symptoms. These symptoms can look like the flu and not all symptoms may be present.

最合乎邏輯和有效阻止抗藥性蔓延、預防傳染病的方法 接種疫苗 – 預防勝於治療 世界衛生組織認同疫苗注射是 最合乎邏輯和有效阻止抗藥性蔓延、預防傳染病的方法 World Health Organization. Overcoming Antimicrobial Resistance: World Health Report on Infectious Diseases 2000.

傳統疫苗: 肺炎鏈球菌多醣疫苗 PPV 針對 23 種血清型肺炎鏈球菌 可直接對付 88% 菌血症 間接對付8%其他疾病 抵抗肺炎的成效較低

傳統多醣疫苗的限制 只適用於兩歲以上兒童，令他們產生抗體 不能觸發T細胞免疫反應及抗體再生反應 免疫作用短暫, 需要不停注射加強劑 抗體抗菌能力低 抗體效能不持久

肺炎鏈球菌Streptococcus pneumoniae 肺炎鏈球菌疫苗科技新突破 肺炎鏈球菌Streptococcus pneumoniae 撤走細菌多醣莢膜外層　 多醣大量發酵及淨化 ７種多醣被分別催化及和CRM197蛋白接合 混合製造成接合疫苗

肺炎鏈球菌接合疫苗的成效 有效讓97.4%幼兒預防感染特定血清型引致的入侵性肺炎鏈球菌疾病 (臨床研究人數: 3萬7千名幼兒) 有效讓89.1%兒童預防感染所有血清型引致的入侵性肺炎鏈球菌疾病 對2歲以下幼兒，能有效減低96%幼兒感染特定血清型引致的入侵性肺炎鏈球菌疾病 ，及80%幼兒感染肺炎鏈球菌疾病 (美國疾病及預防控制中心2003年數據顯示) Clarify vaccination program and catch up component Discuss eligibility Let parents know that the vaccine is FREELY available from their GP as of Jan 1 Let them know that GP will be fully informed and ready to administer the vaccine It will be kept at the GP surgery – no need for a script for children born from 1 Jan 2003.

肺炎鏈球菌接合疫苗的影響： 兩歲以下幼童每年患肺炎鏈球菌疾病發病率（1996年4月至2003年3月） 肺炎鏈球菌接合疫苗引入市場 (2000年2月) 疫苗血清型 相互作用血清型 非疫苗血清型 Shinefield H. et al. Impact of the introduction of pneumococcal conjugate vaccine on the epidemiology of invasive disease in children less than five years of age with Northern California Kaiser Permanente (NCKP), 3rd World congress of pediatric infectious diseases – WSPID, Santiago, Chile, Nov 19-23, 2002

12-15歲兒童接受肺炎鏈球菌 接合疫苗加強劑注射後的免疫反應 28Rennels et al., Pediatrics 1998; 101:604-611 96%-100% of children had >0.15 µg/ml of antibody, and 84%-100% achieved a level of >1 µg/ml against specific serotypes Assuming that antibody concentrations of >0.15 µg/ml and >1 µg/ml are those required for short term and long term protection

肺炎鏈球菌對盤尼西林的抗藥性 (美國, 1979至 2003年) 肺炎鏈球菌對盤尼西林的抗藥性 (美國, 1979至 2003年) 肺炎鏈球菌接合疫苗 2003 為初步獲得之數據 1979-1994: CDC Sentinel Surveillance Network 1995-2002: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program Courtesy: Dr. Cynthia Whitney; U.S. Centers for Disease Control & Prevention; Atlanta, GA, USA

幼兒 – 高危一族 高危一族包括: 芬蘭研究顯示（相對於沒有上托兒所的兩歲幼童）： 兩歲以下幼兒 托兒所內幼童 已使用過抗生素之兒童 最近患上耳部感染之兒童 芬蘭研究顯示（相對於沒有上托兒所的兩歲幼童）： 上非家居托兒所令感染機會增加36倍 上私人托兒所令感染機會增加4.4倍

誰應接種肺炎鏈球菌疫苗? 兩歲以下幼兒受感染的風險最高。 六週以上之幼兒至六歲以下之小童（可延至9歲）。 *Rate per 100,000 population; Source: Active Bacterial Core Surveillance/EIP Network

誰不適合接種疫苗? 對疫苗成份(例如白喉類毒素)過敏人士，不宜接種肺炎鏈球菌接合疫苗。

劑量 首次接種年紀 接種劑量取決於兒童首次接種的年紀 如需接種兩針或以上，每針應相隔兩個月或以上。 所需劑量 0 – 6 個月 4 針(出生後 2, 4, 6 月，12-15 月大加强針) 7 - 11 個月 3針 (1年內接種2針、一歲後接種加強針) 12 - 23 個月 2針 (兩針需相隔兩個月注射) 24 個月以上 1針 Often, children will present for immunisation and have missed out on previously scheduled vaccines. To ensure that these ‘overdue’ children can be protected as quickly as possible, ‘catch-up’ vaccinations are available. To ensure protection in all children, particularly those who are in the ‘at risk age groups’ a catch-up program will provide free vaccine for children born from 1 January 2003. This catch-up program will only be running for 12 months, so it is important that all children born after 1 Jan 2003 are vaccinated during this coming year. The number of doses given will vary according to the child’s age. For example, infants between 7-17 months will require 2 doses, 2 months apart, and it is important that both doses are received. Infants older than 18 months require just 1 dose. The catch-up program means that Australian children born from 1 January 2003 will be protected against pneumococcal disease under the universal vaccination program.

家長所關注的安全問題 十分安全、反應多屬輕微，與其他疫苗一反應相若 注射部位産生反應 (8-12%) 發燒(≥38℃) (<13%) 發燒(≥38℃) (<13%) 煩躁 昏昏欲睡 睡眠不寧 胃口減少 嘔吐、肚瀉及起紅疹 嚴重反應罕有 Discuss some common questions / anticipated questions parents may raise - expect that some parents may have held off on vaccinating their children until January next year so some anticipated questions they may raise are as follows GPs, healthcare professionals and immunisation providers will be able to address all parental queries. They are already aware of the vaccination program and will be receiving further information in the coming weeks. As with all free vaccines listed on the National Immunisation Schedule, parents will not need to a get a prescription before having their children immunised. GPs and immunisation providers will provide the vaccine free of charge. Parents who would like to safeguard their older children, born prior to 1 January 2003, can purchase the vaccine through the private market

幼兒注射後增加羣體保護 (1998-2001) 減低 70% 2002 data are preliminary

接合疫苗適合性比較 Prof YLLau

建議使用肺炎鏈球菌接合疫苗 全民注射：為所有23 個月或以下的幼兒接種 為所有出現以下情況的24至59個月的幼兒進行接種: 高危人士（托兒所、育嬰院、幼稚園） 鐮狀細胞性貧血患者 脾 狀機能失調患者 愛滋病帶菌者 /愛滋病患者 慢性疾病患者 免疫系統失調患者 MMWR. 2000;49(No. RR-9):1-38.

成本效益 治療此病費用昂貴 此病死亡率及引起的傷殘情況嚴重 疫苗可減了入院及治療引起的痛苦 疫苗成本相對輕微 預防勝於治療 Current treatment is antibiotics Discuss antibiotic resistance, occurrence of resistant strains of the bacterium Discuss presentation rates, difficulty to diagnose, WA data which shows that on average patients present three times before they are accurately diagnosed, hospitalisation rates, length of stay in ICU and long term effects. 預防勝於治療

資料庫 香港醫學會 www.hkma.org 香港衛生防護中心 www.chp.gov.hk 美國CDC www.cdc.gov/nip Immunization Action Coalition www.vaccineinformation.org