2008年的一项研究显示1,肺炎是5岁以下儿童死亡的首要原因;全球超过一半的肺炎病例集中分布在6个国家,分别为:印度(4300万)、中国(2100万)、巴基斯坦(1000万),以及孟加拉国、印度尼西亚和尼日利亚(各600万)(见图1和表1、表2)。儿童肺炎主要的致病菌是肺炎球菌,占确诊肺炎的30-50%1。一项关于5岁以下儿童肺炎发病率和死亡率的全球系统综述研究显示2,发展中国家5岁以下儿童肺炎发病率从2000年的329‰下降到2015年的231‰,同期死亡率从15.2‰降至7.4‰。另外,该研究还发现,2015年,全球5岁以下儿童肺炎病例的54%以上集中在印度、尼日利亚、印度尼西亚、巴基斯坦和中国这五个国家。
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表1 每年5岁以下儿童肺炎估计发病率和新发病例数(按WHO组织区域划分)
地区 | <5岁儿童总人数 (百万) | 儿童发病次数 (每人年) | 新增病例数 (百万) |
非洲 | 105.62 | 0.33 | 35.13 |
美洲 | 75.78 | 0.10 | 7.84 |
地中海地区 | 69.77 | 0.28 | 19.67 |
欧洲 | 51.96 | 0.06 | 3.03 |
东南亚地区 | 168.74 | 0.36 | 60.95 |
西太平洋地区 | 133.05 | 0.22 | 29.07 |
发展中国家 | 523.31 | 0.29 | 151.76 |
发达国家 | 81.61 | 0.05 | 4.08 |
合计 | 604.93 | 0.26 | 155.84 |
表2 2008年全球预估肺炎新发病例数最多的15个国家
国家 | 预估新增病例数(百万) | 儿童发病次数 (每人年) |
印度 | 43.0 | 0.37 |
中国 | 21.1 | 0.22 |
巴基斯坦 | 9.8 | 0.41 |
孟加拉国 | 6.4 | 0.41 |
尼日利亚 | 6.1 | 0.34 |
印度尼西亚 | 6.0 | 0.28 |
埃塞俄比亚 | 3.9 | 0.35 |
刚果民主共和国 | 3.9 | 0.39 |
越南 | 2.9 | 0.35 |
菲律宾 | 2.7 | 0.27 |
苏丹 | 2.0 | 0.48 |
阿富汗 | 2.0 | 0.45 |
坦桑尼亚 | 1.9 | 0.33 |
缅甸 | 1.8 | 0.43 |
巴西 | 1.8 | 0.11 |
在耐药性方面,一项针对儿童肺炎链球菌分离株对抗菌素耐药性的系统综述结果显示3,接种PCV后肺炎链球菌分离株对青霉素、磺胺甲恶唑-三甲氧苄啶和第三代头孢菌素的不敏感性和耐药性下降;但在东南亚、东亚和大洋洲地区,青霉素、大环内酯类、第三代头孢菌素类和四环素类的耐药性最高;在南亚、东亚和亚太的高收入国家,儿童肺炎链球菌分离株对青霉素的不敏感性分别为13.1% (95%CI 4.3–21.9%)、56.3% (95%CI 45.7–66.9%)和64.2% (95%CI 43.8–84.4%)(见图2,图3)。此外,点估计结果显示,定植菌对青霉素的耐药性高于侵袭性肺炎链球菌。
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肺炎链球菌肺炎
研究结果显示4,2015年全球5岁以下儿童肺炎链球菌肺炎的病例数为891万,死亡数为25.7万,发病率为1356/10万,死亡率为36/10万,病死率为3%(见表3)。
一项系统综述研究结果显示,非重症肺炎患儿发生至少一种长期严重后遗症的风险为5.5%,而在重症肺炎患儿中,发生至少一种长期严重后遗症的风险为13.6%5。此外,社区获得性肺炎可引发心脏病并发症。另一项系统综述研究结果显示,社区获得性肺炎患者中,心脏疾病、突发心力衰竭、急性冠脉综合征和突发心律失常的发生率分别为2.3-17.7%、1.4-23.9%、0.1-5.3%和0.9-18.5%6。
一项关于2000年至2015年全球5岁以下儿童肺炎的发病率和病死率的系统研究显示,2015年,全球54%的肺炎和重症肺炎病例来自5个发展中国家(印度、尼日利亚、印度尼西亚、巴基斯坦和中国);与2000年相比,75%(99/132)的发展中国家的临床肺炎和重症肺炎发病率至少下降了25%,其中中国的下降率最高,约69%2(图4)。
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肺炎链球菌脑膜炎
2015年全球5岁以下儿童肺炎链球菌脑膜炎病例数为8.39万,死亡数为3.79万,发病率为13/10万,死亡率为5/10万,病死率为44%4(表3)。
一项系统综述研究结果显示,全球肺炎链球菌脑膜炎患者出院后出现至少一种轻微或严重后遗症的中位数风险为34.7%,出现至少一种轻微后遗症的中位数风险为18.6%,出现至少一种严重后遗症的中位数风险为24.7%7。在一项关于高收入国家肺炎球菌性脑膜炎后遗症风险系统综述中显示,31.7%肺炎链球菌脑膜炎患者会发生后遗症;其中,听力损失、癫痫发作、脑积水、痉挛/麻痹、颅神经麻痹和视力障碍的患病比例分别为20.9%、6.5%、6.8%、8.7%、12.2%和2.4%8。
表3 全球各地区2015年肺炎链球菌疾病的发病率和死亡率
全球 | 非洲 | 美洲 | 地中海地区 | 欧洲 | 东南亚地区 | 西太平洋地区 | |||
总体情况 | |||||||||
1–59月龄儿童* | 657,127,399 | 157,167,486 | 73,551,167 | 78,313,066 | 55,681,027 | 175,795,291 | 116,619,363 | ||
死亡人数† | 3,260,731 | 1,835,315 | 106,231 | 428,791 | 60,540 | 664,465 | 165,389 | ||
因肺炎死亡人数s‡ | 761,193 | 395,431 | 19,560 | 111,895 | 10,453 | 188,229 | 36,243 | ||
因脑膜炎死亡人数‡ | 115,173 | 65,735 | 2,756 | 13,801 | 1,515 | 26,955 | 4,388 | ||
因肺炎链球菌造成的疾病负担 | |||||||||
发病率(UR) | 1,419 (1,197–1,737) | 1,603 (1,337–1,997) | 358 (301–441) | 1,261 (1,066–1,542) | 207 (170–261) | 2,509 (2,132–3,048) | 881 (745–1,067) | ||
严重病例发病率(UR) | 559 (411–658) | 619 (452–739) | 142 (104–169) | 491 (362–576) | 129 (94–154) | 986 (729–1154) | 347 (256–404) | ||
病例数(UR) | 9,180,000 (7,870,000–11,400,000) | 2,440,000 (2,100,000–3,140,000) | 259,000 (221,000–325,000) | 968,000 (835,000–1,210,000) | 111,000 (94,800–145,000) | 4,400,000 | 1,010,000 (868,000–1,240,000) | ||
(3,750,000–5,360,000) | |||||||||
严重病例人数(UR) | 3,670,000 (2,700,000–4,320,000) | 973,000 (710,000–1,160,000) | 104,000 (76,300–124,000) | 385,000 (284,000–451,000) | 72,100 (52,600–85,800) | 1,730,000 | 404,000 (298,000–472,000) | ||
(1,280,000–2,030,000) | |||||||||
死亡率(UR) | 45 (29–56) | 92 (60–114) | 8 (5–10) | 47 (31–57) | 9 (6–11) | 50 (32–62) | 13 (9–16) | ||
死亡人数(UR) | 318,000 (207,000–395,000) | 166,000 (109,000–205,000) | 5,700 (3,600–7,800) | 37,100 (24,300–45,300) | 4,900 (3,100–6,100) | 88,500 | 15,300 (10,100–18,700) | ||
(57,200–111,000) | |||||||||
未感染HIV患儿的死亡人数(UR) | 294,000 (192,000–366,000) | 145,000 (94,500–179,000) | 5,700 (3,500–7,700) | 36,700 (24,100–44,800) | 4,800 (3,100–6,100) | 87,200 | 15,200 (10,000–18,600) | ||
(56,400–110,000) | |||||||||
感染HIV患儿的死亡人数(UR) | 23,300 (15,300–28,700) | 21,400 (14,100–26,300) | <100 | 400 (200–500) | <100 | 1,300 (800–1,600) | <100 | ||
肺炎球菌性肺炎 | |||||||||
发病率(UR) | 1,356 (1,170–1,612) | 1,504 (1,298–1,788) | 342 (295–406) | 1,214 (1,047–1,443) | 187 (161–222) | 2,432 (2,098–2,891) | 831 (717–987) | ||
严重病例发病率(UR) | 535 (401–609) | 585 (438–667) | 135 (101–154) | 475 (356–541) | 121 (91–138) | 954 (715–1,089) | 326 (244–372) | ||
病例数(UR) | 8,910,000 (7,690,000–10,600,000) | 2,360,000 (2,040,000–2,810,000) | 251,000 (217,000–299,000) | 951,000 (820,000–1,130,000) | 104,000 (89,600–123,000) | 4,280,000 (3,690,000–5,080,000) | 969,000 (836,000–1,150,000) | ||
严重病例人数(UR) | 3,520,700 (2,640,000–4,010,000) | 919,000 (689,000–1,050,000) | 99,400 (74,500–113,000) | 372,000 (278,000–424,000) | 67,300 (50,400–76,800) | 1,680,000 (1,260,000–1,910,000) | 380,000 (285,000–433,000) | ||
病死率(UR | 3% (2–3) | 6% (4–6) | 2% (1–2) | 3% (2–3) | 4% (3–4) | 2% (1–2) | 1% (1–1) | ||
严重病例病死率(UR) | 7% (5–7) | 15% (11–15) | 5% (3–5) | 8% (6–9) | 6% (4–6) | 4% (3–4) | 3% (2–3) | ||
死亡率(UR) | 36 (26–38) | 76 (54–79) | 6 (4–6) | 39 (28–41) | 7 (5–7) | 39 (28–40) | 10 (7–10) | ||
死亡人数(UR) | 257,000 (182,000–268,000) | 137,000 (96,900–142,000) | 4,600 (3,200–4,800) | 31,000 (22,000–32,300) | 3,800 (2,700–4,000) | 69,200 (49,100–72,100) | 11,600 (8,200–12,100) | ||
未感染HIV患儿的死亡人数(UR) | 238,000 (169,000–248,000) | 119,000 (84,300–124,000) | 4,500 (3,200–4,700) | 30,700 (21,800–32,000) | 3,800 (2,700–4,000) | 68,200 (48,400–71,100) | 11,600 (8,200–12,000) | ||
感染HIV患儿的死亡人数(UR) | 19,300 (13,700–20,100) | 17,800 (12,600–18,600) | <100 | 300 (200–300) | <100 | 1,000 (700–1,000) | <100 | ||
肺炎球菌性脑膜炎 | |||||||||
发病率(UR) | 13 (5–26) | 21 (9–45) | 3 (1–7) | 10 (4–21) | 4 (2–8) | 15 (6–31) | 10 (5–15) | ||
病例数(UR) | 83,900 (36,100–169,000) | 29,400 (11,800–62,300) | 2,300 (900–5,000) | 7,900 (3,200–16,500) | 2,200 (1,000–4,200) | 26,100 (11,200–52,900) | 11,400 (6,300–18,000) | ||
病死率(UR | 44% (18–93) | 61% (24–100) | 27% (8–70) | 52% (21–100) | 25% (10–50) | 39% (16–79) | 17% (8–30) | ||
死亡率(UR) | 5 (2–11) | 13 (5–28) | 1 (0–2) | 5 (2–11) | 1 (0–2) | 6 (2–12) | 2 (1–3) | ||
死亡人数(UR | 37,900 (15,400–79,700) | 20,400 (8,000–43,700) | 600 (200–1,600) | 4,200 (1,600–8,900) | 600 (200–1,100) | 10,200 (4,300–20,800) | 1,900 (1,000–3,500) | ||
未感染HIV患儿的死亡人数(UR) | 35,200 (14,300–73,800) | 17,900 (7,000–38,300) | 600 (200–1,600) | 4,100 (1,600–8,800) | 550 (200–1,100) | 10,100 (4,300–20,500) | 1,900 (1,000–3,500) | ||
感染HIV患儿的死亡人数(UR) | 2,700 (1,100–5,900) | 2,500 (1,000–5,400) | <100 | <100 | <100 | 200 (100–300) | <100 | ||
非肺炎非脑膜炎肺炎球菌性疾病 | |||||||||
发病率(UR) | 50 (22–100) | 77 (31–164) | 13 (5–28) | 37 (15–78) | 17 (7–32) | 62 (27–127) | 41 (22–64) | ||
严重病例发病率(UR) | 11 (5–22) | 13 (5–27) | 4 (1–8) | 6 (2–13) | 5 (2–9) | 17 (7–35) | 11 (6–18) | ||
非严重病例发病率(UR) | 39 (17–78) | 64 (26–137) | 9 (4–21) | 31 (12–64) | 12 (5–23) | 45 (19–92) | 30 (16–47) | ||
病例数(UR) | 326,000 (142,000–653,000) | 122,000 (49,000–257,000) | 9,500 (3,600–21,000) | 29,000 (12,000–60,900) | 9,300 (4,200–18,000) | 110,000 (47,100–223,000) | 47,500 (26,000–75,000) | ||
严重病例人数(UR) | 73,400 (32,400–145,000) | 20,500 (8,400–42,800) | 2,600 (1,000–5,700) | 4,900 (1,900–10,400) | 2,500 (1,100–4,800) | 29,900 (12,800–60,700) | 13,000 (7,100–20,500) | ||
非严重病例人数(UR) | 253,000 (109,000–510,000) | 101,000 (41,000–215,000) | 6,900 (2,600–15,000) | 24,000 (9,600–50,500) | 6,700 (3,000–13,000) | 79,900 (34,300–162,000) | 34,500 (19,000–54,500) | ||
病死率(UR)§ | 31% (13–63) | 44% (17–94) | 21% (6–55) | 38% (14–82) | 19% (8–39) | 30% (13–62) | 13% (7–24) | ||
死亡率(UR) | 3 (1–7) | 5 (2–11) | 1 (0–2) | 2 (1–5) | 1 (0–2) | 5 (2–10) | 1 (1–3) | ||
死亡人数(UR) | 22,700 (9,400–47,200) | 9,000 (3,600–19,100) | 600 (200–1,400) | 1,900 (700–4,100) | 500 (200–1,000) | 9,100 (3,800–18,400) | 1,700 (900–3,100) | ||
未感染HIV患儿的死亡人数(UR) | 21,500 (8,800–44,500) | 7,900 (3,100–16,800) | 600 (200–1,400) | 1,900 (700–4,000) | 500 (200–1,000) | 8,900 (3,800–18,100) | 1,700 (900–3,100) | ||
感染HIV患儿的死亡人数(UR) | 1,300 (500–2,700) | 1,100 (400–2,300) | <100 | <100 | <100 | 100 (100–300) | <100 |
注:数据均为估计值(UR=uncertainty range,不确定范围)。死亡率和发病率的单位为每10万名儿童。发病率和发病人数的估计值包括全部儿童,无论儿童是否感染HIV。除另有说明外,死亡率和死亡人数的估计值不包括HIV感染儿童。
*数据来源于2015年联合国世界人口展望
†数据来源于2015年联合国儿童死亡率评估情况.
‡数据来源于母婴流行病学估计/世界卫生组织联合估计情况
§仅为严重非肺炎非脑膜炎患儿的情况
肺炎链球菌菌血症
关于拉丁美洲的一项系统综述研究显示,在1218名肺炎球菌性疾病病例中,8%(95% CI: 5.3–12.4)为肺炎链球菌菌血症;5岁以下儿童及2岁以下儿童肺炎链球菌菌血症的发病率分别为3.9/10万、5.8/10万9。智利的一项研究结果显示,肺炎链球菌菌血症病例多发生在秋冬季,住院死亡率为33.3%10。
一项系统综述研究发现,在1062例侵袭性肺炎球菌性疾病患者中,16例(1.5%)患有关节炎;69%的原发性化脓性关节炎患者和80%的假肢关节炎患者发生菌血症;肺炎球菌关节炎患者的病死率参差不齐,可高达32%11。
审核校对:李周蓉
参考文献
1 Rudan I, Boschi-Pinto C, Biloglav Z, et al. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ. 2008,86(5):408-416.DOI: 10.2471/blt.07.048769
2 McAllister DA, Liu L, Shi T, et al. Global, regional, and national estimates of pneumonia morbidity and mortality in children younger than 5 years between 2000 and 2015: a systematic analysis. Lancet Glob Health. 2019,7(1): e47-e57. DOI: 10.1016/S2214-109X(18)30408-X
3 Andrejko K, Ratnasiri B, Hausdorff WP, et al. Antimicrobial resistance in paediatric Streptococcus pneumoniae isolates amid global implementation of pneumococcal conjugate vaccines: a systematic review and meta-regression analysis. Lancet Microbe. 2021,2(9): e450-e460.DOI: 10.1016/S2666-5247(21)00064-1
4 Wahl, B., O’Brien, K. L., Greenbaum, A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. The Lancet. Global health, 2018,6(7), e744–e757. DOI: 10.1016/S2214-109X(18)30247-X
5 Edmond K, Scott S, Korczak V. Long term sequelae from childhood pneumonia; systematic review and meta-analysis. PLoS One. 2012,7:e31239. DOI: 10.1371/journal.pone.0031239
6 Corrales-Medina VF, Suh KN, Rose G, et al. Cardiac complications in patients with community-acquired pneumonia: a systematic review and meta-analysis of observational studies. PLoS Med. 2011 ,8(6):e1001048. DOI: 10.1371/journal.pmed.1001048
7 Edmond K, Clark A, Korczak VS, et al. Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis. Lancet Infect Dis. 2010,10(5):317-28.DOI: 10.1016/S1473-3099(10)70048-7
8 Jit M. The risk of sequelae due to pneumococcal meningitis in high-income countries: a systematic review and meta-analysis. J Infect. 2010,61(2):114-24.DOI: 10.1016/j.jinf.2010.04.008
9 Ciapponi A, Elorriaga N, Rojas JI, et al.Epidemiology of pediatric pneumococcal meningitis and bacteremia in Latin America and the Caribbean: a systematic review and meta-analysis. Pediatr Infect Dis J. 2014,33(9):971-8. DOI: 10.1097/INF.0000000000000363
10 Fica A, Bunster N, Aliaga F, et al. Bacteremic pneumococcal pneumonia: serotype distribution, antimicrobial susceptibility, severity scores, risk factors, and mortality in a single center in Chile. Braz J Infect Dis. 2014,18(2):115-23.DOI: 10.1016/j.bjid.2013.06.001
11 Dernoncourt A, El Samad Y, Schmidt J, et al. Case Studies and Literature Review of Pneumococcal Septic Arthritis in Adults. Emerg Infect Dis. 2019,25(10):1824. DOI: 10.3201/eid2510.181695