高疫苗覆盖率下发生水痘暴发的流行因素研究

张磊; 王勇; 刘元宝; 孙翔; 汤奋扬; 周明浩

doi:10.16462/j.cnki.zhjbkz.2019.04.010

高疫苗覆盖率下发生水痘暴发的流行因素研究

doi: 10.16462/j.cnki.zhjbkz.2019.04.010

张磊¹,
王勇¹,
刘元宝²,
孙翔²,
汤奋扬²,
周明浩^{1, 2, ,}

1.
211166 南京, 南京医科大学公共卫生学院
2.
210009 南京, 江苏省疾病预防控制中心免疫规划所

基金项目:

江苏省333高层次人才培养工程 BRA2017538

江苏省医学重点学科建设项目 ZDXKA2016008

详细信息

通讯作者:
周明浩, E-mail: zmh@jscdc.cn

中图分类号: R181
计量
- 文章访问数: 226
- HTML全文浏览量: 75
- PDF下载量: 38
- 被引次数: 0
出版历程
- 收稿日期: 2018-11-18
- 修回日期: 2019-01-25
- 刊出日期: 2019-04-10

Study on epidemic factors of varicella outbreak under high varicella vaccine coverage

1.
School of Public Health, Nanjing Medical University, Nanjing 211166, China
2.
Department of Expanded Programme on Immunization, Jiangsu Provincial Centre for Disease Control and Prevention, Nanjing 210009, China

Funds:

The "333" Project of Jiangsu Province BRA2017538

Construction Project of Key Medical Disciplines in Jiangsu Province ZDXKA2016008

More Information

Corresponding author: ZHOU Ming-hao, E-mail: zmh@jscdc.cn

摘要

摘要: 目的探索1剂次水痘疫苗高覆盖率下水痘暴发的流行因素及1剂次水痘疫苗的保护效果，为控制水痘暴发疫情、调整优化水痘免疫策略提供科学依据。方法采用1：2配对病例对照研究，对2018年发生于江苏省苏中地区一中心小学的一起水痘暴发疫情开展流行病学调查。水痘暴发的流行因素分析采用条件Logistic逐步回归分析。结果该疫情共持续14 d，共报告水痘确诊病例45例，其中突破病例占71.1%。突破病例的发热情况、出疹程度、病程与无免疫史病例相比均较轻(均有P < 0.05)。条件Logistic回归分析提示，参加课外辅导机构(OR=2.6，95% CI：2.0~3.2)，有兄弟姐妹(OR=2.5，95% CI：2.1~4.3)，无水痘疫苗接种史(OR=2.7，95% CI：2.4~4.2)，与水痘患者接触史(OR=2.4，95% CI：1.1~5.3)是水痘暴发的流行因素。接种年限>5年，初次免疫年龄 < 15月龄是发生突破病例的潜在危险因素(均有P < 0.05)。1剂次水痘疫苗的总体保护效果为77.9%(95% CI：53.3%~92.1%)。结论突破病例临床症状较轻，1剂次水痘疫苗不足以控制水痘暴发疫情，其疫苗保护效果有限。建议采用2剂次水痘免疫策略。
- 水痘疫苗 /
- 疫苗保护效果 /
- 突破病例
Abstract: Objective To explore the epidemic factors of varicella transmission under high varicella vacince coverage, assess the vaccine effectineness of one dose of varicella vaccine, so as to provide scientific basis for controlling the varicella outbreak and optimizing the varicella immunization strategy. Methods A 1:2 paired case-control study of a varicella outbreak was conducted in a primary school in central region of Jiangsu Province in 2018. Analysis of varicella epidemic factors was performed using conditional logistic stepwise regression. Results This outbreak lasted for 14 days. A total of 45 students were infected with varicella, of which 71.1% were breakthrough cases. The fever, rash degree and disease course of breakthrough cases were all relatively mild compared with those without immune history (all P < 0.05).The results of conditional logistic stepwise regression suggested that participating in extracurricular tutoring institutions(OR=2.6, 95% CI: 2.0-3.2), having brothers or sisters(OR=2.5, 95% CI: 2.1-4.3), without vaccination history of varicella vaccine(OR=2.7, 95% CI: 2.4-4.2), and contacting with varicella patients (OR=2.4, 95% CI: 1.1-5.3) were risks factor for varicella transmission. Time since vaccination >5 years and the initial immunization age < 15 months were potential risk factors for breakthrough cases. The overall vaccine effectiveness of one dose of varicella vaccine was 77.9%(95% CI: 53.3%-92.1%). The fever, severity of the rash and the course of the disease were all milder than those without the history of immunization (all P < 0.05). Conclusions The clinical symptoms of the breakthrough cases are relatively mild, and one dose of varicella vaccine is insufficient to control the outbreak of varicella with limited vaccine effectiveness. Two doses of varicella immunization strategy is recommended.
- Varicella vaccine /
- Vaccine effectiveness /
- Breakthough cases

HTML全文

图 1 不同免疫史患者出诊日期分布

Figure 1. Date distribution of patients with different immune history

下载: 全尺寸图片幻灯片

表 1 突破病例与无免疫史病例的临床症状比较[n(%)]

Table 1. Comparison of clinical symptoms between breakthrough cases and non-immune cases[n(%)]

特征	突破病例	无免疫史病例	χ²值	P值
发热			5.47	0.019^b
是	10(31.3)	9(69.2)
否	22(68.7)	4(30.8)
皮疹严重程度(个)			7.79	0.020^b
＜50	25(78.1)	5(38.5)
50~	6(18.8)	5(38.5)
>500	1(3.1)	3(23.0)
并发症^a			0.95	0.329
有	2(2.22)	2(6.7)
无	30(97.8)	11(93.3)
出疹部位(个)			-	0.021^b
1~	14(43.8)	5(38.5)
3~	16(50.0)	3(23.0)
≥5	2(6.2)	5(38.5)
病程(d)			-	＜0.001^b
≤10	23(73.3)	2(36.7)
＞10	9(26.7)	11(63.3)
注：^a并发症包括肺炎、脑炎、皮肤继发细菌感染等疾病；^bFisher确切概率法。

下载: 导出CSV

表 2 水痘暴发的流行因素分析[n(%)]

Table 2. Analysis of risk factors for Varicella transmission factors[n(%)]

特征	病例	对照	P值	单因素分析OR (95% CI)值	P值^a	条件Logistic回归OR(95% CI)值
性别
男	25(55.6)	49(54.4)	0.903	0.9 (0.5~1.9)
女	20(44.4)	41(35.6)		1.0
是否有兄弟姐妹
是	28(62.2)	38(42.2)	0.030	2.3 (1.1~4.6)	0.037	2.5 (2.1~4.3)
否	17(37.8)	52(57.8)		1.0		1.0
参加课外辅导机构
是	29(64.4)	39(43.3)	0.021	2.4 (1.1~4.9)	0.019	2.6 (1.9~3.2)
否	16(35.6)	51(56.7)		1.0		1.0
与水痘患者接触史
有	32(71.1)	42(46.7)	0.029	2.8 (1.6~5.8)	0.041	2.4 (1.1~5.3)
无	13(28.9)	48(53.3)		1.0		1.0
上学交通工具
私家车	8(17.8)	42(46.7)	0.264	1.0
校车	22(48.9)	16(17.8)		1.5 (0.8~2.1)
步行	15(33.3)	32(35.5)		1.0
每日洗手频率
高	11(24.4)	27(30.0)	0.427	0.6 (0.2~2.2)
一般	28(62.2)	52(57.8)		1.0
低	6(13.4)	11(12.2)		1.0
免疫接种史
1剂次	32(71.1)	79(87.7)	< 0.001	0.2 (0.1~0.5)	< 0.001	0.2 (0.1~0.4)
无免疫史	13(28.9)	11(12.3)		1.0		1.0
注：^a条件Logistic回归分析中的P值。

下载: 导出CSV

表 3 水痘突破病例潜在危险因素的单变量分析[n(%)]

Table 3. Analysis of potential risk factors for varicella breakthrough cases[n(%)]

变量	突破病例	对照组有免疫史者	χ²/u值	P值
年龄[月，M(P₂₅, P₇₅)]	9.2(7.5, 12.5)	9.3(6.8, 12.3)	11.23	0.735^a
性别			0.03	0.861^b
男	18(56.2)	43(54.4)
女	14(43.8)	36(45.6)
初次免疫年龄(月)			4.23	0.041^b
＜15	19(59.4)	30(37.9)
≥15	13(40.6)	49(62.1)
接种年限(年)			4.06	0.044^b
≤5	14(43.7)	51(64.6)
＞5	18(56.3)	28(35.4)
注: ^aWilcoxon rank-u检验；^bPearson's chi-square检验。

下载: 导出CSV

表 4 水痘疫苗的保护效果分析[n(%)]

Table 4. Analysis of the protective effectiveness of varicella vaccine[n(%)]

	病例	对照	VE(95% CI)^a(%)	P值
总体疫苗VE
有免疫史	32(71.1)	79(87.7)	77.9 (53.3~92.1)	< 0.001
无免疫史	13(28.9)	11(12.3)	Ref ^b
不同免疫时间VE(月)
< 15	19(42.2)	31(34.5)	48.2(0.0~80.7)	0.189
≥15	13(28.9)	48(53.3)	77.1(37.1~91.7)	0.003
无免疫史	13(28.9)	11(12.3)	Ref ^b
不同接种年限VE(年)
≤5	14(31.1)	58(64.4)	79.6(44.9~92.5)	0.002
> 5	18(40.0)	21(23.3)	27.5(0.0~73.9)	0.536
无免疫史	13(28.9)	11(12.3)	Ref ^b
注：^aVE: (1-OR)×100%；^bRef为参照水平(疫苗保护效果)。

下载: 导出CSV

参考文献(15)

[1]	Suo L, Lu L, Wang Q, et al. Varicella outbreak in a highly-vaccinated school population in Beijing, China during the voluntary two-dose era[J]. Vaccine, 2017, 35(34): 4368-4373. DOI: 10.1016/j.vaccine.2017.06.065.
[2]	麦冰, 陈抒豪, 黄劲梅, 等. 水痘疫苗在学校暴发疫情中保护效果的回顾性队列研究[J]. 微生物学免疫学进展, 2013, 41(1): 20-22. DOI: 10.13309/j.cnki.pmi.2013.01.007. Mai B, Cheng SH, Huang JM, et al. A retrospective cohort study on the effetiveness of varicella vaccine against varicella outbreak in school[J]. Prog in Microbiol Immunol, 2013, 41(1): 20-22. DOI: 10.13309/j.cnki.pmi.2013.01.007.
[3]	Michalik DE, Steinberg SP, Larussa PS, et al. Primary vaccine failure after 1 dose of varicella vaccine in healthy children[J]. J Infect Dis, 2008, 197(7): 944-949. DOI: 10.1086/529043.
[4]	Fu J, Wang J, Jiang C, et al. Outbreak of varicella in a highly vaccinated preschool population[J]. Int J Infect Dis, 2015, 37(1): 14-18. DOI: 10.1016/j.ijid.2015.06.003.
[5]	王青海, 王旭, 刘淑岭, 等. 北京市西城区一起学校水痘突发公共卫生事件的调查分析[J]. 中国病毒病杂志, 2017, 7(5): 391-393. DOI: 10.16505/j.2095-0136.2017.05.016. Wang QH, Wang X, Liu L, et al. Investigation of varicella out breakthough cases in a primary school of Xicheng district[J]. Chin J Viral Dis, 2017, 7(5): 391-393. DOI: 10.16505/j.2095-0136.2017.05.016.
[6]	Wu QS, Liu JY, Wang X, et al. Effectiveness of varicella vaccine as post-exposure prophylaxis during a varicella outbreak in Shanghai, China[J]. Int J Infect Dis, 2018, 66(2): 51-55. DOI: 10.1016/j.ijid.2017.10.016.
[7]	Smith-Norowitz TA, Saadia TA, Norowitz KB, et al. Negative IgG Varicella Zoster Virus Antibody Status: Immune Responses Pre and Post Re-immunization[J]. Infect Dis Ther, 2018, 7(1): 175-181. DOI: 10.1007/s40121-017-0182-x.
[8]	Fu C, Wang M, Liang J, et al. The effectiveness of varicella vaccine in China[J]. Pediatr Infect Dis J, 2010, 29(8): 690-693. DOI: 10.1097/INF.0b013e3181d7380e.
[9]	Shady I. Seroprevalence of antibodies against varicella zoster virus and rubella virus among newly recruited expatriate healthcare workers: a cross-sectional study[J]. BMJ Open, 2018, 8(3): e019339. DOI: 10.1136/bmjopen-2017-019339.
[10]	Banz K, Wagenpfeil S, Neiss A, et al. The Burden of Varicella in Germany: Potential Risks and Economic Impact[J]. Eur J Health Econ, 2004, 5(1): 46-53. DOI: 10.1007/s10198-003-0200-7.
[11]	Hobbelen PH, Stowe J, Amirthalingam G, et al. The burden of hospitalisation for varicella and herpes zoster in England from 2004 to 2013[J]. J Infect, 2016, 73(3): 241. DOI: 10.1016/j.jinf.2016.05.008.
[12]	Vaidya SR, Tilavat SM, Kumbhar NS, et al. Chickenpox outbreak in a tribal and industrial zone from the Union Territory of Dadra and Nagar Haveli, India[J]. Epidemiol infect, 2018, 146(4): 476-480. DOI: 10.1017/S0950268818000201.
[13]	Pe? a Blasco G, Blasco Pérez-Aramendía MJ. A cost-benefit analysis of varicella vaccination in Aragon[J]. Arch Argent Pediatr, 2017, 115(5): 432-438. DOI: 10.5546/aap.2017.eng.432.
[14]	Ludwig B, Kraus FB, Allwinn R, et al. Loss of varicella zoster virus antibodies despite detectable cell mediated immunity after vaccination[J]. Infection, 2006, 34(4): 222-226. DOI: 10.1007/s15010-006-5616-9.
[15]	Leung J, Broder KR, Marin M. Severe varicella in persons vaccinated with varicella vaccine(breakthrough varicella): a systematic literature review[J]. Expert Rev Vaccines, 2017, 16(4): 391-400. DOI: 10.1080/14760584.2017.1294069.