【摘要】： 流行性腦脊髓膜炎(簡稱流腦)是由腦膜炎雙球菌引起的一種急性呼吸道傳染病,是我國法定乙類傳染病。安徽省歷來是流腦高發(fā)地區(qū)之一,上世紀(jì)80年代后隨疫苗的推廣使用,流腦的發(fā)病得到有效的控制,但近年來,如一些曾經(jīng)很好控制傳染病死灰復(fù)燃一樣,流腦發(fā)病出現(xiàn)迅速上升態(tài)勢,伴隨發(fā)病率上升,流腦的流行特征也出現(xiàn)明顯變化。安徽省地處我國中部地區(qū),特定的地理環(huán)境使得對安徽省相關(guān)疾病的流行特征的研究具有較普遍的外推價值,同時,作為C群流腦疫情首先發(fā)生省份之一,也為我們開展相關(guān)研究工作提供了可能。為此,我們結(jié)合對安徽省既往流腦疫情資料的回顧,開展了本課題研究工作,希望為流腦以及部分疫苗可預(yù)防疾病的預(yù)防策略及控制措施的制定、改進(jìn)提供參考依據(jù)。 目的 了解安徽省流腦流行特征以及近年來出現(xiàn)的變化情況,為預(yù)防控制策略及措施的制定提供理論依據(jù) 材料方法 1、依托疫情報告系統(tǒng)收集安徽省歷年流腦疫情資料。以10年為一時間段將整個研究時間分成6個年代,以淮河、長江為主要參照標(biāo)記,將安徽省分成江淮、淮北和江南三個地區(qū),比較分析了不同年代、不同地區(qū)流腦發(fā)病變化情況。對研究期間安徽省流腦發(fā)病的人群、地區(qū)、時間分布情況進(jìn)行描述性分析。 2、對2003年7月到2007年6月之間合肥地區(qū)所有報告疑似流腦病例進(jìn)行流腦流行病學(xué)個案調(diào)查和臨床病歷資料回顧性調(diào)查;2005年11月份和2006年4月份,采集不同年齡段健康人群咽拭子。根據(jù)我國在校學(xué)生年齡分布情況將所調(diào)查病例分成6個年齡組,統(tǒng)計時間周期以上年7月1日到第二年6月31日為一個統(tǒng)計年份。分年齡組、城鄉(xiāng)地區(qū)的不同分別統(tǒng)計發(fā)病率和病死率,不同年齡組病例構(gòu)成情況也進(jìn)行描述。不同性別病例年齡中位數(shù)及死亡病例年齡中位數(shù)分別進(jìn)行計算。對分類資料進(jìn)行卡方檢驗,應(yīng)用非參檢驗對不同性別間、死亡病例與成活病例年齡進(jìn)行比較分析。應(yīng)用單因素logistic將年齡、發(fā)病與就診時間間隔及臨床表現(xiàn)等逐個納入分析其與病死結(jié)局關(guān)聯(lián),對其中有意義的因素,再共同納入多因素logistic回歸分析,以了解影響流腦病例死亡結(jié)局的危險因素。 結(jié)果 1951-2007年安徽省共發(fā)生流腦病例799387例,年平均發(fā)病率為28.90/10萬,死亡41337例,死亡率為1.49/10萬,病死率為5.17%。在此期間安徽省范圍出現(xiàn)3次大的流行疫情:最大的一次出現(xiàn)在1975-1979年間,并于1977年達(dá)到此次流行年發(fā)病高峰729.25/10萬;疫苗前時期,安徽省流腦疫情有8-10年流行(峰高不同)的規(guī)律,每次大流行持續(xù)時間大約為6-7年左右。上世紀(jì)80年代后隨A群流腦多糖疫苗的推廣使用,流腦發(fā)病率出現(xiàn)持續(xù)下降趨勢,流腦的流行周期也越來越不明顯,但仍在間隔10年左右出現(xiàn)發(fā)病率小幅度異常波動。2003年我省出現(xiàn)C群流腦局部地區(qū)爆發(fā)疫情后,全省流腦疫情呈現(xiàn)小幅反彈現(xiàn)象。安徽省流腦發(fā)病一般是從每年的10-11月份開始出現(xiàn)疫情上升跡象,至第二年的4-5月份達(dá)到發(fā)病高峰,與流行年份相比,散發(fā)年份發(fā)病率的季節(jié)高峰持續(xù)時間要長一個月左右時間。10或11月份發(fā)病率較前5年同月發(fā)病平均水平明顯升高往往預(yù)示下年度發(fā)病上升。1994-1999年間,15歲以下占中病例的78.94%;2000-2007年間,15歲以下占中病例的17.20%,10-25歲年齡組病例占到63.03%。總的男女病例比為1.46:1,但25歲后,男女比為0.70:1。在發(fā)生全省范圍的流腦流行情況下,淮北地區(qū)早于其他兩地區(qū)1-2年出現(xiàn)疫情上升及出現(xiàn)發(fā)病率高峰,但2002年后的C群流腦流行先發(fā)生于江南地區(qū)。江淮、江南、淮北地區(qū)流腦發(fā)病率分別為33.20/10萬、29.03/10萬和30.44/10萬(P = 0.000),三地區(qū)病死率分別為4.37%、4.92%和6.00%(P = 0.000)。 2003年至2007年合肥市累計發(fā)現(xiàn)報告流腦病例386例,年平均發(fā)病率為2.09/10萬,2006/2007年度發(fā)病率達(dá)到2.86/10萬。經(jīng)實驗室確診病例135例,都為C群流腦。城市地區(qū)病例235例(60.88%)、農(nóng)村地區(qū)病例151例(39.12%)。病例年齡中位數(shù)為15歲(最小為2個月,最大為78歲),發(fā)病率最高年齡組為12-17歲組(6.57/10萬),男性病例219例,占總病例的56.7%。在小于22歲病例中,男女病例比例為1.5:1,在大于22歲病例中,男女性別比例為1:1.8。98.2%的病例發(fā)生11月份到第二年的5月份之間。臨床表現(xiàn):急性起病的有334例(96.53%),371例病例有發(fā)熱(96.11%),其它主要癥狀有:有嘔吐的322例(83.42%),惡心311例(80.57%),頸項強直的285例(77.9%),頭痛278例(72.02)。臨床分型:普通型225例(58.29%),暴發(fā)型54例(13.9%),輕型2例(0.52%)。共發(fā)生死亡病例28例,平均病死率為7.25%,死亡病例年齡中位數(shù)為10歲(2個月齡到27歲),比成活病例年齡低,成活病例年齡中位數(shù)為15歲(6個月齡到78歲),通過非參檢驗,兩者分布差異有統(tǒng)計學(xué)意義(Z=2.54,P=0.01)。分析影響病例死亡的主要因素,單因素logistic回歸分析結(jié)果顯示:頭痛、神志不清、惡心、出血點或瘀斑、瘀點數(shù)目超過3個、頸項強直、抽搐、中性粒細(xì)胞80%、克氏征陽性、布氏征陽性以及年齡小于12歲與病例死亡相關(guān)(P 0.05);將這些因素納入logistic回歸模型進(jìn)行多因素分析,瘀點數(shù)目超過3個、中性粒細(xì)胞80%、布氏征陽性為病例死亡危險因素(P 0.05)。聚集性病例21起,病例年齡中位數(shù)為16歲(1歲到69歲),其中年齡在12-21歲的病例占59.31%;健康人群流腦帶菌率流行期為5.99%,高于流行前期的3.05%, ,流行期B群和C群帶菌率上升明顯;健康人群帶菌率有隨年齡增加而升高的趨勢。 結(jié)論 安徽省是流腦易發(fā)生地區(qū),歷史上A群流腦是本地區(qū)占絕對優(yōu)勢的流行菌株,A群多糖疫苗的推廣使用,有效控制了安徽省流腦的發(fā)病;疫苗后時期流腦的流行周期性不再明顯,但每隔10年左右仍能觀察到發(fā)病率小幅度異常上升的現(xiàn)象;C群流腦代替了A群成為安徽省近幾年的流行優(yōu)勢菌株,并引起流腦疫情的反彈上升,病例年齡分布出現(xiàn)上移趨勢,但目前尚處于菌群轉(zhuǎn)換的不穩(wěn)定的過渡時期,需要進(jìn)一步的監(jiān)測研究;流腦流行優(yōu)勢菌群的轉(zhuǎn)換反映了疫苗接種遠(yuǎn)期副(附)效應(yīng)的影響,提示免疫策略及時修訂變化的必要性;從病例性別構(gòu)成來看,男性病例明顯高于女性,該現(xiàn)象值得進(jìn)一步關(guān)注。合肥地區(qū)針對C群流腦疫情開展的A+C群流腦群體接種效果并不明顯;流腦發(fā)生季節(jié)性明顯,10及11月份發(fā)病情況對下年度疫情變化有一定預(yù)示作用; C流腦病死率高于A群;瘀點數(shù)目超過3個、中性粒細(xì)胞80%、布氏征陽性等影響C群流腦病例死亡結(jié)局。
[Abstract]:Epidemic cerebrospinal meningitis (hereinafter referred to as meningomyelitis) is an acute respiratory infectious disease caused by meningococcus, is a legal class B infectious disease in China. Anhui Province has always been one of the areas with a high incidence of meningococcal meningitis. Like the resurgence of infectious diseases, the incidence of epidemic cerebrospinal meningitis is rising rapidly, and the epidemic characteristics of epidemic cerebrospinal meningitis are also changing obviously. Anhui Province is located in the central region of China. The specific geographical environment makes the study of epidemic characteristics of related diseases in Anhui Province have a widespread extrapolation value. At the same time, it is a group C epidemic situation. First of all, it is possible for us to carry out the related research work. Therefore, we carried out the research work on this subject in combination with the review of the data of epidemic situation of epidemic cerebrospinal meningitis in Anhui Province, hoping to provide a reference for the formulation and improvement of preventive strategies and control measures for epidemic diseases of epidemic cerebrospinal meningitis and some vaccines.
objective
To understand epidemiological characteristics of epidemic cerebrospinal meningitis in Anhui Province and its changes in recent years, so as to provide theoretical basis for the formulation of preventive control strategies and measures.
Material method
1. The epidemic data of epidemic encephalitis in Anhui Province over the years were collected by epidemic information reporting system. The whole research period was divided into six periods in 10 years. With Huaihe River and Yangtze River as the main reference marks, Anhui Province was divided into three regions: Jianghuai, Huaibei and Jiangnan. Descriptive analysis was conducted on the population, area and time distribution of epidemic cerebrospinal meningitis in Anhui province.
2. Epidemiological investigation and retrospective investigation of clinical data of all reported suspected cases of meningitis in Hefei area from July 2003 to June 2007 were carried out; pharyngeal swabs of healthy people of different ages were collected in November 2005 and April 2006. The cases were divided into six groups according to the age distribution of school students in China. Age group, the statistical period from July 1, last year to June 31, the second year is a statistical year. According to the age group, the incidence and mortality in urban and rural areas are calculated separately, and the composition of cases in different age groups is also described. Chi-square test was used to compare and analyze the age of death cases and survival cases among different genders and non-reference test. Age, interval between onset and treatment and clinical manifestations were included in single-factor logistic regression to analyze the correlation between age, onset and outcome of illness and death. Objective to understand the risk factors of death in patients with epidemic cerebrospinal meningitis.
Result
From 1951 to 2007, there were 799 387 cases of epidemic cerebrospinal meningitis in Anhui Province, with an average annual morbidity of 28.90/100 000, death rate of 41 337 cases, mortality rate of 1.49/100 000, fatality rate of 5.17%. During this period, there were three major epidemics in Anhui Province: the largest occurred in 1975-1979, and reached the peak of 729.25/100 000 in 1977. The epidemic of epidemic cerebrospinal meningitis in Anhui Province had an epidemic pattern of 8-10 years (with different peak heights) and the duration of each pandemic was about 6-7 years. After 1980s, with the popularization and use of group A meningitis polysaccharide vaccine, the incidence of epidemic cerebrospinal meningitis continued to decline, and the epidemic cycle of meningitis became less and less obvious, but it still appeared about 10 years apart. The incidence of epidemic cerebrospinal meningitis in Anhui Province showed a slight rebound after the outbreak of epidemic in 2003. The incidence of epidemic cerebrospinal meningitis in Anhui Province generally began from October to November of each year, and reached the peak in April to May of the second year. Compared with the epidemic year, the incidence of epidemic cerebrospinal meningitis in the sporadic year was higher. The seasonal peak duration of the rate is about a month longer. A significant increase in the average incidence in October or November from the previous five years in the same month often indicates an increase in the next year's incidence. The ratio of male to female was 1.46:1, but after 25 years old, the ratio of male to female was 0.70:1. In the case of epidemic of epidemic cerebrospinal meningitis in the whole province, the epidemic situation in Huaibei Prefecture increased 1-2 years earlier than that in the other two areas, and the incidence of group C epidemic cerebrospinal meningitis occurred in the South of the Yangtze River, the south of the Yangtze River and the north of Huaibei Prefecture in 2002. The fatality rates were 4.37%, 4.92% and 6.00% (P = 0.000), respectively.
From 2003 to 2007, a total of 386 cases of epidemic cerebrospinal meningitis were reported in Hefei, with an average annual incidence of 209/100,000 and an incidence of 286/100,000 in 2006/2007. 135 laboratory-confirmed cases were group C epidemic cerebrospinal meningitis. There were 235 cases in urban areas (60.88%) and 151 cases in rural areas (39.12%). The largest age group was 78 years old, the highest incidence was 12-17 years old group (6.57/100,000), male cases 219 cases, accounting for 56.7% of the total cases. Four cases (96.53%) had fever in 371 cases (96.11%). The other main symptoms were vomiting in 322 cases (83.42%), nausea in 311 cases (80.57%), neck stiffness in 285 cases (77.9%) and headache in 278 cases (72.02). Clinical classification: 225 cases of common type (58.29%), 54 cases of outbreak type (13.9%) and 2 cases of light type (0.52%). The median age of the patients was 10 years (2 months to 27 years), lower than that of the surviving cases. The median age of the surviving cases was 15 years (6 months to 78 years). There was a significant difference in the distribution between the two groups (Z = 2.54, P = 0.01). The main factors influencing the death of the patients were analyzed. The results of univariate logistic regression analysis showed that headache and mental retardation were the main causes. Clear, nausea, bleeding spots or ecchymosis, more than 3 blood stasis points, neck stiffness, convulsions, 80% neutrophils, positive Kirschner's sign, positive Brinell's sign and age less than 12 years were associated with death (P 0.05); these factors were included in logistic regression model for multivariate analysis, the number of blood stasis points exceeded 3, 80% neutrophils, and positive Brinell's sign (P 0.05). The median age of 21 cases was 16 years (1 to 69 years), of which 59.31% were 12-21 years old. The prevalence rate of epidemic cerebrospinal meningitis was 5.99% in healthy people, which was higher than 3.05% in pre-epidemic period. The carrier rate of B and C groups increased significantly in epidemic period. And the upward trend.
conclusion
Anhui province is an epidemic area of epidemic cerebrospinal meningitis. In history, group A epidemic cerebrospinal meningitis was the dominant strain in this area. The spread and use of group A polysaccharide vaccine effectively controlled the epidemic of epidemic cerebrospinal meningitis in Anhui province. Meningitis replaced group A as an epidemic dominant strain in Anhui Province in recent years, and caused the rebound of epidemic situation of meningitis to rise. The age distribution of cases showed a trend of upward shift. However, it is still in the unstable transition period of bacterial transformation, which needs further monitoring and research. The results suggest that it is necessary to revise the immunization strategy in time, and that male cases are significantly higher than female cases in terms of sex composition, which deserves further attention. The annual epidemic change has certain predictive effect; the mortality of group C epidemic encephalopathy is higher than that of group A; the number of blood stasis points is more than three, neutrophils are 80%, and Brinell's sign is positive.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R181.3;R515.2

【引證文獻(xiàn)】

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1 鄭鑫;腦膜炎奈瑟氏菌表面蛋白NspA基因的克隆與原核表達(dá)[D];長春理工大學(xué);2011年

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