上海地区儿童社区及院内获得性轮状病毒腹泻的临床与分子流行病学研究
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摘要
目的
     A组轮状病毒(Group A rotavirus,RV)是婴幼儿重症腹泻和脱水的主要病原体,在发展中国家和发达国家都是一个重要的公共卫生问题。全球每年有1.1亿婴幼儿罹患腹泻,2500万需要就医治疗,200万需要住院治疗,造成35.2-59.2万5岁以下儿童死于RV腹泻。正在研制发展的疫苗可有效地降低RV腹泻的发病率和死亡率。疫苗在各地区的引进与使用要求评估当地轮状病毒腹泻病的流行情况以及监测流行株的变化规律。本研究是以医院为基础的前瞻性调查,对2006.11-2008.1上海地区儿童中社区及院内获得性轮状病毒腹泻的临床流行病学和分子流行病学现状作报道,同时探讨了RV的危险因素,为国内轮状病毒腹泻病的防治提供科学依据。
     对象和方法
     1.对象
     收集急性RV腹泻的门诊就诊患儿、住院患儿和院内感染患儿的临床资料和粪便标本,-20℃保存。
     2.方法
     以胶体金法检测RV抗原,以套式RT-PCR确定RV基因型。
     结果
     1.本次调查共收集到腹泻患儿标本1895例,RV阳性735例,阳性检出率38.8%。其中门急诊粪便标本1461例,经胶体金法检测RV阳性的为546例。住院腹泻患儿216例,RV阳性83例。院感腹泻患儿218例,RV阳性106例。从月龄分组上看,腹泻患儿主要集中在3岁以下婴幼儿,各月龄组检出率以6-11月龄组最高,达47.5%,各月龄组之间的阳性检出率有统计学差异。5岁以上腹泻患儿例数较少,但RV的检出率仍有31%。门诊、住院和院感腹泻患儿在RV的阳性检出率上有统计学差异,以院内感染组为高,为48.6%。
     2.RV全年均有流行,不同月份RV阳性检出率有统计学差异。流行季节以10、11、12、1月份检出率较高,2007.4在新生儿病区发生RV院内感染的暴发和流行。
     3.住院组患儿在脱水、腹泻天数、腹泻次数、呕吐次数、体温异常均比其他两组患儿严重,差异有统计学意义。近50%的RV腹泻患儿有肠道外表现,以转氨酶异常、上呼吸道感染和电解质酸碱平衡紊乱为主。年龄越小的患儿更易发生转氨酶异常,呕吐次数和乳糖不耐受与转氨酶异常呈正相关。
     4.RV腹泻住院患儿的住院费用与住院天数呈正相关,在我院每增加一天的住院日,住院费用增加507元,月龄与住院费用呈负相关。院内感染RV腹泻的患儿在住院天数和住院费用上均明显高于无院内感染组,差异有统计学意义。
     5.月龄和与腹泻患儿同居一室与院内RV感染有相关性。母乳喂养是RV感染的保护因素。
     6.G3是近年来上海地区稳定的优势流行血清型,其次是G1(15.9%)、G1/G3混合型(3.7%)、G2(2.7%)和G9(1.8%)。除G3血清型引起的腹泻病发生脱水的几率高于G1血清型以外,G1和G3血清型有关的其他临床症状没有统计学差异。P[8]是最常见流行的P基因型(83.1%),其次是P[4](4.5%)。63P[8]组合最优势流行,占51.6%,其次是G1P[8]占15.1%,G2P[4]占2.0%和G9P[8]占1.8%。G1P[4]和G3P[4]很少检出。
     结论
     1.轮状病毒是上海地区儿童腹泻的重要病原体,从新生儿至5岁以上儿童均有检出,以3岁以下尤其是6-11月龄组检出率最高。全年均可散发或流行,以秋冬季节为主。
     2.RV腹泻可有肠道外表现,院内感染RV腹泻延长住院天数,增加住院费用。母乳喂养是RV感染的保护因素。
     3.G3是主要而且稳定流行的血清型,G3P[8]组合最为常见。
Objective
     Rotavirus is the most common cause of severe gastroenteritis and dehydration in young children in both industrialized and developing countries.It is estimated that about 110 million episodes of gastroenteritis require home care,25 million require clinic visits,2 million require hospitalizations,and 352,000-592,000 result in the death of children<5 years of age annually.Vaccines currently under development have the potential to reduce morbidity and mortality due to rotavirus infection.It is needed to reassess the prevalence of rotavirus and field rotavirus strains circulating in Shanghai before making decision on introducing rotavirus vaccine into Shanghai by public health organization.We conducted a hospital-based prospective investigation to understand the epidemiological profile of rotavirus diarrhea in the community and health-care setting from November 2006 to January 2008 in Shanghai.In the meantime,risk factors of diarrhea caused by rotavirus infection were also explored. Our current research aimed to estimate the incidence of rotavirus diarrhea in the community and hospital setting and monitor the temporal fluctuation of distribution of rotavirus genotype,which provide the background data for the prophylaxis of rotavirus diarrhea in China.
     Methods
     A total of 1895 stool specimens were collected from outpatients and inpatients with community-acquired and hospital-acquired acute diarrhea.All stool specimens were transported to the research laboratory within 24 hours and frozen under -20℃.10 percent of the supernatant was used for detection of rotavirus antigen with rotavirus Group A Diagnostic Kit(Colloidal Gold Device,Beijing Wantia Biological Pharmacy Enterprise Co.Ltd) and polymerase chain reaction nested-PCR was performed to detect rotavirus genotypes.
     Results
     1.Of 1895 stool specimens,735 were positive for rotavirus.The overall positive rate was 38.8%.1461 stool samples were collected from outpatients and rotavirus was detected in 546(37.4%).216 children who were hospitalized primarily for acute diarrhea were enrolled and 83(38.4%) were rotavirus positive.218 inpatients who developed nosocomial diarrhea were analyzed and 108(49.5%) were rotavirus-associated nosocomial diarrhea.Rotavirus infection mainly occurred in children less than 36 months of age and peaked in 6-11month group.There was a statistic difference in the infection rate of rotavirus among age-specific groups. Diarrhea cases were not common in patients above 5 years old,but the detection rate of rotavirus was as high as 31%.Rotavirus-positive rate was significantly higher in nosocomial group than that in community-acquired group.
     2.Rotavirus was prevalent year-round in shanghai.The detection rates of rotavirus were statistically different in different months.Rotavirus peaking season lasted from the October to the January of next year in the community.We observed occurence of nosocomial outbreak of rotavirus diarrhea in neonatal ward in April,2007.
     3.Clinical symptoms were more severe in inpatient group.50%of inpatient with rotavirus diarrhea had concomitantly extra-intestinal symptoms.Liver enzyme abnormality,upper respiratory tract infection and electrolytes disturbance were commonly observed.Liver enzyme abnormality was related with younger age,more vomiting times and lactose intolerance.
     4.Hospitalization cost of rotavirus diarrhea for children was positive correlated to the length of hospital stay.One more prolonged day of hospitalization increases 500 RMB of direct medical cost.The age was inversely correlated to hospitalization cost and the younger the age group was,the more the economic burden of hospitalization was. Compared with pneumonia patients without nosocomial rotavirus diarrhea,those who were admitted to wards for pneumonia and developed nosocomial rotavirus diarrhea had prolonged hospital stay and increased medical cost.
     5.Month age and sharing one room with diarrhea cases were risk factors which were correlated with nosocomial rotavirus infection.Breast feeding was a protective factor for rotavirus diarrhea.
     6.490 rotavirus-positive strains were typed and G3(54.5%) was the most common G serotype followed by G1(15.9%),Gland G3 coinfection(3.7%),G2(2.7%) and G9(1.8%),respectively.There was no significant difference in clinical presentation except for dehydration between G1 and G3 serotypes.P[8]was the most predominant P genotype which accounted for 83.1%and P[4]comprised 4.5%.In a descending order of frequency,G3P[8]was found in 51.6%,G1P[8]in 15.1%,G2P[4]in 2.0% and G9P[8]in 1.8%.G1P[4]and G3P[4]were rarely detected also.
     Conclusions
     Rotavirus was an important pathogen in diarrhea children in Shanghai area.Rotavirus infection mainly occurred in children less than 36 months of age and peaked in 6-11moth age group.Rotavirus was prevalent year-round in shanghai,and the peaking seasons were autumn and winter.Rotavirus diarrhea had concomitant extra-intestinal symptoms.Nosocomial rotavirus diarrhea had prolonged hospital stay and increased medical cost.Breast feeding was a protective factor for rotavirus infection.G3 was the most common G serotype and G9 strain was endemic in Shanghai.G3P[8]was the most predominant.
引文
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