593例社区获得性肺炎住院患儿病毒和非典型细菌病原学分析

发布时间：2018-04-28 12:29

本文选题：社区获得性肺炎 + 病毒　；参考：《中山大学》2012年硕士论文

【摘要】：研究背景社区获得性肺炎(community acquired pneumonia, CAP)是儿童期最常见的感染性疾病，发病率高，危害严重，列于我国儿童死亡的五大疾病之首。我国每年约有2110万5岁以下小儿罹患肺炎（0.22次/人年），发病率明显高于发达国家（0.026次/人年）。儿童CAP的病因通常难以判定，约有40％至60％的肺炎患儿无法找到明确病因。许多研究人员根据患儿的病史、临床表现、体征、实验室及影像学检查资料来判断社区获得性肺炎的病因，但尚未发现足够可靠的证据进行鉴别。关于社区获得性肺炎住院患儿管理的大量报道显示，大约80％的社区获得性肺炎患儿采用了经验性治疗。当患儿被诊断为CAP后，是否使用抗生素进行治疗以及如何选择与病因相关的适当抗生素仍是个很大的问题。一项关于住院儿童社区获得性肺炎的研究表明，绝大多数儿童肺炎是病毒感染所致，故须对不必要的抗生素治疗加以制止。另外，肺炎衣原体和支原体亦日益成为导致儿童获得性肺炎的重要致病因素。这些非典型细菌需要特定的抗生素，而针对典型病原体使用的常规抗生素无效。肺炎病因研究不足及抗生素治疗不当最终可导致社区获得性肺炎病原体的抗生素耐药性，这种抗生素耐药又将成为另一个全球健康问题。基于这些原因，深入了解CAP在日常临床中病原流行病学，不同病原肺炎的临床特点助于提高诊断，采取适当的管理和预防措施，进而减少由于过度治疗和不适当的抗生素治疗所致的经济负担，同时降低社区获得性肺炎相关疾病的死亡率。目的 1、阐明儿童社区获得性肺炎的常见呼吸道病毒病原谱分布； 2、确定病毒和非典型细菌病原体的年龄和季节分布； 3、分析特定病原体的临床特点。方法 1.研究对象本研究在2010年1月至2011年12月期间收集593例住院病区中确诊的社区获得性肺炎病例。患儿年龄范围为1个月至14岁之间，其中：婴儿组（1-12个月）286例（48.2％），学龄前儿童组（12个月至5岁）259例（43.7％），学龄儿童组（5岁以上至14岁）48例（8.1％）。 2.病例收集、病例评估、数据分析所有患儿在入院24小时内均采集2毫升的外周血，用于血常规，肝、心脏、肾功生化和各项炎症指标的血液化验，并采集口咽拭子标本。将咽拭子标本采用实时定量PCR检测方法对病毒和非典型病原体进行同时检测。一个患儿样本中检测出任何一种病原体，则作为一个阳性病例。如一个患儿样本中只发现一种病原体，则该患儿则被认为只有一项感染，即单一感染。如发现了多个病原体，则被认为是混合感染。入院时收集的信息包括填写日期、个人信息、前驱症状、临床表现。在住院期间，患儿每日的病情变化均详细记录，包括呼吸系统的体格检查、临床症状的变化、实验室数据、并发症、治疗措施等。出院日期也被记录在内，以计算患者的住院时间。评估病情严重程度根据临床评分（呼吸频率、三凹征、呼吸音改变、精神状态、肤色）。结果 1、患儿年龄于1个月至14岁之间，中位年龄为14个月。男性占67％，女性占33％。男女之比为2:1。男女中位年龄之间比较差异无统计学意义（U=35112，P0.05）。中位发病时间7天（于1-160天），中位住院时间7天（于2-36天）。 2、593例标本中，阳性标本共367例，总检出率为61.9％。单一病原体感染289例（48.7％），混合病原体感染78例（13.2％）。病原体以RSV最常见，共133例（22.4％）；其它依次为Inf A56例（9.4％），EV52例（8.8％），ADV40例（6.7％），Mpp39例（6.6％），hCoV32例（5.4％），hBoV31例（5.2％），PIV29例（4.9％）， hMPV25例（4.2％），Inf B24例（4％），及Cp7例（1.2％）。病原体不明确的标本226例（38.1％）。593例患儿中，病毒感染（包括单一或混合病毒感染）共318例（53.6％）。单一的非典型细菌感染（包括Mpp或Cp）共31例（5.2％），病毒/非典型细菌混合感染共18例（3％）。 3、289例单一病原体感染标本中，RSV为91例（15.3％）占首位，其次为InfA32例（5.4％），ADV30例（5.1％），Mpp28例（4.7％）。78例混合病原体感染标本中，以2种病原体混合感染为主（57例，9.6％），3种病原体混合感染为次（20例，3.4％），且有1例是五种病原体混合感染。最常见混合感染为RSV合并其他病毒，其中RSV+EV15例，RSV+Inf A9例，RSV+hCoV5例。 4、CAP患儿年龄及病原体分布情况：在婴儿组，RSV阳性检出率最高占33.6％。Inf A、Inf B、hBoV、 hCoV、hMPV常见于学龄前儿童组，而PIV在婴儿组多发。学龄儿童组当中，最常见的病原体是ADV和MPP，各占16.7％。EV感染可见于各年龄组。 5、病原体感染的季节性分布情况：RSV高峰主要集中在2月份和9月份。hMPV在晚冬逐渐增多。Inf A高峰期在秋及晚冬季，而Inf B高峰期在1-2月份。EV和hCoV感染可出现于任何时节；EV感染在5月份及9月份呈现高峰，但hCoV发病率全年均较平稳。hBoV感染多发生于夏季，7月份出现感染高峰。ADV和PIV没有明显的季节变化，但ADV于8-9月份为高峰期。Mpp感染在7月份开始发病，后秋季9月份为感染高峰期。Cp季节分布结果尚未明确。混合感染以冬季多见。病原体阴性的标本四季均有出现。 6、593例CAP患儿病情严重程度分布：轻度病情者358例（60.4％），中度病情者141例（23.8％），重度病情者94例（15.9％）。病情严重程度分布与年龄组有相关关系（χ~2=36.682，P 0.001）。病情重度者多见于婴儿组，而病情轻度者多见于学龄儿童组。 7、单一病原体感染、混合感染及病原体阴性病例间的临床特点比较：呼吸窘迫多见于单一病原体感染患儿，与病原体阴性患儿相比有统计学差异（χ~2=12.876，P 0.001）。粘液痰、细湿Up音、喘息、三凹症，支气管扩张剂及静脉激素治疗多见于单一病原体感染及混合感染患儿，与病原体阴性患儿相比有统计学差异（P 0.05）。肝肿大多见于混合感染患儿，与单一病原体感染患儿（χ~2=5.817，P 0.05）及病原体阴性患儿（χ~2=7.745，P 0.05）相比有统计学差异。 8、病情严重程度分布与感染类型有相关关系（χ~2=53.805，P 0.001)。病情轻度者多见于病原体阴性感染组，而病情中度者和重度者多见于单一病原体感染组和混合感染组。在不同感染类型各组之间的年龄和住院时间均与病情严重程度有显著关联。单一病原体感染组、混合感染组及病原体阴性组的临床评分，与年龄呈负相关（P 0.05）；单一病原体感染组及病原体阴性组的临床评分与住院时间成正相关（P 0.05）。 9、单一RSV、Inf A、ADV、hBoV、hMPV、Mpp、NOS（非特指病原体）感染的临床特点比较：RSV感染组患儿的中位年龄小于其他病原体感染组（χ~2=87.120， P 0.05）。RSV感染组的喘息、呼吸气促和三凹征更常见于InfA、ADV、Mpp、hBoV、NOS、混合感染组和病原体阴性组（P 0.05）。RSV感染患儿更常使用支气管扩张剂及静脉激素治疗，与其它病原体感染患儿比较均有统计学差异（P 0.05），而支气管扩张剂使用与hBoV、Mpp、hMPV感染组和混合感染组比较则无统计学差异（P0.05）。ADV感染患儿常出现发热，与RSV、NOS、混合感染患儿和病原体阴性患儿比较均有统计学差异（P 0.001）。ADV感染组的hsCRP和ESR水平升高更明显，除了Inf A和Mpp感染组（P0.05）外，与其余各组比较均有统计学差异（P 0.05）。各种病原体分布与病情严重程度有相关关系（χ~2=128.975，P 0.001）。绝大多数病原体引起轻度病情，而RSV和ADV感染则多引起重度病情。 10、单一RSV感染组和RSV混合感染组的临床特点比较：RSV混合感染组患儿的发热时间长于单一RSV感染组（U=472，P 0.05）。喘息、气促、流鼻涕多见于单一RSV感染组，与RSV混合感染组比较，差异有统计学意义（P 0.05）。肝肿大及ESR异常多见于RSV混合感染组，与单一RSV感染组比较差异有统计学意义（χ~2=4.855，，P=0.03；χ~2=6.67，P=0.01）。 11、病情严重程度分布与单一RSV感染和RSV混合感染有相关关系（χ~2=6.617，P 0.05）。病情重度者多见于单一RSV感染组，而病情轻度者多见于混合感染组。单一RSV感染中，患儿病情严重程度分布与年龄有相关关系（χ~2=6.8，P 0.05）；患儿的临床评份与住院时间成正相关（ρ=0.213，P 0.05）。RSV混合感染中，患儿病情严重程度分布与年龄无相关关系（χ~2=4.178，P0.05）；患儿的临床评份与住院时间无相关关系（ρ=-0.004，P0.05）。 12、RSV病毒滴度与临床评分呈正相关关系（ρ=0.499，P 0.001）；RSV病毒滴度与住院时间无相关关系（ρ=-0.013，P0.05）。结论 1、广州地区2010-2011年社区获得性肺炎住院患儿以1岁以下婴儿多见，且其病毒病原体感染阳性率最高；男性婴儿比女性更易患感染而需住院治疗。 2、RSV感染组患儿的年龄小于其它病原体感染组，RSV是导致婴儿CAP的最重要病原体；而学龄儿童组当中，最常见的病原体是ADV和Mpp。儿童重症肺炎中RSV或ADV的检出率高。 3、RSV病毒滴度水平与CAP病情严重程度呈正相关；其他病原体混合感染不加重RSV肺炎病情。 4、患儿年龄与疾病严重程度呈负相关；住院时间与疾病严重程度呈正相关。 5、RSV感染以冬末春初高发，秋季再现一小高峰；hBoV和Mpp感染多发生于夏季；ADV和PIV感染呈全年散发；余病原体感染以秋冬季多见。 6、喘息发作、呼吸气促、三凹征、支气管扩张剂及静脉激素治疗多见于RSV和hMPV肺炎患儿；发热、hsCRP升高及ESR升高多见于ADV和Mpp肺炎患儿。
[Abstract]:Research background
Community acquired pneumonia (CAP) is the most common infectious disease in childhood, with high incidence and serious harm. It is the first of the five major diseases of children in our country. The incidence of pneumonia in children under 21 million 100 thousand and 5 years of age in China (0.22 times per year) is significantly higher than that in developed countries (0.026 times / year). Children CAP The causes are often difficult to determine, and about 40% to 60% of the pneumonia children are unable to find a clear cause. Many researchers determine the cause of community-acquired pneumonia based on the patient's history, clinical manifestations, signs, laboratory and imaging data, but there is not enough reliable evidence to identify. A large number of reports from hospital children show that about 80% of children with community-acquired pneumonia have been treated with empirical treatment. When the children are diagnosed with CAP, whether they are treated with antibiotics and how to choose appropriate antibiotics associated with the cause are still a big problem. A study on community acquired pneumonia in hospitalized children. It is clear that most children pneumonia is caused by virus infection, so it is necessary to stop the unnecessary antibiotic treatment. In addition, Chlamydia pneumoniae and Mycoplasma pneumoniae are also increasingly becoming an important cause of acquired pneumonia in children. These atypical bacteria need specific antibiotics, and the conventional antibiotics used for typical pathogens are not effective. The inadequacy of the cause of pneumonia and the improper treatment of antibiotics can eventually lead to antibiotic resistance of the pathogens of community-acquired pneumonia, which will also become another global health problem. Based on these reasons, the clinical epidemiology of CAP in the daily clinic is deeply understood, and the clinical characteristics of different pathogenic pneumonia will help to improve the diagnosis, Appropriate management and prevention measures are taken to reduce the economic burden caused by overtreatment and inappropriate antibiotic treatment, while reducing the mortality of community acquired pneumonia related diseases.
objective
1, elucidate the distribution of common respiratory virus pathogens in children with community-acquired pneumonia.
2, determine the age and seasonal distribution of viruses and atypical bacterial pathogens.
3, the clinical characteristics of specific pathogens were analyzed.
Method
1. research objects
From January 2010 to December 2011, 593 cases of community-acquired pneumonia confirmed in the hospital area were collected. The age range of children was from 1 months to 14 years old, including 286 cases (48.2%) in the infant group (1-12 months), 259 (43.7%) in preschool children (12 months to 5 years), and 48 cases (8.1%) in the school age group (over 5 years to 14).
2. case collection, case assessment, data analysis
All children collected 2 milliliters of peripheral blood within 24 hours of admission to the blood routine, liver, heart, kidney function, biochemical and inflammatory indicators, and collected oropharynx swabs. The pharynx swab specimens were detected by real-time quantitative PCR detection method for simultaneous detection of the virus and atypical pathogens. What kind of pathogen is a positive case. If only one pathogen is found in a sample of a child, the child is considered to have only one infection, that is, a single infection. If multiple pathogens are found, it is considered a mixed infection. The information collected at admission includes the date, personal information, precursor symptoms, and clinical manifestations. During the hospital, the patient's daily changes were recorded in detail, including physical examination of the respiratory system, changes in clinical symptoms, laboratory data, complications, treatment and so on. The discharge date was also recorded to calculate the patient's hospitalization time. The severity of the disease was evaluated according to the clinical score (respiratory frequency, three recess, respiratory sound change, sperm). The state of God, the color of the skin.
Result
1, children aged from 1 months to 14 years of age, median age was 14 months, male accounted for 67%, women accounted for 33%. male and female ratio of male and female between men and women in the middle age of no statistically significant difference (U=35112, P0.05). Median onset time was 7 days (at 1-160 days), median hospital stay was 7 days (at 2-36 days).
Of the 2593 specimens, 367 were positive specimens, the total detection rate was 61.9%. single pathogen infection in 289 cases (48.7%) and mixed pathogen infection (13.2%). The most common pathogens were RSV, 133 cases (22.4%); the others were Inf A56 (9.4%), EV52 (8.8%), ADV40 cases (6.7%), Mpp39 cases (6.6%), hCoV32 cases (5.4%), hBoV31 cases (5.2) (%), PIV29 (4.9%), hMPV25 (4.2%), Inf B24 (4%), and Cp7 (1.2%). Among 226 (38.1%) children with unknown pathogens (38.1%).593 cases, the virus infection (including single or mixed virus infection) in 318 cases (53.6%). A single atypical bacterial infection (including Mpp or Cp) in 31 cases (5.2%), virus / atypical bacteria mixed infection A total of 18 cases (3%).
Among the 3289 specimens of single pathogen infection, RSV was 91 (15.3%), followed by InfA32 (5.4%), ADV30 (5.1%), Mpp28 (4.7%).78 cases of mixed pathogen infection, mixed infection with 2 pathogens (57, 9.6%), 3 pathogens mixed infection (20, 3.4%), and 1 cases of pathogen mixing. The most common mixed infection is RSV combined with other viruses, including RSV+EV15 cases, RSV+Inf A9 cases and RSV+hCoV5 cases.
4, age and distribution of pathogens in children with CAP: in the infant group, the highest RSV positive rate is 33.6%.Inf A, Inf B, hBoV, hCoV, hMPV common in the preschool children group, and PIV in the infant group. Among the school age children, the most common pathogens are ADV and MPP, each of which accounts for the age groups of 16.7%.
5, the seasonal distribution of pathogen infection: the peak of RSV peak mainly concentrated in February and September in the late winter and gradually increased at the peak period of.Inf A in autumn and late winter, while the peak period of Inf B in the peak of.EV and hCoV may appear at any time in the month of 1-2; EV infection peak in May and September, but hCoV incidence rate is more stable throughout the year. The infection occurred most in summer. There was no obvious seasonal change in the peak infection peak.ADV and PIV in July, but the peak period of.Mpp infection in ADV began in July, and the seasonal distribution of.Cp in September was not clear in September.
In 6593 cases of CAP, the severity of the disease was distributed in 358 cases (60.4%), 141 (23.8%) and 94 (15.9%) in severe condition (15.9%). The severity of the disease was associated with age group (x ~2=36.682, P 0.001).
7, comparison of clinical characteristics between single pathogen infection, mixed infection and pathogen negative cases: respiratory distress is mostly seen in children with single pathogen infection, and there are statistical differences compared with those with negative pathogens (x ~2=12.876, P 0.001). Mucous phlegm, fine wet Up sound, wheezing, three concave, bronchiectasis and intravenous hormone therapy are often seen in a single case. There were statistical differences in the infection and mixed infection of the children with the pathogen negative children (P 0.05). Most of the hepatomegaly were found in the children with mixed infection, compared with the children with single pathogen infection (x ~2=5.817, P 0.05) and the children with negative pathogens (x ~2=7.745, P 0.05).
8, the distribution of the severity of the disease was related to the type of infection (x ~2=53.805, P 0.001). The mild cases were mostly found in the pathogen negative infection group, and the moderate and severe cases were found in the single pathogen infection group and the mixed infection group. The age and the time of hospitalization between the different types of infection types were all significant with the severity of the disease. The clinical scores of the single pathogen infection group, the mixed infection group and the pathogen negative group were negatively correlated with age (P 0.05), and the clinical score of the single pathogen infection group and the pathogen negative group was positively correlated with the time of hospitalization (P 0.05).
9, comparison of the clinical characteristics of single RSV, Inf A, ADV, hBoV, hMPV, Mpp, NOS (non specific pathogen) infection: the median age of the children of the RSV infection group is less than the other pathogens infection group (chi ~2=87.120, P 0.05) the gasping of the.RSV infection group, the respiratory shortness and the three concave sign, and the mixed infection group and the pathogen negative group (0.05). RSV infected children often use bronchiectasis and intravenous hormone treatment, compared with other pathogens infected children (P 0.05), but bronchiectasis use and hBoV, Mpp, hMPV infection group and mixed infection group have no statistically significant difference (P0.05) children with.ADV infection often have fever, with RSV, NOS, mixed infection children The levels of hsCRP and ESR in the.ADV infection group were significantly higher than those with negative pathogens (P 0.001). Except for Inf A and Mpp infection group (P0.05), there were statistical differences between the other groups (P 0.05). The distribution of various pathogens was related to the severity of the disease (x ~2=128.975, P 0.001). It causes mild illness, while RSV and ADV infection cause severe disease.
10, comparison of the clinical characteristics of the single RSV infection group and the RSV mixed infection group: the fever time of the RSV mixed infection group was longer than that of the single RSV infection group (U=472, P 0.05). The wheezing, the breath, the runny nose were mostly found in the single RSV infection group, and the difference was statistically significant (P 0.05) compared with the mixed RSV infection group (P 0.05). The hepatomegaly and ESR abnormality were more common in RSV mixture. The difference between staining group and single RSV infection group was statistically significant (x ~2=4.855, P=0.03; Chi ~2=6.67, P=0.01).
11, the distribution of the severity of the disease was related to the single RSV infection and the mixed infection of RSV (x ~2=6.617, P 0.05). Most of the severe cases were found in the single RSV infection group, and the mild cases were mostly seen in the mixed infection group. The severity of the disease was associated with the age of the children (x ~2=6.8, P 0.05); the clinical evaluation of the children was evaluated. In a positive correlation with the time of hospitalization (rho =0.213, P 0.05).RSV mixed infection, the distribution of the severity of the disease was not related to age (x ~2=4.178, P0.05), and there was no correlation between the clinical evaluation and the time of hospitalization (P =-0.004, P0.05).
12, RSV virus titer was positively correlated with clinical score (P =0.499, P 0.001); RSV virus titer was not correlated with length of stay (=-0.013, P0.05).
conclusion
1, the 2010-2011 years of community acquired pneumonia in Guangzhou area are more common in infants under 1 years of age, and the positive rate of viral pathogens is the highest; male infants are more susceptible to infection than women and need to be hospitalized.
2, the age of the RSV infection group is less than the other pathogen infection group. RSV is the most important cause of the infant CAP, and the most common pathogen in the school age group is the high detection rate of RSV or ADV in ADV and Mpp. children's severe pneumonia.
3, the level of RSV virus titer was positively correlated with the severity of CAP, and the mixed infection of other pathogens did not aggravate the condition of RSV pneumonia.
4, the age of the children was negatively correlated with the severity of the disease, and the time of hospitalization was positively correlated with the severity of the disease.
5, RSV infection is high onset in early winter and early spring, and a small peak in autumn; hBoV and Mpp infection occur in summer; ADV and PIV infection show all the year round, and the infection of residual pathogens is more common in autumn and winter.
6, asthma attacks, respiratory shortness, three recess, bronchiectasis and intravenous hormone therapy are mostly found in children with RSV and hMPV pneumonia; fever, elevated hsCRP and elevated ESR are common in children with ADV and Mpp pneumonia.

【学位授予单位】：中山大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.6

【参考文献】