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目的初步了解肠道病毒(EV)在小儿急性呼吸道感染(ARI)中的流行概况。方法2003-09—2005-04,于首都儿科研究所就诊的815例ARI患儿,取其鼻咽深部分泌物,用病毒分离及逆转录聚合酶链反应(RT-PCR)法检测EV,用病毒分离和间接免疫荧光法检测呼吸道合胞病毒(RSV)等7种呼吸道病毒。取144例患儿双份血清,用酶联免疫吸附试验检测EV抗体。结果病毒总检出率50.9%,RSV阳性率最高(24.9%),其次为EV(16.9%)。EV在不同月份阳性率为0~34.2%,冬季阳性率最低。RT-PCR、双份血抗体检测和病毒分离3种检测EV方法的阳性率分别为16.2%、7.6%和1.0%。332例急性喘息患儿中,EV阳性率20.8%,仅次于RSV(42.5%);3岁以上喘息患儿中,EV阳性率最高(33.9%),而3岁以下患儿中,RSV阳性率最高(48.7%)。结论在住院ARI患儿中,EV是仅次于RSV的常见病原,也是引起小儿急性喘息性疾病的主要病原之一。EV在年长儿中阳性率相对较高,冬季阳性率较低。RT-PCR法检测EV,快速、敏感、特异,可用于小儿EV感染的诊断。     

肠道病毒71型和柯萨奇病毒A组16型感染的手足口病患儿的相关特征对比研究

目的：比较由肠道病毒71型（EV71）和柯萨奇病毒A组16型（CA16）感染的手足口病（HFMD）患儿流行病学情况及临床特征的差异。方法：采集108名临床诊断HFMD患儿疱疹液和咽拭子标本,使用RT-PCR进行肠道病毒检测,对EV71和CA16感染患儿的临床资料进行回顾性分析并比较。结果：108名患儿的肠道病毒总阳性率为97.2%（105/108）,其中EV71、CA16、其他肠道病毒及EV71和CA16混合感染分别占51.9%（56/108）,36.1%（39/108）,1.9%（2/108）,7.4%（8/108）。EV71感染患儿和CA16感染患儿两组间年龄、性别差异无统计学意义。单因素分析显示,CA16感染患儿口腔疱疹、膝部皮疹、流涕的发生比率高于EV71感染患儿。进一步多因素分析显示,出现膝部皮疹的患儿CA16感染可能性大。结论：发现口腔无疱疹、膝部无皮疹、无流涕等症状的HFMD患儿时,应考虑EV71感染的可能。     

2010年昆明地区儿童手足口病的流行特征

目的：调查2010年昆明地区儿童手足口病（HFMD）的流行特征。方法：收集2010年1~12月昆明市儿童医院门诊及住院的HFMD患儿13286例的临床资料进行回顾性分析。这些患儿中包括死亡病例8例、重症病例715例和普通病例12563例。结果：人肠道病毒检出8200例,总阳性率为61.72%,其中人肠道病毒71型（EV71）占29.49%（2418/8200）,柯萨奇病毒A16型（CoxA16）占53.21%（4363/8200）,EV71和CoxA16混合感染占0.91%（75/8200）,肠道病毒其他型占16.39%（1344/8200）。四个季度间人肠道病毒总阳性率差异有统计学意义（P0.05）。结论：2010年昆明地区儿童HFMD以CoxA16感染为主,但感染EV71更易导致重症HFMD,且重症患儿集中在3岁以下儿童;病毒载量与患儿病情无关;全年发病高峰期在第二季度。     

北京地区住院急性呼吸道感染患儿的病毒病原检测分析

目的了解北京地区住院急性呼吸道感染(ARI)患儿的病毒病原情况。方法取1260例年龄14岁以下住院ARI患儿的鼻咽深部分泌物,用间接免疫荧光及病毒分离法检测呼吸道合胞病毒(RSV)、流感病毒A、B型、副流感病毒1、2、3型及腺病毒等7种常见呼吸道病毒。用逆转录聚合酶链反应(RT-PCR)法对其中490例患儿标本进行肠道病毒(EV)检测。结果1.ARI1260例中,43.33%检测到了病毒病原,7种常见呼吸道病毒检出率36.19%,RSV阳性率最高(23.97%),以冬春季为著,88.08%的RSV阳性为3岁以下小儿。2.EV阳性率16.33%。3.19例存在2种病毒混合感染,均出现在冬春季,16例为RSV并EV感染。4.入选的510例急性呼气性喘息患儿中,3岁以下RSV阳性率最高(43.20%),3岁以上EV阳性率最高(36.11%)。结论1.RSV是北京地区冬春季婴幼儿ARI的主要病原。2.冬春季EV可并RSV等其他呼吸道病毒感染。3.RSV及EV是引起小儿急性喘息性疾病的主要病毒病原。     

非灰髓炎肠道病毒与婴幼儿急性下呼吸道感染关系的研究

目的了解非灰髓炎肠道病毒(EV)感染在婴幼儿急性下呼吸道感染(ALRI)中的发病情况、临床特点及诊断方法，方法①采用通用引物RT-PCR及病毒分离检测全年住院ALRI婴幼儿鼻咽分泌物(NPS)中的EV。②并用APAAP法检测RW、IFV、PIV和AdV，以资比较。结果①观察组87例M)S中RT-PCR阳性40例，EV分离阳性26例。②阳性病例中同时检出其它呼吸道病毒26例。结论①近半数住院ALRI婴幼儿存在EV感染，且常与其它呼吸道病毒混合感染。②EV-RT-PCR较EV分离敏感、实用。③EV感染无临床特异性。     

西安地区手足口病患儿咽拭子中EV71的检测及分离鉴定

目的 对2009年儿科门诊22例疑似手足口病患儿的咽拭子标本进行EV71病毒检测及分离鉴定.方法 采集的咽拭子标本分别接种于人横纹肌瘤细胞(RD细胞),盲传3代,若细胞圆缩、分散、胞浆内颗粒增加,即出现敛细胞病变效应(CPE),运用RT-PCR方法检测标本和细胞培养物上清液中的EV71,提取RNA,分离鉴定.结果 标本直接用RT-PCR法扩增,阳性率为31.8%(7/22),经细胞培养后出现CPE的阳性率为45.5%(10/22),培养后经RT-PCR再检测阳性率为68.2%(15/22),所分离的病毒株基凶序列同GENEBANK中报道的EV71(序列号EU812461)序列完全一致.结论 病毒分离和RT-PCR 2种检测方法联合应用可以提高肠道病毒EV71的阳性检出率,为临床诊断提供有力依据.     

新型冠状病毒感染期间足月的晚期新生儿咽拭子肠道病毒核酸检测横断面研究

目的 探讨新型冠状病毒感染疫情期间住院的足月的晚期新生儿咽拭子肠道病毒（enterovirus,EV核酸检测阳性率及其临床特征。方法 该研究为单中心横断面研究，研究对象为2020年10月—2021年9月在新生儿内科病房住院的611例足月的晚期新生儿。于入院时采集咽拭子进行柯萨奇病毒A16型/EV71/EV通用型核酸检测。根据EV核酸检测结果分为EV核酸阳性组（8例）和EV核酸阴性组（603例），分析比较两组患儿的临床特征差异。结果 611例患儿中，8例EV核酸检测阳性，阳性率为13.1‰，其中7例在5—10月份入院。EV核酸阳性组与EV核酸阴性组患儿起病前与有呼吸道感染症状的家庭成员接触比例分别为75.0%和10.9%(P<0.001)。两组患儿在人口学信息、临床症状、实验室检验方面差异无统计学意义（P>0.05）。结论 新型冠状病毒感染疫情期间住院的足月的晚期新生儿仍有一定比例的咽拭子EV核酸检测呈阳性但比例较低，其临床表现和实验室常规检测结果无特异性；家庭成员之间的传播可能是新生儿感染EV的重要途径。[中国当代儿科杂志，2023,25 (4):339-343]     

急性下呼吸道感染儿童肠道病毒感染的状况

目的：了解急性下呼吸道感染(ALRTI) 患儿肠道病毒(EV)的感染状况和临床特征。方法：抽取2007年9月至2008年4月因ALRTI在湖南省人民医院儿科医学中心住院的患儿的鼻咽抽吸物单数号样本404份,应用EV5′端非编码区(5′-NCR)保守序列设计引物,采用巢式逆转录RT-PCR法检测标本中EV感染状况。结果：404份ALRTI标本中,检出EV19例（4.7%）,大部分患儿年龄在3岁以下（95%）,男女EV检出阳性率差异无统计学意义。EV阳性患儿临床诊断为支气管肺炎者13例（68%）、毛细支气管炎者6例（32%）,90%患儿有发热症状,84%有咳嗽,63%有气喘,63%有合并症,其中主要为腹泻（6例）、粒细胞减少症（4例）和急性呼吸窘迫综合征（2例）。EV阳性患儿白细胞异常的发生率为26%,一半以上存在肝功能异常,少数有心肌受累。结论：EV是儿童ALRTI不可忽视的病原之一,应密切关注EV感染的流行病学状况和临床特点,并定期测定患儿血常规、肝功能和心肌酶,努力改善其预后。     

肠道病毒中枢神经系统感染患儿脑脊液中VP1序列的分子分型研究

目的 探讨肠道病毒(EV)中枢神经系统感染患儿脑脊液(CSF)中VP1序列分子分型研究的临床价值.方法 2003年1月至2005年12月青岛大学附属医院和滨州医学院附属医院采用通用引物和VP1段分子分型引物分别对63例无菌性脑膜炎和脑炎惠儿急性期和恢复期的CSF标本进行扩增,对VP1分型引物扩增阳性片段进行克隆、测序及分型研究.结果 采用通用引物经2次PCR检测急性期患儿的CSF标本共47例(47/63,74.6%)阳性,恢复期仅3例(3/57,5.3%)阳性.采用分型引物经2次PCR检测通用引物扩增阳性的47例急性期的CSF标本共3l例(62.0%)阳性,其中4例脑炎和20例脑膜炎进行了序列测定.测序结果通过BLAST软件进行同源性对比分析,发现同-型别内序列同源性在97%～99%,不同型别之间同源性只有74%～76%,其中COX B3(9例)、ECHO 12(7例)、ECHO 30(3例)、COX A7(2例)、COX A9(1例)、COX B5(1例)、COX A11(1例).所有CSF进行病毒分离,11例(11/63,17.5%)阳性,阳性率明显低于VP1段分子分型的检测结果,除1例CSF标本病毒分离为ECHO7的患儿,通用引物扩增阳性而VP1分型引物扩增失败外,其余血清型别与VP1段分子分型研究结果完全-致.结论 EV是儿童无菌性脑膜炎和脑炎最重要的病原体;采用通用引物所建的RTPCR是快速检测EV中枢神经系统感染的有效方法;分型引物扩增VP1部分序列并测序,与GENBANK中的EV标准毒株进行对比,根据基因序列的同源性进行EV分型,为EV的分型研究提供了新的方法和思路.     

Etiological diagnosis of enteroviral infection

肠道病毒(EV)感染临床常见,但病原诊断一直是困扰临床医师的一个难题.随着病毒学研究的不断深入,EV感染的诊断方法也逐步完善.传统的EV分离和血清学鉴定技术繁杂费时,从临床标本中检测到EV的阳性率也较低,无法满足病毒感染暴发流行期间同时处理大量样本的需求.RT-PCR技术克服了以上缺点,已成为EV感染快速诊断的重要手段.     

Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a French pediatric unit]

OBJECTIVE: To describe the clinical and biological characteristics of children presenting with enteroviral (EV) meningitis in a French paediatric unit during summer 2005. METHODS: Retrospective study of children with EV meningitis from May to September 2005, diagnosed by PCR and/or viral culture in cerebrospinal fluid (CSF), serum or throat. RESULTS: We reported 99 cases of EV meningitis (96 confirmed and 3 probable). The sex ratio was 2/1, and the median age was 5 years. Peak incidence was reached during the second week of July. The predominant symptom was meningism. ENT (16%), digestive (10%), cutaneous (15%) or respiratory (4%) symptoms were rare. Blood leucocyte count found a predominance of neutrophils (73%), and lymphopenia in half of the children. The mean value of CRP was 25,5 mg/l. The median leukocyte count in CSF was 65 cells/mm(3), with a prevalence of neutrophils in 60% of cases. Pleiocytosis was absent in 20 children. CSF protein level was increased in 20% of cases. The rate of hospitalization was 57,5%. Intravenous antibiotic treatment, initiated among 18 patients, was stopped in 66,6% of the cases on reception of PCR result. The latter result was obtained in 2,3 days on average. CONCLUSION: The epidemic of 2005 EV meningitis was as widespread as that of summer 2000. Characteristics of these meningitis are strong proportion of CSF without pleiocytose and high prevalence of neutrophils in blood and CSF.     

Cost analysis of enteroviral polymerase chain reaction in infants with fever and cerebrospinal fluid pleocytosis

BACKGROUND: Infants with fever and cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital for parenteral antibiotic therapy for potential bacterial meningitis pending results of CSF culture. Published estimates suggest that 90% of all episodes of meningitis are caused by enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of 92% to 100% and a specificity of 97% to 100% in CSF. OBJECTIVE: To compare a management strategy using ePCR with current practice to determine potential savings by allowing earlier discharge. METHODS: Decision analysis comparing 2 strategies for the care of a retrospective cohort of infants with fever and CSF pleocytosis: standard practice vs ePCR testing of all CSF samples. Model assumptions include the following: (1) standard practice patients continue parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2) patients with positive ePCR results would be discharged after 24 hours, (3) patients with positive ePCR results have a negative CSF culture, and (4) costs are calculated from actual patient charges with a cost-to-charge ratio of 0.65. SUBJECTS: All infants aged 28 days to 12 months admitted to an urban teaching hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January 1996 through December 1997. OUTCOME MEASURE: Total cost of hospitalization. RESULTS: A total of 126 infants were identified. One hundred twelve (89%) were discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred during the peak enterovirus season (June to October). Three of 3 patients with positive CSF cultures had bacterial growth within 24 hours of admission. Mean length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4 days). Total cost of hospital care for all 126 infants was $381,145. In our patient population, total patient costs would be reduced by the ePCR strategy if enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the sensitivity of the ePCR assay from 100% to 90% changes the "break-even" prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively. CONCLUSIONS: Enteroviral PCR analysis of CSF for infants admitted to the hospital with meningitis can result in cost savings when the prevalence of enteroviral meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would increase cost savings. A prospective study is needed to validate these results. Arch Pediatr Adolesc Med. 2000;154:817-821     

Diagnosis and outcomes of enterovirus infections in young infants

BACKGROUND: Enterovirus (EV) infections commonly cause fever in infants younger than 90 days of age. The polymerase chain reaction (PCR) has improved our ability to diagnose EV infections. OBJECTIVE: To evaluate the utility of blood and cerebrospinal fluid (CSF) specimens for the diagnosis of EV infections by PCR and to describe a large cohort of EV-infected infants. DESIGN/METHODS: Febrile infants younger than 90 days of age evaluated for sepsis at Primary Children's Medical Center in Salt Lake City, UT, were enrolled in a prospective study designed to identify viral infections from December 1996 to June 2002. All patients had bacterial cultures of blood, urine and CSF. Testing for EV was performed by PCR and/or viral cultures. Patients who were positive for EV were identified for this study. RESULTS: Of 1779 febrile infants enrolled, 1061 had EV testing and 214 (20%) were EV-positive. EV infections were diagnosed by PCR of blood, CSF or both in 93% of infants. PCR testing was positive in blood in 57%, and blood was the only positive specimen for 22% of EV infected infants. PCR of CSF was positive in 74%. The mean age of infants with EV infection was 33 days, with 18% younger than 14 days and 5% younger than 7 days. Fifty percent of EV-positive infants had CSF pleocytosis. Of EV PCR-positive infants, 91% were admitted, and 2% required intensive care. Possible serious EV disease was diagnosed in <1%, and there were no deaths. Twelve infants (5.6%) had concomitant urinary tract infection, and 3 (1%) had bacteremia. CONCLUSIONS: EV infections are common in febrile infants younger than 90 days. Blood and CSF are equally likely to yield positive results by PCR, but the combination of both specimens improved the diagnostic yield.     

Impact of rapid polymerase chain reaction results on management of pediatric patients with enteroviral meningitis

BACKGROUND: Enterovirus (EV) infections can be rapidly detected by PCR. However, several studies suggest that results must be available early in the management of the patient to impact significantly on patient care. We evaluated this hypothesis directly during an outbreak of EV aseptic meningitis. METHODS: From June through November, 1998, EV PCR was performed 5 days a week on cerebrospinal fluid specimens from pediatric patients evaluated for meningitis. We compared antibiotic use, length of stay and hospital charges in a group of patients with EV meningitis whose positive EV PCR results were available within 24 h of specimen collection, to a group of similar patients whose results were available >24 h after collection. RESULTS: Cerebrospinal fluid specimens were submitted for EV PCR from 113 patients with suspected EV meningitis, and 50 of 113 (44%) were positive. Of these 50 EV-PCR-positive patients, 17 of 50 (34%) had EV PCR results available in < or = 24 h and 33 of 50 (66%) had results available in >24 h. Patients with EV-positive results reported < or = 24 h after specimen collection had 20 h less of antibiotic use (P = 0.006) and $2,798 less in hospital charges (P = 0.001) than patients with positive results available in >24 h. Hospitalized patients who received positive results rapidly did not have significantly less antibiotic therapy or shorter length of stay, but hospital charges were reduced by $2,331 (P = 0.009). CONCLUSION: Rapid reporting of PCR results can have a significant impact on several outcome measures for patients with EV meningitis.     

A hospital outbreak of aseptic meningitis due to echovirus type 30 in Antalya,Turkey

We analyzed clinical and laboratory findings of 23 hospitalized patients with aseptic meningitis in the Department of Pediatrics, Akdeniz University Hospital. The patients presented with the classic symptoms and signs of aseptic meningitis. Protein levels of the cerebrospinal fluid (CSF) samples ranged from 18 to 99 mg/dl, with a mean of 36.5 +/- 4.9 mg/dl. The mean ratio of CSF glucose compared to blood samples was 0.73. Echovirus type 30 was identified in CSF and/or stool samples of 19 patients. Four patients had negative virus culture. The outcome was favorable in all patients. We thought that this outbreak of aseptic meningitis in our department might denote a summer outbreak in the city. However, this remained unproven since field investigations could not be completed. Advances in virus culture or polymerase chain reaction techniques and satisfactory medical records may help patient care by promoting early diagnosis and by eliminating unnecessary antibiotic therapy, allowing epidemiological studies.     

The use of blood glucose/cerebrospinal fluid glucose ratio in the diagnosis of central nervous system infection in infants and children.

The diagnosis of bacterial meningitis can be difficult nowadays when antibiotics are freely used in infants and children with fever due to infection, so that a positive smear or culture may be difficult to achieve. In areas where sophisticated methods of diagnosis may be hard to come by, the simple procedure of simultaneously estimating the blood and cerebrospinal fluid (CSF) glucose levels may be helpful in distinguishing bacterial meningitis from viral meningitis. 74 proven cases of bacterial meningitis and aseptic meningitis were investigated prior to treatment. There were 36 cases of bacterial meningitis and 38 cases of aseptic meningitis. The CSF glucose/plasma glucose ratio was calculated for each patient. The cases were divided into two groups; Group A with CSF glucose/plasma glucose ratio of (0.38-2.0) and Group B with CSF glucose/plasma glucose ratio of (0.1-0.35). In Group A, two out of 59 cases died while in Group B, nine out of 15 died (p < 0.01). 44 out of 59 in Group A recovered fully while only two out of 15 in Group B were cured (p < 0.01). It was also found that 54.2% in Group A were admitted in deep coma compared with 86.7% in Group B (p < 0.05) and 25.4% in Group A were admitted with seizures while 66.7% in Group B had convulsion (p < 0.01). Hence, a low CSF glucose/plasma glucose ratio was associated with a poor outcome. The mechanisms responsible for these findings are discussed especially with reference to the blood-brain barrier (BBB).(ABSTRACT TRUNCATED AT 250 WORDS)     

Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children

BACKGROUND: Current laboratory tests often cannot distinguish between bacterial and aseptic meningitis rapidly and accurately. The ability to make a prompt diagnosis has important implications for the management and outcome of children with meningitis. The observation that leukocytes aggregate in the cerebrospinal fluid (CSF) has been previously reported, and it has been advocated as a reliable method to distinguish the causes of meningitis in children. OBJECTIVE: To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis. METHODS: We compared the clinical and laboratory indices of 109 prospectively enrolled patients with meningitis (67 bacterial, 23 viral, 19 undefined etiology) and evaluated the validity of the CSF leukocyte aggregation test. The predefined leukocyte aggregation scores (LAS) were compared among the types of meningitis, and correlations with other markers of inflammation were calculated. RESULTS: The median LAS was significantly higher (P < 0.001) in the bacterial (32.1%; range, 0 to 84.1%) than in the viral (0%; range, 0 to 16.6%) or undefined (0%; range, 0 to 20.7%) groups. The optimal sensitivity of the leukocyte aggregation test, 98.5 to 92.5%, was demonstrated with LAS values of 0 to 3%. The corresponding specificity was 64.3 to 88.1%. The peripheral white blood cell (WBC) count, serum C-reactive protein, CSF WBC count, blood culture, CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually. The LAS was as effective as CSF protein, TNF-alpha, IL-1-beta, IL-6 and IL-8 to predict bacterial meningitis. In a logistic regression model that included routine laboratory tests, the best predictor of bacterial meningitis was the LAS (odds ratio, 1.6 to 3.7). Significant correlations were demonstrated between the LAS and CSF protein, CSF WBC count, IL-1-beta, IL-6 and IL-8. Duration of symptoms before diagnosis, pretreatment with antibiotics, HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS. CONCLUSIONS: There is no single test to diagnose the etiology of meningitis in children promptly and accurately. The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis, recognizing that it has low specificity and potential practical limitations.     

Detection of tubercule antigen in cerebrospinal fluids by ELISA for diagnosis of tuberculous meningitis

An Enzyme Linked Immunosorbent Assay (ELISA) was standardised to detect the presence of tubercule antigen in cerebrospinal fluids from patients with meningitis. CSF samples from clinically suspected cases of tuberculous meningitis, culture proven pyogenic meningitis and non-bacterial aseptic central nervous system (CNS) disorders were tested by ELISA to demonstrate its potential utility for routine diagnostic purpose. Tubercule antigen was detected in 73% cases of tuberculous meningitis and was absent in pyogenic and other non-bacterial CNS disorder cases. The test appears to be a promising approach for a definitive diagnosis of tuberculous meningitis.     

Severity of parechovirus infections in infants under 3 months of age and comparison with enterovirus infections: A French retrospective study

While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n = 34) or EV (n = 278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P < 0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P < 0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P = 0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P < 0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P = 0.004) as well as lower C-reactive protein (CRP) levels (P = 0.006) and neutrophil counts (P < 0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age.     

Rapid diagnosis of pneumococcal meningitis: implications for treatment and measuring disease burden

BACKGROUND: Streptococcus pneumoniae is the leading cause of childhood pneumonia and meningitis worldwide. Isolation of this organism, however, is uncommon in resource-poor countries, in part because of extensive use of prior antibiotics. A rapid, highly sensitive immunochromatographic test (ICT) for S. pneumoniae was evaluated for the diagnosis of meningitis. METHODS: Cerebrospinal fluid (CSF) from 450 children with suspected meningitis was tested with ICT, and results were compared with CSF culture, latex agglutination test (LAT) and/or polymerase chain reaction (PCR). Serial CSF specimens from 11 patients were also evaluated for duration of positive results during effective antimicrobial therapy. FINDINGS: All 122 cases of pyogenic pneumococcal meningitis positive either by culture (N = 87) or PCR (N = 35) were positive by ICT, yielding 100% (122 of 122) sensitivity. All purulent CSF specimens from patients with meningitis caused by other bacteria by culture (N = 149) or by LAT (N = 48) or those negative by culture, LAT and LytA and thus of unknown etiology (N = 20), and normal CSF specimens (N = 104) were negative by ICT. Thus the specificity of ICT also was 100% (321 of 321), although negativity of ICT was not confirmed by PCR, if it was positive for other organisms either by culture or LAT. Serotyping of S. pneumoniae strains revealed 28 different serotypes, indicating that outcome of ICT are independent of diverse capsular serotype of pneumococcus. Antigen was detected by ICT for at least 10 days after presentation, and 1 was still positive on day 20, which was longer than for either LAT or PCR. INTERPRETATION: ICT for pneumococcal antigen in CSF is 100% sensitive and specific in diagnosing pyogenic pneumococcal meningitis and can detect approximately 30% more pneumococcal meningitis cases than with culture alone. The simplicity of the test procedure and the longevity of CSF antigen detection suggest the potential utility of ICT to estimate the true burden of pneumococcal disease, as for Haemophilus influenzae type b using data from meningitis, and to guide selection of appropriate antibiotic treatment, especially in resource-poor countries with widespread prehospital antimicrobial use.