新生儿中枢神经系统单纯疱疹病毒感染的临床横断面研究

目的通过分子生物学方法了解新生儿中枢神经系统单纯疱疹病毒(HSV)感染情况,并对其临床特点进行分析。方法收集考虑中枢神经系统病毒感染新生儿40例的脑脊液(CSF)标本,通过套式PCR检测CSF中HSV-DNA及酶联免疫吸附法检测CSF中特异性HSV-IgM抗体。结果2例患儿检测CSF中HSV-1 DNA( ),其母亲妊娠期均体健,无生殖器疱疹史,无皮损;1例提示为播散性感染,另1例局限为中枢神经系统感染。40例CSF检测HSV-2 DNA均阴性。结论HSV感染占新生儿中枢神经系统病毒感染的5%,不是常见病原;1型可能为新生儿HSV中枢感染的常见类型,可能与我国孕母HSV-2血清感染率较低有关。     

Rapid Tissue Diagnosis of Herpes Simplex Infections in the Newborn

The presence of intranuclear inclusions in tissues is considered to be consistent with viral infections. Further identgication is done by viral cultures. In this study, the direct immunofluorescence technique was utilized to identify herpes simplex virus in the tissues. Positive fluorescence was seen in 8 of 12 specimens. In all these specimens, diagnosis was further confirmed by electron microscopy, viral cultures, or both. Thus, the technique is a specific, sensitive method of diagnosis for herpes simplex infections. Rapidity and simplicity of the technique warrant regular use.     

Neonatal herpes simplex: clinical findings and outcome in relation to type of maternal infection

In 39 mothers of children with neonatal herpes simplex virus infection, maternal infection was serologically characterized retrospectively and was related to maternal clinical symptoms and to the clinical findings and outcome in the child. Thirteen mothers had a primary infection (six type 1, seven type 2), mostly with clinical symptoms. The mean age of onset of the disease of the infants was 7 days and a disseminated disease was most commonly found. Most of the type 1-infected children recovered completely, whereas all but one of the type 2-infected children died. Twenty mothers had a recurrent (2 type 1, 18 type 2) and 4 an intermediate infection (primary type 2, prior infection with type 1), mostly asymptomatic. Their children had a localized disease (of the skin-eye-mouth or the central nervous system) with onset at a mean age of 14 or 13 days, respectively. The frequency of neurological sequelae was high. Two mothers had no serological signs of herpes infection.     

Acute Confusion—an Unusual Form of Cerebral Herpes Simplex Virus Infection?

ABSTRACT. Herpes simplex virus (HSV) infections are common and, if afflicting the central nervous system, may cause death or severe sequelae. Since specific therapy is now available there is an increasing demand for the recognition of the various ways in which cerebral HSV-infections may be manifested. This report describes a 15-year-old boy who presented acutely with mental symptoms of confusion, hallucinations and sleep disturbance. Simultaneously, but without any increase in cerebrospinal fluid cell or protein content, an intrathecal production of HSV-antibodies of transient nature was detected. These findings suggest that the patient may have suffered from an unusual form of herpes infection in the central nervous system. We suggest that similar cases should be thoroughly explored for possible herpes etiology as early as possible during the acute phase of the disease.     

The Effect of Human Gammaglobulin Derivatives on the Human Lymphoblastoid Cell Lines Persistently Infected with Herpes Simplex Virus

Human lymphoblastoid cells (NC–37) were infected with two strains of herpes simplex virus type 1 (HSV–1). Persistent infections with two strains (a freshly isolated strain, Seike strain, and Miyama strain) of HSV–1 were established in NC–37 cells. In NC–37 cells infected with HSV–1 (Seike), the growth of cells was inhibited,6–72% of viable cells were positive for HSV-antigen by immuno-fluorescence, and the percentage of HSV-antigen positive cells seemed to be inversely related to that of viable cells. Growth of cells and infectious virus were seen for more than 396 days without external support. NC-37 cells infected with HSV-1 were subcultured with fresh medium containing human gammaglobulin derivatives. When the percentage of HSV-antigen positive cells was low (6%), the percentages of HSV-antigen positive cells decreased to nearly 0% on the 6th day. When the percentage was high (47-52%), it was not reduced to 0% after one subculture. It was reduced to nearly 0% after three subcultures, and no infectious virus was detected in the treated cells and cultured fluids after more than 16 days. The results of the present study support the speculation that HSV continues to associated with lymphoid cells for a long period of time after appearance of neutralizing antibody, at least for two weeks, and the lymphoid cells infected with HSV have a relation to the pathogenesis of herpetic encephalitis. (Acta Paediatr Jpn 23(3):312–317 1981)     

更昔洛韦对小鼠单纯疱疹病毒性急性脑损伤的保护作用

目的探讨更昔洛韦(GCV)对单纯疱疹病毒(HSV)性急性脑损伤的保护作用及其机制。方法建立小鼠HSV急性脑损伤模型,比较GCV治疗前后小鼠生存状况、死亡率和电镜下脑组织结构变化;接种病毒后d7处死小鼠,通过荧光定量FCR检测脑组织中HSV-ⅠDNA的拷贝数。结果电镜下感染模型组小鼠脑细胞胞浆水肿明显.核仁固缩,核内结构破坏,多数线粒体呈空泡样改变,核仁内可见病毒颗粒内脊破坏、髓鞘严重松解、破坏。GCV治疗后小鼠症状明显好转,体质量增加理想,死亡率明显降低,脑组织病理损害明显减轻,小鼠脑组织中HSV-ⅠDNA拷贝数也显著低于模型组。结论GCV能有效抑制HSV-Ⅰ复制,减轻临床症状、脑组织损伤,降低小鼠HSV急性脑损伤的死亡率。     

Pathology of Chronic Herpes Infection Associated with Seizure Disorder: A Report of Two Cases with Tissue Detection of Herpes Simplex Virus 1 by the Polymerase Chain Reaction

Although uncommon, the association of chronic encephalitis with epilepsy is well recognized. While a viral etiology has been suspected based on the morphology, to date no virus has been successfully cultured from the brain in patients with Rasmussen's encephalitis. We describe the pathologic findings and report the detection of herpes simplex virus 1 (HSV1) in the brain in two patients who presented primarily with intractable seizures. In the first patient, an intrauterine infection was suspected as the underlying basis for the seizure disorder and the extensive cerebral calcification and gliosis. The second patient (with presumed HSV1 encephalitis at age 7 months) underwent a temporal lobectomy for medically refractory seizures at the age of 3 years and pathologic examination revealed a chronic encephalitis. While immunohistochemical, ultrastructural, and culture studies were negative for viral pathogens, molecular analysis by the polymerase chain reaction (PCR) revealed HSV1 DNA sequences in both cases. Thus our cases represent two examples of chronic encephalitis associated with a seizure disorder, where a definitive viral etiology was documented by PCR.     

The Effect of Human Gammaglobulin Derivatives on Human Lymphoblastoid Cell Lines Persistently Infected with Herpes Simplex Virus

Human lymphoblastoid cells (NC-37) were infected with two strains of herpes simplex virus type 1 (HSV-1). Persistent infections with two strains (a freshly isolated strain, Seike strain, and Miyama strain) of HSV-1 were established in NC-37 cells. In NC-37 cells infected with HSV-1 (Seike), the growth of cells was inhibited, 6–72% of viable cells were positive for HSV-antigen by fluorescent antibody technique, and the percentage of HSV-antigen positive cells seemed to be inversely related to that of viable cells. Growth of cells and infectious viruses was seen for more than 396 days without external support. NC-37 cells infected with HSV-1 were subcultured with fresh medium containing human gammaglobulin derivatives. The percentage of HSV-antigen positive cells decreased and no infectious viruses were detected in the treated cells and cultured fluids after more than 16 days. It is thought that HSV continues to associate with T-lymphocytes stimulated in vivo for a long period of time after the appearance of circulating antibody, at least for two weeks, and lymphocytes persistently infect with HSV have a relation to the patho-genesis of herpesvirus encephalitis in oider children and adults similar to the pathogenesis of SSPE. (Acta Paediatr Jpn 23(2): 201–207 1981)     

HCMV HSVⅡ和HPVB-19感染对胎儿畸形的影响

目的：研究人巨细胞病毒(HCMV),单纯疱疹病毒Ⅱ型(HSVⅡ)及人微小病毒B19(HPV B19)感染与胎儿畸形的关系。方法：应用聚合酶链反应技术检测了畸形组16例和对照组25例围生期死亡病例的脑、肝、肺、肾、脾组织和妊母胎盘组织中的HCMV,HSVⅡ及HPV B19 DNA。结果：①畸形组HCMV,HSVⅡ,HPV B19阳性率分别为：50.0%(8/16),37.5%(6/16)和31.3%(5/16),而对照组阳性率分别为8.0%(2/25),8.0%(2/25),12.0%(3/25),两组之间CMV,HSVⅡ感染有显著性差异(P<0.05)。②HCMV易感器官为脑、肝、肺,畸形组中脑组织阳性率43.8%(7/16)与肾组织6.3%(1/16)有显著性差异,HSVⅡ易感器官主要为肝脏,HPV-B19主要为脾脏受累。结论：HCMV,HSVⅡ胎儿与畸形有密切关系,HPV-B19感染因例数较少与畸形无明显关系。     

Clinical Epidemiology of Symptomatic Primary Herpetic Infection in Children

ABSTRACT. We have studied a series of 50 children with clinical primary herpetic infection during 1975–1985. Our data confirm: absence of sex differences and seasonal variations, a peak age of incidence between 6 and 24 months, a prevalence of patients of lower social status, evidence of recurrent herpes labialis as the most frequent source of infection, and frequency of herpes simplex virus 1 gingivostomatitis. The relevant findings of this study were as follows: 1) herpes simplex virus 2 was isolated in 10% of the patients, 2) 6% of cases occurred in the first six months of life, 3) infection was multifocal in 36% of cases, 4) autoinoculation was a frequent route of transmission of genital primary infection in young children, 5) herpetic Kaposi-Juliusberg's pustulosis in infants with atopic dermatitis was the most severe presentation of primary infection and should be more adequately prevented.     

A Prospective Study of Rotavirus Infections in Neonatal and Maternity Wards

ABSTRACT. The occurrence and symptomatology of rotavirus infections was studied at three maternity wards and one neonatal unit. Rotavirus was identified in 12.7% of 553 infants and 1.3% of 542 mothers at the maternity wards. Infections were more frequent in a mixed obstetric/ gynecology ward than in the pure obstetric wards. Only 10% of the infants had symptomatic infections. Subgroups of rotavirus was determined in 41 infants: 22 of subgroup I and 19 of subgroup II, which is the subgroup accounting for the majority of childhood gastroenteritis. Rotavirus was found in faecal samples from 37% of the infants at the neonatal unit during an eight-month survey. A seasonal variation with most infections during colder months was seen. Subgroup determination was possible in 29 cases, 14 subgroup I and 15 subgroup II. Fifteen per cent of the infections demonstrated diarrheal symptoms. No significant difference among other clinical data registered was seen among rotavirus infected compared to the non-infected infants. We conclude that neonatal rotavirus infections occur as an endemic infection at our maternity wards possibly combined with infections due to external sources of virus in mixed wards and neonatal units     

Giant-Cell Myocarditis in a Newborn with Congenital Herpes Simplex Virus (Hsv) Infection: an Immunohistochemical Study on the Origin of the Giant Cells

Giant-cell myocarditis is a rare inflammatory disorder characterized by degeneration and necrosis of myocardial fibers and presence of chronic inflammatory infiltrates associated with multinucleated giant cells forming a granulomatous inflammatory reaction. The etiology of giant-cell myocarditis is unknown. Many conditions have been reported as associated with this phenomenon such as fungi, virus, sarcoidosis, and hypersensitivity or autoimmune reactions.     

长沙市急性下呼吸道感染并粒细胞减少症111例病毒病原学分析

目的 探讨儿童急性下呼吸道感染并粒细胞减少症病毒病原学的特点.方法 选取湖南省人民医院2007年6月- 2008年10月111例急性下呼吸道感染并粒细胞减少症(粒细胞减少组)及1014例急性下呼吸道感染但粒细胞数正常的住院患儿(粒细胞正常组).患儿入院第2天收集鼻咽分泌物标本,采用反转录(RT) -PCR、PCR或巢式PCR扩增方法进行病毒基因检测,并将阳性产物测序,经序列测定及对比分析后确定为所检测病毒.结果 粒细胞减少组与粒细胞正常组病种构成及性别构成比较差异均无统计学意义(Pa＞0.05).粒细胞减少组37例未检出病毒,74例检出至少有1种病毒;各种病毒中,呼吸道合胞病毒(RSV)检出率最高,其次是副流感病毒3(PIV3)、鼻病毒(HRV)及人博卡病毒(HBoV).粒细胞正常组295例术检出病毒,719例检出至少有1种病毒;RSV检出率最高,其次是PIV3、HRV及HBoV.2组病毒总检出率及各种病毒检出率比较差异均无统计学意义(Pa＞0.05).2组年龄段分布差异有统计学意义(x2=8.89,P=0.012).其中1个月～1岁年龄段差异最大(X2=8.83,P=0.003).结论 1.急性下呼吸道感染住院患儿粒细胞减少的发生与病毒感染无明显相关.2.大于1岁的急性下呼吸道感染住院患儿更易出现粒细胞减少.3.急性下呼吸道感染住院患儿粒细胞减少与性别及疾病种类无关.     

Clinical Manifestations of Respiratory Tract Infections due to Respiratory Syncytial Virus and Rhinoviruses in Hospitalized Children

ABSTRACT. From September 1984 to May 1986, nasopharyngeal secretions were obtained from 519 children with some form of respiratory tract infection. The nasal secretions were screened for respiratory syncytial virus (RSV), rhinoviruses, adenoviruses, parainfluenza virus types 1, 2,3, influenza virus types A and B, and enteroviruses by tissue culture virus isolation technique and/or enzyme-linked immunosorbent assay. A uniform questionnaire gave information about age, sex, individual signs and symptoms, findings of the physical examination and clinical diagnosis of the patients. RSV was detected in 119 (23%) specimens and was thus the most frequent causative agent of respiratory infections. After RSV, rhinoviruses were the most frequently recovered pathogens accounting for 60 (12%) cases of acute respiratory disease. A comparison of the individual signs and symptoms, the findings of the physical examination and the clinical diagnosis of RSV and rhinovirus infected children revealed that there was no characteristic clinical pattern associated with either of the two viral respiratory pathogens. According to our results, rhinovirus infections were a major cause of lower respiratory tract infections in hospitalized children ≤3 years old.     

Natural Killing of Varicella-Zoster Virus (VZV)-Infected Fibroblasts in Normal Children, Children with VZV Infections, and Children with Hodgkin's Disease

We studied mononuclear cell (MNC)—mediated natural killing (NK) of varicella-zoster virus (VZV)—infected fibroblasts in normal children, children with VZV infections, and children with Hodgkin's disease. NK activity was tested in 18hr ⁵¹Cr release assays. NK activity for adults was significantly higher than that for children 1–3 years old or 4–6 years old (p< 0.05). Serological status did not affect NK activity. NK activity in normal children was not increased 4–6 weeks after immunization with varicella vaccine. Seven normal children with natural varicella showed significantly higher NK activity against VZV-infected and unin-fected targets. Eight immunosuppressed children with herpes zoster showed significantly reduced NK activity within 72 hours of the onset of herpes zoster. However, their NK activity rose to the normal level one to two weeks later. Children with Hodgkin's disease had low NK activity. These results suggested that NK cells might play an initial defensive role in VZV infections, and that low NK activity in immunocompromised hosts might contribute to their high incidence of herpes zoster.     

Neonatal Follow-up of Very Low Birthweight/Extremely Low Birthweight Infants to School Age: A Critical Overview

ABSTRACT. Neonatal follow-up studies of school age children, published in the last decade, were critically reviewed. Nine studies examined extremely low birthweight infants (≤1000 g) and 16 involved very low birthweight infants (≤1500 8). The majority of children had age appropriate I.Q. scores, however, there was a greater variability of test scores. There was an increased need for special education or remedial therapy. Visual-motor integration deficits were frequently reported. Behavioural difficulties were described. Fine and gross motor incoordination was identified. There was no conclusive correlation between perinatal course and school outcome. Gender did appear to influence outcome, in the small percent of studies which examined this variable, with females generally faring better. Low socioeconomic status was the most frequently reported predictor of poor outcome. Identified methodological limitations included heterogeneous samples, lack of control groups, high attrition, variable diagnostic criteria and lack of consensus regarding correction for prematurity.     

Infections in Children with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome: An Autopsy Study of 30 Cases in South Florida, 1990-1993

Thirty autopsies performed on infants and children with HIV infection and/or AIDS were reviewed for the presence and type of infection. Twenty-six (87%) demonstrated evidence of infection in addition to HIV at the time of postmortem examination. Pathogenic bacterial infections were the most frequently encountered, seen in 15 of the cases. Nine of the 15 (60%) were due to gram-negative rods, most commonly Pseudomonas aeruginosa. Infections with gram-negative organisms often involved multiple organ systems and were frequently undiagnosed both pre -and postmortem because of variability in culture results and difficulties in identification both clinically and in tissue sections. Discussion is presented of unusual staining characteristics and filamentous morphology found with these pathogens. Other pathogenic bacteria encountered were Klebsiella pneumoniae, Escherichia coli, Enterobacter sp., and Staphylococcus. Fungal infections due to Candida species were present in nine cases (31 %) but were invasive in only two of these. One instance of Aspergillus meningo-encephalitis was noted. Proven viral infections were present in five children (three cytomegalovirus, one herpes simplex, and one adenovirus). Pneumocystis carinii pneumonia was diagnosed in five of the patients (17%), and one instance of disseminated Mycobacterium avium-intracellulare was encountered.