Application of a live attenuated varicella vaccine to hospitalized children and its protective effect on spread of varicella infection.

Twenty-three hospitalized children with no history of varicella or no detectable complement fixing (CF) antibody, were vaccinated with a live attenuated varicella vaccine (Oka strain) immediately after the occurrence of a case of varicella in a children's ward of hospital. These children suffered from the nephrotic syndrome, nephritis, purulent meningitis, hepatitis etc., and 12 of them were receiving steroid therapy. An antibody response was noticed in all the vaccinated children, with mild fever in 6 and a mild rash in 2 of 6. It was uncertain whether these reactions were due to vaccinatin or to naturally acquired infection modified by vaccination. No other clinical reactions or abnormalities of the blood or urine were detected. Thus the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. In another trial, 16 children with renal diseases were also vaccinated. All the children showed an immune response with no clinical reactions and no abnormalities in blood and urine examinations. Thus live varicella vaccine (Oka strain) can be used safely and effectively for hospitalized children, and its effectiveness in preventing spread of varicella infection was confirmed.     

Prevention of varicella in urgent cases by passive transfer of vaccine-induced immunity

For the purpose of preventing spread of infection to high risk children whose immunities were severely impaired by intensive chemotherapy or for some other reason, when cases of varicella occurred in a children's ward or in a family, healthy adults (mothers and a doctor) were immediately given live varicella vaccine, blood was collected from these adults 5 to 7 days after vaccination and the whole blood or plasma including the buffy coat was transferred in the high risk children. Subsequently the children showed little or no clinical reaction, and follow-up studies by the neutralizing test and skin test with varicella antigen indicated that their inapparent or subclinical varicella infection occurred in them and that their immunity to varicella was lasting. Skin tests with varicella antigen showed that booster reaction occurred in adults with a previous history of varicella as early as 5 to 7 days after vaccination. The cellular immunity thus induced in the donors may have played a role in preventing a clinical reaction in the high risk children. Thus passive transfer of vaccine-induced immunity seems a convenient and effective method for preventing infection in subjects whose immune capacities are severely impaired.     

Prevention of varicella in immunocompromised patients on unpredictable occurrence of the disease in a children's ward: vaccine-boostered immune whole blood transfusion (VIB) method

For prevention of secondary varicella infection in patients whose immunities were extremely impaired by intensive chemotherapy or immunosuppressive agents, we have been using the vaccine-boostered immune whole blood transfusion (VIB) method when there was an unpredictable case of varicella in the children's ward. By this method passive transfer of humoral and cellular immunity is achieved. There have been 25 unpredictable occurrences of varicella or herpes-zoster in the ward of our children's hospital between April 1977 and May 1983 and during these episodes 16 patients, mostly with malignant diseases, have been treated by this method. There has been no case of secondary varicella infection among these patients and no serious troubles associated with the VIB method.     

Modelling the effects of population structure on childhood disease: the case of varicella

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, at school, or in the community at large. A methodology is first presented for simulating households with births and aging. Transmission probabilities were fitted for schools and community, which reproduced the overall cumulative incidence of varicella over the age range of 0-11 years old.Moreover, the individual-based model structure allowed us to reproduce several observed features of VZV epidemiology which were not included as hypotheses in the model: the age at varicella in first-born children was older than in other children, in accordance with observation; the same was true for children residing in rural areas. Model predicted incidence was comparable to observed incidence over time. These results show that models based on detailed census data on a small scale provide valid small scale prediction. By simulating several scenarios, we evaluate how varicella epidemiology is shaped by policies, such as age at first school enrolment, and school eviction. This supports the use of such models for investigating outcomes of public health measures.     

Varicella infection in a children's hospital: prevention by vaccine and an episode of airborne transmission

Varicella vaccine was used safely and effectively for preventing ward infection with varicella. Ward infection was experienced 34 times in 5 years between 1977 and 1982. During these ward infections, varicella developed in 4 of 142 patients who received vaccine, 21 of 47 patients who did not receive vaccine and 1 of 9 who received transfusion with vaccine-boostered blood. Of the 142 vaccinated patients, the four in whom varicella developed showed symptoms 3 to 10 days after vaccination, indicating that vaccination had been too late. Details of a ward infection with varicella by airborne transmission and its prevention by vaccination are presented.     

Incidence of RS virus infections in premature children's ward

In the course of two years (1974-76) four outbreaks of acute respiratory disease in the premature children's ward of a Prague hospital were studied virologically and clinically. RS virus (RSV) was found to be the aetiological agent. The highest isolation rate of RSV was achieved when using two heteroploid cell lines (L-132 and HEp-2 cells) simultaneously. Of the 30 children examined, 60% showed a severe course of disease (pneumonia and/or bronchiolitis) while in 40% of the children the disease had the form of rhinitis with striking abundance of whitish foamy secretions. In one of the outbreaks under study, two nurses with mild afebrile pharyngitis were detected as the source of RSV infection.     

Clinical application of a live varicella vaccine (Oka strain) in a hospital

A total of 239 children, including 22 high-risk children and 55 non-high risk diseased children have been immunized with a live varicella vaccine (Oka strain) since June, 1978. No clinical reaction attributable to the vaccine has been observed. Of these children, 87 received emergency vaccination. Of 47 children receiving emergency vaccination because they had been in contact with varicella patients either in hospital, school or a playground, only 5 developed varicella and their symptoms were mild. Of 40 children receiving emergency vaccination because of exposure to varicella in their home, 10 developed mild varicella and 30 were protected. Clinical symptoms of varicella when seen seemed to be due to incomplete protection because the vaccine was given too late rather than to clinical reactions to the vaccine. During follow-up period of 6 to 66 months after vaccination, 8 children showed very mild rashes without fever as the result of exogenous varicella infection.     

Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread

Varicella-zoster virus (VZV) causes chickenpox and shingles. While varicella is likely spread as cell-free virus to susceptible hosts, the virus is transmitted by cell-to-cell spread in the body and in vitro. Since VZV glycoprotein E (gE) is essential for virus infection, we postulated that gE binds to a cellular receptor. We found that insulin-degrading enzyme (IDE) interacts with gE through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. These studies indicate that IDE is a cellular receptor for both cell-free and cell-associated VZV.     

Circulation of the causative agent of diphtheria in immune collectives

Prolonged observations on the spread of toxigenic C. diphtheriae carriership, made during a school year in 12 groups of immune children (3809 children), showed that the penetration of diphtherial infection could give rise to the outbreak of bacterial carriership, its level being as high as 20.9-35.1% of the total number of children in the group. The spread of bacterial carriership occurred during the first months after the penetration of the infection, achieving its peak, then followed the subsidence of the infection in the focus. Though some children in the group persistently released C. diphtheriae, almost no new cases of carriership were registered in spring. The highest spread of carriership (55.6-73%) was revealed in the first forms of boarding schools despite a higher level of antitoxic immunity in these children. Cases of the spontaneous cessation of carriership were observed. The spread and subsidence of carriership were determined by the presence or absence of a susceptible contingent. Tests on guinea pigs, carried out in the course of this study to determine the toxigenicity of C. diphtheriae, showed its variability.     

Lymphocyte Deficiencies Increase Susceptibility to Friend Virus-Induced Erythroleukemia in Fv-2 Genetically Resistant Mice

The study of genetic resistance to retroviral diseases provides insights into the mechanisms by which organisms overcome potentially lethal infections. Fv-2 resistance to Friend virus-induced erythroleukemia acts through nonimmunological mechanisms to prevent early virus spread, but it does not completely block infection. The current experiments were done to determine whether Fv-2 alone could provide resistance or whether immunological mechanisms were also required to bring infection under control. Fv-2-resistant mice that were CD4(+) T-cell deficient were able to restrict early virus replication and spread as well as normal Fv-2-resistant mice, but they could not maintain control and developed severe Friend virus-induced splenomegaly and erythroleukemia by 6 to 8 weeks postinfection. Mice deficient in CD8(+) T cells and, to a lesser extent, B cells were also susceptible to late Friend virus-induced disease. Thus, Fv-2 resistance does not independently prevent FV-induced erythroleukemia but works in concert with the immune system by limiting early infection long enough to allow virus-specific immunity time to develop and facilitate recovery.     

108例鼠伤寒沙门氏菌医院内感染临床分析

1988年8月至1991年6月在我院婴儿室及儿科病房发生和收治鼠伤寒沙门氏菌病153例,其中108例占64.1％为医院内感染。发病率龄以12个月以内婴幼儿为主占85.6％。连续两年于8月份在婴儿室呈爆发流行共48例占44.4％。本病全年均可发病,以8～10月为发病高峰。医院内感染的主要传染源为院外感染的散发病例收住院的患者及陪住家属的带菌者。消毒隔离制度不严格是引起传播的重要因素。该病原菌耐药性强,尤其院内感染菌株。院内感染延长住院时间,增加病人痛苦及经济负担,因此医院内感染必须引起重视,急待控制。     

A five-year immunological follow-up study of the institutionalized handicapped children vaccinated with live varicella vaccine or infected with natural varicella

Twenty-two institutionalized handicapped children who were susceptible to varicella were vaccinated with live varicella vaccine of the Oka strain and their immune status was followed for 5 years under conditions without exposure to natural varicella. Simultaneously, 7 children infected with natural varicella were followed. Of the 22 vaccinees, 16 showed sero-positive conversion by the fluorescent antibody to membrane antigen (FAMA) test, the other 6 remaining seronegative during 5 years of observation period. All the 16 cases showing seroconversion had detectable antibody for 5 years after vaccination, and 14 of them gave a positive reaction in the varicella skin test. All the 7 cases after natural varicella gave positive reactions in both the FAMA and skin test. These results suggest that immunity conferred by the vaccination would persist long even in the absence of exposure to natural varicella, though further follow-up studies are needed.     

Insulin Degrading Enzyme Induces a Conformational Change in Varicella-Zoster Virus gE,and Enhances Virus Infectivity and Stability

Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE), through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE) enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.     

水痘患儿血浆C反应蛋白检测及意义

目的:探讨C反应蛋白(CRP)测定在水痘患儿中的变化及临床意义。方法:对82例水痘患儿血浆CRP值与45例正常对照组(无感染)儿童血浆CRP值进行统计比较。结果:水痘患儿中合并细菌感染组CRP值明显高于单纯病毒感染组与正常对照组,CPR水平差异有显著性(P<0.01),单纯病毒感染组与正常对照组CRP值比较,差异无统计学意义(P>0.05)。结论:水痘患儿血浆CRP水平对鉴别是否合并细菌感染、判断病情变化与疗效、从而指导抗生素的正确使用具有一定价值。     

潍坊市2007-2012年水痘流行病学分析

目的：了解潍坊市2007-2012年水痘的流行病学特征,为控制水痘策略提供科学依据。方法对2007-2012年疾病监测信息报告系统上报的水痘病例资料进行描述流行病学分析。结果2007-2012年潍坊市共报告水痘病例2256例,年均发病率为4．22/10万,11月至次年1月及4-6月为发病高峰期;发病主要集中于4～9岁和10～24岁者,其发病率分别为28．76/10万和6．85/10万。发病者主要是学生、散居儿童和托幼儿童,分别占总病例数的52．13％、19．99％、16．93％。报告暴发疫情12起,主要发生在学校和托幼机构。结论潍坊市发生的水痘以4～9岁和10～24岁者为高发人群,应加强对适龄儿童水痘疫苗的查漏补种工作,加强学校及托幼机构传染病管理,减少发生暴发疫情。     

Antibody prophylaxis of varicella in immunosuppressed patients

ZIG prophylaxis was administered to a total of 39 children immunosuppressed under antitumour therapy and presenting a negative varicella history. Varicella developed in only 2 of them. 47 children received a substitutive prophylaxis consisting of ordinary gammaglobulin NORGA. Fourteen of the children fell ill with varicella, two of the cases being complicated. With a few exceptions, the cases represented hospital contacts, because most children with anticancer therapy are in hospital. The difference between the numbers of varicella cases after ZIG and after NORGA was statistically highly significant in the group of seronegative children. On the other hand, the difference between the numbers of cases among preprophylactically seropositive children in both prophylactic groups was not substantial. Varicella was not encountered either among children with a titre of minimally 1:128 at the time of contact with the disease. In contrast, varicella developed in 20-30% of children with a titre of at most 1:64. Four children were serologically followed up for 35-49 days after the injection of ZIG. The degradation of VZV antibodies in these children under immunosuppression was far more rapide than that of known passively transferred IgG in normal individuals. In states of deep immunosuppression a quantitatively or qualitatively different mechanism of passively transferred antibody clearance is probably involved.     

Varicella zoster virus vaccines: potential complications and possible improvements

Varicella zoster virus(VZV) is the causative agent of varicella(chicken pox) and herpes zoster(shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine(v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia(PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.     

An analysis of the seasonal rise in hepatitis A morbidity at a children's center and ways to improve the sanitary epidemiologic surveillance for this infection among organized preschoolers

The spread of hepatitis A in children's institution occurred through everyday contacts, the boundaries of the focus of infection embraced the whole institution, and the active detection of the prevailing subclinical forms of the disease proved to be possible by means of virological and biomedical tests. The enhancement of the effectiveness of clinical and epidemiological surveillance by its orientation to the control of the spread of this infection through water and everyday contacts, the rational organization of sanitary, microbiological and serological studies, the development of criteria of epidemiological safety of children's institutions is proposed.     

深部真菌感染调查及耐药性分析

目的了解住院患者真菌感染的临床特点及对药物的敏感情况。方法采用回顾性调查．对2002年8月至2005年8月住院病例中的真菌感染病例进行统计分析。结果3年间住院患者真菌感染536例,占检出病原菌的8．37％。引起深部感染的真菌以白色念珠菌为主,占39．37％;毛霉菌与曲霉菌的感染次之,分别达到16．79％和13．62％。呼吸内科、老年内科和ICU病房住院患者较易发生医院真菌感染。真菌感染的部位以呼吸道最高,其次为泌尿道。真菌对酮康唑、咪康唑和益康唑耐药率相对较高,对5一氟胞嘧啶、两性霉素B、制霉菌素相对敏感。结论医院深部真菌感染主要多发生于年老体弱、免疫功能低下、病情危重和长期使用抗生素的患者,已成为医院感染的主要因素之一。医院感染真菌的耐药性日趋严重,临床应用抗真菌药物尽量参考药敏试验结果。