水痘疫苗接种的成本效益

水痘是一种常见的急性、高传染性的疾病 ,可感染儿童、成人。 1974年日本首先研制成功Oka株水痘减毒活疫苗 ,1984年世界卫生组织批准水痘减毒活疫苗用于婴幼儿预防接种 ,许多国家陆续开展了水痘疫苗预防接种 ,不仅能取得良好的防病效果 ,而且可较大地减轻疾病负担。对儿童、青少年、成人、育龄期妇女和免疫功能抑制患者分别进行的经济学评价表明 ,接种水痘疫苗具有较好的成本效益结果。     

Allodynia in rats infected with varicella zoster virus—a small animal model for post-herpetic neuralgia

The most common complication of herpes zoster is post-herpetic neuralgia (PHN), which has been defined as severe pain occurring 1 month after rash onset or persisting for greater than 3 months. PHN is classed as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful. The development of therapies to treat PHN has been hampered by the lack of animal models, which mimic the clinical situation. We have previously reported that varicella zoster virus (VZV) infection in the rat results in mechanical allodynia and thermal hyperalgesia. Here, we report that following VZV infection of the left footpad rats develop a chronic mechanical allodynia, which is present for longer than 60 days post-infection and which resolves by 100 days PI. The model is robust and reproducible with animals consistently developing allodynia by 3 days PI and continuing to present with symptoms for at least 30 days. The reproducible nature of the induction and course of the allodynia allows the use of this model to determine the effect of various compounds on, and to investigate the pathogenic mechanisms underlying the development of VZV-induced allodynia. Comparative studies using HSV-1 show that the induction of the chronic allodynia is VZV-specific and is not a result is of virus replication-induced tissue damage or accompanying inflammation.Therefore, we propose that the rat VZV infection model could prove useful in studying the mechanisms underlying post-herpetic neuralgia.     

Prevalence of viral infection markers by polymerase chain reaction amplification and interferon-alpha measurements among patients undergoing lumbar puncture in an emergency department

Aseptic meningitis is a frequent diagnosis in emergency departments. Nevertheless, viral investigations are not carried out currently and the viral etiology in adult population has not been studied extensively. We conducted a prospective study including all consecutive patients undergoing lumbar puncture during a 15 months period in an adult emergency department. Bloody and purulent cerebrospinal fluid (CSF) were excluded. The main tests undertaken were: CSF genomic amplification by the polymerase chain reaction (PCR) for neurotropic viruses and serum and CSF interferon-alpha (IFN-alpha) measurements. Among 194 patients included, 45 had and 149 did not have aseptic meningitis. Of 45 patients with aseptic meningitis, 10 had alternative non-virological final diagnosis, and 35/45 were presumed to have neurological disorders of viral origin. Patients (27/35) completed virological analysis: 21/27 (78%) had either positive viral PCR (enterovirus: 8 patients, Varicella zoster virus (VZV): 5, Epstein-Barr virus (EBV): 2, herpes simplex virus (HSV): 1, human herpes virus 6: 1) or only raised serum or CSF IFN-alpha (4 patients). Overall, 59% of patients with a positive viral PCR had either CSF or serum raised IFN-alpha. Twentyone patients without meningitis had either positive viral PCR (enterovirus: 3 patients) or only high serum IFN-alpha level (18 patients). In the setting of aseptic meningitis diagnosed in an adult emergency department, viruses are the most common agents encountered, with enterovirus and VZV as the two main etiological agents. Current CSF viral genome amplification and IFN-alpha measurement are informative and could be useful to confirm the viral origin of various neurological disorders, although the sensitivity and specificity of IFN-alpha measurement for the diagnosis of viral infection need further confirmation.     

Long-term survivors following autologous haematopoetic stem cell transplantation have significant defects in their humoral immunity against vaccine preventable diseases,years on from transplant

Current international guidelines recommend routinely vaccinating haematopoetic stem cell transplant (HSCT) recipients. Despite significant infection-related mortality following autologous HSCT, routine vaccination programmes (RVP) completion is poor. For recovered HSCT recipients, it is uncertain whether catch-up vaccination remains worthwhile years later.To determine potential susceptibility to vaccine preventable infections, we measured antibody titres in 56 patients, a median of 7 years (range 0–29) following autologous HSCT, who had not completed RVP. We found that almost all participants had inadequate titres against diphtheria (98.2%) and pneumococcal infection (100%), and a significant proportion had inadequate titres against measles (34.5%). Of those subsequently vaccinated according to available guidelines, many mounted adequate serological responses.These data suggest a pragmatic catch-up approach for autologous HSCT recipients who have not completed RVP is advisable, with universal vaccination against some pathogens (e.g. Streptococcus pneumoniae and diphtheria) and serologically-guided approaches for others (e.g. measles and varicella zoster virus).     

上海市部分地区儿童水痘疫苗免疫后流行病学效果观察

[目的]观察水痘疫苗接种情况和接种水痘疫苗1~7年后的水痘发病情况。[方法]在本市部分地区选择接种组和未接种组儿童,采用统一调查问卷调查水痘疫苗接种情况和水痘发病情况。[结果]调查地区儿童水痘疫苗累积接种率为4.12%,12岁以下人群为26.90%。1999~2005年接种组总发病率为1.00%,未接种组为4.35%,水痘疫苗接种保护率为77.0%;各年接种组发病率分别为1.62%、2.06%、0.29%、0.43%和0.66%,疫苗接种保护率在67.9%~90.3%之间;接种进口和国产水痘疫苗后水痘发病率分别为0.8%和1.0%,疫苗接种保护率分别为81.6%和75.3%。[结论]本市儿童水痘疫苗接种率呈上升趋势。水痘疫苗对接种者具有较好的保护率,进口和国产水痘疫苗的保护率相似。     

The economic impact of prenatal varicella immunity among pregnant women in Alberta

In light of the changing epidemiology of varicella, we sought to examine varicella antibody levels in the prenatal population in the Canadian province of Alberta. All prenatal varicella screening tests performed between August 1, 2002 and February 2, 2014 (454,592) were included in this study. Test results, demographics and vaccination status were examined to identify varicella seroprevalence and correlates for being seronegative. An overall seroprevalence for varicella of 95.8% was found across all pregnancy screenings. Significant independent correlates of seronegativity included younger age (AOR: 4.72 (95% CI: 3.87–5.77) for <20 years of age vs. >40 years of age) and having immigrated to Alberta from Africa or Asia (AOR: 4.55 (95% CI: 4.10–5.05) and AOR: 5.83 (95%CI; 5.48–6.19), respectively). Women who were initially seronegative for varicella antibodies and who received both postnatal vaccination and post-vaccination prenatal screening (2566) were examined to assess seroconversion. 66.3% of women who were tested up to six months post-vaccination were seropositive, however only 36.9% of women tested after 36 months were seropositive. Finally, 40.9% of all prenatal varicella specimens tested were deemed redundant, i.e. women had either a history of (1) ⩾2 doses of varicella vaccine, (2) varicella infection, or (3) a previous positive varicella serology. Eliminating this redundant screening could provide an estimated $96,000 in savings annually in laboratory and Public Health follow-up costs alone. As the number of women with vaccine-derived immunity through universal childhood vaccination increase in the prenatal population, screening methods may need to adapt to ensure varicella immunity is accurately conducted and assessed.     

Low prevalence of human herpesvirus-6 and varicella zoster virus in blood of multiple sclerosis patients,irrespective of inflammatory status or disease progression

Herpesviruses, including human herpesvirus-6 and varicella zoster virus, have been implicated in the disease aetiology of multiple sclerosis. These viruses are capable of reactivation, reminiscent of the relapsing-remitting nature of multiple sclerosis. However, viral DNA has also been reported present in healthy controls, often at similar prevalence rates. This study aimed to determine whether prevalence could be associated with different stages of activity of the disease as well as the inflammatory status of the patients. Polymerase chain reaction assays were used to screen for human herpesvirus-6 and varicella zoster virus DNA in blood from 31 Caucasian patients with multiple sclerosis and 30 healthy age, sex and race matched control subjects. The patients were screened for inflammation using C-reactive protein as a marker and were also categorized according to their remitting/relapsing status. Results were positive for human herpesvirus-6 in blood from only one patient (3.2%) and human herpesvirus-6 DNA was not present in any control subjects. Varicella zoster virus was not detected in either the patients or control subjects. Similar to some other studies we saw an absence or very low viral positivity in blood from both patients and controls. These findings were irrespective of relapse episodes, increased inflammatory status or duration of the disease. Results therefore do not support a causative role for either human herpesvirus-6 or varicella zoster virus in the disease aetiology of multiple sclerosis, but rather that prevalence in patients may be linked to that of the general population.     

Varicella vaccination in Japan: necessity of implementing a routine vaccination program

Varicella-zoster virus (VZV) is the causative agent of varicella (chickenpox). It shows extremely high infectivity and is spread by airborne, droplet, and contact transmission. After a person is infected with VZV, the virus remains dormant in the dorsal root ganglia, but can be reactivated under circumstances where specific immunity declines, leading to the development of herpes zoster (shingles). Although varicella is a disease that usually resolves after about 1 week, it can cause various complications such as secondary bacterial skin infection, pneumonia, and encephalitis. In addition, varicella can become severe in immunocompromised persons, whereas VZV infection transmitted from an infected mother can cause the congenital varicella syndrome or serious neonatal varicella. In 1974, a live varicella vaccine (Oka strain) was developed in Japan for the prevention of varicella, and clinical trials performed during the development were mainly focused on high-risk children. In 1985, the Oka strain was recognized as the best varicella vaccine strain by the World Health Organization (WHO). Today, all the varicella vaccines used worldwide to immunize approximately 32 million people annually contain the Oka strain. In Japan, it has been commercially available since 1987 for the voluntary vaccination program, in which children over the age of 1 year with no history of previous varicella infection receive a single dose. In addition to healthy children, this vaccine can be used for immunocompromised children, and vaccination of elderly persons can also be done to enhance their immunity against VZV. Varicella vaccine is a highly safe vaccine with sufficient immunogenicity. The preventive effect of single-dose vaccination is believed to be approximately 80 % for all types of varicella, including mild cases; it is 95 % or greater for moderate to severe disease. Implementation of a two-dose vaccination schedule has proved to be effective against breakthrough varicella, which is observed in approximately 20–30 % of children vaccinated with a single dose. Because it is administered as part of the voluntary vaccination program, the varicella vaccination coverage rate in Japan has remained low until recently at around 20–30 %, with no sign of a decrease in the number of varicella patients. It is necessary to maintain a vaccination rate of 90 % or higher to prevent varicella epidemics. To achieve this goal, implementation of a routine vaccination program for varicella and introduction of a two-dose vaccination schedule, which is more effective than a single-dose schedule, would be highly desirable.     

Detection of IgG-class antibodies to measles,mumps, rubella,and varicella-zoster virus using a multiplex bead immunoassay

Serologic testing for measles, mumps, rubella, and varicella (MMRV) IgG is traditionally performed by immunofluorescence assay or enzyme immunoassay (EIA). Although sensitive and specific, these methods are labor intensive, time consuming, and require separate assays for each analyte. This study evaluated the performance of the MMRV IgG AtheNA Multi-Lyte® assay using nonclinically characterized serum specimens submitted to our laboratory for routine MMRV IgG testing. Mumps (n = 492) or rubella (n = 500) IgG were initially tested by enzyme-linked fluorescent antibody (ELFA), whereas measles (n = 494) or varicella (n = 497) were analyzed by EIA. Each sample was also tested by the AtheNA Multi-Lyte assay. Discordant results were retested by the predicate method and the multiplex assay, with further discrepancies being arbitrated by a third test. Compared to EIA/ELFA for MMRV IgG, the AtheNA assay demonstrated an overall agreement of 97.4%, 98.2%, 97.6%, and 100%, respectively. Use of this multiplex assay allows for the simultaneous detection of MMRV IgG, potentially decreasing cost, sample volume requirements, aliquot errors, and hands-on testing time.