荧光PCR法检测2008年-2017年单纯疱疹病毒Ⅱ型感染的临床结果与分析

目的了解浙江地区疑似生殖器疱疹患者单纯疱疹病毒Ⅱ型(HSV-Ⅱ)感染情况,为临床诊断治疗提供依据。方法实时荧光PCR法对浙江省人民医院2008年-2017年2 230例疑似泌尿生殖道疱疹患者进行HSV-Ⅱ核酸检测。结果在2 230例疑似泌尿生殖道疱疹患者中,女性1 554例,男性676例,共检测出HSV-Ⅱ型阳性557例,阳性率为24.98%。557例HSV-Ⅱ感染患者中女性405例,阳性率为26.06%;男性152例,阳性率为22.49%,男、女感染率差异无统计学意义(P> 0.05)。557例HSV-Ⅱ型阳性患者分5个年龄段即<20岁、20岁~29岁、30岁~39岁、40岁~49岁、≥50岁分析,阳性率分别为3.05%、42.01%、29.80%、14.72%、10.23%。结论泌尿生殖道HSV-Ⅱ感染检出率较高,提示临床需重视对疑似生殖道疱疹病毒感染患者进行HSV-Ⅱ核酸检测;HSV-Ⅱ感染无性别差异,但感染主要集中在20岁~29岁患者。实时荧光PCR法在HSV-Ⅱ检测中具有快速、灵敏度高、简便等优点,适用于临床检测。     

35例EB病毒性脑炎临床分析

目的:探讨EB病毒性脑炎(Epstein-Barr virus encephalitis,EBE)临床特点及诊断依据。方法:通过多重PCR方法检测脑脊液确诊35例EBE和96例病原分别为肠道病毒(EV)、疱疹病毒(HSV)Ⅰ、Ⅱ型或巨细胞病毒(CMV)脑炎患儿,对其临床资料进行回顾性分析。结果:EBE脑脊液恢复时间、IgG蛋白定量和热程与其它病毒性脑炎比较,差异显著(P<0.05);EBE在头痛和惊厥发作持续时间上与其他病毒性脑炎无明显差异(P>0.05);在中枢神经系统影像学和脑脊液改变方面,EBE与HSV脑炎相似,但较其它病毒性脑炎改变明显,差异显著(P<0.05)。结论:EBE对中枢神经系统损害较重,临床上具有易迁延特点,免疫性损害可能是EBE的主要原因。     

Hypothetical vaccination of the Dutch population with a herpes simplex virus vaccine: estimation of the profitability using a demographic projection model

The apparently increasing evidence of herpes simplex virus infections of the genital tract has focused attention on preventing the infection by vaccination. Herpes genitalis is not, however, the most quantitatively important clinical manifestation of herpes simplex virus infections. Because 41% of the hospitalized patients are younger than 20 years, vaccination of birth cohorts would be more favourable. In this paper the financial benefits of a hypothetical herpes simplex virus vaccination were calculated with the use of a population projection model. For the Netherlands, if the price of the hypothetical herpes simplex virus vaccine equals the cost price of the mumps component of the combined mumps-measles-rubella vaccine, the herpes vaccine would be profitable within 8 years.     

Virus infections in immunocompromised patients: their importance and their management.

Opportunistic viral infections were investigated in 156 adult patients admitted over one year to a medical oncology service: 35% of the total group and 65% of those with acute leukaemia experienced viral infections, 79% of which were with viruses of the herpes group. Surprisingly few enteric viruses were recovered. Reactivation of herpes simplex virus in the brains of these immunosuppressed patients was suggested by the demonstration by nucleic acid hybridization of herpes simplex virus DNA sequences in neurones and endothelial cells in patients with evidence of past infection with virus. Acyclovir was effective in therapy and prophylaxis. Twenty-three strains from 7 patients were tested for sensitivity to this antiviral: in 3 instances clinical resistance was observed but the strains were fully sensitive in vitro, as were all other strains tested.     

Divergence and genotyping of human α-herpesviruses: An overview

Herpesviruses are large DNA viruses that are highly disseminated among animals. Of the eight herpesviruses identified in humans, three are classified into the α-herpesvirus subfamily: herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which are typically associated with mucocutaneous lesions, and varicella–zoster virus (VZV), which is the cause of chicken pox and herpes zoster. All three viruses establish lifelong infections and may also induce more severe symptoms, such as neurological manifestations and fatal neonatal infections. Despite thorough investigation of the genetic variability among circulating strains of each virus in recent decades, little is known about possible associations between the genetic setups of the viruses and clinical manifestations in human hosts. This review focuses mainly on evolutionary studies of and genotyping strategies for these three human α-herpesviruses, emphasizing the ambiguities induced by a high frequency of circulating recombinant strains. It also aims to shed light on the challenges of establishing a uniform genotyping strategy for all three viruses.     

Experience with multiplex nested PCR and fluorescent antibody tests in the diagnosis of acute central nervous system infections with herpes simplex virus type 1 and 2

The specific diagnosis of herpes simplex virus type 1 and 2 infections has an extreme importance in acute infections of central nervous system due to both availability of specific antiviral therapy and the possible serious consequences of the disease. Aims: Evaluation of the relevance and interpretation of the results of PCR and the specific antibody testing. Methods: Home made multiplex nested herpes simplex virus PCR and immunofluorescent IgM, IgA, IgG antibody tests were carried out in a total of 474 cerebrospinal fluid and 555 serum samples of 396 patients with acute infection of the central nervous system between 1. January, 2003 and 31. December, 2009. Results: The herpes simplex virus etiology was verified in 21% of 396 patients (82 patients, mean 12 cases per year): 26 were diagnosed by both methods (32%), 41 by PCR only (50%), 15 by the detection of intrathecal antibody production only (18%) (p<0.0001). HSV type1 or 2 DNA remained detectable in 35% of the samples drawn after the 30th day of the disease. These patients were all younger than two years of age. Conclusions: 1. PCR increased the ratio of verified herpes simplex virus etiology in acute central nervous infections. 2. Testing the specific antibody response cannot be ceased even in the availability of PCR. 3. Herpes simplex virus type 1 or 2 DNA might persist in central nervous system in spite of the specific antiviral therapy especially in the infants. 4. Herpes simplex virus PCR can be repeated if an early sample is negative or if it is suspected false positive. 5. There is a need for cooperation between clinicians and virologists in the appropriate interpretation of the results and in finding etiology.     

Prevalence of antibodies to four herpesviruses among adults with glioma and controls.

The authors previously reported statistically significant inverse associations between adult onset glioma and histories of chickenpox and shingles among 462 cases and 443 controls in the San Francisco Bay Area Adult Glioma Study (1991--1995) and a suggestive but nonsignificant inverse association with immunoglobulin G antibodies to varicella-zoster virus in a small subset of these cases. This report considers antibodies to four common herpesviruses (varicella zoster, herpes simplex, cytomegalovirus, and Epstein Barr) among 134 cases and 165 controls that represent all subjects for whom usable blood specimens were available. The prevalences of immunoglobulin G antibodies to varicella-zoster virus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus were 90%, 71%, 57%, and 90%, respectively. After adjustment for age, White versus non-White ethnicity, and gender, glioblastoma cases were less likely than controls to have immunoglobulin G antibodies to varicella-zoster virus (odds ratio = 0.4; 95% confidence interval: 0.1, 0.9). They were also somewhat less likely to have antibodies to Epstein-Barr virus but somewhat more likely to have antibodies to herpes simplex virus and cytomegalovirus. Antibody prevalences to all four herpesviruses were similar between cases with other glioma histologies and controls. These results corroborate our previously suggestive findings of an inverse association of varicella-zoster virus antibodies with adult onset glioma.     

Acyclovir-resistant herpes simplex virus infections in immunocompromised patients]

In order to determine the sensitivity of herpes simplex virus (HSV) isolates from immunocompromised patients treated with antiviral compounds, a retrospective study was carried out in the Clinical Virology Department of the University Medical Centre, Amsterdam. Virus isolates from four AIDS patients and one bone marrow transplant recipient were examined for their sensitivity for the antiviral compounds used by means of plaque reduction assay. In some of the virus isolates, from patients in whom resistance was assumed on clinical grounds, in vitro resistance of the HSV to acyclovir (ACV) could be demonstrated, both after oral and after parenteral administration. There was a clear correlation between the clinical course of the HSV infection and in vitro resistance. ACV resistant virus isolates were sensitive to foscarnet, both clinically and in vitro. In immunocompromised patients treated for some time with ACV for HSV infection, resistance should be considered at lack of results or progression of the lesion and when necessary be demonstrated in vitro. Alternative therapy then consists of intravenous foscarnet treatment.     

256例自诉不明原因感染患者的临床特征分析

目的 分析有关临床资料,探索自诉不明原因感染患者的临床特征,为其诊治提供参考依据.方法 收集在医院门诊及住院的自述不明原因感染患者256例,对其流行病学、临床症状及体征、辅助检查、实验室病原体检测以及心理测试量表等各项资料进行综合分析,并探讨与人疱疹病毒的相关性.结果 256例患者,男性占86.72％,女性占13.28％;67.9％患者有高危性行为史、临床主诉多、并反复出现,仅37.1％患者有阳性体征,重要脏器功能无异常;仅4.3％的患者出现CD4+减少;全部患者HIV检测阴性;73.0％患者在多种标本中检出入疱疹病毒阳性;12例接受心理测试发现异常有9例.结论 患者无重要器官病变,可排除HIV感染,是否与人疱疹病毒感染相关,有待进一步研究.     

Genital herpes and human immunodeficiency virus: double trouble

The synergistic relationship between herpes simplex virus type 2 (HSV-2) and transmission of human immunodeficiency virus (HIV) can be substantial in developing countries that have high prevalences of both viral infections. Genital herpes, most frequently caused by HSV-2, has become the leading cause of genital ulcer disease worldwide. This review of recent research on genital herpes and enhanced susceptibility to, and transmission of, HIV is part of the "Advances in HIV/AIDS research series" which endeavours to form a bridge between the research into HIV and acquired immunodeficiency syndrome (AIDS) and the practice of HIV/AIDS prevention, care and support in developing countries. Research findings have shown that being seropositive for HSV-2 can increase the risk of HIV acquisition among high-risk HIV-negative people exposed to HIV and, likewise, the infectiousness of individuals co-infected with HIV-1 and HSV-2 can increase during periods of HSV-2 reactivation. These observations have led to the initiation of several intervention trials and could ultimately lead to the setting of new priorities in public health and clinical practice. WHO has recently issued new guidelines for the syndromic management of genital ulcer disease that include antiviral treatment for lesions consistent with genital herpes. The United States Centers for Disease Control and Prevention issued updated Sexually Transmitted Diseases Treatment Guidelines in 2002 that recommended the use of type-specific serological tests for diagnosing HSV-2. Recently launched proof-of-concept, HSV-2 intervention trials in several countries will help to determine the proportion of new HIV infections that could be prevented by suppression of HSV-2, and the findings from these studies will inform those involved in setting prevention and treatment priorities and strategies in developing countries.     

Recommendation for post-exposure prophylaxis after potential exposure to herpes b virus in Germany

Although the risk of a herpes B virus (Cercopithecine herpes virus 1) infection is low, the clinical course of the infectious disease is generally unfavourable. A high safety standard can be achieved if people with professional contact to primates apply proper organisational, technical and personal safety precautions. The risk can be considerably reduced if animal keepers, laboratory assistants and scientists receive adequate information about the pathology of herpes B virus and are well trained in the necessary procedures and the precautions. For this reason, comprehensive and regular training, information and instruction must be provided to all primate workers and to laboratory workers who come into contact with potentially infectious material. After potential contamination, the risk for the affected worker must be assessed immediately and post-exposure chemoprophylaxis performed if necessary. This necessitates internal risk assessment. An interdisciplinary group of experts has developed an action plan for Germany.     

Control of herpes simplex virus infections of the genital tract by vaccination

The apparent increasing incidence of herpes simplex virus infections of the genital tract has focused attention on the efficacy of vaccination in preventing infection or modifying established disease. Results of an 'open trial' using a DNA-free inactivated virus subunit vaccine have shown that vaccination of subjects at risk of contracting infection from their sexual partner reduced the transmission rate from 34% in unvaccinated controls to 0.5%. In a separate study, vaccination of patients who had experienced their first overt attack of herpes genitalis (the initial clinical episode) had significantly fewer recurrences over the follow-up period of 12 months than the unvaccinated control group. The results, we feel, justify a placebo controlled trial.     

Construction and properties of a herpes simplex virus 2 dl5-29 vaccine candidate strain encoding an HSV-1 virion host shutoff protein

The replication-defective herpes simplex virus 2 (HSV-2) dl5-29 mutant virus strain with deletions in the U_L5 and U_L29 genes has been shown to protect mice and guinea pigs against challenge with wild-type (wt) HSV-2 and to protect against ocular disease caused by HSV-1 infection. The dl5-29 strain is currently being prepared for clinical trials as a herpes vaccine candidate. As a possible approach to improve the efficacy of dl5-29 as a genital herpes vaccine, we replaced the U_L41 gene encoding the virion host shutoff function (vhs) with the U_L41 gene from HSV-1. While the HSV-2 U_L41 and HSV-1 U_L41 gene products have analogous functions, vhs-1 is 40-fold less active than vhs-2. Previously, it was shown that disruption of the U_L41 gene can increase the efficacy of dl5-29 as a vaccine against HSV-2. These properties led us to hypothesize that replacement of vhs-2 by vhs-1 would decrease cytopathic effects in infected host cells, allowing longer survival of antigen-presenting cells and induction of stronger immune responses. The new recombinant dl5-29-41.1 virus shows nearly the same immunogenicity and protection against HSV-2 challenge as the parental dl5-29 virus or a triply deleted mutant virus, dl5-29-41, in the murine model of infection, and grows to higher titers than the parental strain in complementing cells, which is important for GMP production. The results have implications for the design of future HSV-2 vaccine candidates and mechanisms of induction of protective immunity against genital herpes.     

Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.

Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.     

单纯疱疹病毒感染在妇产科疾病的研究现况

人类单纯疱疹病毒（HSV）为人类易感病毒之一,其感染后具有潜伏、发病及复发的复杂性和致畸性。近年来随着性病发病率的上升和危害性的增大,单纯疱疹病毒引起的疾病及生殖器疱疹（GH）逐渐被重视,本研究着重单纯疱疹病毒的流行病分布以及妇科感染和对妊娠发病对新生儿的危害做一综述如下。     

The epidemiology of infection with the human herpesviruses in Navajo children

Investigations of serum antibody status to the five human herpesviruses--herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus--were conducted on 197 Navajo children, aged 1-15 years, at a reservation pediatric outpatient clinic in Crownpoint, New Mexico, from 1981-1984. To determine the severity of infection with the human herpesviruses, the authors reviewed lifetime medical records of 166 of the children for evidence of herpesvirus-related diseases, and to illuminate potential modes of transmission of the viruses, they completed home interviews on the families of 87 of the children. The investigation showed that the children had a high prevalence of antibody to herpes simplex virus type 1 (73% of total sample), cytomegalovirus (78%), Epstein Barr virus (98%), and varicella-zoster virus (77%), and that prevalence tended to increase with age. None of the children demonstrated herpes simplex virus type 2 antibodies. The medical records showed that 30% of the children had suffered from gingivostomatitis prior to the study. When age was controlled for, the study showed herpes simplex virus type 1 seropositivity to be associated with children who slept in the same bed as their parents during infancy (p = 0.003) and with frequent attendance at community events (p = 0.02); cytomegalovirus seropositivity was shown to be associated with female sex (p = 0.007) and with living in a traditional Navajo dwelling (p = 0.007). The Navajo children also demonstrated a greater frequency of symptomatic oral herpes simplex virus type 1 infection than is usually recorded. The findings suggest a relation between certain patterns of cultural behavior and transmission of herpesvirus infections.     

女性生殖道性传播疾病病原体混合感染的检测及意义

目的探讨昆明地区女性生殖道5种性传播疾病病原体混合感染的检测现状及临床意义。方法采用荧光聚合酶链反应技术(PCR)进行淋菌、沙眼衣原体、解脲脲支原体、人乳头状瘤病毒、单纯疱疹病毒5种常见病原体检测。结果4601例女性患者中有>2种病原体混合感染者279例,占6.1%;21~40岁年龄段患者占89.6%。结论采用PCR进行性传播疾病病原体定量检测,具有灵敏度高、方便快速的特点,应重视性传播疾病的监测与控制工作。     

Seroepidemiology of cytomegalovirus and herpes simplex virus in twins and their families

To determine the importance of intrafamilial transmission of cytomegalovirus and herpes simplex virus (types 1 and 2), the authors investigated the presence of immunoglobulin G antibody to one or both of these viruses in the sera collected between 1976 and 1985 from 1,115 members of 301 kinships from Virginia consisting either of juvenile twins and their parents or of adult twins, their spouses, and offspring. The sample included 486 children and 629 adults, aged 1-68 years. Among the 125 couples in whom the wives were seropositive, 78 (62%) of the husbands were found to be seropositive. Among 77 couples in whom the wives were seronegative, only 32 (42%) of the husbands were seropositive (p less than 0.01). Of 105 couples in whom the wives were seropositive for herpes simplex virus, 81 (77%) husbands were seropositive compared with 20 (47%) of 43 husbands with herpes simplex virus-seronegative wives (p less than 0.001). In families with cytomegalovirus-seropositive mothers, 54 (25%) of 213 children were seropositive for cytomegalovirus compared with 13 (8%) of 168 children in families with seronegative mothers (p less than 0.001). Childhood cytomegalovirus infections showed no association with infection in the father. In contrast, among families in which both parents were seropositive for herpes simplex virus, 48 (31%) of 156 children were seropositive compared with only two (4%) of 48 children without herpes simplex virus-seropositive parents (p less than 0.001). Among all siblings, there were strong associations for both herpes simplex virus and cytomegalovirus infections. These data are consistent with the venereal transmission of cytomegalovirus in married couples, provide evidence for the intrafamilial spread of herpes simplex virus, and confirm the importance of the maternal-child transmission of cytomegalovirus.     

Intrauterine infections

A broad variety of microorganisms are capable of causing fetal infections. Among viral agents prominent are the human cytomegaly virus (HCMV), herpes simplex virus (HSV), human immundeficiency virus (HIV), varicella, herpes zooster, rubella, parvovirus B19, measles and the hepatitis B and C viruses. Protozoa such as toxoplasma and spirocheta pallida, causing congenital syphilis are equally important. Bacterial infections are responsible for in uterus aquired listeriosis, tuberculosis, and group B streptococcus infections. Fungi including candida albicans complete the circle of infections pathogens. Infectious microrganisms may reach the fetus through the placenta are may ascend through the birth canal. The quoted pathological agents threaten the health and life of the fetus directly by the biological derangements they cause and also by inducing abortion or premature birth. The clinical manifestations include retarded growth, central nervous system damage and skin lesions. The invariable therapeutic measures vary but in general, are limited value in cases of in utero acquired infections.     

Impact of CCR5 Δ32/+ Deletion on Herpes Zoster Among HIV-1-Infected Homosexual Men

The association between the presence of CCR5 Δ32 heterozygosity and incidence of clinical herpes zoster was studied among 296 homosexual men from the Amsterdam cohort study (ACS) infected with human immunodeficiency virus type I (HIV-1) with an estimated date of seroconversion. Of them 63 were CCR5 Δ32 heterozygotes and 233 CCR5 wild-type. The incidence rate of a first episode of herpes zoster was 4.2% and 5.3% per person-year, respectively. A higher occurrence of herpes zoster was strongly related to a lower CD4 + cell count. After adjustment for age, presence of CCR2b 64I heterozygosity, HIV RNA load, time since seroconversion, and CD4 + cell count, the rate ratio for herpes zoster of CCR5 Δ32 was 0.9 (95%CI 0.5–1.6). In conclusion, in HIV-1-infected homosexual men, a CCR5 Δ32 heterozygous genotype has no protective effect on the incidence of herpes zoster.