2012 — 2015年云南省病毒性腹泻病原监测分析

  目的  了解宁夏回族自治区腹泻患者腺病毒感染状况,流行病学特点和基因进化特征,为腺病毒所致疾病的科学防控提供理论依据。  方法  收集2015 — 2020年宁夏哨点监测医院门诊腹泻病例粪便样本,使用Real-time PCR方法筛选腺病毒阳性样本,通过PCR扩增腺病毒六邻体区基因,测序后进行病毒型别鉴定和基因进化分析。  结果  2015 — 2020年共收集腹泻病例样本6695份,共检测到腺病毒阳性样本278份（4.2 %）。其中,2017年腹泻样本数最多（1241份）,且腺病毒阳性率最高（7.7 %,96份）;腺病毒阳性率在不同季节和不同年龄组的差异均具有统计学意义（P < 0.05）。278份腺病毒阳性样本中,测序获得80份腺病毒基因序列,经鉴定有3种基因型别,以F41型为主,其次为F40型和C1型。  结论  腺病毒F41型是造成宁夏回族自治区肠道腺病毒性腹泻的优势型别,全年均有病例,全年龄组人群均易感。     

An outbreak of adenovirus serotype 41 infection in infants and children with acute gastroenteritis in Maizuru City, Japan.

A total of 337 fecal specimens were collected from infants and children with acute gastroenteritis in Maizuru City, Japan from July 2004 to June 2005 and tested for the presence of rotavirus, norovirus, sapovirus, astrovirus, and adenovirus by RT-multiplex PCR. Among diarrheal viruses detected, norovirus was the most prevalent (13.6%, 46 of 337), followed by adenovirus (8%, 27 of 337), group A rotavirus (5%, 17 of 337), astrovirus (1.8%, 6 of 337), and sapovirus (1.8%, 6 of 337), respectively. Adenovirus was subjected to molecular genetic analysis by sequencing. Adenovirus detected in this study was classified into five serotypes, namely Ad1, Ad2, Ad3, Ad5, and Ad41. Of these, Ad41 was the most predominant serotype that accounted for 85.2% (23 of 27). It was noteworthy to point out that Ad41 infection was apparently confined only to the period of 4 months (October 2004 through January 2005). This pattern of infection implied the outbreak of Ad41 in these subjects, which was the first outbreak of acute gastroenteritis attributed to adenovirus in Maizuru City, Japan. Another interesting feature of the study was the existence of two Ad41 subtypes co-circulating in this outbreak. This report confirmed the presence of adenovirus as one of an important cause of acute gastroenteritis among Japanese infants and children.     

Epidemic outbreaks of adenovirus 7 with special reference to the pathogenicity of adenovirus genome type 7b

Adenovirus type 7 (Ad 7) is the serotype among the 36 recognized adenovirus types which most frequently has been associated with severe illness. Three different epidemic patterns of Ad 7 infection can be distinguished: 1) the first appears during the winter among infants with median age below two years, has characteristic symptoms of high fever and pneumonia and an outcome that may be fatal: 2) the second appears in the fall among children with median age seven years, has characteristic symptoms of high fever, pneumonia, abdominal symptoms and meningism and an outcome that is favorable; 3) and the third has been seen as acute respiratory disease among military recruits. In the United States, the last mentioned outbreaks require prophylaxis in the form of a live enteric-coated vaccine. DNA restriction site mapping demonstrated the occurrence of three distinct viral entities of Ad 7, which have been designated Ad 7 prototype, Ad 7a (the vaccine strain) and the Ad 7b genome type. In the present study, 36 isolates obtained from outbreaks with the first and the second epidemic patterns were analyzed by restriction endonucleases Bam HI and Sma I. All were identified as the newly recognized Ad 7b genome type. It is concluded that this genome type is responsible for a large portion of the severe infections caused by Ad 7. The epidemic nature of Ad 7 and the severe illness noted among infants indicate that vaccination of institutionalized infants could be considered during years when Ad 7 epidemics appear.     

Work characteristics and incidence of type 2 diabetes in women

The authors prospectively investigated associations between potentially stressful work characteristics and type 2 diabetes incidence in 62,574 young and middle-aged women, aged 29-46 years at baseline in 1993, from the Nurses' Health Study II; 365 cases of type 2 diabetes accrued over 6 years of follow-up. Cox proportional hazards regression was used to simultaneously evaluate associations of hours per week in paid employment, years of rotating night-shift work, and job strain with incidence of type 2 diabetes. In multivariate-adjusted analyses, women working less than 20 hours per week had a lower risk of diabetes (relative risk = 0.80, 95% confidence interval: 0.50, 1.30), and those working overtime (> or =41 hours/week) had an elevated risk of diabetes (relative risk = 1.23, 95% confidence interval: 0.98, 1.55) compared with women working 21-40 hours/week (referent) in paid employment (p(trend) = 0.03). In subsequent analysis, the elevated association appeared stronger in unmarried women (p(interaction) = 0.02). A positive association between years in rotating night-shift work and diabetes was mediated entirely by body weight. Job strain was unrelated to risk of type 2 diabetes. In conclusion, working overtime predicted a slightly elevated risk of type 2 diabetes in young and middle-aged female nurses.     

Vaccine Preventability of Meningococcal Clone,Greater Aachen Region,Germany

Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.     

Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia,Hanoi, Vietnam, 2014

During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.     

Therapeutic action of MK-436 (2,5-nitroimidazole) on Trypanosoma cruzi infections in mice: a parasitological, serological, histopathological, and ultrastructural study

The anti-protozoal drug MK-436 (3-(1-methyl-5-nitroimidazol-2-yl)-3a,4,5,6,7,7a-hexahydro-1,2-benzisoxazole) was found to be effective against Trypanosoma cruzi infections in mice (2 daily doses of 250 mg per kg body weight). Parasitaemia disappeared within 24 hours of treatment which was commenced during the early or late stages of acute infection. Intracellular T. cruzi parasites were also affected by the drug, ultrastructural findings showing severe cytoplasmic vacuolization and membrane alterations. Positive serological responses persisted in the majority of treated and parasitologically cured mice in the study. Cure rates varied from 72% to 100% and were similar regardless of the T. cruzi strain used (Y strain, type I; 12 SF strain, type II; or Colombian strain, type III). However, the proportion of positive serological tests and the frequency of inflammatory lesions were greatest for mice that were infected with the Colombian strain of the parasite.     

Molecular biological virus identification in dilated cardiomyopathy

Enteroviruses have been considered to be the most common cause of acute myocarditis and possible consequence of dilated cardiomyopathy. Some publications shed light to the role of other viruses in this disease as well. Our molecular investigation has demonstrated that adeno- and herpes viruses might also frequently occur in dilated cardiomyopathy. AIM: The aim of our study was to screen virus genomes in heart tissues from heart-transplanted patients to prove their possible role in the pathogenesis of dilated cardiomyopathy. METHODS: DNA and RNA were isolated from five regions of the heart muscle. Amplification for Adenovirus Type 3, Human Herpes Virus Type 6 and Enterovirus genomes were performed by nested-Polymerase Chain Reaction. Finally the virus-positive samples were direct sequenced. RESULTS: In 2 patients Adenovirus Type 3 and in 1 patient both Adenovirus Type 3 and Human Herpes Virus Type 6 were detected. No enteroviruses were found in any heart tissue. CONCLUSIONS: In our study the adenovirus genome was found to be the most frequent virus genome in explanted heart tissues. The identified viral sequences proved previous viral infection, which could have played a role in the development of dilated cardiomyopathy. Detection of different viruses in the myocardium by molecular biological examinations might contribute to adequate treatment of these patients.     

2013-2014年北京市怀柔区散发腹泻患者的 腺病毒感染调查

摘要:目的　了解北京怀柔地区腹泻患者腺病毒感染情况及其分子特征。方法　采集怀柔区2013年4月至2014年3月120例腹泻患者粪便标本,用聚合酶链反应（PCR）方法检测腺病毒hexon区域,然后对PCR阳性扩增产物进行测序。采用Mega软件对序列进行比对并构建进化树。结果　120例标本中腺病毒阳性24例,检出率为20.0%;其中7月龄到2岁婴幼儿患者检出率最高,为26.7%（16/60）;2个感染高峰分别为6-8月和10-11月,其余月份有腺病毒感染的散发。对其中18例腺病毒hexon区域PCR阳性产物测序和系统进化分析显示,13例为腺病毒F组41型（72.2%,13/18）,2例为F组40型（11.1%,2/18）,2例为C组的Ad2和Ad6（11.1%,2/18）,A组31型1例。结论　腺病毒是怀柔地区2013-2014年病毒性腹泻的重要病原之一,F组41型为优势流行株,同时有其他型别的散发。     

一起儿童腺病毒肺炎疫情调查

目的了解2009-02发生在陕西省汉中市,以西乡县为主要区域的一起儿童"不明原因肺炎"疫情的病因。方法建立病例定义,采用统一的流行病学个案调查表对病例进行调查,描述流行特征,采集患儿咽拭子标本进行病原学检测。结果 2009-01/02,汉中市共计发生儿童"不明原因肺炎"病例32例,发病高峰为1月下旬,病例主要为农村儿童,占病例的81.25%;临床表现为持续发热伴咳嗽、肺部出现影像学改变,无死亡病例。PCR检测证实为腺病毒感染,对PCR阳性产物进行序列测定和分析,确定为腺病毒7型。结论发生在汉中市以西乡县为主要区域的儿童"不明原因肺炎"疫情是由腺病毒7型感染为主引起的儿童肺炎局部流行。     

Impact of adenoviruses in human disease

Eleven of 33 adenovirus serotypes produce acute disease in man and have their greatest effect in semiclosed populations of military recruits, particularly types 4 and 7. Pediatric adenovirus disease due to types 1, 2, 3, 5, and 7 accounts for a significant proportion of childhood illness but insignificant mortality. Adenovirus infection in military recruits can be markedly reduced by administration of an enteric-coated capsule of live type 4 vaccine which produces a silent infection of the intestinal tract and protects against subsequent respiratory disease. Studies with a similar vaccine against type 7 promise equally effective results.     

Epidemic spread of adenovirus type 4-associated acute respiratory disease between U.S. Army installations

A large outbreak of adenovirus type 4-associated acute respiratory disease (ARD) occurred at Fort Jackson, South Carolina, in 1997. A laboratory-based ARD surveillance program was initiated at Fort Gordon, Georgia, where advanced individual training was heavily populated with Fort Jackson soldiers. Adenovirus type 4 was isolated from 50% of 147 trainees hospitalized with ARD. Most (88%) introduced cases were in trainees from Fort Jackson.     

登革1型病毒荧光定量PCR快速检测

目的建立登革1型病毒的快速特异的荧光定量PCR检测方法。方法设计登革1型病毒特异的引物和TaqMan探针,制作标准曲线,并检测其特异性、重复性、再现性和敏感性,采用荧光定量PCR和常规PCR对临床标本进行检测比较。结果成功构建了标准曲线,回归方程为Y=-3.410logX+45.10,相关系数R²=0.999,扩增效率Eff=96.5%,灵敏度可达10³ copies/mL,此荧光定量PCR方法对登革1型病毒检测高度特异,与其他3型登革病毒和乙型脑炎病毒之间并无交叉反应;采用登革病毒种特异引物探针和本研究建立的登革1型病毒型特异引物探针对166份cDNA样本进行荧光定量PCR检测,均发现126份为阳性,阳性率均为75.9%,Ct值为20.84～36.36,浓度范围为1～1.3×104copy/μL;常规PCR方法检测到其中36份为阳性,阳性率为21.7%。结论荧光定量PCR方法能够快速灵敏地检测登革1型病毒,并能实现对病毒滴度的绝对定量。     

小双节病毒在成都地区腹泻婴幼儿中流行情况分析

摘要:目的　了解小双节病毒在成都市腹泻婴幼儿中的感染情况。方法　收集成都市儿童医院、成都市第三人民医院2010年7-12月腹泻婴幼儿（≤5岁）粪便样本428份,用实时荧光RT-PCR方法检测小双节病毒,同时检测轮状病毒、诺如病毒、札如病毒、人星状病毒和肠道腺病毒。结果　检出小双节病毒感染36份,检出率为8.41%（36/428）。其中Ⅰ型9份、Ⅱ型25份、Ⅰ和Ⅱ型共同感染2份,检出率分别为2.10%（9/428）、5.84%（25/428）和0.47%（2/428）。小双节病毒与其他腹泻病毒合并感染共31份。调查期间小双节病毒检出高峰为8、9月,主要感染2岁以下婴幼儿。结论　小双节病毒是引起成都市婴幼儿腹泻的病原之一,以小双节病毒Ⅱ型为主,2岁以下婴幼儿是其高发人群,8、9月为其下半年高发季节。     

Safety and efficacy of an infectious bronchitis virus used for chicken embryo vaccination

Commercial vaccines for in ovo vaccination have not yet been developed for infectious bronchitis virus (IBV), the major coronavirus in the poultry industry. Recombinant IBVs based on the Beaudette strain expressing the Beaudette spike protein (Beau-R) or that from the virulent M41 strain (BeauR-M41(S)) were assessed for their potential as prototype vaccines for application to 18-day-old embryos. Pathogenicity was assessed by observing the effect on hatchability, and/or the production of nasal discharge and/or the effects on ciliary activity in the trachea at various time points post hatch. In contrast to commercial IBV vaccines given in ovo, the Beau-R and BeauR-M41(S) strains did not reduce hatchability or cause nasal discharge, and caused minimal damage to the ciliated epithelium of the trachea. The presence of the spike protein from a virulent virus did not increase the pathogenicity of the virus according to the criteria used. Assessment of the BeauR-M41(S) strain for efficacy showed that it protected up to 90% of chicks against challenge with virulent IB virus (M41) in a dose dependent manner. Further egg passage of the BeauR-M41(S) strain (BeauR-M41(S) EP10) did not increase its pathogenicity though it did improve its efficacy, based on serology and protection against a virulent challenge. BeauR-M41(S) EP10 was more efficacious than BeauR-M41(S) protecting more birds against virulent challenge and providing a better serological antibody response. BeauR-M41(S) EP10 induced a serological response similar to that of a commercial vaccine given at day-old though the commercial vaccine provided slightly higher efficacy. These results are promising for the development of embryo safe efficacious IBV vaccines for in ovo application.     

An outbreak of Staphylococcus aureus in a pediatric cardiothoracic surgery unit.

OBJECTIVE: To investigate an outbreak of Staphylococcus aureus surgical-site infections. DESIGN: Case-control study. SETTING: Pediatric cardiothoracic surgery service of a tertiary-care university medical center. METHOD: Molecular typing was used to identify healthcare workers who carried the epidemic strain. RESULTS: Three children acquired surgical-site infections caused by a single strain of S. aureus. Fourteen (25%) of the staff members in the operating room and 17 (11%) on nursing units carried the epidemic strain (P = .01). A case-control study identified 4 healthcare workers who were associated statistically with the outbreak, 2 of whom (a cardiothoracic surgeon and a perfusionist) carried the epidemic strain in their nares. The surgeon also carried the epidemic strain on his hands. Each staff member who carried the epidemic strain was treated with mupirocin; those carrying the strain on their hands were required to wash their hands with chlorhexidine. The surgeon was not allowed to perform surgery until 2 of his hand cultures did not grow S. aureus. CONCLUSIONS: Only three children were infected with the epidemic strain, but it was disseminated widely among staff who cared for children who underwent cardiothoracic surgery. No additional cases were identified after staff members who carried the epidemic strain were decolonized. Both classic epidemiologic methods and molecular typing techniques were necessary to identify the source and extent of this outbreak.     

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.     

Community Outbreak of Adenovirus,Taiwan, 2011

In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14–October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008–2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People’s Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.     

History of the restoration of adenovirus type 4 and type 7 vaccine,live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system

Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that “The more successful a vaccine is, the more quickly the need for it will be forgotten.”, sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment.     

CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5-7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses

The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5-7) before the development of classical antigen-specific CD8(+) and CD4(+) T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8(+) gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4(+) T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination.