Adenovirus eye infections in an Australian city, 1972-9.

A number of adenovirus serotypes have been associated with both sporadic cases and outbreaks of conjunctivitis and pharyngoconjunctival fever but only adenovirus type 8 and adenovirus type 19 have been responsible for wide-spread epidemic kerato-conjunctivitis. In Melbourne, Australia, in the past eight years these two serotypes have been prevalent, resulting in an outbreak of adenovirus type 8 kerato-conjunctivitis in 1976-7 followed by adenovirus type 19 kerato-conjunctivitis in 1978-9. During these two periods of peak incidence, 53 cases of adenovirus type 8 and 43 cases of adenovirus type 19 kerato-conjunctivitis were confirmed by isolation.     

Five-year analysis of adenovirus 8 antibody levels in an industrial community following an outbreak of keratoconjunctivitis.

Serum hemagglutination-inhibition (HI) antibody titers were monitored for five years with samples from 79 keratoconjunctivitis patients with type 8 adenovirus (AV-8) infection. Geometric mean antibody titers declined from 1:161 at the peak of the epidemic to 1:56 after five years. Computerized analysis of the decline in geometric mean antibody titer indicates that most patients will have a serum HI titer of 1:25 by 10 years after their clinical infection. These residual antibody levels and the consistent failure to document re-infection with AV-8 suggest that recurrent episodes of keratoconjunctivitis are caused by adenovirus serotypes other than type 8.     

Neutralizing antibodies against 33 human adenoviruses in normal children in Rome.

There are few data about the distribution of neutralizing antibodies (NA) against adenovirus types in the Italian population, especially the high-numbered ones. We tested the sera from 453 children and 51 young adults to evaluate NA against adenovirus prototypes 1-33. Using the microneutralization test, 338 (74.6%) of the children''s sera were positive for at least one adenovirus type. Antibody to type 2 was the most frequently detected followed, in descending order, by antibody to types 5, 1 and 3. All these types are known to be associated with disease but antibody to type 7, a type also associated with disease, was less frequent than that to other serotypes such as 18 and 31, the pathogenicity of which in man is not clearly established. The antibody positivity rate rose with age for the more frequent types while it did not vary for the less frequent ones. The number of sera with NA against more than one adenovirus type increased with age. With regard to types 1-8, we found that their frequencies in Italy were similar to those found in the U.S.A.     

Viruses in sewage as an indicator of their presence in the community.

The results of a three year study of the viruses isolated from sewage by means of five tissue culture types are reported. The enteroviruses identified demonstrated a seasonal pattern which was similar to that of clinical isolates. Echoviruses and coxsackieviruses displayed a changing pattern of dominant serotypes in both sewage and clinical isolates; echovirus 6, 19, 3 and coxsackievirus B4, B5, A9 successively became the most common serotypes. The poliovirus in sewage was all vaccine-like in character. Reovirus, type 2 was abundant; adenovirus, of several serotypes, were the least often identified.     

Emergence of antimicrobial-resistant serotype 19A Streptococcus pneumoniae--Massachusetts, 2001-2006

Streptococcus pneumoniae (pneumococcus) is a leading cause of otitis, sinusitis, pneumonia, and meningitis worldwide. Treatment of the most serious type of pneumococcal infection, invasive pneumococcal disease (IPD), is complicated by antimicrobial resistance. Widespread introduction in 2000 of heptavalent pneumococcal conjugate vaccine (PCV7) against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F resulted in a decline in antimicrobial-nonsusceptible IPD in the United States, including in Massachusetts. However, development of antimicrobial resistance in serotypes not covered by PCV7 is a growing concern. In Massachusetts during 2001-2006, IPD surveillance identified an increased number of cases in children caused by pneumococcal serotypes (most notably 19A) not covered by PCV7 and an associated increase in antimicrobial resistance among these isolates. This report examines these trends and clinical characteristics of Massachusetts patients with antimicrobial-nonsusceptible, non-PCV7-type IPD. The findings indicated that, despite increases in incidence of antimicrobial-nonsusceptible IPD, overall rates of IPD remained stable during 2001-2006. In addition, persons with IPD caused by antimicrobial-nonsusceptible S. pneumoniae had clinical outcomes comparable to persons with IPD caused by antimicrobial-susceptible serotypes. Although PCV7 is effective in preventing IPD, these results confirm that antimicrobial resistance among serotypes not covered by PCV7 remains a concern.     

Inactivation of human adenovirus genome by different groups of disinfectants

Human adenoviruses are model viruses for testing the virucidal efficacy of disinfectants. However, a recent study has shown that the chemical sensitivity of adenovirus serotypes varies significantly, possibly due to the composition of the viral capsid and/or the resistance of nucleic acids. We have investigated the effect of molecular changes in the viral genome of the human adenovirus subgenera C and D. A common oligonucleotide fragment within the hexon gene was amplified by polymerase chain reaction (PCR) after exposure to liposomal povidone-iodine (PVP-I), peracetic acid (PAA), and formaldehyde. The findings were compared with infectivity in cell cultures. PVP-I (0.125%) destroyed the infectivity of most serotypes within 60 min. However, PCR revealed no destruction of the adenoviral genome in most serotypes, even after exposure to higher PVP-I concentrations. PAA (0.5%) failed to inactivate the hexon gene of adenovirus types 22 and 44. Furthermore, the hexon gene of adenovirus type 22 was not altered by 0.7% formaldehyde. In conclusion, the genomes of human adenoviruses show considerably more chemical resistance than the complete viral particle. The molecular resistance of individual serotypes also varies. However, there was no clear correlation between the differences in the effect of disinfectants on infectivity of the complete viral particle and destruction of the viral genome.     

Comparative studies on aetiology and epidemiology of viral conjunctivitis in three countries of East Asia--Japan, Taiwan and South Korea

A total number of 1105 cases with viral conjunctivitis, mainly epidemic kerato-conjunctivitis (EKC) consisting of 354 cases from Sapporo, Japan, of 628 from Kaohsiung, Taiwan and of 123 from Busan, Korea, encountered during the periods, 1980-81 and/or 1983, were studied aetiologically and epidemiologically. Patients were aged from 27 days to 88 years with a peak in the 20-29 year age group. Aetiological diagnoses were established in 610 cases (55%), consisting of 536 cases (49%) caused by adenoviruses and of 74 (7%) by EV 70. The most frequently detected agent was Ad 8 (57%), followed by EV 70 (12%), Ad 3 (9%) and Ad 19 (7%). The aetiological profiles of viral conjunctivitis were generally similar in three cities of East Asia. EKC (70%) was mainly caused by Ad 8, Ad 19 and Ad 37, but AHC (13%) by EV 70 and PCF (5%) by Ad 3 and Ad 11. Ad 19 and Ad 37 isolates in three cities were compared with the cleavage patterns with restriction endonucleases, BamHl, Smal, Sall and Hindlll. All of the Ad 19 isolates tested were identical to Ad 19a reported by Wadell et al, and all but three isolates of Ad 37 were identical to the Ad 37 prototype prevalent in Europe and the US. The three isolates of Ad 37, different from the prototype in cleavage pattern with Hindlll, designated as Ad 37A, were detected in Sapporo and Kaohsiung in 1980. From the cleavage patterns with four restriction endonucleases, Hindlll, BamHl, Sa1l and Sstl, the Ad 8 isolates in 1983 were divided into three subtypes, which were associated with the cities isolated.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

浙江省奉化市一起腺病毒感染暴发疫情调查

目的 对奉化市一起腺病毒暴发疫情进行流行病学调查和实验室检测,为及时采取有效控制措施提供依据.方法 对2016年奉化市某游泳池腺病毒暴发疫情进行现场调查,描述分析病例发病过程及流行病学特征.采集病例样本进行实时荧光定量PCR检测,并对阳性样本进行病毒分离.以腺病毒六邻体基因(Hexon gene)为目的基因,对分离株进行扩增测序.将测序结果提交GenBank进行BLAST比对,MEGA 5.2软件对腺病毒的六邻体基因序列构建进化树,确定其型别.结果 该起疫情历时15d,共出现18例住院患儿,临床症状以发热、扁桃体化脓和眼红为主,在发病前1～5天内有某游泳馆暴露史j 10份患儿咽拭子样本的PCR检测结果显示,均为呼吸道腺病毒(RADV)阳性,CT值在17～26之间.测序比对结果表明分离到的6株腺病毒序列相同,基因亲缘关系树显示该批分离株均为腺病毒B亚群,与人腺病毒3型参考株同处一支,同源性为99.1％～99.8％.结论 此次游泳池暴露的疫情系人腺病毒3型引起.     

Partial protection against H5N1 influenza in mice with a single dose of a chimpanzee adenovirus vector expressing nucleoprotein

The development of adenoviral vectors based on non-human serotypes such as the chimpanzee adenovirus simian adenovirus 24 (AdC7) may allow for their utilization in populations harboring neutralizing antibodies to common human serotypes. Because adenoviral vectors can be used to generate potent T cell responses, they may be useful as vaccines against pandemic influenza such as may be caused by the H5N1 strains that are currently endemic in avian populations. The influenza nucleoprotein (NP) is known to provide MHC Class I restricted epitopes that are effective in evoking a cytolytic response. Because there is only low sequence variation in NP sequences between different influenza strains, a T cell vaccine may provide heterosubtypic protection against a spectrum of influenza A strains. An AdC7 vector expressing the influenza A/Puerto Rico/8/34 NP was tested for its efficacy in protecting BALB/c mice against two H5N1 strains and compared to a conventional human adenovirus serotype 5 vaccine. The AdC7 NP vaccine elicited a strong anti-NP T cell response. When tested in a mouse challenge model, there was improved survival following challenge with two strains of H5N1 that have caused human outbreaks, Vietnam/1203/04 and Hong Kong/483/97, although the improved survival reached statistical significance only with the strain from Vietnam.     

Sensitivity of human adenoviruses to different groups of chemical biocides

As it is no longer readily permissible to propagate polioviruses, adenoviruses will probably become more frequently used for virucidal testing of broad-spectrum disinfectants. We tested prototype strains of different adenovirus serotypes belonging to the subgenera C and D for sensitivity to liposomal povidone-iodine (PVP-I), peracetic acid (PAA) and formaldehyde. Virucidal assays were performed as suspension tests in accordance with the German guidelines for testing the effectiveness of chemical disinfectants against viruses. The sensitivity of the adenovirus serotypes to test disinfectants varied greatly. Prototype strains of adenovirus 5 and 44 statistically selected as 'little sensitive' to PVP-I, PAA and formaldehyde were found to be the most resistant. These might be suitable as model viruses for testing the broad-spectrum virucidal activity of disinfectants and might even replace the resistant poliovirus type 1. The main reason for the different chemical sensitivity of adenovirus serotypes may be the composition of the viral capsid proteins. Alternatively a different chemical inactivation of the viral genome could be involved.     

Adenovirus type 8 keratoconjunctivitis--an outbreak and its treatment with topical human fibroblast interferon

An outbreak of keratoconjunctivitis is described which involved at least 186 people; adenovirus type 8 was identified in 50 of the cases. Topical human fibroblast interferon was assessed in a double-blind, placebo-controlled study in which 34 patients participated. Seventeen of the 34 trial patients yielded adenovirus type 8; three were infected with adenovirus type 7. The outbreak was curtailed by control of infection measures: principally careful hand-washing by medical personnel between cases and by discouraging attendance of new cases at the Eye Infirmary. Consequently the trial numbers are small. In addition there was a wide interpatient variation in the severity of infection. Therefore it was not possible to make any statistically valid conclusions concerning the recovery rate of patients receiving interferon or placebo.     

Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model

The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar^® (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar^® at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar^® were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.     

The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species

Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ⁺ CD8⁺ T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5.     

Adenovirus type 8 keratoconjunctivitis--an outbreak and its treatment with topical human fibroblast interferon.

An outbreak of keratoconjunctivitis is described which involved at least 186 people; adenovirus type 8 was identified in 50 of the cases. Topical human fibroblast interferon was assessed in a double-blind, placebo-controlled study in which 34 patients participated. Seventeen of the 34 trial patients yielded adenovirus type 8; three were infected with adenovirus type 7. The outbreak was curtailed by control of infection measures: principally careful hand-washing by medical personnel between cases and by discouraging attendance of new cases at the Eye Infirmary. Consequently the trial numbers are small. In addition there was a wide interpatient variation in the severity of infection. Therefore it was not possible to make any statistically valid conclusions concerning the recovery rate of patients receiving interferon or placebo.     

Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine

Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval −18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period.     

Assignment of opsonic values to pneumococcal reference serum 007sp and a second pneumococcal OPA calibration serum panel (Ewha QC sera panel B) for 11 serotypes

Pneumococcal conjugate vaccines (PCVs) have been effective in reducing the disease burden caused by Streptococcus pneumoniae. The first licensed PCV (PCV7) was composed of capsular polysaccharides from seven serotypes. This was followed by PCV10, then PCV13, and currently there are a number of higher valency vaccines in development. As part of licensure, new vaccine iterations require assessment of immunogenicity. Since some antibodies can be non-functional, measuring functional antibodies is desirable. To meet this need, opsonophagocytic assays (OPAs) have been developed. Previous studies have shown there can be significant variations in OPA results from different laboratories. We have previously shown that standardizing OPA data using reference serum 007sp can decrease this variation.To extend this approach to additional serotypes, a panel of sera was tested by five laboratories using a multiplexed OPA for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F. Each sample was tested in five runs with 007sp tested three times in each run. Results were analyzed using a mixed effects ANOVA model.Standardization of the results significantly decreased the inter-laboratory variation for some serotypes. For serotypes 2, 8, and 11A, the variability was reduced by 40%, 45%, and 40%, respectively. For serotypes 12F, 17F, and 20B, the reductions were more modest (14%, 19%, and 24%, respectively). Standardization had little effect for the remaining serotypes. In many cases, the impact of normalization was blunted by the results from five sera that were collected after an extended post-vaccination interval.We have previously reported consensus values for 007sp for 13 serotypes, as well as the creation of a calibration serum panel (“Ewha Panel A”). Here, we report consensus values for 11 additional serotypes for 007sp and the creation of a second serum panel (“Ewha Panel B”). These consensus values will facilitate the development of next-generation PCVs.     

Plasmid profiles of drug resistant Shigella boydii types 1-5, 8, 10, 12-14 from Ethiopia (1974-85).

Plasmid profile analysis by agarose gel electrophoresis was performed on 42 drug resistant strains of Shigella boydii serotypes 1-5, 8, 10, 12-14, collected between 1974 and 1985 from endemic cases of shigellosis in Ethiopia, and their Escherichia coli K12 transconjugants. Resistance factors (R factors) were further characterized by incompatibility testing. Patterns of small plasmids, less than 15 kb, were similar within each of the individual S. boydii serotypes. Plasmids of about 3.3-3.7 kb were found in all strains of serotypes 2 and 4. Plasmids of about 4.3-4.6 kb were found in about 86% of strains. Serotypes 1, 2 and 3 were characterized by plasmids of about 5.6-5.7 kb. The 6.4-6.7 kb plasmid was found consistently in serotypes 1, 2, 3, 5, 8, 12 and 13 which were resistant to SSu or had an SSu resistance component in their phenotypes. Large plasmids (155-186 kb) were found in most S. boydii strains. Conjugative drug resistance plasmids, most often coding for three or less drugs, were found in about 26% of drug resistant strains. R-factors, coding for AT resistance (in types 2 and 8), and ASSuT resistance (in type 4), were compatible with all reference plasmids tested. Plasmids belonging to incompatibility groups X and N were found in serotypes 5 and 10, respectively.     

中国≤18岁人群肺炎球菌相关病例中肺炎球菌血清型分布的系统评价

目的了解中国≤18岁人群肺炎球菌相关病例中肺炎球菌血清型分布,及7价肺炎球菌多糖结合疫苗（7-valent Pneumococcal Polysaccharide Conjugate Vaccine,PPCV7）、13价（13-valent）PPCV（PPCV13）血清型覆盖情况,为制定疫苗免疫策略提供参考。方法采用系统评价方法,在中国医院知识数据库、万方数据库和美国国立图书馆（Pubmed）中检索相关文献,对符合条件文献的信息进行提取,采用中位数（Median,M）和四分位数区间（Quartile Range,Q）对血清型分布和疫苗的血清型覆盖情况进行分析。结果系统评价共收集符合条件的文献28篇,结果显示,中国1996-2004年≤18岁人群肺炎球菌相关病例中,肺炎球菌主要血清型分布是：23F占16.7%（Q：11.6%-20.4%）、19F占13.8%（Q：11.9%-34.1%）、6A占9.9%（Q：7.1%-13.2%）。在南方,19F占30.2%（Q：16.3%-35.3%）、23F占16.9%（Q：14.0%-19.6%）、6A占9.4%（Q：7.6%-11.0%）;在北方,6A占13.2%（Q：6.6%-16.5%）、23F占11.6%（Q：10.8%-20.9%）、19F占10.0%（Q：8.7%-11.9%）。2005-2013年,19F占28.7%（Q：20.8%-42.2%）、19A占15.2%（Q：10.2%-19.7%）、23F占9.7%（Q：5.9%-12.3%）。在南方,19F占42.3%（Q：28.6%-62.2%）、19A占16.9%占（Q：3.3%-19.6%）、23F占11.5%（Q：4.3%-15.2%）;在北方,19A占20.6%（Q：6.4%-33.9%）、19F占18.6%（Q：11.5%-28.6%）、23F占9.8%（Q：9.3%-13.6%）。≤5岁人群侵袭性肺炎球菌血清型分布是：19A占33.3%（Q：31.2%-33.3%）、19F占16.7%（Q：14.1%-19.6%）、14占12.9%（Q：9.2%-16.3%）。≤18岁人群疫苗血清型覆盖情况为：1996-2004年,PPCV7为59.5%（Q：40.0%-64.2%）,南方为63.6%（Q：60.4%-65.4%）,北方为40.0%（Q：36.8%-46.7%）;PPCV13为75.7%（Q：66.7%-83.3%）,南方为79.5%（Q：68.9%-83.8%）,北方为70.0%（Q：58.4%-75.1%）。2005-2013年,PPCV7为60.2%（Q：52.0%-67.1%）,南方为68.1%（Q：60.9%-80.0%）,北方为49.2%（Q：46.0%-54.0%）;PPCV13为84.8%（Q：82.1%-91.9%）,南方为91.5%