Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

New genome type of adenovirus serotype 19 causing nosocomial infections of epidemic keratoconjunctivitis in Japan

Twelve strains of adenovirus serotype 19, isolated from cases of epidemic keratoconjunctivitis in Japan in 1992, 1993, 1997, and 1998, were analyzed by DNA restriction analysis, using restriction endonucleases BamHI, BglI, BglII, EcoRI, HindIII, KpnI, PstI, SacI, SalI, SmaI, and XhoI. Among these 11 restriction endonucleases, EcoRI, PstI, SacI, and SmaI were discriminative enzymes, showing restriction patterns different from those reported previously for the prototype and the variant 19a. This new genome type was isolated in 1997 and 1998, when an increase of epidemic keratoconjunctivitis cases caused by adenovirus serotype 19 was observed for both sporadic and nosocomial infections. Strains from 1992 and 1993 showed restriction patterns similar to those of the worldwide reported variant 19a for all enzymes used. The changes detected in strains from 1997 and 1998 could be the reason for the recent epidemic.     

Behavior of the dengue virus in solution

The dengue virus consists of four antigenically related but distinct viruses, termed Dengue virus 1-4 (DEN 1-4). We have established that the dengue virus loses infectivity over time in solution in an exponentially declining manner. The four strains examined (one from each serotype) have half-lives that range from 2.5 to 7.5 hr in defined medium. The half-life is temperature and pH-dependent and is affected by the nature of the host cell in which it is produced, but is not dependent upon the presence of either Mg(2+) ions or chelating agents. Electron microscopy (EM) of solutions of the dengue virus show almost complete virus aggregation after 24 hr at room temperature, while RT-PCR shows an intact RNA genome. These results show that the solution environment of the dengue virus is an important determinant of dengue virus infectivity.     

The Foot and Mouth Disease Virus Type O Outbreak of 1992 Is Not Related to Vaccine Strain (O/R2/75)

Vaccination is the only pragmatic approach to control foot and mouth disease in India. Strict quality control measures are essential to supply potent vaccine to the field application, in addition to monitoring the performance of the vaccine in the field. During the process of monitoring, an outbreak of FMD in vaccinated animals caused by type “O” virus in Tanjavur district of Tamil Nadu and a type “O” virus from unvaccinated herd of Karnataka were studied. Field isolates and vaccine virus were sequenced and analyzed. Data indicated that the virus from the outbreak in vaccinated cattle was a variant which could escape neutralization by antibodies against vaccine virus. This revised version was published online in August 2006 with corrections to the Cover Date.     

The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria

BackgroundUreaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP).MethodsThis study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months.ResultsForty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH.ConclusionsUP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.     

A highly predictable animal model of retinoblastoma

Summary A new animal model of retinoblastoma was developed in newborn inbred CDF rats by intravitreous inoculation of retinal tumor cells (5×10⁴/5 l) derived from the cultured tumor cell line EXP-5. The retinal tumor from which the cell line originated was induced by a single intravitreous inoculation of human adenovirus serotype 12 (5 l of 10⁸ TCID 50/0.1 ml) in syngeneic rats. Within 1 month after intravitreous moculation of EXP-5 cells, a clinically recognizable ocular tumor was obtained in all 39 rats. Ad 12-specific T-antigens were demonstrated in the cultured tumor cells using immunofluorescent techniques. Morphologically these tumor cells closely resembled retinoblastuma, with poorly differentiated intracytoplasmic organelles, solitary cilia with a 9+0 tubule pattern, and abnormal nuclear membrane associated with a set of basal bodies. The significance of this highly manipulable retinal tumor cell line is the capability of providing a full-fledged intravitreous tumor in 1-month-old CDF rats, whose actual life span is known to be 42 months. Transplantable retinal tumors described to date are reviewed breifly and compared with the presently reported cell line.Supported by USPHS grants EY-CA01667, R01-EY-03171, and P30 EY-01784, by grants from the Retina Research Foundation, Houston, Texas, and by the Massachusetts Lions Eye Research Fund Inc.     

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%     

广西玉林市住院患者肺炎链球菌的血清型分布及耐药性分析

目的 分析住院患者肺炎链球菌分离株的血清型分布、耐药率及耐药基因携带,评估疫苗对本地区肺炎链球菌血清型的覆盖率,为临床合理使用抗菌药物提供参考。方法 收集2015年1月—2019年12月广西玉林市第一人民医院住院患者送检标本分离的非重复肺炎链球菌150株,进行血清分型及抗菌药物敏感性试验。用PCR方法检测pbp2b、ermB、tetM三种耐药基因的携带率。结果 150株肺炎链球菌经PCR技术分型率为93.1%,经荚膜肿胀试验分型率为100%,共分出19种血清型,以19F和6B为主。儿童血清型以19F、6B和15A为主;成人血清型以19F、14和23F为主。PCV7、PCV10、PCV13和PPV23疫苗的覆盖率依次分别为36.8%、42.1%、57.9%和68.4%。血清型为19F、6B、3和23F的菌株对抗菌药物的耐药率较高。肺炎链球菌对青霉素的敏感率大于96.0%。侵袭性与非侵袭性菌株中耐药率有显著差异的抗菌药物为青霉素、莫西沙星和左氧氟沙星。菌株同时携带ermB和tetM两种耐药基因占96.0%,pbp2b、ermB、tetM三种耐药基因与耐药表型的一致率>98.0%。共检...     

2011～2012年赤峰市松山区动物中检出41株小肠结肠炎耶尔森菌

目的了解赤峰市松山区境内鼠类,家畜家禽携带小肠结肠炎耶尔森菌情况,为疾病预防控制工作提供科学依据。方法采集鼠类、家畜家禽的粪便、脏器等样品,进行小肠结肠炎耶尔森菌的分离、培养、鉴定和生物血清分型,并用PCR方法进行毒力因子检测。结果 2011～2012年共检验各类样品412份,检出小肠结肠炎耶尔森菌41株,皆来自猪咽拭子。2011年总检出率为16.02%,猪咽拭子的检出率高达28.28%。41株小肠结肠炎耶尔森菌中,携带了ail,ystA,yadA,virF,rfbc基因的3/O：3生物血清型菌株占95.12%;4/O：4生物血清型菌株占2.32%;其他占2.32%。结论赤峰市松山区境内的猪咽部携带小肠结肠炎耶尔森菌,猪是致病性小肠结肠炎耶尔森菌的重要携带者。     

Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide

Capsular polysaccharides are important virulence factors of Streptococcus pneumoniae. The polysaccharide has been used as a component of vaccines against pneumococcal diseases either as plain polysaccharide or better conjugated to a protein. The last one is the vaccine of choice to target child protection. The immune responses depend on several polysaccharide physicochemical properties that can be affected during either purification or modification in the case of conjugate vaccines. In serotype 18C, the repeating unit has a complex structure having a branched pentasaccharide with two apparently labile subtituents: glycerol-phosphate and O-acetyl group. The loss of these groups may potentially reduce the ability of the 18C polysaccharide to induce the desired immune response. Therefore, the relationship of both groups with the antigenicity and immunogenicity of 18C capsular polysaccharide is explored. It is shown that glycerol-phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide. At the same time, it was proved that O-acetyl groups do not play any role for the antigenicity and immunogenicity.