Inter‐serotype reassortment among epizootic haemorrhagic disease viruses in the United States

First described in 1955 in New Jersey, epizootic haemorrhagic disease (EHD) causes a severe clinical disease in wild and domestic ruminants worldwide. Epizootic haemorrhagic disease outbreaks occur in deer populations each year from summer to late autumn. The etiological agent is EHD virus (EHDV) which is a double‐stranded segmented icosahedral RNA virus. EHD virus utilizes point mutations and reassortment strategies to maintain viral fitness during infection. In 2018, EHDV serotype 2 was predominantly detected in deer in Illinois. Whole genome sequencing was conducted for two 2018 EHDV2 isolates (IL41747 and IL42218) and the sequence analyses indicated that IL42218 was a reassortant between different serotypes whereas IL41747 was a genetically stable strain. Our data suggest that multiple strains contribute to outbreaks each year.     

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.     

Serotype‐specific polysaccharide of Streptococcus mutans contributes to infectivity in endocarditis

Streptococcus mutans and other viridans streptococci have been implicated as major etiological agents of infective endocarditis. The serotype‐specific rhamnose‐glucose polysaccharide (RGP) of S. mutans has several biological functions that appear to be essential for the induction of infective endocarditis. The aim of this study was to examine the contribution of RGP to the infectivity of S. mutans in infective endocarditis using a rat model. The RGP‐defective mutant of S. mutans showed reduced ability to induce infective endocarditis compared to the parental strain. The ability of S. mutans to induce infective endocarditis was not consistent with the binding capacity of the organism to extracellular matrix proteins. The results suggest that S. mutans containing whole RGP is more virulent than the RGP‐defective mutant, and the RGP has an important role for the induction of infective endocarditis by S. mutans.     

Sequence Analysis of the RNA Polymerase Gene of Foot-and-Mouth Disease Virus Serotype Asia1

The complete nucleotide (nt.) sequence of the RNA polymerase (3D) gene and 81 nt. in the 3-untranslated region of foot-and-mouth disease virus (FMDV) serotype Asia1 (IND63/72) was determined and compared with the sequence of other FMDV serotypes. The 3D genomic region was 1410 nt. long encoding 470 amino acids with an inframe stop codon (TAA) at nt. position 1411–1413. The deduced amino acid sequence of the protein showed 8 conserved motifs as reported in other picornaviruses, 2 of which are 100% identical across the serotypes. Antigenic regions in the polymerase protein were predicted and found to be located at the N-terminus of the protein. The phylogenetic analysis showed that the FMD viruses were segregated into different clusters based on geographical origin; the Asia1 virus did not cluster tightly with any of the geographical groups.     

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.     

我国5岁以下儿童小肠结肠炎耶尔森菌感染临床特征及病原学分析

目的 了解我国5岁以下儿童小肠结肠炎耶尔森菌腹泻病例临床与病原学特征,分析其可能的感染来源,为小肠结肠炎耶尔森菌病的防控与诊断提供科学依据。 方法 收集2010—2020年间来自全国10个省市自治区哨点医院儿童腹泻标本、调查及回访问卷;对标本进行小肠结肠炎耶尔森菌的分离鉴定;菌株进行生物分型、血清型鉴定;毒力基因检测以及脉冲场凝胶电泳(pulsed field gel electrophoresis,PFGE)分型。 结果 2010—2020年共监测11 377例,分离到致病性小肠结肠炎耶尔森菌63株,包括61株O:3血清型、2株O:9血清型菌株,5岁以下腹泻儿童感染率0.55%(63/11 377)。不同性别儿童对致病性小肠结肠炎耶尔森菌的感染率差异无统计学意义,1～5岁感染率高于≤1岁病例(χ²=44.836,P＜0.05),感染患儿中1～5岁发热比例高于≤1岁(χ²=11.508 ,P<0.05),随访病例未发现后遗症。我国儿童感染O:3血清型致病性小肠结肠炎耶尔森菌的PFGE带型存在多样性,优势带型为K6GN11C30021、K6GN11C30012。 结论 我国5岁以下儿童感染致病性小肠结肠炎耶尔森菌的生物血清型以3/O:3为主,偶有4/O:3与2/O:9。根据患儿感染特点与高发季节推测食源为主要感染来源,需进一步调查研究。     

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.