Hongjun Dong

Association between the various mutations in viral core promoter region to different stages of hepatitis B, ranging of asymptomatic carrier state to hepatocellular carcinoma.

OBJECTIVES:The objective of this study was to determine the association of 19 mutations with frequencies ≥10% in the core promoter region of hepatitis B virus (HBV) with chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC).METHODS:Eight hundred forty-six asymptomatic hepatitis B surface antigen carriers (ASCs), 235 CHB patients, 188 cirrhosis patients, and 190 HCC patients with intact data of HBV genotyping, DNA sequencing, and serological parameters were studied. Nucleotides with the highest frequencies in HBV genotypes B and C from all ASCs were treated as wild-type nucleotides.RESULTS:Mutations at nt.1674, nt.1719, nt.1762, nt.1764, nt.1846, nt.1896, and nt.1913 in genotype C were significantly associated with CHB, cirrhosis, and HCC, as compared with ASCs. C1673T, A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C were significantly associated with cirrhosis compared with the CHB patients, whereas these mutations were inversely associated with HCC compared with the cirrhosis patients. Multivariate regression analyses showed that age, male, abnormal alanine aminotransferase (ALT), T1768A, A1762T/G1764A, and A1846T were independently associated with cirrhosis compared with ASCs and the patients with CHB. Age, abnormal ALT, HBV DNA (≥104 copies/ml), genotype C, C1653T, T1674C/G, T1753V, and A1762T/G1764A were independently associated with HCC compared with those without HCC. Haplotypic carriages with two or more HBV mutations were significantly associated with HCC. T1674C/G, C1653T, and T1753V were specific for HCC. A1762T/G1764A had a moderate sensitivity and specificity for HCC.CONCLUSIONS:C1673T, A1726C, A1727T, C1730G, C1766T, T1768A, C1773T, and C1799G in genotype C are specific for cirrhosis. A1846T and T1674C/G are novel factors independently associated with cirrhosis and HCC, respectively.

Epidemiological and etiological characteristics of hand, foot, and mouth disease in Ningbo, China, 2008–2011

BACKGROUND Outbreaks of hand, foot, and mouth disease (HFMD) in central China have caused public health concerns since 2007. It is of particular public health significance to update epidemiology of HFMD in port cities. OBJECTIVE To investigate epidemical, etiological and clinical characteristics of HFMD in Ningbo, China, from 2008 to 2011. STUDY DESIGN From May 2008 to December 2011, a total of 37,404 HFMD cases including 196 severe and 12 fatal cases were investigated. Human enteroviruses from 2360 cases were determined by real-time RT-PCR. The VP1 gene of EV71 from 78 cases and CA16 from 21 cases, the VP4 gene from 28 cases, and full-length genomes of 10 isolates were analyzed. Neutralizing antibodies were evaluated in 258 healthy subjects. Parameters associated with severe HFMD were evaluated. RESULTS Annual incidence of HFMD was 3066.8/100,000 in the population of ≤5 years. EV71 C4a, CA16 B1, and other enteroviruses accounted for 63.7%, 24.0% and 12.3%, respectively. The genomes of EV71 from fatal and non-fatal cases were nearly identical. The positive rates of neutralizing antibody to EV71 increased from 13.5% to 67.6% in 1- to 5-year healthy groups. The neutralizing antibody to CA16 B1 isolate was negative. EV71, exposure history and certain early manifestations including fever, vomiting, limb exanthema and peripheral neutrophil ratio were significantly associated with HFMD severity. CONCLUSIONS HFMD mainly caused by EV71 C4a and CA16 B1 is seriously epidemic in Ningbo. Future emphasis should be paid on EV71 immuno-prophylaxis and early identification of severe cases upon the etiological and clinical characteristics.

β-Haemolytic group A streptococci emm75 carrying altered pyrogenic exotoxin A linked to scarlet fever in adults

OBJECTIVE To determine the etiological cause of a food-borne outbreak of scarlet fever in adults. METHODS Swabs from the throats of the patients and asymptomatic control were cultured on blood agar plates individually. Biochemical identification of all isolates was performed with a VITEX automated system. Antibiotic susceptibility was examined by using the Kirby-Bauer disc diffusion method. emm gene and extracellular pyrogenic exotoxins of each isolate were amplified by using polymerase chain reaction and subjected to DNA sequencing. Sequence differences between the isolated and the highly similar reference sequences were compared on BLAST. Bioinformatics was used to predict protein structures. RESULTS Beta-haemolytic group A streptococci (GAS) emm75 were identified from 10 of 13 available patients. The isolates were susceptible to penicillin, ampicillin, vancomycin, cefatriaxone, ofloxacin, linezolid and quinupristin. All of the isolates carried pyrogenic exotoxin A (speA) and cysteine protease (speB). Isolated speA was phylogenetically different from 30 highly similar references on BLAST. Differences in the primary sequence of the deduced protein were 14.37-20.12% between the speA and each of 11 references. Secondary protein structure of the speA was different from the references at the N-terminal. CONCLUSIONS GAS emm75 encoding altered speA was responsible for the food-borne outbreak of scarlet fever in adults.

Varicella breakthrough infection and effectiveness of 2-dose varicella vaccine in China

BACKGROUND 2-dose varicella vaccination has been available in Ningbo city, China since 2014 in the private sector. This study aimed to evaluate the breakthrough varicella infection rate, and to examine overall and incremental effectiveness of 2-dose varicella vaccination among Chinese children. METHODS A retrospective investigation was done among native children born from 2008 to 2013 in active surveillance area in Ningbo, China. Between 2009 and 2016, demographic information and data on varicella vaccination were collected by Ningbos Immunization Information System, and information of varicella infections were obtained from China Information System for Disease Control and Prevention. The logistic regression was conducted to estimate varicella vaccine effectiveness (VE). RESULT A total of 107,324 local children were enrolled in the cohort analysis and 95.11% of these children with no varicella disease history received at least 1-dose varicella vaccine from 2009 to 2016. The total breakthrough varicella infection rate (BVR) was 0.37% for all the vaccinated children and 0.04% for 2-dose vaccination. The annual BVR ranged from 0.01% to 0.49% for 1-dose of varicella vaccine and from 0.01% to 0.02% for 2-dose. The infection rates both in the unvaccinated children and the 1-dose children were decreasing after 2-dose vaccination implemented in 2014 (Unvaccinated: P < 0.001 for trend; 1-dose: P = 0.003 for trend). The VE against all varicella was 50.3% (95% CI: 39.8%-59.0%) for 1-dose (P < 0.001) and 98.7% (95% CI: 98.1%-99.1%) for 2-dose (P < 0.001), and the incremental VE was 97.4% (95% CI: 96.2%-98.2%) compared with 1-dose (P < 0.001). CONCLUSION The 2-dose regimen provided excellent protection to prevent all varicella, and the universal 2-dose regimen of varicella vaccine should be recommended to prevent the varicella disease among children in China.

Determinants of healthcare workers’ willingness to recommend the seasonal influenza vaccine to diabetic patients: A cross-sectional survey in Ningbo, China

ABSTRACT Background: Seasonal influenza vaccine uptake among diabetic patients is low in China. Recent studies showed healthcare workers’(HCWs’) recommendation is an effective way to promote influenza vaccination. This study aimed to assess HCWs’ willingness to recommend influenza vaccine to diabetic patients and identify the predictors of this willingness. Methods: During Dec 2016-Jan 2017, a self-administered questionnaire on perceptions, attitudes and practices related to influenza vaccination for diabetic patients was distributed to 1370 HCWs in 20 hospitals and 20 community health centers in Ningbo. Predictors of HCWs’ willingness to recommend influenza vaccine were analyzed by logistic regressions. Results: Of 1340 HCWs who completed the survey, 58.13%(779/1340) participants reported willingness to recommend influenza vaccine to diabetic patients. Factors positively associated with the recommendation willingness included awareness of national influenza vaccination guideline(OR: 6.33; 95%CI: 4.66–8.60) and regional reimbursement policy(OR: 1.62; 95%CI: 1.19–2.20), training on influenza and diabetes (OR: 1.65; 95%CI: 1.21–2.23), influenza vaccination history(OR: 1.35; 95%CI: 1.01–1.79), beliefs in vaccine effects on reducing serious consequences(OR: 1.38; 95%CI: 1.01–1.91), reduction in hospitalization costs(OR: 1.43; 95%CI: 1.05–1.94) caused by influenza, and more than 10 years of practitioner experience(OR: 1.60; 95%CI: 1.04–2.46). Worries about side-effects of influenza vaccine were identified as the barriers of recommendation. Conclusion: The present study demonstrates that knowledge about national guideline and reimbursement policies, training programs, perceptions about effectiveness and safety of influenza vaccine increase HCWs’ willingness to recommend the influenza vaccination to diabetic patients. These measures should be taken to ensure HCWs’ role in the administration of influenza vaccination among diabetic patients.

Safety, immunization coverage and determinants of a new kind of Hepatitis B vaccine firstly applied in Ningbo, China

Evaluate safety and immunization coverage of a new kind of recombinant Hepatitis B vaccine (HepB) in Ningbo city, China. Two groups were carried out in 2 of 11 randomly selected countries in Ningbo in 2009. All of the infants born from July 1 to December 31, 2009 were enrolled as subjects and received 3 doses of HepB at 0, 1, 6 month. Control group (N = 3452) received current HepB derived from Saccharomyces Cerevisiae Yeast (HepB made by recombinant DNA techniques in Saccharomyces Cerevisiae Yeast, HepB-SCY; 5 μg/0.5 ml per dose) and experimental group (N = 5104) received the new kind of HepB derived from Hansenula polymorpha Yeast (HepB made by recombinant DNA techniques in Hansenula polymorpha Yeast, HepB-HPY; 10 μg/0.5 ml per dose). 3-dose and timely birth dose (TBD) coverage were available and compared between 2 groups. Standard structured questionnaires were applied to record information from parents and hospitals for selecting determinants of coverage. The data were analyzed using stepwise multiple logistic regression models. After each dose, HepB-related adverse events (AEs) and recta-temperature were recorded for 7 days. 3-dose coverage in control group (89.98%) was higher than that in experimental group (χ2 = 575.1173, P < 0.0001). TBD coverage in control and experimental group were 98.41% and 98.53%, respectively. No statistically significant difference in TBD coverage was found between 2 groups (χ2 = 0.0623, P = 0.8029). A total of 9 local AEs were reported, 4 for control group and 5 for experimental group. The percentages of subjects reporting AEs were similar across the 2 vaccination groups. No serious or immediate reactions were found in this study. From logistic models, receiving 10 μg vaccine (odds ratio [OR]:0.38; 95% confidence interval [95%CI]: 0.34–0.44) and mother migrating from other cities (OR: 0.45; 95%CI: 0.42–0.47) were the determinants for non-acceptance of 3 doses of HepB; infants born from low grade hospitals and native mothers contributed to administrate the TBD.