[Preliminary analysis on the prevalence and causes of breakthrough hepatitis B virus infection among children in Shandong province, China].

OBJECTIVE: To know the prevalence and probable causes of breakthrough hepatitis B virus (HBV) infection among children born after the introduction of universal infant hepatitis B vaccination in Shandong province, China. METHODS: The subjects of this study were selected from the provincial hepatitis B serosurvey conducted in 2006, who were born between 1992 and 2005 (aged 1-15 years) and were confirmed to have completed three or more doses of hepatitis B vaccine. Finally 3527 subjects were involved in this study and were investigated using a unified question are. Blood samples were collected from them to detect hepatitis B surface antigen (HBsAg), antibody against HBsAg (Anti-HBs) and antibody against hepatitis B core antigen (Anti-HBc). The parents of children positive for HBsAg were followed up. Blood samples were collected from their parents to detect for HBsAg. The rate and correlative factors of breakthrough HBV infection were gotten by single-factor and multiple-factor analysis. RESULTS: For the 3527 subjects, the overall prevalence rates of breakthrough HBV infection were 3.15% (111/3527), which decreased while birth year grew (χ(2)(Trend) = 44.83, P < 0.01) , the rate of subjects born in 1992 was the highest (9.9%, 16/161) , subjects born in 2000 was the least (0.8%, 2/258) , the rate of the self-report positive HBsAg status of mother, father and the other family members (15.22%, 7/46;34.09%, 15/44;17.65%, 6/34) were higher than the negative (2.99%, 104/3481, 2.76%, 96/3483, 3.01%, 105/3493) (χ(2) values were 22.28, 13.97, 23.68, respectively, all P values were < 0.01) , timely first dose of hepatitis B vaccine (5.37%, 41/763) was higher than the subjects that not in time (2.53%, 70/2764) (χ(2) = 15.596, P < 0.01) . The overall prevalence rates of breakthrough chronic HBV infection was 1.08% (38/3527), which decreased while birth year grew (χ(2)(Trend) = 9.96, P < 0.05) , the rate of subjects born in 1992 was the most (3.1%, 5/161) , subjects born in 1997 was the least (0.4%, 1/261) , the rate of the self-report positive HBsAg status of mother, father and the other family members (13.04%, 6/46;29.55%, 13/44;17.65%, 6/34) were higher than the negative (0.92%, 32/3481;0.72%, 25/3483;0.92%, 32/3493) (χ(2) values were 62.62, 338.80, 88.44, respectively, all P values were < 0.05) , timely first dose of hepatitis B vaccine (1.83%, 14/763) was lower than the subjects that not in time (0.87%, 24/2764) (χ(2) = 5.16, P = 0.02) . Multiple factors analysis showed that compared to the negative, the self-report positive HBsAg status of father, mother increased the risk of breakthrough HBV infection,OR (95%CI) values were 3.73 (1.09-12.75) and 26.76 (11.86-60.37) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western cities were the highest (OR (95%CI) = 6.00 (2.50-14.40) , P < 0.05) the risk of children born in 1992-2001 was higher than those born in 2002 ( (OR (95%CI) = 1.91 (1.10-3.32) , P < 0.05) . Compared to the negative, the self-report positive HBsAg status of father, mother and the other family members increased the risk of breakthrough chronic HBV infection,OR (95%CI) values were 7.51 (1.44-39.17) , 99.99 (34.29-291.62) , 8.94 (1.81-44.10) , respectively (all P values were < 0.05) , compared with eastern cities, the risk of western rural areas were the highest (OR (95%CI) = 12.51 (2.78-56.25) , P < 0.05) , sharing tooth brush with the others increased the risk (OR (95%CI) = 8.67 (1.14-66.14) , P < 0.05) . Among HBsAg-positive children, those with HBsAg positive mother and father accounted for 12/23 and 6/19, respectively. CONCLUSION: The prevalence of breakthrough HBV infection and breakthrough chronic HBV infection among children was low in Shandong province. Mother to infant transmission might be the main reason for the infection while the role of the horizontal transmission within the family shouldn't be ignored.

Molecular epidemiological analysis of echovirus 19 isolated from an outbreak associated with hand, foot, and mouth disease (HFMD) in Shandong Province of China.

OBJECTIVE: To elucidate the genetic characterization and molecular epidemiological features of Echovirus 19 (E19) isolates collected from an outbreak associated with hand, foot and mouth disease (HFMD) in Tai'an city of Shandong Province of China from July to September, 2003. METHODS: Thirty seven Echovirus 19 isolates were isolated from stool specimens and throat swabs collected during the outbreak, then major capsid (VP1) genomic sequence was determined, and phylogenetic tree was done based on the VP1 sequences among these 37 and other E19 viruses deposited in the Genbank. Also a representative strain named CHN-SD03-TN12 was selected for sequencing of 5'-untranslated regions (5'-UTR). RESULTS: The identity rate was about 98.9%-100% among all these 37 E19 viruses. The genetic relationships between these 37 E19 isolates and other strains reported were also depicted. The identity rate was about 78.4%-78.9% compared with E19 reference strain Burke. The substitutions in the sequence of 5'-UTR resulted in changes in the conjectural properties of 5'-UTR of E19 viruses. CONCLUSION: The genetic features of E19 viruses isolated during the outbreak in Shandong Province in 2003 may be associated with a genetic and antigenic drift that changes the virulence of the Shandong isolates, but the molecular changes in Shandong E19 viruses contributing to their phenotype remain to be further illuminated. However, the sequences described in this paper substantiate the changes taken place in capsid VP1 and 5'UTR regions. These substitutions may contribute to their tropism and virulence, and play a significant role in pathogenesis and clinical manifestations of the disease.

[Epidemiology of hand, foot, and mouth disease and genetic characterization of enterovirus A71: a survey from 2007 to 2012 in Linyi of Shandong Province, China].

To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong Province, China during 2007-2012. The number of reported HFMD cases were obtained from the National Notifiable Disease Reporting System (NNDRS) were analyzed by descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD patients in Linyi was amplified and sequenced. Finally, the genetic variability and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The results showed that HFMD incidence was reported in each year from 2007 to 2012 in Linyi, and the highest incidence and mortality were reported in 2009, when there were total 14697 cases and 9 of death. The reported incidence was 140.28/100000, and the mortality was 0.086/100000. The peak incidence usually occurred between April and July, and the summit occurred in May. Scattered children accounted for 77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5 years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were reported in the 6 consecutive years, accounting for 2.98% of the gross number. Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012. Incidence varied significantly among different counties. The peak incidence in each year lasted from April to July. Most of the patients were children under 3 years of age, and scattered children took the highest proportion. Co-circulation of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been prevalent continuously in Linyi for 6 years.

[Progress in research of new human enterovirus types].

More and more new human enteroviruses (HEVs) types were identified with the broad application of the molecular serotyping methods for enteroviruses. Since enterovirus 71 (EV71) was first reported in 1969, numerous epidemic outbreaks associated with new enteroviruses have occurred all around the world, and pose a significant threat to public health . The epidemics of hand, foot and mouth disease (HFMD) caused by EV71 infection in China have raised great concern of global scholars. This paper reviewed research progress in recent years of the molecular typing, evolution, epidemiology, and pathogenesis attributable to new enterovirus types.

[Identification and genetic characterization of coxsackieviruses A2, 6, 8 and 12 isolated in Shandong Province].

In previous study, molecular typing method was performed to identify human enteroviruses (HEVs) isolates collected from acute flaccid paralysis (AFP) cases from 1989 to 2011 and hand, foot and mouth disease (HFMD) patients, and 8 HEV-A serotypes were identified. In order to explore the genotypes and molecular evolution characteristics of HEV-A in Shandong province, viral RNA of the remaining isolates was extracted and entire VP1 coding region was amplified, sequenced and identified with HEV-A primers. Another 7 HEV-A Shandong isolates were obtained, and identified as Coxsackievirus A (CVA) 2, 6, 8 and 12 by molecular typing method. Homologous comparison showed that the nucleotide acid identities of Shandong strains ranged from 80.8% to 85.0% with prototype strains. Phylogenetic analysis based on VP1 sequences indicated that CVA8 and CVA12 strains were genetically related with domestic strains. However, CVA2 and CVA6 strains were distinct from both domestic and foreign strains. In addition, multiple transmission chains of CVA2 and CVA6 existed within Shandong province. So far, a total of 12 HEV-A serotypes were identified in Shandong province. This study enriched the distribution of serotypes and genetic evolution characteristics of HEV-A isolates in Shandong, and revealed different transmission chains of CVA2, 6, 8, 12 serotypes co-circulated in Shandong province or in China.

An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China.

BACKGROUND: An outbreak of hand, foot, and mouth disease (HFMD) included 1149 people in Linyi City, Shandong Province, China, in 2007: three children died. OBJECTIVES: To characterize the pathogens responsible for this outbreak and to analyze their genetic features. STUDY DESIGN: A total of 233 clinical specimens were collected from 105 hospitalized patients, including 11 patients with severe HFMD. Virological investigations (direct RT-PCR, viral isolation and molecular identification) and phylogenetic analysis were performed. RESULTS: Human enterovirus 71 (HEV71) was the main pathogen that caused this outbreak, based on clinical manifestations, epidemiological data, and laboratory results. Phylogenetic analysis indicated that the Shandong HEV71 isolates belonged to 3 lineages in subgenotype C4. Subgenotype C4 could be further divided into two clusters (C4a and C4b), which corresponded to two time periods. Cluster C4a HEV71 has been the predominant virus circulating in mainland China in the past 5 years. CONCLUSIONS: The 2007 HFMD outbreak was mainly caused by HEV71 subgenotype C4 with 3 transmission chains. This virus has been continuously circulating in China since 1998. The Shandong strains co-evolved with isolates from other provinces in mainland China and neighboring countries.

[Estimation of disability weights on malignant neoplasms in Shandong province].

OBJECTIVE: To determine stage-specific and average disability weights (DWs) of malignant neoplasm and provide support and evidence for study on burden of cancer and policy development in Shandong province. METHODS: Health status of each cancer patient identified during the cancer prevalence survey in Shandong, 2007 was investigated. In line with the GBD methodology in estimating DWs, the disability extent of every case was classified and evaluated according to the Six-class Disability Classification version and then the stage-specific weights and average DWs with their 95% confidence intervals were calculated, using SAS software. RESULTS: A total of 11 757 cancer cases were investigated and evaluated. DWs of specific stage of therapy, remission, metastasis and terminal of all cancers were 0.310, 0.218, 0.450 and 0.653 respectively. The average DW of all cancers was 0.317 (95%CI: 0.312 - 0.321). Weights of different stage and different cancer varied significantly, while no significant differences were found between males and females. DWs were found higher (> 0.4) for liver cancer, bone cancer, lymphoma and pancreas cancer. Lower DWs (< 0.3) were found for breast cancer, cervix uteri, corpus uteri, ovarian cancer, larynx cancer, mouth and oropharynx cancer. CONCLUSION: Stage-specific and average DWs for various cancers were estimated based on a large sample size survey. The average DWs of 0.317 for all cancers indicated that 1/3 healthy year lost for each survived life year of them. The difference of DWs between different cancer and stage provide scientific evidence for cancer prevention strategy development.