Long-term efficacy of a hepatitis E vaccine.

BACKGROUND: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. METHODS: In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. RESULTS: During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups. CONCLUSIONS: Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

[An epidemiological investigation of the rabies between 1999 - 2008 in Yancheng city, Jiangsu province.].

OBJECTIVE: To better understand the epidemiology of rabies during the past ten years in Yancheng city, Jiangsu province. METHODS: Data was collected and analyzed on rabies cases in Yancheng. Density and vaccination rate on Canine, Rate of injured people bit by dogs, and the information of post-exposure prophylaxis were studied. Rabies virus in the dog brains, collected around the epidemic areas of Yancheng, were detected and analyzed. RESULTS: A total of 135 human rabies cases occurred from 1999 through 2008, and formed the second epidemic peak since 1958. Of these victims, 84% (114) were farmers. In general, the rate of people having dogs were 3% - 6% per 100 people, and the injured person-times of 100 dogs were 6.37 per year. Notably, the vaccination rate of dogs was only 20%. Of those people injured by dogs and other animals, 77% had received post-exposure treatment, and only 5% - 10% had been administered anti-rabies serum. Rabies virus antigen was found in 4 (3.6%) of 111 brain specimens among dogs collected from epidemic areas. Genetic analysis of N and G genes, which were amplified from brain specimens, indicated that these viruses belong to genotype I rabies and expressing a close relationship with the Chinese vaccine strain CTN. CONCLUSION: The large number of dogs with low vaccination rate among them, together with the incorrect and low post-exposure treatment in rural areas seemed to be responsible for the outbreak of rabies in Yancheng city.

Genetic diversity of Chinese rabies viruses: evidence for the presence of two distinct clades in China.

There have been three major rabies epidemics in China since the 1950s. To gain more insights into the molecular epidemiology of rabies viruses (RVs) for the third (the current) epidemic, we isolated RV from dogs and humans in major endemic areas, and characterized these isolates genetically by sequencing the entire glycoprotein (G) gene and the G-L non-coding region. These sequences were also compared phylogenetically with RVs isolated in China during previous epidemics and those around the world. Comparison of the entire G genes among the Chinese isolates revealed up to 21.8% divergence at the nucleotide level and 17.8% at the amino acid level. The available Chinese isolates could be divided into two distinct clades, each of which could be further divided into six lineages. Viruses in clade I include most of the Chinese viruses as well as viruses from southeast Asian countries including Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. The viruses in the other clade were found infrequently in China, but are closely related to viruses distributed worldwide among terrestrial animals. Interestingly, most of the viruses isolated during the past 10 years belong to lineage A viruses within clade I whereas most of the viruses isolated before 1996 belong to other lineages within clades I and II. Our results indicated that lineages A viruses have been predominant during the past 10 years and thus are largely responsible for the third and the current epidemic in China. Our results also suggested that the Chinese RV isolates in clade I share a common recent ancestor with those circulating in southeast Asia.

FDJS03 isolates causing an outbreak of aseptic meningitis in China that evolved from a distinct Echovirus 30 lineage imported from countries of the Commonwealth of Independent States.

We compared echovirus 30 strains (FDJS03) which caused an outbreak of aseptic meningitis in China in 2003 with other human enterovirus B strains. Sequencing of the complete genome of FDJS03_84, a representative strain from this outbreak, revealed a mosaic structure with a putative recombination spot within the 2B gene. It was most similar to a strain of the same serotype, E30-14125-00, in the 5' half of the genome but was almost equidistant to all strains analyzed in most of the 3' half of the genome. Phylogenetic relationships in the 5'-untranslated region and the VP1 gene indicated that the FDJS03 isolates were closely related to a distinct lineage of E30 which circulated in countries of the Commonwealth of Independent States during 1999 and 2000. It is most likely that the ancestor of FDJS03 isolates experienced multiple recombination events in the nonstructural protein coding region, which were partly observed in the phylogenetic analysis of the 3D region.

Molecular characterization of rabies virus isolates in China during 2004.

Human rabies cases have been on the rise during the past few years in China and a total of 2651 cases were reported in 2004. To better understand the current rabies epidemics in China, we isolated rabies viruses from dogs and humans from five provinces and characterized these isolates genetically by sequencing the entire nucleoprotein (N) gene. Comparison of the N genes among these isolates revealed 86.6-99.9% homology and these viruses can be grouped into three lineages. Phylogenetic analysis indicates that all the Chinese isolates have a close relationship with viruses circulating in Asian canine population. When compared with rabies viruses isolated previously, the three lineages were similar to three of the four groups. Thus, our data suggest that rabies viruses currently circulating in China were similar, if not identical, to those reported in the previous epidemics.

[Sequence analysis of Echovirus type 30 isolated from an aseptic meningitis outbreak in northern Jiangsu province in 2003].

OBJECTIVE: To determine the partial sequence of virus strains causing an aseptic meningitis outbreak in northern part of Jiangsu province in 2003 and to compare them with the same serotype strains isolated in other countries to better understand its genetic characteristics and hereditary trend of development. METHODS: Virus RNA was amplified using two sets of specific enteroviral 3' half of VP1 primers 012/011 and 040/011. Polymerase chain reaction (PCR) products were purified and sequenced. BLAST program was then used to perform on nucleotide and amino acid pairwise-alignment with all available sequences in NCBI database. Phylogenetic trees were drawed to compare with other enteroviral sequences using PHYLIP software. RESULTS: Under BLAST program, three sequences we submitted to GenBank were identically inferred as echovirus type 30, which had been identified by neutralization test in previous study. Phylogenetic analysis demonstrated that strains isolated from this outbreak were aggregated into a cluster, and the closest relationships with them were those isolated in 1999 and 2000. This phenomenon indicated that Echo30 from this outbreak was different from other strains in different epidemic area. CONCLUSION: 3' half of VP1 sequence could be used to quickly identify the serotype of isolated enterovirus. Strains isolated from this outbreak had the similar hereditary developing trend comparing with Echo30 strains isolated from other countries.

Echovirus 30, Jiangsu Province, China.

An outbreak of aseptic meningitis occurred in the northern area of Jiangsu Province in China from January to July in 2003. A total of 1,681 cases were involved in this outbreak, and 99% of patients were <15 years of age. To identify the etiologic agent, 66 cerebrospinal fluid specimens were tested by cell culture. Eighteen showed an enteroviruslike cytopathic effect on MRC-5 human fetal diploid lung cells. An enterovirus primer-mediated reverse transcriptase-polymerase chain reaction, a standard neutralization assay, and sequencing of the complete capsid-encoding (VP1) gene identified the 18 isolates (FDJS03) as echovirus 30. At least a 10% difference was seen in nucleotide sequences of VP1 between FDJS03 isolates and other global strains of echovirus 30. Phylogenetic analysis based on complete sequences of VP1 was performed to further characterize the FDJS03 isolates. This report is the first to identify a distinct lineage of echovirus 30 as a probable cause of this outbreak.

[Study on the effects of controlling hepatitis A epidemics by building the colony immune defence].

OBJECTIVE: To build the colony immune defence and to control the periodic epidemics of hepatitis A after a mass vaccination of live attenuated hepatitis A vaccine. METHODS: Through yearly observing the correlation of the accumulative inoculation rates of live attenuated hepatitis A vaccine, the crowd immune standard and the morbidity of hepatitis A after administered live attenuated hepatitis A vaccine among susceptible population and surveilling anti-HAV IgG in the different epidemic areas. RESULTS: (1) The accumulative inoculation rates of live attenuated hepatitis A vaccine was 34.15% in 8 years from 1993 to 2000, among which they were 84.46%, 82.23% and 15.14% in the preschool children, primary and middle school student and 15 - 45 age groups respectively. The morbidity of hepatitis A decreased to 8.26/100,000 in 2000. (2) The crowd positive rates of anti-HAV IgG were 74.24% in 1998 and 83.68% by 2000. Among which they were 74.02%, 68.49%, 79.41%, 85.71% and 90.80% in 2 - 4, 6 - 8, 13 - 15, 20- and 30 - 39 age groups respectively. (3) The accumulative inoculation rates were 37.36%, 51.08% and 28.68% in the inspection areas of Tongtai, Binhai and Yandu respectively. The crowd positive rates of anti-HAV IgG in three inspect area were 85.71%, 85.94% and 78.63% respectively. It was noticed the correlation between the accumulative inoculation rates and the crowd positive rates of anti-HAV IgG was (r(city) = 0.91, F = 15.10, P < 0.03). CONCLUSION: The results showed that the crowd positive rates of anti-HAV IgG had increased to 85% while, the colony immune defence of hepatitis A was effectively built to break the periodic epidemics of hepatitis A. The morbidity of hepatitis A decreased to the lowest level in the history.

[Study on the strategy of Japanese encephalitis immunization using live attenuated vaccine combined with inactivated vaccine].

OBJECTIVE: Using the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine. METHODS: Observing the safety and immune effects of different groups. RESULTS: Data on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05). CONCLUSION: Results showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.