Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

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.).

Acoustic Insulation Characteristics and Optimal Design of Membrane-Type Metamaterials Loaded with Asymmetric Mass Blocks.

Membrane-type acoustic metamaterials (MAMs) are the focus of the current research due to their lightweight, small size, and good low-frequency sound insulation performance. However, there exists difficulties for extensive application because of the narrow sound insulation band. In order to achieve broadband sound isolation under the premise of lightweight, a novel MAM with asymmetric rings is firstly proposed in this paper. The sound transmission loss (STL) of this MAM is calculated by an analytical method and is verified by the finite element model. The different properties of the membrane when it is loaded with one, two, or four mass blocks are analyzed. The comparison with the traditional MAM proves the superior performance of this novel MAM. Moreover, by discussing the influence of the eccentricity and distribution position of the masses on the results, the tunability of the sound insulation performance of this MAM is proven. Finally, the Isight platform is used to optimize the MAM to further improve the broadband sound insulation performance: the average STL of the MAM is improved by 15.7%, the bandwidth above 30 dB is improved by 11.5%, and the mass density is reduced by 30.01%.

Acoustic Insulation Mechanism of Membrane-Type Acoustic Metamaterials Loaded with Arbitrarily Shaped Mass Blocks of Variable Surface Density.

Membrane-type acoustic metamaterials (MAMs) have recently received widespread attention due to their good low-frequency sound-transmission-loss (STL) performance. A fast prediction method for the STL of rectangular membranes loaded with masses of arbitrary shapes and surface density values is proposed as a semi-analytical model for calculating the STL of membrane-type acoustic metamaterials. Through conformal mapping theory, the mass blocks of arbitrary shapes were transformed into regular shapes, which simplified the calculation model of acoustic propagation loss prediction, and the prediction results were verified by finite element simulations. The results show that the change in mass surface density was closely related to the size and frequency distribution of STL. The influence of the mass center on the STL and characteristic frequency of the film metamaterial is discussed.

Sound Insulation Performance of Composite Double Sandwich Panels with Periodic Arrays of Shunted Piezoelectric Patches.

The existing sandwich structure of the aircraft cabin demonstrates a good sound insulation effect in medium and high frequency bands, but poor in the low frequency band. Therefore, we propose an infinite new lightweight broadband noise control structure and study its sound transmission loss (STL). The structure is an orthogonally rib-stiffened honeycomb double sandwich structure with periodic arrays of shunted piezoelectric patches, and demonstrates lighter mass and better strength than the existing sandwich structure. The structure is equivalent according to Hoff's equal stiffness theory and the effective medium (EM) method. Using the virtual work principle for a periodic element, two infinite sets of coupled equations are obtained. They are solved by truncating them in a finite range until the solution converges. The correctness and validity of the model are verified by using simulation results and theoretical predictions. Eventually, a further study is performed on the factors influencing the STL. All the results demonstrate that the STL in low-frequency can be improved by the structure, and the sound insulation bandwidth is significantly broadened by adding shunted piezoelectric patches. The structure can provide a new idea for the design of broadband sound insulation.

Disease burden concerning hepatitis E-infected inpatients in Jiangsu province, China.

OBJECTIVE: This study aimed to determine the disease burden of hepatitis E virus (HEV)-infected inpatients in Jiangsu province, China. METHODS: Between July 1, 2016 and October 31, 2018, 1152 HEV-infected inpatients were identified from four cities in Jiangsu province, namely, Nanjing, Suzhou, Yancheng, and Zhenjiang. The disease burden comprised the economic burden and loss of health due to HEV infection. Factors influencing the disease burden were analyzed using univariate and multivariate analyses. RESULTS: The average direct, indirect, and total economic burden for 1152 HEV-infected inpatients was US$ 4,986.40, US$ 1,507.28, and US$ 6,493.68, respectively, accounting for 46.66%, 14.11%, and 60.77% of per capita disposable income (PCDI) in Jiangsu province, respectively. The disease burden for HEV-infected inpatients with hepatitis B was significantly higher than that for other inpatients. The average EQ-5D utility value of 1152 HEV-infected inpatients was 0.72 ±â€¯0.18 quality-adjusted life years (QALYs) and the average EQ-visual analogue score (EQ-VAS) was 0.66 ±â€¯0.17 points. Multivariate analysis showed that the direct economic burden and the total economic burden were influenced by variables such as hospitalization days, outcomes, past history of other diseases, and regions (P < 0.05). It was estimated the direct economic burden, the indirect economic burden, and the total economic burden for all HEV-infected inpatients in Jiangsu province in 2018 was approximately US$ 9.2 million, US$ 2.8 million and US$ 12.0 million, respectively. CONCLUSION: The disease burden of HEV infection in Jiangsu province is severe, and more attention should be paid to the prevention of hepatitis E and the treatment of comorbidities.

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.

A Cluster of Bunyavirus-Associated Severe Fever With Thrombocytopenia Syndrome Cases in a Coastal Plain Area in China, 2015: Identification of a Previously Unidentified Endemic Region for Severe Fever With Thrombocytopenia Bunyavirus.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a typical tick-borne, natural focal disease. The natural foci of SFTS were considered to exist in hilly and mountainous areas before 2015. A cluster of 3 patients exposed to a patient with a fulminant disease consistent with SFTS occurred from July to August 2015 in Dongtai County, which is characterized by alluvial plains; this prompted investigation. METHODS: The epidemiological, clinical, and laboratory features of 4 patients in the cluster were analyzed. Serum samples from the indigenous healthy population and native domesticated animals were collected to conduct laboratory tests, along with small wild animals and ticks. RESULTS: In 3 secondary case patients, high fever, thrombocytopenia and leukopenia developed within 8-13 days after contact with blood or bloody secretions from the index patient; SFTS was then diagnosed by means of reverse-transcription polymerase chain reaction. Genomic sequencing and analysis of S and L segments of 2 viral strains isolated from 2 secondary case patients showed that they shared 99.8%-99.9% homology in nucleotide sequence. The seroprevalences among indigenous healthy population, native livestock, native poultry, and small wild animals was 0.74%, 17.54%, 6.67%, and 1.12%, respectively. Three questing ticks, 61 feeding ticks, and 178 small wild animals were collected in August 2015. Survey on tick density and seasonal fluctuation in 2016 showed that ticks were active from March to October. All ticks were identified as Haemaphysalis longicornis. Severe fever with thrombocytopenia bunyavirus (SFTSV)-specific RNA was detected in the ticks collected in 2016, and the minimum SFTSV infection rate in these ticks was 0.54% (1 of 185).Wild mammals and ticks collected in August 2015 tested negative for SFTSV-specific RNA. CONCLUSIONS: Aside from hilly or mountainous area, a coastal plain was identified as the natural foci of SFTSV in Dongtai County, China. The involvement of migration in the evolution of SFTSV might lead to a transregional transmission event of SFTSV.

Chemical vapor deposition growth of ReS2 nanowires for high-performance nanostructured photodetector.

Rhenium disulfide (ReS2) is a recently discovered next-generation transition metal dichalcogenides (TMDs) material that exhibits unique properties, which have resulted in its wide use in the fabrication of electronic and optoelectronic devices. Studies on ReS2 have mainly focused on the synthesis and applications of two-dimensional (2D) materials, while studies on one-dimensional (1D) ReS2 have yet to be reported. Herein, 1D single-crystal ReS2 nanowires have been synthesized successfully for the first time via chemical vapor deposition (CVD) and utilized as the active layer in a nanostructured photodetector. The crystal structure, phonon vibration modes, and chemical states of the single-crystal ReS2 nanowires have been investigated. Furthermore, the nanostructured photodetector using single-crystal ReS2 nanowires as the active layer and Ag nanowire networks as the transparent electrodes exhibited excellent performance, including a higher photoresponsivity (5.08 × 105), the highest external quantum efficiency (1.07 × 106), and the largest specific detectivity (6.1 × 1015) among ReS2 nanostructure-based photodetectors reported to date. Furthermore, the photodetector performance under vacuum conditions was investigated, which provides some information on the work mechanism of the ReS2 photodetector.

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.

Interleukin-32 stimulates osteosarcoma cell invasion and motility via AKT pathway-mediated MMP-13 expression.

As a pro-inflammatory cytokine, interleukin-32 (IL-32) is reported to play an important role in tumor development and progression. However, its effects on the invasion and motility of osteosarcoma cells remain elusive. The aim of the present study was to determine the molecular mechanisms of IL-32 in osteosarcoma cells using RT-PCR and western blot analysis. The results showed that IL-32 stimulation dose-dependently promoted the invasion and motility of osteosarcoma cells. Knockdown of endogenous IL-32 by siRNA inhibited osteosarcoma cell invasion and motility. Moreover, IL-32 induced the activation of AKT in a time-dependent manner. IL-32 stimulation was also capable of increasing the expression and secretion of matrix metalloproteinase (MMP)-13, which is involved in tumor invasion and metastasis. In addition, blockade of AKT activation suppressed IL-32-mediated invasion, motility and MMP-13 upregulation in osteosarcoma cells. Taken together, our results suggest that IL-32 stimulation promotes the invasion and motility of osteosarcoma cells, possibly via the activation of AKT and the upregulation of MMP-13 expression. Thus, IL-32 may serve as a marker for diagnosis, as well as for the treatment of osteosarcoma.

The association of MDM2 c.346G>A genetic variant with the risk of osteosarcoma in Chinese.

Previous studies suggest that the MDM2 gene is one of the most important candidate genes for influencing the risk of osteosarcoma. This study aims to investigate the potential association of MDM2 c.346G>A genetic variant with the risk of osteosarcoma in Chinese. A total of 738 subjects were recruited in this study. The genotypes of MDM2 c.346G>A genetic variant were detected by the created restriction site-polymerase chain reaction. Our data suggest that the MDM2 c.346G>A genetic variant is associated with the increased risk of osteosarcoma in the homozygote comparison (AA vs. GG: odds ratio [OR]=2.36, 95% confidence interval [CI] 1.30-4.28, χ2=8.35, p=0.004), recessive model (AA vs. GA/GG: OR=2.32, 95% CI 1.30-4.13, χ2=8.50, p=0.004), and allele comparison (A vs. G: OR=1.27, 95% CI 1.01-1.60, χ2=4.34, p=0.037). Results from this study indicated that the allele-A and genotype-AA of MDM2 c.346G>A genetic variant could be an increased risk factor for the susceptibility to osteosarcoma and might be used as a potential molecular marker for evaluating the risk of osteosarcoma.

Two-stage nicking enzyme signal amplification combined with DNAzyme amplification for the detection of bone morphogenetic protein 6 mRNA.

Highly sensitive detection of bone morphogenetic protein 6 (BMP6) mRNA is essential to monitor bone regeneration in the regenerating defects. In this work, we proposed a quantitative approach based on two-stage nicking enzyme signal amplification (NESA) and DNAzyme amplification for highly sensitive detection of BMP6 mRNA. The two-stage NESA involves two templates and two-stage amplification reactions under isothermal conditions. The first template contains two repeat sequences that could hybridize to the target RNA, triggering an exponential amplification. The amplified product was a short single-stranded DNA with the same sequence as the target RNA. The single-stranded DNA can trigger another linear NESA and produces a large amount of horseradish peroxidase (HRP)-mimicking G-quadruplex DNAzyme. This proposed assay showed a quantitative analysis of BMP6 mRNA in a wide range from 1 fM to 100 nM with a detection limit of 0.01 fM.

Prospective cohort study of the safety of an influenza A(H1N1) vaccine in pregnant Chinese women.

To monitor and evaluate the safety of the influenza A(H1N1) vaccine in pregnant women and its influence on the fetus and neonate, we performed a prospective study in which 122 pregnant Chinese women who received the influenza A(H1N1) vaccine and 104 pregnant women who did not receive any vaccine (serving as controls) were observed. The results indicated that the seroconversion rate in the vaccinated group was 90.4% (95% confidence interval [CI], 82.6% to 95.5%). The rate of adverse events following immunization in the pregnant women who received the influenza A(H1N1) vaccine was 3.3%. The spontaneous abortion rates in the vaccinated group and the unvaccinated group were 0.8% and 1.9%, respectively (exact probability test, P = 0.470), the prolonged-pregnancy rates were 8.2% and 4.8%, respectively (χ(2) = 1.041, P = 0.308), the low-birth-weight rates were 1.6% and 0.95%, respectively (exact probability test, P = 1.000), and the spontaneous-labor rates were 70.5% and 75%, respectively (χ(2) = 0.573, P = 0.449). All newborns who have an Apgar score of ≥7 are considered healthy; Apgar scores of ≥9 were observed in 38.5% and 57.7% of newborns in the vaccinated group and the unvaccinated group, respectively (χ(2) = 8.274, P = 0.004). From these results, we conclude that the influenza A(H1N1) vaccine is safe for pregnant women and has no observed adverse effects on fetal growth. (This study has been registered at ClinicalTrials.gov under registration no. NCT01842997.).

Vibrations of cylindrical objects obstructing a Poiseuille-type flow.

Using the lattice Boltzmann equation, we numerically studied the dynamics of a physical model system, the Poiseuille flow-induced vibrations (PFIV). At a moderate Reynolds number, for flows past a cylinder that is free to move in the cross-flow direction while being fixed in the streamwise direction, between two parallel walls, a variety of distinct vibration regimes involving symmetrical periodic vibration, deflective quasiperiodic vibration, and deflective periodic vibration with corresponding wake states were observed. The data analysis shows that the distribution of the lift coefficient depending on the blockage ratio plays an important role in such a system. A further study of the case of two side-by-side identical cylinders demonstrates the existence of two distinct cooperative vibrations of the cylinders, e.g., in-phase-synchronized vibration (IPSV) and anti-phase-synchronized vibration (APSV). The result reveals that there is a critical blockage ratio, beyond which a phase transition between IPSV and APSV occurs. For the phenomena observed here, PFIV can be considered a new type of vortex-induced vibration, and such a system is expected to find applications in fluid mixing.

[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.

Serologic study on the outbreak of acute upper respiratory tract infections caused by adenovirus 3.

From April to June, 2004, an outbreak of acute upper respiratory tract infections (AURTI) occurred in the north area of Jiangsu Province, China. Twenty throat swabs were collected with 13 of them presenting an adenovirus (Ad)-like cytopathogenic effect on HEp-2. These were verified as Ad by the electron microscope, direct immunofluorescence assay and Ad primer-mediated PCR. Moreover, they were identified as adenovirus type 3 (Ad3) by type-specific PCR and sequencing of the amplification products. Subsequent serologic studies were carried out to finally diagnose and document the outbreak. The neutralization test of paired serum of six in nine cases show obviously increased antibodies titers. The positive rate of IgM, IgG and recovery phase neutralization antibodies of the cases were 3.7%, 44.4% and 59.5% respectively while those of the controls were 0%, 8.3% and 33.3% respectively. The P values of Chi-Square were 0.510, 0.018 and 0.226 respectively. The concordance between IgG detected by ELISA and neutralization anti bodies detected by the neutralization test was 61.4% and the P value of Kappa was 0.070. By the serologic study, we can definitively diagnose that this outbreak of acute respiratory infections was caused by Adenovirus 3.

[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.

[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.