Neutralizing Antibody Responses against Five SARS-CoV-2 Variants and T Lymphocyte Change after Vaccine Breakthrough Infections from the SARS-CoV-2 Omicron BA.1 Variant in Tianjin, China: A Prospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.@*METHODS@#Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.@*RESULTS@#The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.@*CONCLUSION@#Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.

Distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region, 2008-2009 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the distribution of HIV-1 subtypes in Guangxi Zhuang Autonomous Region.</p><p><b>METHODS</b>294 participants who were infected by HIV-1 in 2008 - 2009 and residing in 13 cities in Guangxi were enrolled into this study. Epidemiological information showed that heterosexual transmission was the main transmitting route. 1584 bp full length gag gene, 3147 bp full length pol gene and 558 bp env (C2V3) fragments were amplified by using RT-PCR and then directly sequenced. NCBI genotyping tool and Mega 5.03 software were used to determine the HIV subtypes. Simplot and Recombinant HIV-1 Drawing Tool were used for the analysis of recombination.</p><p><b>RESULTS</b>A total of 739 sequences, including 270 gag, 246 pol and 223 env (C2V3), were successfully obtained from 294 plasma specimens. Genotypes of HIV from 272 participants were determined. CRF01_AE was found the dominant (77.6%), followed by CRF08_BC (10.7%) and CRF07_BC (7.4%). 7 unique recombinant forms, 4 subtype B (B') and 1 subtype G were also identified. No significant difference on the distribution of subtypes among different regions and ethnics was found. Among the 7 unknown recombinant forms, 6 strains were mosaic B and/or C fragments with CRF01_AE genome as the backbone, while one strain originated from CRF07_BC and CRF08_BC.</p><p><b>CONCLUSION</b>Currently, CRF01_AE was found the major subtype of HIV epidemic in Guangxi. New recombinant forms with CRF01_AE as backbones had been emerging, which called for serious attention.</p>

On-site assessment on the definition and classification of suspected cases in the manual of WHO Japanese Encephalitis Surveillance Standards / 中华流行病学杂志

Objective To assess the new edition of WHO Japanese Encephalitis (JE) Surveillance Standards (WHO Standards) based on syndrome surveillance data and to provide field evidence regarding the standards. Methods Based on syndrome surveillance data, acute encephalitis syndrome (AES) case was categorized, according to the WHO Standards. A cohort study was applied to estimate the AES definition set in the Standard and relative risk was computed to estimate the existence and intensity of statistical correlation between AES and JE cases. Percentage of attributable risk was counted to describe the coverage of AES for JE cases in the studied population. Sensitivity,specificity, Youden index and positive predictive value of AES components were calculated for the purpose of identifying the clinical values under the screening program. Results 1424 suspected cases were evaluated in the surveillance program and 1396 cases with ELISA result, of which 109 positive cases were detected. According to the "standardized" classification, a total of 706 cases in line with AES case deftuition, were categorized into 83 cases of JE, 425 cases of AES unknown and 198 cases of AES other agent. In the cohort study,a relative risk of 4.62 (95% CI:2.80-7.63 ) and the percentage of attributable risk as 78.35% (95% CI: 64.25% -86.89% ) were observed. Conclusion The AES definition for JE was significantly effecting on the screening programs and a strong correlation strength was observed in the study. AES syndrome could cover most of the JE cases. "Convulsions",with appreciative screening value, was recommended to be involved into the new version of the WHO Standards.

Surveillance and research on acute meningitis, encephalitis syndrome in Guangxi, China / 中华预防医学杂志

<p><b>OBJECTIVE</b>To estimate disease burden and epidemiological characteristics of acute meningitis/encephalitis, and provide the basis for the disease control strategy development.</p><p><b>METHODS</b>A syndrome surveillance system was established in Guigang city with a population of 5 020 000. For the suspected cases, serum and CSF were collected, and bacterial culture, latex agglutination test, real-time PCR and ELISA tests were carried out. All involved cases were identified to 6 categories according to WHO case definition.</p><p><b>RESULTS</b>1424 suspected cases were evaluated in a surveillance of 30 months, yielding the incidence, mortality and mortality of 11.35/100 000 (1424/12 546 500 person years), 0.43/100 000 (54/12 546 500 person years), 3.79% (54/1424) respectively. A total of 103 and 51 cases were confirmed for JE, bacterial meningitis, with a incidence of 0.82/100 000 (103/12 546 500 person years), 0.41/100 000 (51/12 546 500 person years). 96.10% (99/103) of JE cases and 37.30% (19/51) bacterial meningitis cases occurred in < 10 years old children and < 5 years old children. A clinical misdiagnosis rate of 19.42% (20/103) and 15.69% (8/51) were observed for JE and bacterial meningitis.</p><p><b>CONCLUSION</b>Acute encephalitis, meningitis syndrome can cause a higher burden of disease, of which the main components of viral encephalitis. Most of syndrome is occurred in summer and autumn, mainly reported in children of younger than 10 years old. A quite misdiagnosis would be made among meningitis and encephalitis syndrome cases.</p>

Analysis of human rabies high-occurrence factors in Guangxi from 2004 to 2008 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>Analysis the epidemiological characteristics on rabies cases occurred in Guangxi from 2004 to 2008 and summarize the result of healthy-dog infection rabies virus investigation from 2006 to 2008. Exploring the high-occurrence and correlated factors on rabies in Guangxi.</p><p><b>METHODS</b>Data collected from the National Disease Surveillance System and the National Active Surveillance System for Rabies from 2004 to 2008 and Data of healthy-dog infection rabies virus investigation from 2006 to 2008 were analyzed.</p><p><b>RESULTS</b>The total rabies cases were 2463 in Guangxi from 2004-2008 and average incidence rate was 0.98 per 100 thousand per year. There were 95 counties had rabies case reported, anyway more than 10 cases occurred county number was declined while less than 5 cases rose year by year. The rabies case incidence area was expanded and the cases in middle and west area of Guangxi rose significantly. Rabies cases were reported whole year and no seasonal peak. Human rabies cases mainly were farmers, students and children. Yanger than 20 years old and elder 40 years old were the highest age groups in the population of the investigation, 83.79% cases were attacked by dogs. 78.5% cases classification category III. 83.17% cases had exposed on the upper and lower limbs, 10.56% exposed to the head, face or neck. But 67.88% cases did not receive any PEP and only 18.31% cases vaccinated and 3.63% category III exposure cases combined administration of RIG. The incubation median was 60 days. The rabies virus infection rate among randomly collection healthy-dog brain samples from 2006 to 2008 was 1.92%, 0.93% and 0.89%.</p><p><b>CONCLUSION</b>Unsuccessful and inadequate PEP of patients were the main factors leading to the high-occurrence of human rabies in Guangxi. And there are a lot of infection rabies virus healthy-dogs alive in Guangxi also as a high-occurrence factor.</p>

A prospective study of the relationship between serum hepatitis B virus DNA and the risk of primary liver cancer / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the relationship between the serum hepatitis B virus (HBV) DNA and the risk of primary liver cancer (PLC).</p><p><b>METHODS</b>Farmers aged 30 to 55 years in Long An county were recruited in this study Blood samples were collected and the sera were tested for HBsAg using Enzyme-Linked ImmunoSorbent Assay (ELISA), and the HBsAg-positive sera were further tested for viral DNA using nested polymerase chain reaction (nPCR). The study subjects were divided into three groups. The first group was positive for both HBsAg and HBV DNA. The second group was positive for HBsAg but negative for HBV DNA. Age-, sex-, residence-matched HBsAg negative controls for group 1 and group 2 were enrolled in the third group. The cohort was followed up for four years.</p><p><b>RESULTS</b>The positive rate of HBsAg in these farmers was 14.52% (3975/27,379), and the HBV DNA positive rate in HBsAg positive subjects was 40.35% (1604/3975). The total PLC incidence rate in Group 1 and 2 was 672.45 /100,000 person-years (PY), significantly higher than that in Group3 (17.19 /100,000 PY). The relative risk (RR) was 39.123, and the 95% confidence interval (CI) was 9.018-159.146. The PLC incidence rate of Group 1 (984.03/100,000 PY) was significantly higher than that of Group2 (324.38 /100,000 PY). The RR was 3.034, and the 95% CI was 1.795-5.125. Multivariate analyses of Group1 and 2 with Cox model showed that sex, age, serum HBV DNA, and family history of PLC were independent risk factors of PLC.</p><p><b>CONCLUSION</b>HBV DNA and HBsAg positive subjects have a higher chance to develop PLC than HBV DNA negative-, HBsAg positive subjects.</p>

Expression of recombinant rubella virus E1 protein and initial application for detecting of antibody / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To apply recombinant rubella virus envelope protein-1 (E1) to detect human rubella virus IgG antibody.</p><p><b>METHODS</b>Rubella virus E1 protein was expressed in E. coli, purified E1 protein was used as the antigen for the detecting of anti rubella in human sera in the way of enzyme linked Immunosorbant assay (ELISA).</p><p><b>RESULTS</b>The antigenicity of the recombinant protein was checked by WHO rubella sera panel. We detected 200 sera samples, which came from Guangxi Guilin. 93% of these samples were positive.</p><p><b>CONCLUSION</b>The antigenicity of recombinant E1 is a satisfied candidate antigen for the detecting of human rubella virus antibody. The prevalence of anti rubella virus IgG in Guangxi is 93%. It is at the some level compared with other provinces in China.</p>

Dynamic study on the anti-HBs level of immunized children born to HBsAg-positive and HBsAg-negative mothers in hyperendemic area of hepatitis B / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of the anti-HBs level among immunized newborn infants born to HBsAg-positive and HBsAg-negative mothers in hyper-endemic area of Hepatitis B.</p><p><b>METHODS</b>Infants who were regularly vaccinated with Hepatitis B vaccine and tested to be anti-HBs positive were divided into two groups according to HBsAg-positive or negative mothers in Long-an, Guangxi. Each subject was followed up 3 times during age 5 to 8. SPRIA was used to test HBsAg, anti-HBs and anti-HBc. Results During the follow-up period, positive rates of anti-HBs in children born to HBsAg-positive mothers ranged between 52.00% and 78.00%, and those with HBsAg-negative mothers was between 43.84% and 54.74%. GMT in two groups was between 55.36 mIU/ml and 95.66 mIU/ml as well as between 39.90 mIU/ml and 65.47 mIU/ml, respectively. There was no statistical significance in both positive rates and GMT between age groups. The anti-HBs level in the follow-up period of children born to HBsAg-positive mothers was higher than that of those born to HBsAg-negative mothers in the same age group. In the age group of 6-8 years with HBsAg-negative mothers, the positive rates in the follow-up period of children with high anti-HBs titers in the primary vaccination were 2.29-2.84 times of those with low titers. The anti-HBs titer of children in a follow-up period was lower than that in the primary vaccination, no matter whether they were born to HBsAg-positive mothers. However, the decline rate of children born to HBsAg-negative mothers was significantly higher than those born to HBsAg-positive mothers (84.91% vs. 61.54%; chi2 = 28.7982, P = 0.000). The incidence rate (25.64%) of a 4-fold increase in antibody titers of children born to HBsAg-positive mothers was significantly higher than that of children born to HBsAg-negative mothers (7.37%) from the primary vaccination to the follow-up period (chi2 = 6.7661, P = 0.009) with was 3.5 times of the latter. Subjects with HBsAg seroconvertion were those with low anti-HBs titers in primary vaccination.</p><p><b>CONCLUSION</b>The anti-HBs level decreased slowly in successfully immunized children from age 5 to 8. The chance of natural booster yielded by natural infection increased in immunized children born to HBsAg-positive mothers. The anti-HBs level in the primary vaccination played an important role in prevention of seroconversion of HBsAg.</p>

Study on the variations of hepatitis B virus status among people having received hepatitis B vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the epidemiological pattern and trends of hepatitis B virus (HBV) in the area where people had been immunized by HBV vaccine for long time.</p><p><b>METHODS</b>Through cluster sampling and cross-sectional study, relative information and blood samples from people in Long-an county by families were collected. Signals of HBV infection were tested by solid-phase reverse immunosorbent test.</p><p><b>RESULTS</b>(1) The average HBsAg positive rate was 7.5% with anti-HBs as 44.5 %, and anti-HBc as 47.8%. The positive rates of HBsAg and anti-HBc among 0-19 year-olds were lower than those of > or = 20 year-olds. (2) The positive rates of HBsAg, anti-HBc and HBV infection among HBV vaccine immunized group were 2.8%, 12.0% and 12.5% respectively, comparing with which among the un-immunized group as 10.2%, 69.8% and 71.2% respectively. (3) The HBsAg positive rate of male was higher than the female's but with no significant difference of anti-HBs and anti-HBc between different sexes. (4) The average HBsAg positive rate of 0-19 years old group was only 2.4%, while that of 20-30 years old group was 13.6%-17.7% and dropped from 60 years old group and on. The anti-HBs positive rate of 0-19 years old people started to drop significantly by age. The anti-HBs and anti-HBc positive rates of > or = 20 years people were showing a rising trend by ages.</p><p><b>CONCLUSION</b>It seemed obviously that the HBV epidemiological patterns had changed after HBV vaccine had been universally used for long time in newborns. The age peak of infection had been pushed backward for nearly 20 years. It had been proved that the HBV vaccine immunization program had obtained excellent efficacy.</p>

Variations of hepatitis B virus infection epidemic pattern after long-term HBV vaccine immunization / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the epidemic pattern and trend of HBV infection in the area where the people had been immunized by HBV vaccine for 20 years.</p><p><b>METHODS</b>The whole sampling method was applied in combination with cross-sectional investigation. Blood samples were taken from every member of families. Markers of HBV infection were determined by using solid-phase radioimmunoassay (SPRIA).</p><p><b>RESULTS</b>(1) The average HBsAg positive rate was 7.5%. The positive rate of markers for HBV infection of 0-19 years old subjects were lower than those of > or = 20 years old subjects. (2) The positive rate of HBsAg of 0-19 years old subjects in 1985 was higher than that in 2005. The anti-HBs positive rate in 1985 stemmed to be higher with age. It was 12.4% in 1- age group to 53.8% in >60 years age group. While the result of 2005 showed that the anti-HBs positive rate of 0-19 years old subjects dropped with age. The anti-HBc positive rate in 1985 also tended to be higher with age. But the result of 2005 showed that the rate of 0-19 years old subjects was just 1.4% to 16.8%.</p><p><b>CONCLUSION</b>The epidemic patterns of HBV infection have had significant variations in the target population. HBV vaccine immunization has obtained excellent efficacy.</p>

Efficacy of hepatitis B vaccination on hepatitis B prevention and on hepatocellular carcinoma / 中华流行病学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of hepatitis B vaccination on hepatitis B prevention and on hepatocellular carcinoma.</p><p><b>METHODS</b>Birth cohort study, cross-sectional seroepidemiological survey, and surveillance of hepatitis B (HBV) and hepatocellular carcinoma were used to evaluate the efficacy of hepatitis B vaccination.</p><p><b>RESULTS</b>During the 14 years after hepatitis B vaccination, the HBsAg positive rates were found to be 0.7% - 2.9%, with an average of 1.5%, and the protective rates were 83.5% - 96.6%. Hepatitis B virus infection rates of children immunized with hepatitis B vaccine were 1.1% - 5.1%, with an average of 2.2% and the protective rates of 93.5% - 98.4%. 15 years after hepatitis B vaccination, the incidence of hepatitis B dropped from 3.27/10 000 to 0.17/10 000, a 94.8% decrease, in the group of 0 - 19 year-olds.</p><p><b>CONCLUSION</b>The universal infant hepatitis B vaccination has proved to be effective in reducing the incidence rate of acute hepatitis B as well as the mortality of hepatocellular carcinoma.</p>

Core promoter mutations of HBV isolated from patients with chronic hepatitis B in Guangxi / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the relationship between HBV core promoter mutations and liver damage or HBeAg status.</p><p><b>METHODS</b>Nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA core promoter in 59 sera from patients with chronic hepatitis B in Guangxi, then the HBV DNA positive products were sequenced by direct sequencing.</p><p><b>RESULTS</b>The HBV DNA positive rate of was 59.3%(35/59). All the patients were infected by mutants. The commonest mutation was the double mutation (A --> T at nt1762 and G --> A at nt1764), counting for 57.1% (20/35). The next was C --> G at nt1799, counting for 54.4% (19/35), but this was no function. A --> G at nt1752 (resulting in isoleucine to valine) was seen in 37.1% (13/35) of the HBV DNA positive patients, and T --> C at nt1753 was seen in 20% (7/35). The significant difference in the frequency of T1762A1764 mutant was found between HBeAg positive patients (31.3%) and negative patients (79.0%).</p><p><b>CONCLUSIONS</b>HBV core promoter mutations are common among patients with chronic hepatitis B in Guangxi. T1762A1764 mutant is associated with HBeAg status and chronic hepatitis.</p>

Long-term efficacy of infant hepatitis B immunization program / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the long-term efficacy of infant hepatitis B (HB) immunization program on preventing hepatitis B virus (HBV) infection, and to assess its impact on the incidence of HB in children.</p><p><b>METHODS</b>Since 1986, the universal HB vaccination for newborn babies with standard, pediatric dose had been launched without serologic prescreening of pregnant women for HBsAg, in a high endemic county of Long-An. A hepatitis surveillance system was set up to evaluate the possible impact on the incidence of hepatitis B. To serologically evaluate the effectiveness of the program, a stratified random sampling of 1000 children in 1987 birth cohorts, who received plasma-derived HB vaccine, was recruited for long-term follow up at the age of 1 to 13 years. A cross-sectional seroepidemiological survey was conducted in the county in 1985, before the program, and in 2001, for 1551 children born in 1996-2000 who were administered yeast recombinant HB vaccine.</p><p><b>RESULTS</b>During the 1 to 13 years after the program, the rates of HBsAg-positive were 0.7% to 2.9% with an average of 1.7% and the protective rates were 83.5% to 96.6%. HBV infection rates were 1.1% tp 5.1% with an average of 2.4% and the protective rates were 93.5% to 98.4%. For the population aged 1 to 4 years who were immunized with recombinant HB vaccine, HBsAg positive rates were 1.8% to 2.4% with an average of 2.0% and the protective rates were 78.4 to 85.2%. 14 years after the program, the cumulative incidence of acute hepatitis B in the children aged 1 to 14 years fell to 1.5 cases per 100,000 children, down 91.8% as compared with that in 1985 to 1987. However, the cumulative incidence of 14.4 cases per 100,000 population in unvaccinated children was not significantly different from that in the history controls. Acute hepatitis B children had not been reported, showing that the vaccination program was 100% protective in children.</p><p><b>CONCLUSION</b>The universal infant HB vaccination program in a hyperendemic area has proved to be effective in controlling HBV infection and decreasing the incidence of acute hepatitis B in children. Booster dose is unnecessary in 13 years after the immunization. The protective efficacy of yeast recombinant HB vaccine is similar to that of plasma-derived HB vaccine.</p>

Prevalence of hepatitis B virus core promoter mutant isolated from asymptomatic carriers from areas with higher and lower incidence of hepatocellular carcinoma in Guangxi / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To understand the prevalence of HBV core promoter mutant (T1762 A1764 mutant) isolated from asymptomatic carriers from areas with higher and lower incidence of hepatocellular carcinoma (HCC) in Guangxi.</p><p><b>METHODS</b>A nested polymerase chain reaction (nPCR) was used for amplification of HBV DNA core promoter in sera, and then HBV DNA nPCR products were sequenced by direct sequencing.</p><p><b>RESULTS</b>The results show that 50.6% (39/77) of all HBV asymptomatic carriers were positive for HBV DNA HBV DNA positive rates of the samples from HCC higher incidence area, Longan County, and from lower incidence area, Guilin city were 55.6% (20/36) and 46.3% (19/41), respectively. HBV core promoter mutants could be seen in 35% in Longan positive samples and 47.4% in Guilin. The common mutations in both regions were all double mutations (nt 1,762 A-->T; nt 1,764 G-->A), accounting for 25% and 21%, respectively. The difference of the double mutant between Longan County and Guilin city was not significant (P>0.05).</p><p><b>CONCLUSIONS</b>These data implicated that the prevalence of HBV core promoter mutant isolated from asymptomatic carriers may not be correlated with the incidence of HCC in Guangxi.</p>