Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine. METHODS: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247. FINDINGS: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33). INTERPRETATION: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity. FUNDING: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological.

Antimicrobial susceptibility of Streptococcus sp. to quinupristin-dalfopristin in China.

This study aimed to determine the in vitro activity of quinupristin-alfopristin against Streptococcus sp. isolated in China. This agent is not yet available for clinical use, but it has been tested against a high proportion of resistant Staphylococcus aureus strains. A total of 156 streptococcal isolates, which were recovered from various geographic areas and diseases, were tested using the Etest (AB Biodisk, Solna, Sweden). Quinupristin-alfopristin showed excellent activity against all of the tested streptococci isolates. These results provide useful data for the clinical use of quinupristin-alfopristin in China.

Safety observation study on haemophilus influenza type B conjugate vaccines injected at different sites in Chinese infants.

In the present study, the safety of Haemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.

Molecular epidemiological characteristics of Streptococcus pyogenes strains involved in an outbreak of scarlet fever in China, 2011.

OBJECTIVE: To investigate molecular characterization of streptococcus pyogenes isolates involved in an outbreak of scarlet fever in China in 2011. METHODS: Seventy-four Streptococcal pyogenes involved in an outbreak of scarlet fever were isolated from pediatric patients in the areas with high incidence in China from May to August of 2011. Emm genotyping, pulsed-field gel electrophoresis (PFGE), superantigen (SAg) genes and antimicrobial susceptibility profiling were analyzed for these isolates. RESULTS: A total of 4 different emm types were identified. Emm12 was the most prevalent type which contained four predominating PFGE patterns corresponding to four different virulence and superantigen profiles. Emm12 (79.7%) and emm1 (14.9%) accounted for approximately 94% of all the isolates. The speA gene was all negative in emm12 isolates and positive in emm1 isolates. All strains were resistant to erythromycin, and 89.4% of them were resistant to erythromycin, tracycline, and clindamycin simultaneously. CONCLUSION: Several highly diversified clones with a high macrolide resistance rate comprise a predominant proportion of circulating strains, though no new emm type was found in this outbreak. The data provide a baseline for further surveillance of scarlet fever, which may contribute to the explanation of the outbreak and development of a GAS vaccine in China.

[The sexual behavior characteristics and STD infection status of women who have sex with women in Beijing].

OBJECTIVE: To study sexual behavioral characteristics, infection status of HIV and sexually transmitted infections (STDs) among women who have sex with women (WSW) in Beijing. METHODS: A total of 150 WSWs were recruited by snowball sampling in several main types of activity sites of WSW (including NGOs, salons, bars, etc.) in Beijing during September 2010 to April 2011. Information on demographic factors, sexual behavioral characteristics, infection status of STDs, and use of medical care were collected by questionnaire investigation. Serum samples, vaginal and cervical swabs were taken for each subject to test HIV, hepatitis B (HBV), hepatitis C (HCV), syphilis, herpes simplex virus (HSV), neisseria gonorrhoeae, chlamydia trachoma, bacterial vaginosis, trichomonas vaginalis and mycotic vaginitis. RESULTS: The age range of the subjects was from 19 to 46 years old. Approximately 82.67% (124/150) of them aged 20 to 29 years old, and 54.00% (81/150) were unmarried. Approximately 76.67% (115/150) had an education level of college degree or above, and 70.67% (106/150) were migrants. Approximately 66.66% (100/150) of the subjects considered themselves as homosexual, 28.00% (42/150) as bisexual. The age at first homosexual sex ranged from 11 to 30 years old. The median of number of female sex partners in last 1 year was 1, and 33.78% (50/148) of the subjects had 2 or more female sex partners. Approximately 20.27% (30/148) of the subjects applied sex instruments, of which 66.67% (20/30) never or seldom used condoms. Hand-clitoris and hand-vagina contacts were the main types of woman-to-woman sex, accounting for 91.22% (135/148). 12.00% (18/150) of the subjects had sex with men during last year. Among them, 50.00% (9/18) used condoms at last heterosexual sex, and 66.67% (12/18) never or seldom used condoms at last heterosexual sex in past 1 year. One subject provided paid sex service for men, and used condoms every time. In the past one year, 45.33% (68/150) of the subjects had symptoms of STDs, but only 36.76% (25/68) of them sought medical care. The infection rate of STDs was 34.67% (52/150). The infection rates of NG and GV were both 16.11% (24/149), and those of mycotic vaginitis, chlamydia trachoma, and TV were 8.72% (13/149), 4.03% (6/149), and 0.67% (1/150), respectively. The numbers of subjects tested positive for HBV, HCV, and syphilis were all 1. No subjects were found HIV positive or HSV-2 positive. CONCLUSION: Multiple sexual partners and heterosexual sex behavior were common among WSW in Beijing. More than 1/3 of the subjects were infected with STD.

[Incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men in Beijing].

OBJECTIVE: To study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing. METHODS: A total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test. RESULTS: A total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion. CONCLUSION: The seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.

[Analysis of safety and effects on the oral whole cell/recombinant B subunit cholera vaccine in university students and workers].

OBJECTIVE: To evaluate the safety, immunogenicity and protective efficiency of the oral whole cell/recombinant B subunit cholera vaccine in Beijing Olympic volunteers and workers. METHOD: Analyzing the incidence rate of adverse reaction and Protective Rate (PR) after taking the vaccine in Olympic volunteers in 6 universities in Beijing; comparing the anti-cholera toxin (CT) detected with ELISA prior and after taking the vaccine in Olympic workers. RESULTS: The total rate of adverse reaction of Olympic volunteers was 0.38%; the main side effects were gastrointestinal symptoms, such as bellyache and diarrhea which were mild and temple; the acute diarrhea incidence rate of Olympic volunteers after taking the vaccine was significantly lower than those not taking it, the PR was 76.27%; the positive rate of anti-CT of Olympic workers after taking the vaccine was significantly higher than those before taking it, the levels of anti-CT titers declined after 6 months since they had taken the vaccine. CONCLUSION: The results from above two observed population indicate that the oral rBS-WC cholera vaccine is efficient and safe.

Impact of Antiretroviral Therapy on the Spread of Human Immunodeficiency Virus in Chaoyang District, Beijing, China: Using the Asian Epidemic Model.

BACKGROUND: Successful antiretroviral therapy (ART) has been demonstrated to be effective in reducing the infectivity of human immunodeficiency virus (HIV). We conducted a study to predict the potential effect of ART on the spread of HIV in Chaoyang District, Beijing, China, using the Asian Epidemic Model (AEM). METHODS: The AEM baseline workbook was used to determine the current infection status and to project the future spread of HIV under current conditions. We changed the input on the ART coverage from 2014 to 2025 and also modified the treatment eligibility in the AEM intervention workbook, in order to allow for analysis of the projected downstream impact of ART. RESULTS: By gradually increasing the ART coverage rate from 29.7% (rate of 2013) to 40.0%, 50.0%, 60.0%, 70.0%, 80.0%, and 90.0% (at CD4+ ≤350 cells/µl), and by changing the dates of coverage from 2014 to 2020, the number of new infections showed a cumulative decline of 0.60%, 1.59%, 2.94%, 5.33%, 9.32%, and 14.98%, respectively. After 2020, the projected rates of infection rebounded slightly, so with the exception of the years with very high coverage (90.0%), new infections continued to decrease. When we changed the initial threshold of therapy to CD4+ cell counts ≤500 cells/µl, new infections decreased 6.00%, 11.64%, 15.92%, 21.11%, 26.92%, 33.05%, and 38.75%, respectively, under varying ART coverages. CONCLUSION: Our study demonstrates that the early initiation of ART for people living with HIV/acquired immune deficiency syndrome (AIDS) has a positive effect in slowing the spread of HIV.

Immunogenicity and safety of three 2010-2011 seasonal trivalent influenza vaccines in Chinese toddlers, children and older adults: a double-blind and randomized trial.

The 2009 influenza A(H1N1) pandemic strain was for the first time included in the 2010-2011 seasonal trivalent influenza vaccine (TIV). We conducted a double-blind, randomized trial in Chinese population to assess the immunogenicity and safety of the 2010-2011 TIV manufactured by GlaxoSmithKline and compared it with the counterpart vaccines manufactured by Sanofi Pasteur and Sinovac Biotech. Healthy toddlers (6-36 mo), children (6-12 y) and older adults (≥60 y) with 300 participants in each age group were enrolled to randomly receive two doses (toddlers, 28 d apart) or one dose (children and older adults). The immunogenicity was assessed by hemagglutination-inhibition (HI) assay. The solicited injection-site and systemic adverse events (AEs) were collected within 7 d after vaccination. All the three TIVs were well-tolerated with 15.1% of participants reporting AEs, most of which were mild. No serious AEs and unusual AEs were reported. Fever and pain were the most common systemic and injection-site AEs, respectively. The three TIVs showed good immunogenicity. The seroprotection rates against both H1N1 and H3N2 strains were more than 87% in toddlers after two doses and more than 95% in children and more than 86% in older adults after one dose. The seroprotection rates against B strain were 68-71% in toddlers after two doses, 70-74% in children and 69-72% in older adults after one dose. In conclusion, the three 2010-2011 TIVs had good immunogenicity and safety in Chinese toddlers, children and older adults and were generally comparable in immunogenicity and reactogenicity.

[Study on the incidence of HIV and associated risk factors through a prospective cohort among men who have sex with men in Beijing, China].

OBJECTIVE: To investigate the dynamic change and associated risk factors of HIV sero-conversion rate in Beijing. METHODS: 809 sero-negative men who have sex with men (MSM) were recruited in the cohort from August to December in 2009. HIV sero-antibody, medicinal examination and behavior questionnaire interview were carried out every six months. RESULTS: 962 MSM with overall baseline prevalence of HIV infection as 6.34% (61/962) together with 809 sero-negative MSM, were enrolled in the cohort. Of the 809 sero-negative participants, 95.1% (769/ 809), 85.5% (692/809) and 71.0% (574/809) of them were retained in the 6-month, 12-month and 18-month follow-up visits, with 19, 29 and 17 of them became HIV sero-conversion at 6-month, 12-month, and 18-month follow-up visits and the HIV incidence rates appeared to be 5.47, 12.37 and 6.86 per 100 person-years respectively. The HIV incidence was 7.59 per 100 person-years in the 18 months follow-up visit. Factors including: younger than 25-years old (HR = 2.32, 95%CI: 1.39 - 3.87), having more than 8 MSM partners (HR = 2.50, 95%CI: 1.49 - 4.20), less than 2000¥ every month income (HR = 1.76, 95%CI: 1.05 - 2.95), having more than 4 homosexual partners in the last six months (HR = 3.50, 95%CI: 2.11 - 5.81), showing phimosis and redundant prepuce (HR = 2.47, 95%CI: 1.50 - 4.07) as well as positive syphilis test (HR = 2.62, 95%CI: 1.53 - 4.49) etc., were significantly associated with HIV incidence. CONCLUSION: High HIV incidence was shown among MSM in Beijing and had spread fast in this population, calling for more favorable prevention measures to be taken.

Optimal vaccination strategies for 2009 pandemic H1N1 and seasonal influenza vaccines in humans.

A randomized clinical trial was conducted to assess whether the immunogenicity of seasonal and pandemic (H1N1/09) influenza vaccines is affected by the order of vaccine administration. 151 healthy adult volunteers were randomized into three groups. All groups received one dose (15 µg haemagglutinin) each of a pandemic H1N1 vaccine and a seasonal trivalent vaccine. Group 1 received the pandemic H1N1 vaccine first, followed by the seasonal vaccine 21 days later. Group 2 received vaccinations in vice versa and Group 3 received both vaccines simultaneously. Post-vaccination blood samples were collected to determine the immunogenicity by hemagglutination-inhibition (HI), microneutralization (MN), and B cell ELISPOT assays. All three vaccination strategies were well-tolerated and generated specific immune responses. However, we found a significant difference in magnitude of antibody responses to pandemic H1N1 between the three groups. Pre- or co-vaccination with the seasonal flu vaccine led to a significant reduction by 50% in HI titre to pandemic H1N1 virus after pandemic vaccination. Pre- or co-vaccination of pandemic H1N1 vaccine had no effect on seasonal flu vaccination. MN and ELISPOT assays showed a similar effect. Vaccination with pandemic H1N1 vaccine first is recommended to avoid an associated inhibitory effect by the seasonal trivalent flu vaccine.

[Study on the relationship between behavioral factors, psychological status and HIV infection among men who have sex with men in Beijing.].

OBJECTIVE: To study the prevalence and risk factors of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in Beijing. METHODS: A sample of 550 MSM was recruited between March and June in 2008 in Beijing. Interviewer-administered interviews were conducted to collect information on demographics and behaviors. Blood samples were collected to test for HIV, syphilis, HBsAg and HCV infections. Chi-square test and logistic regression model were used to identify risk factors associated with HIV infection. RESULTS: Of the 550 eligible MSM surveyed, HIV prevalence appeared to be 4.5% (25/550). Data from multivariate logistic regression analysis demonstrated that factors as reporting unprotected anal intercourse with causal male sexual partners in the last month (chi(2) = 11.381, P = 0.001), rectal douching after homosexual anal intercourse in the past three months (chi(2) = 5.326, P = 0.021), feeling sad in the last month (chi(2) = 8.809, P = 0.003) were significantly associated with HIV infection. CONCLUSION: Health education on safer sex behavior and mental health care should be taken to hinder the speed of HIV transmission among MSM.

[The effective evaluation on the supplementary immunization activities among the migrant pre-school children in Chaoyang District of Beijing].

OBJECTIVE: To evaluate the effect of Supplementary Immunization Activities (SIAs) among the migrant preschool children in Chaoyang district of Beijing since 2005 to 2007, and to provide reference for formulating the strategies for Expanded Program on Immunization (EPI). METHODS: The descriptive epidemiology was used to analyze the data of SIAs among the migrant preschool children in Chaoyang district since 2005 to 2007. RESULTS: The SIAs data demonstrated an increasing number of the floating preschool children in Chaoyang district from 2005 to 2007, and the increase rate of year-on-year in 2006 to 2007 was 12.67% and 4.60% respectively. The registration rates of immunization card and identification among the floating preschool children increased by years from 2005 to 2007. The zero-dose rates of Oral Polio Vaccine (OPV), Measles Vaccine (MV), Diphtheria-Pertus-sis-Tetaus vaccine (DPT), Meningococcal Polysaccharide Vaccine (MPV) and Japanese Encephalitis Vaccine (JEV) showed a decrease trends since 2005 to 2007. The age special incidence rate and proportion of vaccine-preventable diseases for the people who were 1- 4-years-old decreased. CONCLUSION: It is an effective management pattern that the government plays a dominated role in Supplementary Immunization Activities (SIAs).

[Case-control study on the relationship between varicella vaccine inoculation and varicella morbidity].

OBJECTIVE: To analyse and find out the influence of varicella vaccine inoculation to varicella morbidity. METHODS: The case-control study was conducted. During October 1st 2006 to July 31st 2007, 193 varicella cases were identified, and 342 control subjects were matched. RESULTS: 1. The proportion of nonvaccinated in case group was higher than that of control group (odds ratio 1.49, 95% confidence interval 0.99-2.24, P=0.043). 2. The morbidity to the people who received one dose varicella vaccine was obviously higher than that of people who reiceived more than 2 dose (odds ratio 3.04, 95% confidence interval 1.25-7.72, P=0.007). 3. Significant differences were not observed between the domestic vaccine and the impoted vaccine (odds ratio 1.38, 95% confidence interval 0.53-3.71 P=0.483). 4. Clinical symptom of the vaccine was lighter than that of the unvaccinated, and rash was not typical. CONCLUSION: 1. Inoculation varicella vaccine was effective measures to prevent varicella. 2. The risk to get varicella of one-dose vaccinated was higher than that of more than 2-dose vaccinated. 3. The effectiveness of domestic varicella vaccine was as high as impoted vaccine. 4. The clinical symptom of varicella would be alleviated if the person had vaccinated.

[Observation on two kinds of recombinant hepatitis B vaccines used in populations with different immunity].

OBJECTIVE: To evaluate the immunity status on different hepatitis B vaccines currently being used in Beijing. METHODS: College students who had not received hepatitis B vaccine and children who had received whole-course immunization at birth, were tested HBsAg, anti-HBs and anti-HBc. All the test-negative cases were served as research subjects. 3 doses recombinant hepatitis B vaccines were given to the college students, following the 0, 1, 6 months schedule. Among which, 140 cases received recombinant beer yeast hepatitis B vaccine (BY vaccine, 10 microg, 5 microg, 5 microg), and 140 cases with recombinant hansenula polymorpha hepatitis B vaccine (HP vaccine, 10 microg, 10 microg, 10 microg). 1 dose was given for boosting immunization to 98 children, in which 49 cases with BY vaccine (5 microg) and 49 cases with HP vaccine (10 microg). Anti-HBs was tested 1 month after. RESULTS: The total positive (> or = 10 mIU/ ml) rate was lower among BY vaccine group than HP vaccine group for the college students (93.5 %, 99.3% , P<0.05), but no statistical difference on GMT(81.2 mIU/ml, 94.6 mIU/ml, P>0.05) was found. For males, the positive rate and GMT were lower in BY vaccine group than in HP vaccine group (85.7% ,100.0%, P<0.01)(56.6 mIU/ml, 98.6 mIU/ml, P<0.01), but with no statistical difference for females (98.8%, 98.5%, P> 0.05) (103.4 mIU/ml, 90.3 mlU/ml, P> 0.05). For the same vaccine, the positive rate and GMT were lower in males than in females when using BY vaccine (85.7% , 98.8%, P<0.01)(56.6 mIU/ml,103.4 mIU/ml, P< 0.01), but no statistical difference was found on HP vaccine(100.0%, 98.5%, P>0.05)(98.6 mIU/ml, 90.3 mIU/ml, P>0.05). The positive rate of anti-HBs was decreasing along with age among the children who had received a whole-course immunization at birth (P <0.01). 98.6 % of the 70 negative cases appeared positive conversion after receiving 1 dose and the GMT raised significantly by 15 times. No statistical difference was found between the two kinds of vaccines(100.0%, 97.4%, P>0.05)(80.5 mIU/ml, 68.5 mIU/ml, P>0.05). CONCLUSIONS: The type of vaccine and sex were related to the effects, better with HP vaccine than BY vaccine in males but was the same for females in adults receiving basic immunization according to the conventional doses. Both kinds of vaccines were ideal when children receiving boosting immunization. The immune memory was good for persons who had received primary immunization with recombinant vaccine but antibody appeared negative conversion. It was not necessary to boost immunization within 6 years after a whole-course immunization with recombinant hepatitis B vaccine in infancy.

[Application of exponent curve model to study the hepatitis B DNA recombinant yeast derived vaccine antibody levels].

OBJECTIVE: To introduce exponent curve model methods in the study of the hepatitis B vaccine antibody level. METHODS: After the China made vaccine of hepatitis B DNA recombinant yeast derived vaccine (YDV) had been carried out for 5 years, data on the anti-HBsAg's titer were used to construct an exponent curve model. When the vaccination program had been carried out for 8 years, the predicating results of the model were further tested by observed number. RESULTS: The exponent curve model was Y = 165.67 exp (-0.019X) and the R(2) was 0.98. After 8 years, the practical observed number became 35 mIU/ml, and the predicating result of the model was 27 mIU/ml, 8 mIU/ml lower than the observed number. When the vaccine had been carried out for 12 years, the predicating results of the model became 10.74 mIU/ml, still higher than 10 mIU/ml but was still in the effective range. CONCLUSION: An exponent curve model could be constructed, as long as the data of the antibody's titer was in accordance with the tendency of exponent curve. The model could be used to predict the persistence lever of vaccine antibody under certain conditions. The results showed that after 8 years, the predicting results of the model were reliably lower than the observed number.