Identification and control of a poliomyelitis outbreak in Xinjiang, China.

BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011.

BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.

Safety of influenza A (H1N1) vaccine in postmarketing surveillance in China.

BACKGROUND: On September 21, 2009, China began administering vaccines, obtained from 10 different manufacturers, against 2009 pandemic influenza A (H1N1) virus infection in priority populations. We aimed to assess the safety of this vaccination program. METHODS: We designed a plan for passive surveillance for adverse events after immunization with the influenza A (H1N1) vaccine. Physicians or vaccination providers were required to report the numbers of vaccinees and all adverse events to their local Center for Disease Control and Prevention (CDC), which then reported the data to the Chinese CDC through the online National Immunization Information System's National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC. RESULTS: A total of 89.6 million doses of vaccine were administered from September 21, 2009, through March 21, 2010, and 8067 vaccinees reported having an adverse event, for a rate of 90.0 per 1 million doses. The age-specific rates of adverse events ranged from 31.4 per 1 million doses among persons 60 years of age or older to 130.6 per 1 million doses among persons 9 years of age or younger, and the manufacturer-specific rates ranged from 4.6 to 185.4 per 1 million doses. A total of 6552 of the 8067 adverse events (81.2%; rate, 73.1 per 1 million doses) were verified as vaccine reactions; 1083 of the 8067 (13.4%; rate, 12.1 per 1 million doses) were rare and more serious (vs. common, minor events), most of which (1050) were allergic reactions. Eleven cases of the Guillain-Barré syndrome were reported, for a rate of 0.1 per 1 million doses, which is lower than the background rate in China. CONCLUSIONS: No pattern of adverse events that would be of concern was observed after the administration of influenza A (H1N1) vaccine, nor was there evidence of an increased risk of the Guillain-Barré syndrome.

[Analysis on reported data of immunization monitoring system for category II vaccine in China, 2012].

OBJECTIVE: To analyze the immunization status of category II vaccine in Chinese Mainland in 2012. METHODS: The completeness of report unit by township and county, including 31 provinces (cities, municipalities) and Xinjiang Production and Construction Corps, the number of doses and the number of counties covered for category II vaccine at different areas, average types of category II vaccine by county were analyzed by descriptive epidemiological methods, according to monthly report of vaccination data for category II vaccines by township in 2012 which all of provinces and population were almost covered, through the National Immunization Program(NIP) monitoring information system of China. RESULTS: A total of 29 kinds of category II vaccine with 90 843 530 doses were reported in 2012, and the total average dose was 674.2 per 10 000 people. The report completeness by county and township were 83.32% (29 557/35 472) and 80.01% (396 652/495 756) respectively. The reported doses of rabies vaccine for human use, Haemophilus influenza type b vaccine and influenza vaccine was the top third vaccine, among those for all kinds of category II vaccine, which were 17 027 259, 13 996 206, 11 324 518 respectively, and 126.4, 103.9, 84.1 doses per 10 000 people. In 2773 county units, varicella attenuated live vaccine, influenza vaccine, rabies vaccine for human use were the top three kinds of category II vaccine in terms of the number of county where vaccines have been used in 2012, which were 2442(88.06%), 2415(87.09%), 2366(85.32%) respectively. Guangdong province with 12 266 531 doses was the highest report doses for category II vaccine whereas Qinghai province with 57 767 doses was the lowest number in 2012. Regarding to the average report doses by province, the highest or lowest number was 2425.0 doses per 10 000 people in Shanghai province, and 101.7 doses per 10 000 people in Qinghai province separately. CONCLUSION: Many kinds of category II vaccine with a large amount have been used in China, and there are significant different among areas. Surveillance and management for category II vaccines should be future improved.

A novel influenza A (H1N1) vaccine in various age groups.

BACKGROUND: There is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus. METHODS: A split-virus, inactivated candidate vaccine against the 2009 H1N1 virus was manufactured, and we evaluated its safety and immunogenicity in a randomized clinical trial. Subjects were between 3 and 77 years of age, stratified into four age groups. The immunization schedule consisted of two vaccinations, 21 days apart. Subjects were injected with placebo or with vaccine, with or without alum adjuvant, at doses of 7.5 microg, 15 microg, or 30 microg. Serologic analysis was performed at baseline and on days 21 and 35. RESULTS: A total of 2200 subjects received one dose, and 2103 (95.6%) received the second dose, of vaccine or placebo. No severe adverse side effects associated with the vaccine were noted. In the nonadjuvanted-vaccine groups, injection-site or systemic reactions, most mild in nature, were noted in 5.5 to 15.9% of subjects. Among the subjects receiving 15 microg of nonadjuvanted vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between 12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects 61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%, 97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine, with or without adjuvant. Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant. CONCLUSIONS: These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age. Lesser immune responses were seen after a single dose of vaccine in younger and older subjects. (ClinicalTrials.gov number, NCT00975572).

Effect of aluminum hydroxide adjuvant on the immunogenicity of the 2009 pandemic influenza A/H1N1 vaccine: multi-level modeling of data with repeated measures.

OBJECTIVE: To evaluate the effect of the aluminum hydroxide (Al-OH) adjuvant on the 2009 pandemic influenza A/H1N1 (pH1N1) vaccine. METHODS: In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 µg hemagglutinin antigen, with or without aluminum hydroxide (Al-OH). We classified the participants into six age categories (>61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years) and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer (GMT) of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. RESULTS: The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. CONCLUSION: The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

Factors influencing the routine immunization status of children aged 2-3 years in China.

OBJECTIVES: To examine the factors associated with the routine immunization status of children aged 2-3 years in China for gaining a better understanding of the Expanded Program on Immunization and to provide evidence for formulating specific strategies to guide the allocation of health resources. METHODS: We analyzed data from 45095 children aged 2-3 years in the 2013 National Immunization Coverage Survey to identify the sociodemographic and provider-associated factors affecting the full immunization status of children. Univariate and multiple logistic regression analyses were performed. RESULTS: The immunization rate for children aged 2-3 years ranged from 95.9% (diphtheria and tetanus toxoid with pertussis vaccine, 4th dose) to 99.5% (Japanese encephalitis vaccine, 1st dose) and was 93.1% for full immunization. In terms of sociodemographic factors, male children [adjusted OR (AOR): 1.115; 95% confidence interval(CI):1.016-1.222], minority children (AOR: 1.632; 95% CI: 1.457-1.828), children of fathers with less than high school education (AOR: 1.577; 95% CI: 1.195-2.081), those born at home (AOR: 4.655; 95% CI: 3.771-5.746), those who immigrated from an adjacent county (AOR: 2.006; 95% CI: 1.581-2.546), and those living in urban-rural fringe areas (AOR: 1.807; 95% CI: 1.475-2.214) or mountainous areas (AOR: 1.615; 95% CI: 1.437-1.814) had significantly increased odds of not being fully immunized. In terms of provider-associated factors, administration of vaccines at home (AOR: 2.311; 95% CI: 1.316-4.059), household reminders (AOR: 2.292; 95% CI: 1.884-2.789), and travel time to vaccination providers of >40 minutes (AOR: 1.622; 95% CI: 1.309-2.010) were negatively associated with immunization rates. In addition, compared to 3-year-old years, 2-year-old children (AOR: 1.201; 95% CI: 1.094-1.318) were less likely to be fully immunized. CONCLUSIONS: All included factors except maternal education level and distance from home to vaccination providers significantly affected immunization rates. Appropriate reminders and accessibility of immunization services played key roles in improving the immunization status. More attention to high-risk groups identified in this study may reduce the disparities in routine childhood immunization in China.

Sero-survey of polio antibodies during wild poliovirus outbreak in southern Xinjiang Uygur Autonomous Region, China.

BACKGROUND: After being polio free for more than 10 years, an outbreak following importation of wild poliovirus (WPV) was confirmed in Xinjiang Uygur Autonomous Region, China, in 2011. METHODS: A cross-sectional study was conducted prior to supplementary immunization activities (SIAs), immediately after the confirmation of the WPV outbreak. In selected prefectures, participants aged ≤ 60 years old who visited hospitals at county-level or above to have their blood drawn for reasons not related to the study, were invited to participate in our study. Antibody titers ≥ 8 were considered positive. RESULTS: Among the 2,611 participants enrolled, 2,253 (86.3%), 2,283 (87.4%), and 1,989 (76.2%) were seropositive to P1, P2 and P3 respectively, and 1744 (66.8%) participants were seropositive to all the three serotypes. Lower antibody seropositivities and geometric mean titers were observed in children <1 year of age and in adults aged 15-39 years. CONCLUSION: Serosurveys to estimate population immunity in districts at high risk of polio importation might be useful to gauge underlying population immunity gaps to polio and possibly to guide preparedness and response planning. Consideration should be given to older children and adults during polio risk assessment planning and outbreak response.

An outbreak of type π vaccine-derived poliovirus in Sichuan province, China: emergence and circulation in an under-immunized population.

BACKGROUND: During August 2011-February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. METHODS: A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. RESULTS: One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8-1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5-12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February-May, 2012, and the strain has not been isolated since. CONCLUSION: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.

[Evaluation on effectiveness of training for the national expanded program on immunization].

OBJECTIVE: To evaluate the effectiveness of training for the national expanded program on immunization. METHODS: 384 trainees were selected random. A questionnaire was developed and distributed to the trainees before and after training. A satisfactory survey was conducted by questionnaire after training. RESULTS: The knowledge level increased obviously after training. <60 score decreased from 41.7% to 1.8%, > or = 60 score increased from 58.4% to 98.2% (chi2=179.12, P = 0.00). Total 384 trainees, the average correct rate of knowledge before and after training were 60% and 83% respectively. The age, working year, ethnic, gender and education level were factors influencing the effectiveness of training. Working unit and training location had no significant statistic difference. 78% trainees thought that the training materials were easy understand, 81% and 80% trainees were satisfied with training logistic and training skill respectively. It was suggested that training time should be longer; the training contents should base on the real case; and frequency of training should be increased in the future. CONCLUSION: National expanded immunization program should strengthen training to the staff so as to improve the immunization service ability.

[Study on comprehensive strategies of strenghening routine immunization program].

OBJECTIVE: To explore the feasibility and effectiveness of the comprehensive strategies to strengthen the routine immunization program, and to provide the evidence for adjusting the strategies for implementing the project in coming years. METHODS: Five townships were selected from each county according to the location of east, west, south, north and middle. Four villages were selected from each township, and seven children were selected from each village randomly. There were 2215 children were investigated totally. RESULTS: Compared with results of the baseline survey, the rate of holding immunization card increased from 89.4% to 96.3%. The coverage of 5 kinds of EPI vaccines increased between 10%-35%. The difference of coverage before and after implementing the project was significant P < 0.001. The frequency of cold chain running increased than before implementing the project. The targeted school number of immunization card school entry, the number of children checked, the number of redistributed immunization card, and the number of children catched-up vaccine increased obviously. CONCLUSION: The comprehensive strategies of the strengthening routine immunization program have a great effect.

[Evaluation on the safety and efficacy of lyophilized purified human rabies vaccine (CTN-Vero-RV)].

OBJECTIVE: To observe the safety and efficacy of lyophilized purified human rabies vaccine CTN-Vero RV, CTN strain produced in Vero cells. METHODS: 450 healthy volunteers were divided into two groups, with 300 of them receiving CTN-Vero-RV (rabies vaccine for human use made in Vero cells with CTN strain) while 150 of them receiving PVRV to serve as control group. All the subjects were immunized on days 0, 3, 7, 14 and 28 at deltoid muscle respectively. Local and systemic reactions were observed and sera were collected for neutralizing antibody testing using RFFIT. 365 and 730 days after the first dose, sera from the 212 and 176 subjects of the studied group while 97 and 80 subjects from the control group were collected to test for neutralizing antibody. RESULTS: No severe local or systemic reactions were observed after immunization was performed in the two groups. On days 3, 7, 14, 28 and 365 after the first dose, the antibody positive rates appeared to be 2.35%, 80.78%, 100.00%, 100.00%, 98.58% and 73.30% in the study group and 4.00%, 87.20%, 100.00%, 100.00%, 97.94% and 76.25% in the controls respectively. On day 0, 3, 7, 14, 28, 365 and 730, GMT of the neutralizing antibody level were 0.12, 1.01, 9.83, 12.61, 3.68 and 2.81 IU/ml in the study group while 0.13, 1.18, 10.24, 11.61, 4.18 and 1.92 IU/ml were seen in the control group respectively. There were no significant differences in both antibody positive rates and GMT between the two groups on days 3, 7, 14, 28, 365 or 730 (P > 0.05). CONCLUSION: CTN-Vero-RV was safe and effective as well as could generate a persistent immune response.