Combining high-throughput micro-CT-RGB phenotyping and genome-wide association study to dissect the genetic architecture of tiller growth in rice.

Manual phenotyping of rice tillers is time consuming and labor intensive, and lags behind the rapid development of rice functional genomics. Thus, automated, non-destructive methods of phenotyping rice tiller traits at a high spatial resolution and high throughput for large-scale assessment of rice accessions are urgently needed. In this study, we developed a high-throughput micro-CT-RGB imaging system to non-destructively extract 739 traits from 234 rice accessions at nine time points. We could explain 30% of the grain yield variance from two tiller traits assessed in the early growth stages. A total of 402 significantly associated loci were identified by genome-wide association study, and dynamic and static genetic components were found across the nine time points. A major locus associated with tiller angle was detected at time point 9, which contained a major gene, TAC1. Significant variants associated with tiller angle were enriched in the 3'-untranslated region of TAC1. Three haplotypes for the gene were found, and rice accessions containing haplotype H3 displayed much smaller tiller angles. Further, we found two loci containing associations with both vigor-related traits identified by high-throughput micro-CT-RGB imaging and yield. The superior alleles would be beneficial for breeding for high yield and dense planting.

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.

[Re-examination sampling methods of national immunization survey for national immunization program vaccines coverage at the township level by the national level in 2013, China].

OBJECTIVE: To review the re-examination sampling method and procedure of national immunization survey for the national immunization program vaccines coverage at the township level by the national level in 2013, China. METHODS: According to the result of immunization coverage at the township level through self-assessment by county, all townships were stratified by whether a township with ≥ 90% immunization coverage for the second dose of measles-containing vaccines (MCV2), and a township was urban or rural. After then, 2 townships for each province were randomly sampled from those strata through the surveyselect procedure of the statistics analysis system 9.2 (SAS 9.2). RESULTS: 64 townships were randomly sampled from 32 provincial units for the re-examination, i.e. an urban township and a rural township each province, of which there were 38 townships with ≥ 90% MCV2 coverage and 26 townships with < 90% MCV2 coverage. There were 24 urban townships, 2 rural townships with < 90% MCV2 coverage and 8 urban townships, 30 rural townships with ≥ 90% MCV2 coverage, respectively. CONCLUSIONS: Based on the information of the self-assessment result of immunization coverage survey by counties, Stratified randomized sampling were employed for the re-examination through the Surveyselect procedure of statistics analysis system (SAS) to implement the sampling procedure. This can enhance the sampling efficiency, ensure the randomness of the sample, and make the survey much more representative and comparable.

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.

Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults.

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

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).

Effectiveness of Booster Doses of the SARS-CoV-2 Inactivated Vaccine KCONVAC against the Mutant Strains.

As the COVID-19 epidemic progresses with the emergence of different SARS-CoV-2 variants, it is important to know the effectiveness of inactivated SARS-CoV-2 vaccines against the variants. To maximize efficiency, a third boost injection of the high-dose SARS-CoV-2 inactivated vaccine KCONVAC was selected for investigation. In addition to the ancestral strain, KCONVAC boost vaccination induced neutralizing antibodies and antigen-specific CD8 T cells to recognize several variants, including B.1.617.2 (Delta), B.1.1.529 (Omicron), B.1.1.7 (Alpha), B.1.351 (Beta), P.3, B.1.526.1 (Lota), B.1.526.2, B.1.618, and B.1.617.3. Both humoral and cellular immunity against variants were lower than those of ancestral variants but continued to increase from day 0 to day 7 to day 50 after boost vaccination. Fifty days post-boost, the KCONVAC-vaccinated CD8 T-cell level reached 1.23-, 2.59-, 2.53-, and 1.01-fold that of convalescents against ancestral, Delta, Omicron and other SARS-CoV-2 variants, respectively. Our data demonstrate the importance of KCONVAC boosters to broaden both humoral and cellular immune responses against SARS-CoV-2 variants.

Immune persistence induced by three doses of 60 µg hepatitis B vaccine in non-responders following standard primary vaccination in Chinese adults.

This study consisted of two rounds of cross-sectional observations designed to evaluate the persistence of immune protection induced high antigen content hepatitis B (HB) vaccine at 60 µg/1.0 ml formulations administered at a three-dose schedule (Days 0, 28, and 56) in non-responders to routine HB vaccination. In the original phase 3 study, we enrolled 1091 healthy participants (16-60 years old) seronegative for antibody against HB surface antigen (anti-HBs) after primary vaccination. Participants were randomized (2:2:1) to receive three booster doses of HB vaccine containing 60 µg, 30 µg, or 10 µg of antigen per dose 28 days apart. In the group receiving the 60 µg HB vaccine, 428 participants' serum samples were available at pre-vaccination and 28 days after each vaccine dose and were included in immunogenicity analysis. With two written informed consents, we collected blood samples from 276 (67.2%) participants in 2014 and 239 (58.2%) in 2019, who had completed the full course of revaccination and reached the seropositive (anti-HBs≥10 mIU/ml) standard in the 60 µg vaccine group of the original phase 3 study. The HBV seropositive rate was found to decrease from 96.0% in 28 days after receiving the third dose of 60 µg HB vaccine, to 48.2% in 2014, and to 40.6% in 2019, with anti-HBs GMC of seropositive individuals was 584.0 mIU/ml, 142.4 mIU/ml, and 169.1 mIU/ml, respectively. Analysis of 181 vaccinees who had serologic test results available both in 2014 and in 2019, and results revealed a dynamic trend in anti-HBs titer similar to that for the whole immune persistence cohort. Of paramount importance, the serologic test results found that 24.9% (45/181) participants had higher anti-HBs concentrations in 2019 than in 2014, this could be interpreted as natural boosters, secondary to HBV exposure without infection because protected. In conclusion, protective antibody persists about 11 years after immunization of Chinese non-responders with 3 doses of 60 µg HB vaccine. Booster doses of vaccine do not seem necessary to ensure long-term protection.

Immunization information system status in China, 2017.

Immunization Information Systems (IIS) are computerized population-based systems with individual-level vaccination-related information used to help ensure protection from vaccine preventable diseases. The Chinese Center for Diseases Control and Prevention (China CDC) conducted a survey of the 32 mainland China provincial CDCs to determine IIS coverage and implementation of key functions: individual vaccination records, vaccine management, cold-chain management, and school entry vaccination status verification. Twenty-seven IISs collectively managed 252 million immunization records, 43.8% for children under 6 years; 20 could exchange records with other IISs. The within-province duplicate-record rate varied from 0.3% to 4.0%, but compared with National Statistical Bureau's census estimates, 138.0% of births from 2012 to 2017 were represented in the IISs, implying significant across-province record duplication. China CDC should consider developing a national-level IIS center for data exchange and analysis.

Deaths reported to national surveillance for adverse events following immunization in China, 2010-2015.

BACKGROUND: The national Adverse Events Following Immunization (AEFI) surveillance system in China (CNAEFIS) has collected AEFI reports -including deaths following all vaccines used in China since 2008. AIMS: To review reports of AEFI-associated death cases from 2010 to 2015 to assess potential vaccine safety issues. METHODS: Descriptive analysis of epidemiologic characteristic of AEFI-associated death cases and standard causality assessment for reported causes of deaths. To estimate the risk of death after vaccination, we used population data, administered doses and live births to calculate denominators. RESULTS: During 2010-2015, 753 deaths were reported to CNAEFIS from mainland China. Highest numbers were reported in 2013 and 2014 when reporting peak of AEFI-associated deaths occurred after media reports concerning "death following Hepatitis B vaccination" in China. About 95% of deaths were in children <5 years of age and males accounted for 60%. Most common vaccines associated with reports of fatal AEFIs were vaccines in national immunization schedule. In causality assessment, 120 (16.0%) deaths were classified as vaccine-associated reactions such as anaphylactic reactions and disseminated BCG infections; 594 (78.9%) deaths were identified as coincidental events. The main causes of death were asphyxia, and Sudden Infant Death Syndrome. The overall estimated AEFI-associated death rates were: 0.26 per million vaccination doses administered and 0.09 per million population. The neonatal AEFI death rate was 0.77 per million live births. CONCLUSIONS: These data provide reassuring information about the small risk of death following immunization. They also illustrate sensitivity of passive reporting to public information and that peaks in serious AEFI reports should be interpreted with caution. Continuous monitoring and scientific causality assessment for serious AEFIs, including AEFI-associated deaths is imperative to ensure public confidence in the immunization program.

Evaluation of the impact of Shandong illegal vaccine sales incident on immunizations in China.

A case of illegal vaccine sales in Shandong province, China, (hereinafter, the incident), which caused a lack of confidence among vaccination recipients and public panic, was uncovered in March 2016. We conducted a study comprising two cross-sectional surveys: at two months (May 2016) and seven months (October 2016) after the incident. The study aimed to evaluate the impact on immunizations; investigate the variation of the immunization coverage of the National Immunization Program Vaccines (NIPV) and the sales volume growth rate of Category II vaccines; and understand the reasons for non-vaccination and perspectives on immunization. The immunization coverage of NIPV decreased by 5.6 percentage points in the first survey, with a decline of 11.1 in the region of the incident, and decreased by 0.6 in the second survey compared to same period in 2015. The sales volume growth rate of Category II vaccines decreased by 25.8% in the study area and by 48.8% in the region of the incident in April 2016 compared to April 2015. Overall, 15.8% of respondents in the first survey and 7.0% in the second survey did not vaccinate their children according to the NIPV schedule because of the incident (χ2 = 78.463, P < 0.05). The vaccination was likely affected by the incident in varying degrees, especially in the involved region and particularly in relation to Category II vaccines. Overall, 34% of respondents avoided Category II vaccines for their children, indicating that it will take considerable time to eliminate the negative stigma associated with the incident.

Evaluation of a school entry immunization record check strategy in 4 counties of Ningxia and Hubei provinces, China.

China has a national requirement that children's vaccination status is to be checked upon entry to kindergarten and school; children who have missed vaccine doses are to be referred to vaccination clinics to receive the necessary vaccinations. Most provinces have Immunization Information Systems (IIS) that contain and manage vaccination records of children served by immunization clinics. We conducted an evaluation in Hubei and Ningxia provinces using IIS data to determine the effect of their school entry immunization record checking strategy (SECS) on vaccination coverage and rate of catch-up for selected vaccines. We selected two counties with well-functioning IISs from each province. Names and demographic information of children enrolled in 185 kindergartens and 125 primary school in 2016 were used to identify children in the IIS and obtain their vaccination records. We calculated vaccination coverage before and after implementation of the SECS and determined catch-up rates for 5 vaccines, of which 3 are given before 2 years of age and 2 are given after 2 years of age. Among the 20,215 newly-enrolled children, 75% were able to be matched with IIS records. Few children who had missed one or more doses of the 3 vaccines recommended in the first two years of life received catch-up doses after SECS. For vaccines scheduled after 2 years of age, there was a statistically significant (p < 0.05) coverage increase in both provinces following the school-entry record check. Among children who were age-eligible for the selected vaccines before SCES, the catch-up rate was <50%. SECS provides opportunities to identify incompletely vaccinated children, improve coverage, and remind families of school-age children about up-coming vaccinations; SECS has potential to improve completeness of IIS data and enrollment of children in immunization clinics. Evidence-based policy with implementation guidance and routine monitoring are necessary to improve China's school entry checking strategy.

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.

Recipient vaccine-associated paralytic poliomyelitis in China, 2010-2015.

INTRODUCTION: Vaccine-associated paralytic poliomyelitis (VAPP) is one of the most important adverse effects of vaccines that are in current use globally. The Chinese national adverse event following immunization information system (CNAEFIS) is a passive surveillance system which collects data on VAPP. AIMS: To describe the epidemiological characteristics of VAPP and estimate the risk of recipient VAPP in China. METHODS: We retrieved information from reported cases of recipient VAPP from CNAEFIS from 2010 to 2015, examined the demographic characteristics of the cases, and used administrative data on vaccination doses and the estimated number of births as denominators to calculate VAPP incidence. RESULTS: During 2010-2015, 157 cases of recipient VAPP were reported to CNAEFIS (male-to-female ratio, 8.2:1); 151 cases (96.2%) were less than six months old. All cases were associated with trivalent OPV (tOPV), and 89.8% occurred after the receipt of first dose. Of the 157 recipient VAPP cases, type II, type III, and type I poliovirus vaccine strains were isolated from 27 (17.2%) , 25 (15.9%) , and 16 (10.2%) cases, respectively. One case died and one case recovered completely; the other 155 cases had various physical disabilities, such as monolateral or bilateral limping. Using the administered doses of OPV as the denominator, the incidence of recipient VAPP during the study period was estimated at 0.4 per million doses. The estimated recipient VAPP per million births ranged from 1.0 to 2.4 during 2010-2015. CONCLUSION: The epidemiological characteristics of recipient VAPP cases in China, such as age distribution, were comparable to those in previous studies from other countries. The risk of recipient VAPP, using either estimated births or vaccination doses, was comparable to that in the US and Japan. We recommend using an inactive poliovirus vaccine to decrease the number of recipient VAPP cases in China.

Routine immunization services costs and financing in China, 2015.

OBJECTIVE: To estimate the costs of routine immunization (RI) services in China in 2015, to provide objective data relevant to investment in the Expanded Program on Immunization, and to contribute to global data on costing and financing of RI. METHODS: The study was conducted between January and March 2016. We selected 276 villages, 138 townships, 46 counties, and 40 prefectures from 15 provinces as investigation sites at random, stratified by eastern, middle, and western regions. Direct cost items included vaccines, personnel, cold chain, surveillance, communication, training, and supervision at the national, provincial, prefecture, county, township, and village levels. We obtained financial data from governmental and external sources. Indirect costs of RI included parents' transportation costs and productivity lost due to taking their children for vaccination. RESULTS: Total direct costs were $92.42 for each child fully immunized ($4.20/dose), which equates to $1529.55 million per birth cohort. RI costs were higher in the eastern region than in the western region, and higher than that of the central region. Vaccination coverage was positively associated with direct routine immunization costs. The cost of the recommended vaccines was $19.08/child and vaccine only accounted for 20.64% of total costs. Operational cost, including surveillance, communication, training and supervision, was $217.31/child, accounting for 14.21% of total cost. The indirect cost per child was $72.86; the total indirect cost was $1205.83 million for the birth cohort. Government investment in RI accounted for about 70% of total costs. Revenue from sales of private-sector vaccine supported the remaining 30% of RI costs. CONCLUSIONS: While government financing has increased, some operating costs continue to be provided from revenue generated by sales of Category 2 (private-sector) vaccines to families. China could benefit from bringing new and underutilized vaccines into the EPI system based on evidence that includes routine immunization vaccine and operations costs.

Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

INTRODUCTION: Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. METHODS: We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. RESULTS: A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). CONCLUSIONS: While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals.

Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China.

BACKGROUND: China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. METHODS: We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. RESULTS: HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. CONCLUSIONS: The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization.

Meta-analysis of vaccine effectiveness of mumps-containing vaccine under different immunization strategies in China.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of mumps-containing vaccine (MuV) under different immunization strategies. METHODS: We conducted Medline, Embase, China National Knowledge Internet (CNKI), and Wan Fang Database (WF) searches for Chinese and English language articles describing studies of mumps VE in a Chinese population. Evaluated articles were scored on quality using the Newcastle-Ottawa Scale. Meta-analysis was conducted using random effects models. Sensitivity analysis, subgroup analysis and meta-regression were conducted to explore heterogeneity. RESULTS: A total of 32 studies in 19 papers were included; 14 were case-control studies, and 18 were cohort studies. Half of the studies were of high quality; 41% were of moderate quality. The overall VE for mumps containing vaccine (either one dose or two doses) was 85% (95% CI 76-90%) for cohort studies and 88% (95% CI 82-92%) for case-control studies. Using random effects meta-regression we found significant differences in some study covariates; for instance, VE varied by population (VE=88% in day care versus 69% in pupil, p=0.008) and emergency versus routine immunization (VE=80% for routine immunization versus 95% for emergency immunization, p=0.041). However, these results must be interpreted with caution due to the low number of studies in subgroups, with the permutation test giving non-significant results that indicated that the results may be due to chance. CONCLUSIONS: MuV provides good protection from mumps infection. Further studies of mumps VE with larger sample sizes enabling subgroup analyses will be needed to confirm our findings.