Jingshan Zheng

A Novel Influenza A (H1N1) Vaccine in Various Age Groups

BACKGROUNDnThere is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus.nnnMETHODSnA 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.nnnRESULTSnA 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.nnnCONCLUSIONSnThese 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).

Safety of Influenza A (H1N1) Vaccine in Postmarketing Surveillance in China

BACKGROUNDnOn 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.nnnMETHODSnWe 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 Systems National Adverse Event Following Immunization Surveillance System. Data were collected through March 21, 2010, and were verified and analyzed by the Chinese CDC.nnnRESULTSnA 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.nnnCONCLUSIONSnNo 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.

Identification and Control of a Poliomyelitis Outbreak in Xinjiang, China

BACKGROUNDnThe 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.nnnMETHODSnWe 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.nnnRESULTSnBetween 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.nnnCONCLUSIONSnThe 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.

The role of the China Experts Advisory Committee on Immunization Program

The Experts Advisory Committee on Immunization Program (EACIP) of China was founded in 1982, and currently consists of 33 experts in immunization and related fields, selected by the Ministry of Health, to provide advice and guidance on the control of vaccine-preventable diseases. The main tasks of the EACIP are to advise on the national immunization schedule, to participate in the drafting and review of technical documents, and to participate in field supervision and staff training. In 2007, the EACIP used evidence-based methods to formulate a revised national immunization schedule. The EACIP has played and is playing an increasingly important role in guiding immunization policy in China.

Coverage of and Influences on Timely Administration of Hepatitis B Vaccine Birth Dose in Remote Rural Areas of the People’s Republic of China

A survey was conducted in 2006 to assess the coverage and timeliness of the birth dose of hepatitis B vaccine (HepB(1)) and related influences among children in rural areas of Guangxi, Guizhou, Tibet, and Shaanxi provinces, Peoples Republic of China. A total of 3,390 children born in 2004 were surveyed in four counties in each province, where a project to strengthen routine immunization is being implemented by the China Ministry of Health, supported by the United National Childrens Fund. Two-stage stratified cluster sampling was undertaken to select those surveyed. A questionnaire was administered to parents or guardians and vaccination records were assessed. HepB(1) administration was timely for 31.6% of the sample. Timeliness of HepB(1) for children delivered at home (13%) was lower than for children born at county-level or higher facilities (54%) (odds ratio [OR] = 6.52, (95% confidence interval [CI] = 5.29-8.04, P < 10 (-3)), at township hospitals (49%, OR = 7.14, 95% CI = 5.68-8.98, P < 10 (-3)), or private clinics (59%, OR = 5.64, 95% CI = 3.68-8.64, P < 10 (-3)). Children of Tibetan (24.8%, OR = 0.16, 95% CI = 0.12-0.21, P < 10 (-4)), Zhuang (27.8%, OR = 0.73, 95% CI = 0.57-0.94, P < 0.02) or Meng, Miao, and Hui ethnicity (14.2%, OR = 0.36, 95% CI = 0.29-0.45, P < 10 (-4)) were less likely than children of Han ethnicity (33.2%) to have received a timely birth dose. Children lacking vaccination registration cards (OR = 0.64, 95% CI = 0.51-0.80, P < 10 (-4)) and children whose parents or guardians did not know the importance of timely HepB immunization (OR = 0.62, 95% CI = 0.46-0.84, P < 10 (-2)) were also less likely to have received a timely birth dose. Parental knowledge and prioritization of birth-dosing was low among children who did not receive it. The timeliness of HepB(1) should improve with increasing rates of hospital delivery, training of birth attendants, increasing staff and community awareness of the importance of the birth dose, and by focusing on vulnerable groups.

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

OBJECTIVEnTo evaluate vaccine effectiveness (VE) of mumps-containing vaccine (MuV) under different immunization strategies.nnnMETHODSnWe 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.nnnRESULTSnA 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.nnnCONCLUSIONSnMuV 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.

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

BACKGROUNDnChina 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.nnnMETHODSnWe 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.nnnRESULTSnHepB 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.nnnCONCLUSIONSnThe 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.

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

BackgroundAfter more than 10xa0years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region.MethodsAcute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients.ResultsThere 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 <1xa0years, however, 24/44 (54.5%) polio cases were reported among adults aged 15–39 years.ConclusionsHigh 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.

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

INTRODUCTIONnVaccine-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.nnnAIMSnTo describe the epidemiological characteristics of VAPP and estimate the risk of recipient VAPP in China.nnnMETHODSnWe 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.nnnRESULTSnDuring 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.nnnCONCLUSIONnThe 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.

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

INTRODUCTIONnTwo 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.nnnMETHODSnWe 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.nnnRESULTSnA 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).nnnCONCLUSIONSnWhile 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.