Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

Immunogenicity of 23-Valent Pneumococcal Polysaccharide Vaccine in Patients with Chronic Obstructive Pulmonary Disease - Hebei Province, China, September-December, 2019.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: The global burden of chronic obstructive pulmonary disease (COPD) is serious. Pneumococcal infection is associated with acute exacerbations of COPD (AECOPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for COPD patients to decrease AECOPD due to pneumococcus, but evidence on the immunogenicity of PPSV23 in COPD patients is limited. WHAT IS ADDED BY THIS REPORT?: This study showed good immunogenicity of one dose of PPSV23 in COPD patients. Antibody levels against all 23 vaccine serotypes were assessed before and four weeks after vaccination of COPD patients with one dose of PPSV23. The percent of COPD patients who had two-fold increases in pneumococcal antibody levels following vaccination ranged from 65.2% (serotype 3) to 94.4% (serotype 2). There were statistically significant differences in immunogenicity by serotype. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: This study supports current recommendations for PPSV23 vaccination of COPD patients in China to provide protection from pneumococcal diseases.

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease.

Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients.Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events.Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post-vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion (P = .10) and seroprotection (P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0-25.1), 12.2 (95% CI: 9.6-15.4), and 31.8 (95% CI: 26.1-38.8) at baseline, and 267.0 (95% CI: 213.8-333.4), 190.3 (95% CI: 151.7-238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination.Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.

Immunogenicity of three sequential schedules with Sabin inactivated poliovirus vaccine and bivalent oral poliovirus vaccine in Zhejiang, China: an open-label, randomised, controlled trial.

BACKGROUND: The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. METHODS: This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560. RESULTS: Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups. INTERPRETATION: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen. FUNDING: Chinese Center for Disease Control and Prevention and China National Biotec Group Company.

Immunogenicity and safety of measles-rubella vaccine co-administered with attenuated Japanese encephalitis SA 14-14-2 vaccine in infants aged 8 months in China: a non-inferiority randomised controlled trial.

BACKGROUND: In China, measles-rubella vaccine and live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at 8 months of age, which is the youngest recommended age for these vaccines worldwide. We aimed to assess the effect of the co-administration of these vaccines at 8 months of age on the immunogenicity of measles-rubella vaccine. METHODS: We did a multicentre, open-label, non-inferiority, two-group randomised controlled trial in eight counties or districts in China. We recruited healthy infants aged 8 months who had received all scheduled vaccinations according to the national immunisation recommendations and who lived in the county of the study site. Enrolled infants were randomly assigned (1:1) to receive either measles-rubella vaccine and LJEV simultaneously (measles-rubella plus LJEV group) or measles-rubella vaccine alone (measles-rubella group). The primary outcome was the proportion of infants with IgG antibody seroconversion for measles 6 weeks after vaccination, and a secondary outcome was the proportion of infants with IgG antibody seroconversion for rubella 6 weeks after vaccination. Analyses included all infants who completed the study. We used a 5% margin to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT02643433). FINDINGS: 1173 infants were assessed for eligibility between Aug 13, 2015, and June 10, 2016. Of 1093 (93%) enrolled infants, 545 were randomly assigned to the measles-rubella plus LJEV group and 548 to the measles-rubella group. Of the infants assigned to each group, 507 in the measles-rubella plus LJEV group and 506 in the measles-rubella group completed the study. Before vaccination, six (1%) of 507 infants in the measles-rubella plus LJEV group and one (<1%) of 506 in the measles-rubella group were seropositive for measles; eight (2%) infants in the measles-rubella plus LJEV group and two (<1%) in the measles-rubella group were seropositive for rubella. 6 weeks after vaccination, measles seroconversion in the measles-rubella plus LJEV group (496 [98%] of 507) was non-inferior to that in the measles-rubella group (499 [99%] of 506; difference -0·8% [90% CI -2·6 to 1·1]) and rubella seroconversion in the measles-rubella plus LJEV group (478 [94%] of 507) was non-inferior to that in the measles-rubella group (473 [94%] of 506 infants; difference 0·8% [90% CI -1·8 to 3·4]). There were no serious adverse events in either group and no evidence of a difference between the two groups in the prevalence of any local adverse event (redness, rashes, and pain) or systemic adverse event (fever, allergy, respiratory infections, diarrhoea, and vomiting). Fever was the most common adverse event (97 [19%] of 507 infants in the measles-rubella plus LJEV group; 108 [21%] of 506 infants in the measles-rubella group). INTERPRETATION: The evidence of similar seroconversion and safety with co-administered LJEV and measles-rubella vaccines supports the co-administration of these vaccines to infants aged 8 months. These results will be important for measles and rubella elimination and the expansion of Japanese encephalitis vaccination in countries where it is endemic. FUNDING: US Centers for Disease Control and Prevention, US Department of Health and Human Services; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.

Utilization pattern of Haemophilus influenza type b vaccine in eight provinces of China.

OBJECTIVE: In China, Hib vaccine is a private-sector vaccine that is an option for parents to select to give to their children; it must be paid for out-of-pocket because it is not included in the government's Expanded Program on Immunization (EPI). We evaluated utilization patterns of Hib vaccine to provide evidence in support of development of a national Hib vaccination strategy. METHODS: We obtained lists of children from immunization information systems (IIS) of counties or districts in 8 provinces of China. Using these lists, we selected 10 children at random from each birth cohort from 2008 through 2012. We obtained Hib vaccination dates from official vaccination certificates. The target sample size was 1,000 children. RESULTS: We were able to obtain records for 978 subjects of the selected subjects; of these, 44.79% had received at least 1 dose of Hib vaccine, and 15.54%, 5.83%, 12.27%, and 11.15% had received one, two, three, and four doses, respectively. Per capita GDP was positively correlated with receipt of at least one dose of Hib vaccine. Among the 438 subjects who received Hib vaccine, 27% received 1 dose after 12 months of age; 15%, 7%, and 23% received one of three other patterns of Hib vaccination recommended by the World Health Organization (WHO) [a 3-dose primary series; 2 primary series doses and 1 booster; or 3 primary series doses and 1 booster]. The other 28% of subjects received patterns of Hib vaccination not recommended by WHO. Considering protection from Hib disease as receipt of a WHO-recommended Hib vaccine schedule, 29% of subjects could be considered protected after 12 months of age, 52% could be considered protected during infancy and beyond, and 19% could be considered to not have been protected adequately, despite being vaccinated. CONCLUSIONS: Coverage with Hib vaccine was low. There were significant differences between WHO recommendations and actual patterns of use of Hib vaccine, with half of vaccine recipients receiving no protection during infancy and one fifth receiving non-protective Hib vaccination patterns. Inclusion of Hib vaccine into China's EPI system, which provides vaccine at no charge to parents and makes specific vaccination schedule standards, has potential to make more effective use of Hib vaccine.

The varicella vaccination pattern among children under 5 years old in selected areas in China.

BACKGROUND: Vaccine is the most effective way to protect susceptible children from varicella. Few published literature or reports on varicella vaccination of Chinese children exist. Thus, in order to obtain specific information on varicella vaccination of this population, we conducted this survey. METHODOLOGY: We first used purposive sampling methods to select 6 provinces 10 counties from eastern, middle and western parts of China with high quality of Immunization Information Management System (IIMS), and then randomly select children from population in the IIMS, then we checked vaccination certificate on-site. PRINCIPAL FINDINGS: Based on the varicella vaccination information collected from 481 children's vaccination certificates from all ten selected counties in China, overall coverage of the first dose of varicella vaccine was 73.6%. There is a positive linear correlation between per capita GDP and vaccine coverage at county level (r=0.929, P < 0.01). The cumulative vaccine coverage among children at 1 year, 2 years and ≥3 years old were 67.6%, 71.9% and 73.6% respectively (X2=4.53, P =0.10). The age of vaccination was mainly concentrated in 12-17 months. CONCLUSIONS: The coverage rate of the first dose of varicella vaccine in selected areas was lower than that recommended by WHO position paper. The coverage rate was relatively low in areas of low social-economic status. The cumulative coverage had no significant statistical difference among different age group. Most children received varicella vaccine before 3 years old. We suggest introducing the varicella vaccine into routine immunization program, to ensure universal high coverage among children in China. We also suggest that varicella vaccination information should be checked before entering school, in order to control and prevent varicella outbreaks in schools.

Household survey analysis of the impact of comprehensive strategies to improve the expanded programme on immunisation at the county level in western China, 2006-2010.

OBJECTIVE: To evaluate interventions to improve routine vaccination coverage and caregiver knowledge in China's remote west, where routine immunisation is relatively weak. DESIGN: Prospective pre-post (2006-2010) evaluation in project counties; retrospective comparison based on 2004 administrative data at baseline and surveyed post-intervention (2010) data in selected non-project counties. SETTING: Four project counties and one non-project county in each of four provinces. PARTICIPANTS: 3390 children in project counties at baseline, and 3299 in project and 830 in non-project counties post-intervention; and 3279 caregivers at baseline, and 3389 in project and 830 in non-project counties post-intervention. INTERVENTION: Multicomponent inexpensive knowledge-strengthening and service-strengthening and innovative, multisectoral engagement. DATA COLLECTION: Standard 30-cluster household surveys of vaccine coverage and caregiver interviews pre-intervention and post-intervention in each project county. Similar surveys in one non-project county selected by local authorities in each province post-intervention. Administrative data on vaccination coverage in non-project counties at baseline. PRIMARY OUTCOME MEASURES: Changes in vaccine coverage between baseline and project completion (2010); comparative caregiver knowledge in all counties in 2010. ANALYSIS: Crude (χ(2)) analysis of changes and differences in vaccination coverage and related knowledge. Multiple logistic regression to assess associations with timely coverage. RESULTS: Timely coverage of four routine vaccines increased by 21% (p<0.001) and hepatitis B (HepB) birth dose by 35% (p<0.001) over baseline in project counties. Comparison with non-project counties revealed secular improvement in most provinces, except new vaccine coverage was mostly higher in project counties. Ethnicity, province, birthplace, vaccination site, dual-parental out-migration and parental knowledge had significant associations with coverage. Knowledge increased for all variables but one in project counties (highest p<0.05) and was substantially higher than in non-project counties (p<0.01). CONCLUSIONS: Comprehensive but inexpensive strategies improved vaccination coverage and caretaker knowledge in western China. Establishing multisectoral leadership, involving the education sector and including immunisation in public-sector performance standards, are affordable and effective interventions.

Quick assessment of the influence of the Hepatitis B vaccine event on children's vaccination.

OBJECTIVE: From December 2013 to January 2014, a large number of medias in China reported negative information about Hepatitis B vaccine (HepB) safety issues using eye-catching titles, such as "3 infants in Hunan inoculated with HepB occurred adverse event, and 2 died," and that caused crisis of confidence in vaccination, which we called "HepB event." The progress of "HepB event" could be divided into 3 stages which were initiation, peak and ending stages. In order to evaluate the influence of "HepB event" on the attitudes of participants toward Hepatitis B vaccine safety and their intention of vaccinating their children in different stages, and provide evidence for authority departments as soon as possible to take measures to prevent decrease of HepB coverage rate, a quick field investigation was carried out. METHODS: Using convenience sampling methods during the initiation, peak and ending stages of the "HepB event." RESULTS: In the 3 stages of the "HepB event," the awareness rate of the event among participants was rapidly rising, showing that the participants paid great attention to the event, and the information was spread very quickly. The proportion of participants who knew the event but thought that the Hepatitis B vaccine was unsafe were 31%, 37% and 26% respectively in 3 stages. In addition, the acceptance of vaccination by the participants was influenced, the proportion of participants who would like to delay or reject vaccinating their children was up to 43% in the peak stage of the event. CONCLUSIONS: The "HepB event" had impacted on the participants' confidence in the safety of Hepatitis B vaccine. For such event, relevant authority departments need effectively communicate with the media and the public, and promptly issue positive information and the investigation result, thereby reducing the negative impact of the event, and improve the vaccine confidence among the public.