Dataset Information

Evaluation of the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine in a cluster-randomised trial.

ABSTRACT:

Background

In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes.

Methods

Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009-2011. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010-2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5-7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010.

Results

From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years.

Conclusions

This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.

SUBMITTER: Rinta-Kokko H

PROVIDER: S-EPMC8730423 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Diseases caused by Streptococcus pneumoniae represent a major public health problem. The purpose of this study was to compare, in the Japanese context, the projected health benefits, costs and cost-effectiveness of the latest generation of pneumococcal conjugate vaccines which may provide important insight into the potential public health impact of interventions in the context of local disease-specific epidemiology. A Markov model was used to compare two vaccination strategies which involve routine infant immunization with either the 13-valent pneumococcal conjugate vaccine (PCV-13; Prevenar 13™, Pfizer, Pearl River, NY, USA) or the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Biologicals SA, Rixensart, Belgium) over a time horizon of 5 years from the healthcare provider and societal perspectives. Estimates for key model parameters were obtained from locally available databases and published literature. Incremental benefits in terms of costs and quality-adjusted life-year and cost-effectiveness were assessed. A 3 + 1 vaccination schedule for infants with PHiD-CV is expected to have a similar impact on invasive pneumococcal disease and pneumonia and a larger impact on acute otitis media-related outcomes compared with PCV-13. Assuming price parity for these vaccines, the model projected that vaccination with PHiD-CV would result in cost savings of 1.9 and 3.9 billion Japanese yen from the provider and societal perspectives, respectively. This was largely due to a reduction in highly prevalent acute otitis media. Vaccination with PHiD-CV was expected to generate a gain of 433 quality-adjusted life-years compared to PCV-13 translating into dominance over PCV-13. Sensitivity analyses showed robustness of model outcome to changes in key model parameters and substantiated that the model outcome was consistently driven by the incremental benefit of PHiD-CV in averting acute otitis media. In comparison to PCV-13, vaccination with PHiD-CV is projected to be cost saving for Japan from both the healthcare provider and societal perspectives.

Project description:BackgroundAboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), with recommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months.MethodsIn an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2-4-6 months (_PPP), Synflorix™ (S) at 2-4-6 months (_SSS), or Synflorix™ at 1-2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severity hierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM).ResultsBetween September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86, and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence of any form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57, 82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7 months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM.ConclusionsDespite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life.Trial registrationACTRN12610000544077 registered 06/07/2010 and ClinicalTrials.gov NCT01174849 registered 04/08/2010.

Project description:BackgroundPneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants.MethodsThis phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age.ResultsWithin 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or considered causally related to vaccination.ConclusionsPHiD-CV had a clinically acceptable safety profile when co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants. The reactogenicity of PHiD-CV was comparable to that observed in other South-East Asian populations.

Project description:BackgroundStreptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan.MethodsA published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results.ResultsPHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations.ConclusionsPHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.

Project description:BackgroundGambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies.MethodsTwenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2-30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study.Results57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022) and (HR 1.52 [1.11-2.10], p = 0.010 respectively) were significantly higher.ConclusionPCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring.Trial registrationISRCTN Register 51695599.