Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial (original) (raw)
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Human Vaccines & Immunotherapeutics, 2017
We previously reported 10-valent pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) efficacy in a double-blind randomized trial (ClinicalTrials.gov: NCT00466947) against various diseases, including acute otitis media (AOM). Here, we provide further analyses. In the Panamanian subset, 7,359 children were randomized (1:1) to receive PHiD-CV or control vaccine at age 2/ 4/6 and 15-18 months. Of these, 2,000 had nasopharyngeal swabs collected. AOM cases were captured when parents sought medical attention for children with AOM symptoms; surveillance was enhanced approximately 2 y into the study through regular telephone calls or home visits by study personnel, who advised parents to visit the clinic if their child had AOM symptoms. Mean follow-up was 31.4 months. Clinical AOM (C-AOM) cases were assessed by physicians and confirmed by otorhinolaryngologists. Middle ear fluid samples, taken from children with C-AOM after specific informed consent, and nasopharyngeal samples were cultured for pathogen identification. For 7,359 children, 2,574 suspected AOM cases were assessed by a primary healthcare physician; 649 cases were C-AOM cases as per protocol definition. From the 503 MEF samples collected, 158 resulted in a positive culture. In the intent-to-treat cohort (7,214 children), PHiD-CV showed VE against first C-AOM (24.0% [95% CI: 8.7, 36.7]) and bacterial (B-AOM) episodes (48.0% [20.3, 66.1]) in children <24 months, which declined thereafter with age. Pre-booster VE against C-AOM was 30.7% [12.9, 44.9]; post-booster, ¡6.7% [¡36.4, 16.6]. PHiD-CV VE was 17.7% [¡6.1, 36.2] against moderate and 32.7% [¡20.5, 62.4] against severe C-AOM. VE against vaccine-serotype pneumococcal NPC was 31.2% [5.3, 50.3] 3 months post-booster, and 25.6% [12.7, 36.7] across all visits. NTHi colonization rates were low and no significant reduction was observed. PHiD-CV showed efficacy against C-AOM and B-AOM in children younger than 24 months, and reduced vaccine-serotype NPC.
Vaccine, 2018
Background: Pneumococcal conjugate vaccines have potential to prevent significant proportion of childhood pneumonia. Finnish Invasive Pneumococcal disease vaccine trial was designed to assess the vaccine effectiveness (VE) of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against several outcomes. We now report results for pneumonia. Methods: In this nationwide, cluster-randomised, double-blind trial, children younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants younger than 7 months at the first vaccination received either 3+1 or 2+1 vaccination schedule, children aged 7-11 months received 2+1, and those 12-18 months of age two-dose schedule. All hospitalizations and outpatient visits to hospital associated with ICD-10 codes compatible with pneumonia were identified through the National Care Register and 1-3 frontal chest X-ray images per event were collected. External readers who were unaware of the patients' vaccination status retrospectively interpreted the images. The evaluated outcomes were hospital-diagnosed, hospital-treated pneumonia as primary diagnosis, and radiologically confirmed pneumonia during the blinded, intention-to-treat follow-up period from the first vaccination to the end of 2011. Total VE was calculated as 1 minus rate ratio of all pneumonia episodes. Results: 47 366 children were enrolled from February 2009, to October 2010. VE against all episodes of hospital-diagnosed pneumonia was 27% (95% confidence interval [CI]: 14%, 38%), 32% (95% CI: 3%, 52%), and 23% (95% CI: À5%, 44%) in subjects enrolled at age <7, 7-11, and 12-18 months, respectively. Corresponding rate reductions were 3.4, 4.7, and 2.5 per 1000 person-years. VE estimates against pneumonia with alveolar consolidation or pleural effusion (WHO criteria) in the three cohorts were 45% (95% CI: 26%, 60%), 56% (95% CI: 14%, 77%), and 48% (95% CI: 2%, 73%), respectively. Conclusion: PHiD-CV10 vaccination remarkably reduced disease burden due to pneumonia in infants and young children. Clinical trial registration: Main trial NCT00861380, nested carriage and otitis media trial NCT00839254 (ClinicalTrials.gov).
The Pediatric Infectious Disease Journal, 2014
Vaccine RepoRts Background: In 1994, Uruguay included Haemophilus influenzae b (Hib) conjugated vaccine in a 3 + 1 schedule. In March 2008, 7-valent pneumococcal conjugate vaccines (PCV7) was included in a 2 +1 schedule. In 2010, 13-valent PCV replaced PCV7. Catch-up immunization was offered. The aim of this study was to describe the etiology of community-acquired pneumonia (CAP) in children 0-14 years of age hospitalized at the Hospital Pediatrico-Centro Hospitalario Pereira Rossell between 2003 and 2012. Methods: Annual hospitalization rates (per 10,000 discharges) for CAP and bacterial-confirmed CAP in children 0-14 years of age was described prior PCV7 vaccination (2003-2007), during the year of implementation of PCV7 (2008) and after the introduction of PCV7 (2009-2012). Data regarding age, strains isolated from pleural fluid and/or blood, vaccination status, pneumococcal and H. influenzae serotypes were obtained from Hospital Pediatrico-Centro Hospitalario Pereira Rossell databases and vaccination records. Results: Hospitalization rates for CAP and pneumococcal CAP between prevaccine years and the last year after introduction of vaccination with PCV (2012) significantly decreased by 78.1% and 92.4%, respectively. Significant reduction for 13-valent PCV vaccine serotypes and significant increase for nonvaccine serotypes was observed. A decrease in Staphylococcus aureus pneumonia was observed. Hospitalization rates for H. influenzae CAP remain stable before and after pneumococcal vaccination. Conclusions: Three years after PCV7/13 introduction into the routine vaccination schedule, there was a rapid and significant reduction in rates of CAP and P-CAP. An increase of etiology of CAP by other agents was not observed.
The Lancet Respiratory Medicine, 2014
Background Vaccine effectiveness of pneumococcal conjugate vaccines against culture-confirmed invasive pneumococcal disease has been well documented. In the Finnish Invasive Pneumococcal disease (FinIP) trial, we reported vaccine effectiveness and absolute rate reduction against laboratory-confirmed invasive pneumococcal disease (confirmation by culture or antigen or DNA detection irrespective of serotype). Here, we assessed vaccine effectiveness of PHiD-CV10 against clinically suspected invasive pneumococcal disease in children by use of diagnoses coded in hospital discharge registers. Methods For this phase 3/4 cluster-randomised, double-blind trial, undertaken between Feb 18, 2009, and Dec 31, 2011, in municipal health-care centres and the Tampere University Vaccine Research Centre (Finland), we randomly assigned (2:2:1:1) 78 clusters into PHiD-CV10 three plus one, PHiD-CV10 two plus one, control three plus one, control two plus one groups (26:26:13:13 clusters) to give PHiD-CV10 in either three plus one or two plus one schedule (if enrolled before 7 months of age; infant schedules), two plus one (if enrolled between 7 and 11 months; catch-up schedules), and two doses at least 6 months apart (if enrolled between 12 and 18 months; catch-up schedules). Children were eligible if they had not received and were not anticipated to receive any of the study vaccines and had no general contraindications to vaccinations. We collected all inpatient and outpatient discharge notifications from the national hospital discharge register with International Classification of Diseases (ICD) 10 diagnoses compatible with invasive pneumococcal disease or unspecified sepsis, and verified data with patient files. We excluded invasive pneumococcal disease cases confirmed by positive culture or DNA/RNA detection from normally sterile body fluid. The primary objective was to estimate vaccine effectiveness against all register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis and patient-file verified non-laboratory-confirmed invasive pneumococcal disease in infants younger than 7
pneumococcal conjugate vaccine in children in six Latin American countries
2013
Background: A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in
BMC infectious diseases, 2014
The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjust...
The Pediatric infectious disease journal, 2017
Streptococcus pneumoniae is the leading cause of acute otitis media (AOM). Pneumococcal non-typable Haemophilus influenzae Protein D Conjugate Vaccine (PCV-10) was introduced to the Chilean national immunization program (NIP) in 2011. The aim of this study was to estimate the frequency of AOM in children < 24 months of age attending the Emergency Department (ED) of Hospital Sótero del Río (HSR) 4 years before and 4 years after the introduction of PCV-10 in the Chilean NIP. Register-based nested case-control study. Cases (n = 1,907) were all children < 24 months of age with a clinical diagnosis discharge of AOM at the ED of HSR, and controls (n = 244,334) were all other children < 24 months of age attended at the same ED in the same time period, with any other discharge diagnosis. The data were obtained through HSR Statistical Service. In the study period there was a mean of 30,695 children < 24 months managed each year at the ED of HSR. The percentage with AOM in the pre...
Vaccine, 2011
In Australia the 7-valent pneumococcal conjugate vaccine (PCV7) is administered at 2, 4 and 6 months of age, with no booster dose. Information on bacterial carriage and the aetiology of recurrent acute otitis media (rAOM) after introduction of PCV7 using the 3 + 0 schedule is required to evaluate the potential impact of second generation pneumococcal vaccines. We found that 2-4 years after introduction of PCV7 in the National Immunisation Program, nontypeable Haemophilus influenzae (NTHi) was the predominant pathogen isolated from the nasopharynx and middle ear of children with a history of rAOM. Compared with healthy controls (n = 81), NTHi and Streptococcus pneumoniae carriage rates were significantly higher in children with a history of rAOM (n = 186) (19% vs. 56% p < 0.0001 and 26% vs. 41%, p = 0.02, respectively). Carriage of PCV7 pneumococcal serotypes was rare, whereas PCV7-related and non-PCV7 serotypes were isolated of 38% of cases and 24% of controls. Serotype 19A was the most common serotype isolated from the nasopharynx and middle ear and accounted for 36% (14/39) of total pneumococcal isolates with reduced susceptibility to cotrimoxazole. Of the 119 children carrying NTHi, 17% of isolates were -lactamase positive. The scarcity of PCV7 serotypes in children with and without a history of rAOM indicates that the 3 + 0 PCV7 schedule is preventing carriage and rAOM from PCV7 serotypes. Introduction of new vaccines in Australia with increased pneumococcal serotype and pathogen coverage, including 19A and NTHi, should decrease the circulation of antibiotic-resistant bacteria and reduce the burden of rAOM.