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PLoS Medicine Jun 2024In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.
BACKGROUND
In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.
METHODS AND FINDINGS
OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again).
CONCLUSIONS
Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups.
TRIAL REGISTRATION
Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).
Topics: Humans; Infant; Double-Blind Method; Immunoglobulin E; Female; Male; Diphtheria-Tetanus-Pertussis Vaccine; Immunization Schedule; Australia; Vaccines, Combined; Pertussis Vaccine; Food Hypersensitivity; Poliovirus Vaccine, Inactivated; Haemophilus Vaccines; Whooping Cough; Immunogenicity, Vaccine; Antibodies, Bacterial
PubMed: 38857311
DOI: 10.1371/journal.pmed.1004414 -
China CDC Weekly May 2024In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated...
WHAT IS ALREADY KNOWN ON THIS TOPIC?
In China, there is limited data available on the use and coverage of the non-program, combined diphtheria, tetanus toxoid, acellular pertussis adsorbed, inactivated poliovirus and haemophilus influenzae type b (DTaP-IPV/Hib) pentavalent vaccine, and its role as a substitute for the separately administered standalone program vaccines.
WHAT IS ADDED BY THIS REPORT?
We evaluated the use and coverage of the pentavalent vaccine in nine provincial-level administrative divisions (PLADs) spanning eastern, central, and western China from 2019 to 2021. Initial use and coverage were low, but demonstrated annual growth albeit with regional and urban-rural discrepancies. The pentavalent vaccine was increasingly substituted for standalone vaccines over the course of this period.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
Parents in China are increasingly opting to replace the standard program vaccines with voluntarily purchased combination vaccines, particularly the pentavalent vaccine. The development of combination vaccines should thus be promoted in China, as it could enhance utilization and coverage rates, and decrease the economic burden.
PubMed: 38854752
DOI: 10.46234/ccdcw2024.083 -
PloS One 2024Polio eradication is a current and common strategy throughout the globe. The study of the newly introduced inactivated poliovirus vaccine provides a grasp on the current...
INTRODUCTION
Polio eradication is a current and common strategy throughout the globe. The study of the newly introduced inactivated poliovirus vaccine provides a grasp on the current status of immunization and identifies any disparities in the implementation of the vaccine throughout Ethiopia. Thus, this study aimed to demonstrate the spatial distribution, coverage, and determinants of inactivated poliovirus vaccine immunization in Ethiopia.
METHOD
Spatial distribution and determinants of inactivated poliovirus vaccine immunization in Ethiopia were conducted using Ethiopian mini-demographic and health survey 2019 data. A total of 2,056 weighted children aged 12 to 35 months were included in the analysis. The association between the outcome and explanatory variables was determined by commuting the adjusted odds ratio at a 95% confidence interval. The p-value of less than 0.05 was used to declare factors as significantly associated with the inactivated poliovirus vaccine immunization.
RESULT
The weighted national coverage of inactivated poliovirus vaccine immunization in Ethiopia was 51.58% at a 95% confidence interval (49.42, 53.74). While the rates of inactivated poliovirus vaccine immunization were observed to be greater in Addis Ababa, Tigiray, Amahara, and Benishangul Gumuz provinces and lower in the Somali, Afar, and SNNPR provinces of Ethiopia, Antenatal care follow-up, place of delivery, place of residence, and region were significantly associated with inactivated poliovirus immunization in Ethiopia.
CONCLUSION
The distribution of inactivated poliovirus immunization was spatially variable across Ethiopia. Only about half of the children aged twelve to thirty-five months received the inactivated poliovirus vaccine in the country. The factors, both at the individual and community level, were significantly associated with inactivated poliovirus immunization. Therefore, policies and strategies could benefit from considering antenatal care follow-up, place of delivery, place of residence, and region while implementing inactivated poliovirus vaccine immunization.
Topics: Humans; Ethiopia; Poliovirus Vaccine, Inactivated; Female; Infant; Poliomyelitis; Male; Child, Preschool; Vaccination Coverage; Vaccination; Immunization Programs; Immunization
PubMed: 38820454
DOI: 10.1371/journal.pone.0301933 -
Science (New York, N.Y.) May 2024
Topics: Humans; Pakistan; Poliomyelitis; Poliovirus; Vaccination; Poliovirus Vaccines
PubMed: 38815030
DOI: 10.1126/science.adp5269 -
Expert Opinion on Drug Safety May 2024Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals.
BACKGROUND
Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of oral poliovirus vaccines (OPV), particularly affecting immunodeficient individuals.
RESEARCH DESIGN AND METHODS
This study aimed to (1) Assess the association between OPV and VAPP using Vaccine Adverse Event Reporting System (VAERS) database (2) Outline patient characteristics and risk factors associated with the occurrence of VAPP in OPV recipients through a systematic review of case reports and case series. A disproportionality analysis was conducted using the data from VAERS, encompassing adverse events reported from 1990 till February 2023. Additionally, we conducted a systematic review of case reports and case series using PubMed, Scopus, and Embase databases.
RESULTS
The VAERS data revealed 130 VAPP reports among 1,739,903 OPV linked adverse events, with year 2010 reporting the strongest association. The systematic review of 37 studies highlighted VAPP occurrence within 2 months to 4 years post-vaccination, typically with acute flaccid paralysis. Immunodeficiency and perianal abscess emerged as major risk factors. Out of the 37 included studies, 27 showed consistent causal association of VAPP with OPV using WHO-AEFI causality assessment tool.
CONCLUSION
The study emphasized the seriousness of VAPP and highlights its association with OPV, identifying immunodeficiency as a prominent contributor to VAPP manifestation.
PubMed: 38813942
DOI: 10.1080/14740338.2024.2359616 -
Expert Review of Vaccines 2024Despite multiple revisions of targets and timelines in polio eradication plans since 1988, including changes in supplemental immunization activities (SIAs) that increase... (Review)
Review
BACKGROUND
Despite multiple revisions of targets and timelines in polio eradication plans since 1988, including changes in supplemental immunization activities (SIAs) that increase immunity above routine immunization (RI) coverage, poliovirus transmission continues as of 2024.
METHODS
We reviewed polio eradication plans and Global Polio Eradication Initiative (GPEI) annual reports and budgets to characterize key phases of polio eradication, the evolution of poliovirus vaccines, and the role of SIAs. We used polio epidemiology to provide context for successes and failures and updated prior modeling to show the contribution of SIAs in achieving and maintaining low polio incidence compared to expected incidence for the counterfactual of RI only.
RESULTS
We identified multiple phases of polio eradication that included shifts in targets and timelines and the introduction of different poliovirus vaccines, which influenced polio epidemiology. Notable shifts occurred in GPEI investments in SIAs since 2001, particularly since 2016. Modeling results suggest that SIAs play(ed) a key role in increasing (and maintaining) high population immunity to levels required to eradicate poliovirus transmission globally.
CONCLUSIONS
Shifts in polio eradication strategy and poliovirus vaccine usage in SIAs provide important context for understanding polio epidemiology, delayed achievement of polio eradication milestones, and complexity of the polio endgame.
Topics: Poliomyelitis; Humans; Disease Eradication; Global Health; Poliovirus Vaccines; Immunization Programs; Incidence; Poliovirus
PubMed: 38813792
DOI: 10.1080/14760584.2024.2361060 -
The Journal of Infectious Diseases May 2024Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on...
BACKGROUND
Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine-induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool.
METHODS
To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2 to 5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs.
RESULTS
PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received four IPV doses. Across the three PV serotypes, both nasal (Spearman's rho ≥ 0.87, p≤0.0003 for all) and adenoid (Spearman's rho ≥0.57, p≤0.05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization.
CONCLUSIONS
Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine-induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.
PubMed: 38809190
DOI: 10.1093/infdis/jiae264 -
BMC Infectious Diseases May 2024To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV,...
BACKGROUND
To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV).
METHODS
A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose.
RESULTS
There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group.
CONCLUSIONS
Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.
Topics: Humans; Poliovirus Vaccine, Inactivated; Poliomyelitis; Infant; Poliovirus Vaccine, Oral; Male; Immunization Schedule; Female; Antibodies, Viral; Cross-Sectional Studies; China; Antibodies, Neutralizing; Poliovirus; Immunogenicity, Vaccine; Vaccination
PubMed: 38807038
DOI: 10.1186/s12879-024-09389-8 -
Microorganisms Apr 2024Enterovirus (EV) infections are widespread and associated with a range of clinical conditions, from encephalitis to meningitis, gastroenteritis, and acute flaccid...
Enterovirus (EV) infections are widespread and associated with a range of clinical conditions, from encephalitis to meningitis, gastroenteritis, and acute flaccid paralysis. Knowledge about the circulation of EVs in neonatal age and early infancy is scarce, especially in Africa. This study aimed to unveil the frequency and diversity of EVs circulating in apparently healthy newborns from the Free State Province, South Africa (SA). For this purpose, longitudinally collected faecal specimens (May 2021-February 2022) from a cohort of 17 asymptomatic infants were analysed using metagenomic next-generation sequencing. Overall, seven different non-polio EV (NPEV) subtypes belonging to EV-B and EV-C species were identified, while viruses classified under EV-A and EV-D species could not be characterised at the sub-species level. Additionally, under EV-C species, two vaccine-related poliovirus subtypes (PV1 and PV3) were identified. The most prevalent NPEV species was EV-B (16/17, 94.1%), followed by EV-A (3/17, 17.6%), and EV-D (4/17, 23.5%). Within EV-B, the commonly identified NPEV types included echoviruses 6, 13, 15, and 19 (E6, E13, E15, and E19), and coxsackievirus B2 (CVB2), whereas enterovirus C99 (EV-C99) and coxsackievirus A19 (CVA19) were the only two NPEVs identified under EV-C species. Sabin PV1 and PV3 strains were predominantly detected during the first week of birth and 6-8 week time points, respectively, corresponding with the OPV vaccination schedule in South Africa. A total of 11 complete/near-complete genomes were identified from seven NPEV subtypes, and phylogenetic analysis of the three EV-C99 identified revealed that our strains were closely related to other strains from Cameroon and Brazil, suggesting global distribution of these strains. This study provides an insight into the frequency and diversity of EVs circulating in asymptomatic infants from the Free State Province, with the predominance of subtypes from EV-B and EV-C species. This data will be helpful to researchers looking into strategies for the control and treatment of EV infection.
PubMed: 38792747
DOI: 10.3390/microorganisms12050920 -
Pathogens (Basel, Switzerland) May 2024Despite coordinated efforts at global level, through the Global Polio Eradication Initiative (GPEI), poliomyelitis disease (Polio) is still a major public health issue....
Polio Surge Capacity Support Program Contributions to Building Country Capacities in Support of Polio Outbreak Preparedness and Response: Lessons Learned and Remaining Challenges.
Despite coordinated efforts at global level, through the Global Polio Eradication Initiative (GPEI), poliomyelitis disease (Polio) is still a major public health issue. The wild poliovirus type-1 (WPV1) is still endemic in Afghanistan and Pakistan, and new circulations of the WPV1 were confirmed in southeast Africa in 2021, in Malawi and Mozambique. The circulating vaccine derived polioviruses (cVDPV) are also causing outbreaks worldwide. The Task Force for Global Health (TFGH)'s Polio Surge Capacity Support Program, established in 2019, is an effort to reinforce the existing partnership with the GPEI to strengthen countries' capacities for polio outbreak preparedness and response. In four years, its coordinated efforts with GPEI partners have resulted in a remarkable improvement in the early detection of poliovirus circulation and reducing the missed children gaps in many countries. However, these encouraging results cannot hide an increasingly complex programmatic environment with numerous funding and operational challenges.
PubMed: 38787229
DOI: 10.3390/pathogens13050377