Trend of measles-rubella vaccination coverage and impact on measles epidemiology in the Savannah Region, Ghana; 2018-2022: A secondary data analysis.

INTRODUCTION: Ghana witnessed an outbreak of measles in 2022 following the COVID-19 pandemic, and Savannah Region was among the regions severely impacted. The objective of this study was to conduct trend analysis of measles case incidence and measles-rubella (MR) vaccination coverage in the Savannah Region to identify gaps and propose remedial actions to mitigate future outbreaks of vaccine preventable diseases (VPDs). METHODS: Analysis of measles surveillance and measles-rubella vaccination data for 2018-2022 was conducted to assess relationship between immunization coverage and measles case incidence. Data were extracted from the District Health Information Management System (DHIMS) platform and loaded into Microsoft Excel 16.0 spreadsheet for analysis. Coverages for first (MR1) and second (MR2) doses of measles-rubella vaccination, dropout rates, and measles incidence (per 100,000) were calculated. RESULTS: The coverage trend for both vaccine doses followed similar trajectories, increasing from 2018 to a peak in 2019, and declining sequentially thereafter to the lowest (for the study period) in 2022. Generally, MR1/MR2 dropout rate was high across all districts during the entire study period. The regional incidence of confirmed measles rose sharply from less than 1/1,000,000 in 2018-2021 to 94 in 2022. Wide variations in vaccination coverage and dropout rates were observed among the districts. There was moderate to fairly strong negative correlation between MR vaccination coverage and measles case incidence. CONCLUSIONS: The MR vaccination coverage in the Savannah Region declined probably due to pre-existing weaknesses in the immunization programme accentuated by impact of the COVID-19 pandemic. The lowered population immunity likely contributed to occurrence of the measles outbreak in 2022. Pragmatic actions are needed to catch-up on missed children, restore coverage to pre-pandemic levels, and strengthen the immunization programme as part of global efforts towards achieving the Immunization Agenda 2030 (IA2030) trajectory.

Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia-Results of a phase 1/2 randomized, double-blinded, controlled trial.

BACKGROUND: A more affordable pneumococcal conjugate vaccine (PCV) that provides comparable protection to current PCVs is needed to ensure sustainable access in resource-limited settings. Serum Institute of India Pvt. Ltd.'s PCV candidate (SIIPL-PCV) has the potential to meet this need as manufacturing efficiency has been optimized and the vaccine targets the most prevalent disease-causing serotypes in Africa and Asia. We report SIIPL-PCV's safety, tolerability, and immunogenicity in adults, toddlers, and infants in The Gambia. METHODS: This phase 1/2, randomized, double-blind trial sequentially enrolled 34 PCV-naive adults (18-40 years old), 112 PCV (Prevenar 13® [PCV13])-primed toddlers (12-15 months old), and 200 PCV-naive infants (6-8 weeks old), who were randomized (1:1) to receive SIIPL-PCV or a licensed comparator vaccine. Infants received three-doses of SIIPL-PCV or PCV13 at 6, 10, and 14 weeks of age co-administered with routine Expanded Program on Immunization (EPI) vaccines. Reactogenicity was solicited through seven-days post-vaccination; unsolicited adverse events (AEs) were assessed throughout the study. The safety and immunogenicity of a matching booster at 10-14 months of age were evaluated in a subset of 96 infants. Immune responses were evaluated post-primary and pre- and post-booster vaccinations. RESULTS: Reactogenicity was primarily mild-to-moderate in severity. In infants, the most common solicited reactions were injection-site tenderness and fever, with no meaningful treatment-group differences. There were no serious or severe vaccine-related AEs and no meaningful trends in SAEs, vaccine-related AEs, or overall AEs. Infant post-primary seroresponse rates (IgG level ≥ 0.35 µg/mL) were ≥89% for all serotypes except 6A (79%) in the SIIPL-PCV group. IgG GMCs were >1 µg/mL for all serotypes in both SIIPL-PCV and PCV13 groups. Post-booster GMCs were comparable between groups. CONCLUSION: SIIPL-PCV was well-tolerated, had an acceptable safety profile, and was immunogenic for all vaccine serotypes. Results support the evaluation of SIIPL-PCV in a phase 3 non-inferiority trial. Clinicaltrials.gov: NCT02308540.

Recall and decay of consent information among parents of infants participating in a randomized controlled clinical trial using an audio-visual tool in The Gambia.

Communicating essential research information to low literacy research participants in Africa is highly challenging, since this population is vulnerable to poor comprehension of consent information. Several supportive materials have been developed to aid participant comprehension in these settings. Within the framework of a pneumococcal vaccine trial in The Gambia, we evaluated the recall and decay of consent information during the trial which used an audio-visual tool called 'Speaking Book', to foster comprehension among parents of participating infants. The Speaking Book was developed in the 2 most widely spoken local languages. Four-hundred and 9 parents of trial infants gave consent to participate in this nested study and were included in the baseline assessment of their knowledge about trial participation. An additional assessment was conducted approximately 90 d later, following completion of the clinical trial protocol. All parents received a Speaking Book at the start of the trial. Trial knowledge was already high at the baseline assessment with no differences related to socio-economic status or education. Knowledge of key trial information was retained at the completion of the study follow-up. The Speaking Book (SB) was well received by the study participants. We hypothesize that the SB may have contributed to the retention of information over the trial follow-up. Further studies evaluating the impact of this innovative tool are thus warranted.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial.

BACKGROUND: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). METHODS: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35µg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. RESULTS: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35µg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. CONCLUSIONS: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.

The Immunogenicity of Fractional Intradermal Doses of the Inactivated Poliovirus Vaccine Is Associated With the Size of the Intradermal Fluid Bleb.

The immunogenicity of fractional (one-fifth, 0.1 mL) intradermal doses of the inactivated poliovirus vaccine (ID fIPV) is positively correlated with the size of the intradermal fluid bleb. Training of vaccinators for campaign and routine ID fIPV administration should focus on generating an 8- to 10-mm bleb with each injection. Clinical Trials Registration NCT01847872.

Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.

BACKGROUND: The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. METHODS: We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. FINDINGS: Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7]; serotype 2, 0·0% [-2·1 to 2·1]; serotype 3, 0·0% [-3·8 to 3·9]). Poliovirus seroprevalence was universally high (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route. There were no safety concerns. INTERPRETATION: The data support the future co-administration of IPV, measles-rubella, and yellow fever vaccines within the Expanded Programme on Immunization schedule at 9 months. The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated, although it results in a high post-vaccination poliovirus seroprevalence. FUNDING: Bill & Melinda Gates Foundation.