Doses Of Pneumococcal Conjugate Vaccine Research Articles

Epidemiology of childhood invasive pneumococcal disease in Australia: a prospective cohort study

BackgroundThe widespread use of pneumococcal conjugate vaccines (PCV) has changed the epidemiology of invasive pneumococcal disease (IPD) in children globally.MethodsMulticentre prospective audit of IPD episodes from five paediatric hospitals in...

Spatial variation and predictors of incomplete pneumococcal conjugate vaccine (PCV) uptake among children aged 12-35 months in Ethiopia: spatial and multilevel analyses.

Despite the Ethiopian government included the Pneumococcal Conjugate Vaccine (PCV) in the national expanded program for immunization in 2011, only 56% of children aged 12-23 months received the full dose of PCV. Despite some studies on PCV uptake in Ethiopia, there was a dearth of information on the geographical distribution and multilevel factors of incomplete PCV uptake. Hence, this study aimed to identify the spatial variations and predictors of incomplete PCV uptake among children aged 12-35 months in Ethiopia. The study was based on an in-depth analysis of 2016 Ethiopia Demographic Health Survey data, using a weighted sample of 3,340 women having children aged 12-35 months. Arc-GIS version 10.7 and SaTScan version 9.6 statistical software were used for the spatial analysis. To explore spatial variation and locate spatial clusters of incomplete PCV, the Global Moran's I statistic and Bernoulli-based spatial scan (SaTScan) analysis were carried out, respectively. A multilevel mixed-effect multivariable logistic regression was done by STATA version 16. Adjusted odds ratio (AOR) with its corresponding 95% CI was used as a measure of association, and variables with a p < 0.05 were deemed as significant determinants of incomplete PCV. The overall prevalence of incomplete PCV in Ethiopia was found to be 54.0% (95% CI: 52.31, 55.69), with significant spatial variation across regions (Moran's I = 0.509, p < 0.001) and nine most likely significant SaTScan clusters. The vast majority of Somali, southeast Afar, and eastern Gambela regions were statistically significant hot spots for incomplete PCV. Lacking ANC visits (AOR = 2.76, 95% CI: 1.91, 4.00), not getting pre-birth Tetanus injections (AOR = 1.84, 95% CI: 1.29, 2.74), home birth (AOR = 1.72, 95% CI: 1.23, 2.34), not having a mobile phone (AOR = 1.64, 95% CI: 1.38, 1.93), and residing in a peripheral region (AOR = 4.63; 95% CI: 2.34, 9.15) were identified as statistically significant predictors of incomplete PCV. The level of incomplete PCV uptake was found to be high in Ethiopia with a significant spatial variation across regions. Hence, the federal and regional governments should collaborate with NGOs to improve vaccination coverage and design strategies to trace those children with incomplete PCV in peripheral regions. Policymakers and maternal and child health program planners should work together to boost access to maternal health services like antenatal care and skilled delivery services to increase immunization coverage.

Will two doses of pneumococcal conjugate vaccine be enough?

Will two doses of pneumococcal conjugate vaccine be enough?

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12–36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines

ObjectivesIn remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. MethodsIn two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28–38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12–36 months, by booster dose. ResultsFrom March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference −3% [95% Confidence Interval −11, 5]). At each age prevalence of bilateral OM was 52%–78%, and tympanic membrane perforation was 10%–18%. ConclusionDespite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study

BackgroundThe impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18–24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. MethodsIndigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. Results11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87–1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16–1.35) and specified (HR 0.89; 95% CI: 0.49–1.62) from unspecified causes (HR 1.13; 95% CI: 0.86–1.49). During the baseline period before PPV23 vaccination (12–18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30–2.28). ConclusionIn this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18–30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

Antibody response to pneumococcal conjugate vaccine 10 among Nigerian children under 5 years.

Invasive pneumococcal diseases have been a major contributor to childhood mortality, particularly in the developing world and pneumococcal vaccines were introduced to reduce the burden. The Pneumococcal Conjugate Vaccine 10 (PCV 10) was incorporated into the Nigerian National Programme on Immunization (NPI) in 2014 to reduce the incidence of childhood pneumococcal infections. This study was done to determine the immunogenicity of the vaccine in our clime. This cross-sectional study was carried out between September 2019 and January 2020 at the Children Outpatient Clinic of the Federal Medical Center, Owerri, Nigeria. Two hundred and forty five children between the ages of 20 weeks and 59 months, who had received three doses of Pneumococcal Conjugate Vaccine 10 (PCV 10) at 6, 10 and 14 weeks according to the NPI schedule, were recruited into the study. The anti-pneumococcal PCV 10 IgG concentration was determined using Human Anti-Pneumococcal CPS 10 IgG vaccine ELISA Kit ®. Simple proportions, means and median (as appropriate) were used to analyse the data. Kruskal Wallis test and Spearman's correlation were done to test association. Significance was set as p< 0.05. The mean anti-pneumococcal IgG concentration was 11.01±1.23 IU/ml and all the study participants formed protective levels of anti-pneumococcal IgG. There was a slight positive correlation between antibody response and age (r=0.13, p=0.04), and the antibody response was slightly more in males than females. All the children under the age of five years who had received PCV 10 at 6, 10 and 14 weeks of age, who participated in this study formed protective levels of antibodies to the vaccine. Antibody levels increased slightly with age. The PCV 10 currently used in the Nigerian programme is sufficiently antigenic and a downward trend in pneumococcal diseases should soon be noticeable.

A phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in allogeneic hematopoietic cell transplant recipients (PNEU-STEM).

Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk for pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE™), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients. Participants received 3 doses of V114 or PCV13 in one-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV (if they experienced chronic graft versus host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group. A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and higher for V114 serotypes 22F and 33F. Study results support use of V114 in allo-HCT recipients.

Adherence to vaccination guidelines of patients with complete splenectomy in Norway, 2008–2020

The spleen is responsible for blood filtration and mounting an immune response against pathogens. In some people the spleen must be surgically removed because of traumatic events or oncological and hematological conditions. These patients are at higher risk of developing diseases caused by encapsulated bacteria throughout their lives. Thus, immunisations are advised for splenectomised persons to prevent infection caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). This study assessed vaccination coverage (VC) among Norwegian patients with surgical asplenia. Using the Nomesco Classification of Surgical Procedures codes, patient information (age, sex, date of initial diagnosis and date of surgery) was acquired from the Norwegian Patient Registry. The National Immunization Register provided information on vaccination status and data of any subsequent invasive bacterial infections were obtained from the Norwegian Surveillance System for Communicable Diseases. From the total population of Norway, 3155 patients who had undergone complete splenectomy were identified. Of these, 914 (29.0%) had received at least one dose of pneumococcal conjugate vaccine (PCV), 1324 (42.0%) at least one dose of pneumococcal polysaccharide vaccine and 589 (18.7%) had received both. Only 4.2% of the patients had received two doses of a meningococcal ACWY conjugate vaccine, while 8.0% of 1467 patients splenectomised after 2014 had received at least two doses of a serogroup B meningococcal vaccine. The VC for Hib was 18.7%. Nearly all splenectomised children under the age of 10 were vaccinated with Hib and PCV as these vaccines are included in the childhood immunisation program. For all vaccines, VC decreased with age. Twenty-nine invasive bacterial infections were registered post-splenectomy in 25 patients. Vaccination according to national recommendations could have prevented at least 8 (28%) of these infections. Our study showed that efforts are required to increase VC of splenectomised individuals in Norway.

What is associated with reported acute respiratory infection in children under 5 and PCV vaccination in children aged 1-36 months in Malawi? A secondary data analysis using the Malawi 2014 MICS survey.

Acute respiratory illness (ARI) is a leading cause of mortality in children under 5 (CU5) in Malawi and can be prevented with 3-dose pneumococcal conjugate vaccine (PCV). There has been no national study in Malawi that seeks to associate social economic factors leading to PCV vaccine uptake and reported acute respiratory infections (RARI). The objectives of our study were to do this. We conducted a cross-sectional analysis of secondary data from the 2014 UNICEF Malawi Multiple Indicator Cluster Survey to construct mutlivariable logistic regression models for independent associations with PCV 1/2/3 immunisation and RARI. 56% of CU5 in Malawi RARI in the 2 week recall period of the survey. Independent associations with reduced odds of RARI were central region living (OR 0.82, 95%CI (0.71-0.93)) middle (OR 0.84, (0.73-0.97)) fourth (OR 0.79, (0.68-0.92)) and richest wealth quintiles (OR 0.73, (0.60-0.88)). Using straw/shrubs for fuel was associated with increased RARI (OR 3.13, (1.00-9.79)). Among 1-36 month olds, in 2014, 93.3% received PCV1, 86.8% PCV2 and 77.0% PCV3. Between 2011-2014, the average age in months for a child to receive PCV1/2/3 reduced by 26.6 for PCV1, 26.4 for PCV2, and 26.1 for PCV 3. Independent predicators for increased odds of all 3 PCV doses, relative to 0-5 age group, were age group 6-11 (OR 21.8, (18.2-26.1) 12-23 (OR 27.5, (23.5-32.2) 24-36 months (OR 9.09, (7.89-10.5), mothers having a secondary (OR 1.52, (1.25-1.84)) or higher education (OR 2.68, (1.43-5.04) when compared to no education, and children in the middle (OR 1.24, (1.07-1.43)) fourth (OR 1.27, (1.09-1.48)) richest (OR 1.54, (1.27-1.88)) wealth quintiles relative to the lowest. Children living with 4-6 other children was independently associated with reduced odds of receiving all 3 PCV doses (OR 0.56, (0.33-0.96). We report nationally representative social economic associations with RARI and PCV vaccine uptake and coverage estimates. We found reductions in the average age a child receives all 3 PCV vaccine doses between 2011-2014.

P07 A Phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114 pneumococcal vaccine in haematopoietic cell transplant recipients (PNEU-STEM)

Abstract Background Allogeneic haematopoietic cell transplant (allo-HCT) represents a definitive therapy for a variety of haematological diseases. Immunosuppressive therapy following allo-HCT and graft-versus-host disease (GVHD) render the patient susceptible to infectious complications, including invasive pneumococcal disease. Post-allo-HCT pneumococcal vaccination is recommended 3–6 months after transplant in a multi-dose series to help prevent pneumococcal disease. Objectives V114 is a 15-valent pneumococcal conjugate vaccine (PCV) approved in adults, containing all 13 serotypes in Prevnar 13™ (PCV13; contains serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) as well as epidemiologically important serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 when given to allo-HCT recipients. Methods Individuals ≥3 years of age were randomized 1:1 to receive 3 doses of V114 or PCV13 in one-month intervals starting 3–6 months after allo-HCT. At 12 months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV if they experienced chronic GVHD. All participants or their legal representatives provided informed consent at enrolment. Primary safety objective was to evaluate the proportion of participants with adverse events (AEs) within each vaccination group for 3 to &amp;lt;18 years old and ≥18 years old age groups. Primary immunogenicity objective was to evaluate serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) for all 15 V114 serotypes at 30 days following the third PCV dose (Day 90) in each vaccination group. A key secondary objective was to evaluate opsonophagocytic activity (OPA) geometric mean titres (GMTs) for all V114 serotypes at Day 90. Results A total of 274 subjects (14 children [3 to &amp;lt;18 years of age] and 260 adults ≥18 years old) were enrolled and vaccinated in the study. The proportion of participants with systemic AEs and serious AEs after any dose of study vaccine were generally comparable between intervention groups in the paediatric and adult cohorts. V114 recipients reported a higher proportion of injection-site AEs and vaccine-related systemic AEs compared with PCV13 in the adult cohort. Of all vaccinated participants, 32.4% experienced serious AEs during the study (28.8% in V114 group, 36.3% in PCV13 group). Seventeen participants (5.8% in V114 group, 6.7% in PCV13 group) died during the study. None of the deaths was determined by the investigator to be related to study vaccines. For both IgG GMCs (Table 1) and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. Conclusions V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13 for both paediatric and adult participants. Despite the immunocompromised status of the participants, the study vaccines induced serotype-specific immunogenicity and V114 induced generally comparable responses to PCV13 by IgG GMCs and OPA for the 13 shared serotypes at Day 90. In addition, V114 induced higher antibody responses than PCV13 for serotypes unique to V114 (22F and 33F). Study results support the use of V114 in allo-HCT recipients.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

ABSTRACT This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Reduced risk of serious pneumococcal infections up to 10years after a dose of pneumococcal conjugate vaccine in established arthritis.

To examine rates of serious pneumococcal infections up to 10years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. In total, 595 adult arthritis patients (rheumatoid arthritis; RA=342, 80% women and spondylarthropathy; SpA=253, 45% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14years, respectively. For each patient, 4 matched reference subjects were identified. At vaccination, 420 patients received bDMARDs (anti-TNF=330, tocilizumab=15, abatacept=18, anakinra=1, rituximab=56). Methotrexate was given as monotherapy (n=86) or in combination with bDMARD (n=220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections. Among vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10years in patients with arthritis receiving immunomodulating treatment.

Coverage and Equity of Childhood Vaccines in China

Measuring vaccination coverage rates and equity is crucial for informing immunization policies in China. To estimate coverage rates and multidimensional equity for childhood vaccination in China. This cross-sectional study was conducted via a survey in 10 Chinese provinces between August 5 and October 16, 2019, among children ages 6 months to 5 years and their primary caregivers. Children's vaccination records and their primary caregivers' demographics and socioeconomic status were collected. Data were analyzed from November 2019 to March 2022. Vaccine coverage rates were measured as a percentage of National Immunization Program (NIP) and non-NIP vaccines administered before the day on which the child was surveyed. A multidimensional equity model applied a standardized approach to ranking individuals from least to most unfairly disadvantaged by estimating differences between observed vaccination status and estimated vaccination status as function of fair and unfair variation. Fair sources of variation in coverage included whether the child was of age to receive the vaccine, and unfair sources of variation included sex of the child and sociodemographic characteristics of caregivers. Absolute equity gaps (AEGs), concentration index values, and decompositions of factors associated with vaccine equity were estimated in the model. Vaccine records and sociodemographic information of 5294 children (2976 [52.8%] boys and 2498 [47.2%] girls; age range, 6-59 months; 1547 children aged 12-23 months) and their primary caregivers were collected from 10 provinces. Fully immunized coverage under the NIP was 83.1% (95% CI, 82.0%-84.1%) at the national level and more than 80% in 7 provinces (province coverage ranged from 77.8% [95% CI, 74.3% to 81.3%] in Jiangxi to 88.4% [95% CI, 85.7%-91.1%] in Beijing). For most non-NIP vaccines, however, coverage rates were less than 50%, ranging from 1.8% (95% CI, 1.3%-2.2%) for the third dose of rotavirus vaccine to 67.1% (65.4% to 68.8%) for the first dose of the varicella vaccine. The first dose of Haemophilus influenzae type b vaccine had the largest AEG, at 0.603 (95% CI, 0.570-0.636), and rotavirus vaccine dose 3 had the largest concentration index value, at 0.769 (95% CI, 0.709-0.829). The largest share of non-NIP vaccine inequity was contributed by monthly family income per capita, followed by education level, place of residence, and province for caregivers. For example, the proportion of explained inequity for pneumococcal conjugate vaccine dose 3 was 40.94% (95% CI, 39.49%-42.39%), 22.67% (95% CI, 21.43%-23.9%), 27.15% (95% CI, 25.84%-28.46%), and 0.68% (95% CI, 0.44%-0.92%) for these factors, respectively. This cross-sectional study found that NIP vaccination coverage in China was high but there was inequity for non-NIP vaccines. These findings suggest that improvements in equitable coverage of non-NIP vaccination may be urgently needed to meet national immunization goals.

The determinants of immunization coverage among children aged between 12 and 35 months: a nationwide cross-sectional study in Lao People’s Democratic Republic

BackgroundImmunization is one of the most important public health interventions for reducing morbidity and mortality in children. However, factors contributing to low immunization coverage are not fully understood in the Lao People’s Democratic Republic (Lao PDR). Therefore, this study aimed to identify factors associated with full immunization coverage among children between 12 and 35 months, providing up-to-date information for immunization programs in Lao PDR.MethodsWe analyzed the subpopulation of a nationwide cross-sectional survey using a multistage cluster sampling procedure to evaluate the measles and rubella seroepidemiology. In addition, we categorized children aged between 12 and 35 months into two groups: “fully immunized” children with a birth dose of Bacillus Calmette and Guérin vaccine, hepatitis B vaccine (Hep B), one and three doses for the measles-containing vaccine (MCV) and pentavalent vaccine and pneumococcal conjugate vaccine (PCV) and “partially immunized” children who missed any dose of vaccine. Immunization coverage was calculated as the ratio of “fully immunized” to the total. We compared the groups’ demographic characteristics and health service utilization as independent variables. Multivariate logistic regression was used to assess the relationship between immunization coverage, various demographic factors, and health service utilization.ResultsOverall, 256 of the 416 targeted pairs were included in the analysis. In total, 67.6% of the children were fully immunized. Childbirth at hospitals or health facilities (adjusted odds ratio: 9.75, 95% confidence interval: 5.72–16.62, p < 0.001) was the predictor of full immunization coverage. The 83 children in the partially immunized groups were attributed to Hep B at birth (46, 55.4%), three doses of PCV (34, 41.0%), and the first dose of the MCV (27, 32.5%).ConclusionOur study elucidated that the immunization status among children aged between 12 and 35 months in Lao PDR is satisfactory in improving access to healthcare by strengthening communication with residents regarding health service utilization, and expanding mobile outreach services may play a pivotal role in this endeavor. Further research is warranted to evaluate efforts to increase immunization coverage and target populations with limited access to healthcare.

Effect of different schedules of ten-valent pneumococcal conjugate vaccine on pneumococcal carriage in Vietnamese infants: results from a randomised controlled trial

WHO recommends a three-dose infant pneumococcal conjugate vaccine (PCV) schedule administered as a two-dose primary series with booster (2+1) or a three-dose primary series (3+0). Data on carriage impacts of these and further reduced PCV schedules are needed to inform PCV strategies. Here we evaluate the efficacy against carriage of four different PCV10 schedules. Participants within an open-label, randomised controlled trial in Ho Chi Minh City, Vietnam, were allocated to receive PCV10 in a 3+1 (2,3,4,9 months, n=152), 3+0 (2,3,4 months, n=149), 2+1 (2,4,9.5 months, n=250) or novel two-dose (2,6 months, n=202) schedule, or no infant doses of PCV (two control groups, n=197 and n=199). Nasopharyngeal swabs collected between 2 and 24 months were analysed (blinded) for pneumococcal carriage and serotypes. Trial registration: ClinicalTrials.gov NCT01953510. Pneumococcal carriage prevalence was low (10.6-14.1% for vaccine-type (VT) at 12-24 months in unvaccinated controls). All four PCV10 schedules reduced VT carriage compared with controls (the 2+1 schedule at 12, 18, and 24 months; the 3+1 and two-dose schedules at 18 months; and the 3+0 schedule at 24 months), with maximum reductions of 40.1%-64.5%. There were no differences in VT carriage prevalence at 6 or 9 months comparing three-dose and two-dose primary series, and no differences at 12, 18, or 24 months when comparing schedules with and without a booster dose. In Vietnamese children with a relatively low pneumococcal carriage prevalence, 3+1, 2+1, 3+0 and two-dose PCV10 schedules were effective in reducing VT carriage. There were no discernible differences in the effect on carriage of the WHO-recommended 2+1 and 3+0 schedules during the first two years of life. Together with the previously reported immunogenicity data, this trial suggests that a range of PCV schedules are likely to generate significant direct and indirect protection. NHMRC, BMGF.

Antibody Response against Vaccine Antigens in Children after TCRαβ-Depleted Haploidentical Stem Cell Transplantation: Is It Similar to That in Recipients with Fully Matched Donors?

Recipients of hematopoietic stem cell transplantation (HSCT) with HLA-mismatched donors are more immune suppressed than those with fully matched donors. The immunologic response to vaccines also may differ in HLA-mismatched haploidentical HSCT recipients. In this study, we aimed to evaluate the antibody response to vaccines in pediatric TCRαβ-depleted haploidentical HSCT recipients. This longitudinal study included a study group of 21 children who underwent haploidentical HSCT without CD19 depletion and with TCRαβ depletion and a control group of 38 children who underwent fully matched donor HSCT. Antibody levels were quantified by serologic tests before vaccination and after each dose against tetanus, diphtheria, pneumococcus, hepatitis B, hepatitis A, measles, rubella, mumps, and varicella. The median recipient age was significantly lower (P=.037) and the median donor age was significantly higher (P=.000) in the haploidentical group compared with the fully matched group. At the months 1, 3, 6, 9 and 12 post-transplantation, the median CD4, CD8, and CD19 cell counts and lymphocyte counts were similar in the haploidentical and fully matched groups. The median natural killer cell count was higher in the haploidentical group at the months 1, 3, and 6 post-transplantation (P=.001, .006, and .004, respectively). The median time to first vaccination was similar in the 2 groups (12.5 [range, 11 to 14] months for the haploidentical group and 11 [range, 9 to 13] months for the fully matched group; P=.441). Seroprotection rates were 100% in both groups after the second and third doses of diphtheria vaccine, the third dose of tetanus vaccine, the third dose of hepatitis B vaccine, the second and third doses of pneumococcal conjugate vaccines (PCV13), and pneumococcal polysaccharide vaccine (PSPV23), although lower after the initial doses and before vaccination. Seroprotection for hepatitis A, rubella, and varicella was >90% in the fully matched group and 100% for the haploidentical group after the second doses. Measles and mumps seroprotection rates were >80% in the haploidentical group and approximately 70% for the fully matched group after the second dose. Antibody response and seroprotection rates against vaccine antigens were similar in the haploidentical group and the fully matched when revaccination was started at 12 months post-transplantation. These findings support the idea that TCRαβ-depleted haploidentical HSCT recipients can be revaccinated according to the same vaccination schedule as fully matched HSCT recipients. Revaccination earlier after transplantation and vaccine responses for recipients of different types of HSCT should be evaluated in future studies.

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials

Australian First Nations children are at very high risk of early, recurrent, and persistent bacterial otitis media and respiratory tract infection. With the PREVIX randomised controlled trials, we aimed to evaluate the immunogenicity of novel pneumococcal conjugate vaccine (PCV) schedules. PREVIX_BOOST was a parallel, open-label, outcome-assessor-blinded, randomised controlled trial. Aboriginal children living in remote communities of the Northern Territory of Australia were eligible if they had previously completed the three-arm PREVIX_COMBO randomised controlled trial of the following vaccine schedules: three doses of a 13-valent PCV (PCV13; PPP) or a ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10; SSS) given at 2, 4, and 6 months, or SSS given at 1, 2, and 4 months followed by PCV13 at 6 months (SSSP). At age 12 months, eligible children were randomly assigned by a computer-generated random sequence (1:1, stratified by primary group allocation) to receive either a PCV13 booster or a PHiD-CV10 booster. Analyses used intention-to-treat principles. Co-primary outcomes were immunogenicity against protein D and serotypes 3, 6A, and 19A. Immunogenicity measures were geometric mean concentrations (GMC) and proportion of children with IgG concentrations of 0·35 μg/mL or higher (threshold for invasive pneumococcal disease), and GMCs and proportion of children with antibody levels of 100 EU/mL or higher against protein D. Standardised assessments of otitis media, hearing impairment, nasopharyngeal carriage, and developmental outcomes are reported. These trials are registered with ClinicalTrials.gov (NCT01735084 and NCT01174849). Between April 10, 2013, and Sept 4, 2018, 261 children were randomly allocated to receive a PCV13 booster (n=131) or PHiD-CV10 booster (n=130). Adequate serum samples for pneumococcal serology were obtained from 127 (95%) children in the PCV13 booster group and 126 (97%) in the PHiD-CV10 booster group; for protein D, adequate samples were obtained from 126 (96%) children in the PCV13 booster group and 123 (95%) in the PHiD-CV10 booster group. The proportions of children with IgG concentrations above standard thresholds in PCV13 booster versus PHiD-CV10 booster groups were the following: 71 (56%) of 126 versus 81 (66%) of 123 against protein D (difference 10%, 95% CI -2 to 22), 85 (67%) of 127 versus 59 (47%) of 126 against serotype 3 (-20%, -32 to -8), 119 (94%) of 127 versus 91 (72%) of 126 against serotype 6A (-22%, -31 to -13), and 116 (91%) of 127 versus 108 (86%) of 126 against serotype 19A (-5%, -13 to 3). Infant PCV13 priming mitigated differences between PCV13 and PHiD-CV10 boosters. In both groups, we observed a high prevalence of otitis media (about 90%), hearing impairment (about 75%), nasopharyngeal carriage of pneumococcus (about 66%), and non-typeable H influenzae (about 57%). Of 66 serious adverse events, none were vaccine related. Low antibody concentrations 6 months post-booster might indicate increased risk of pneumococcal infection. The preferred booster was PCV13 if priming did not have PCV13, otherwise either PCV13 or PHiD-CV10 boosters provided similar immunogenicity. Mixed schedules offer flexibility to regional priorities. Non-PCV13 serotypes and non-typeable H influenzae continue to cause substantial disease and disability in Australian First Nation's children. National Health and Medical Research Council (NHMRC).

P1576: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, COMPARATOR-CONTROLLED STUDY TO EVALUATE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF V114 PNEUMOCOCCAL VACCINE IN HEMATOPOIETIC CELL TRANSPLANT RECIPIENTS (PNEU-STEM)

Background: Allogeneic hematopoietic cell transplant (allo-HCT) represents a definitive therapy for a variety of hematological diseases. Immunosuppressive therapy following allo-HCT and graft-vs-host disease (GVHD) render the patient susceptible to infectious complications, including invasive pneumococcal disease. Post-allo-HCT pneumococcal vaccination is recommended 3-6 months after transplant in a multi-dose series to help prevent pneumococcal disease. Aims: V114 is a 15-valent pneumococcal conjugate vaccine (PCV) approved in adults, containing all 13 serotypes in Prevnar 13™ (PCV13; contains serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) as well as epidemiologically important serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 when given to allo-HCT recipients. Methods: Individuals ≥3 years of age were randomized 1:1 to receive 3 doses of V114 or PCV13 in one-month intervals starting 3-6 months after allo-HCT. At 12 months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV if they experienced chronic GVHD. All participants or their legal representatives provided informed consent at enrollment. Primary safety objective was to evaluate the proportion of participants with adverse events (AEs) within each vaccination group for 3 to <18 years old and ≥18 years old age groups. Primary immunogenicity objective was to evaluate serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) for all 15 V114 serotypes at 30 days following the third PCV dose (Day 90) in each vaccination group. A key secondary objective was to evaluate opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes at Day 90. Results: A total of 274 subjects (14 children [3 to <18 years of age] and 260 adults ≥18 years old) were enrolled and vaccinated in the study. The proportion of participants with systemic AEs and serious AEs after any dose of study vaccine were generally comparable between intervention groups in the pediatric and adult cohorts. V114 recipients reported a higher proportion of injection-site AEs and vaccine-related systemic AEs compared to PCV13 in the adult cohort. Of all vaccinated participants, 32.4% experienced serious AEs during the study (28.8% in V114 group, 36.3% in PCV13 group). Seventeen participants (5.8% in V114 group, 6.7% in PCV13 group) died during the study. None of the deaths were determined by the investigator to be related to study vaccines. For both IgG GMCs (Table 1) and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. Image:Summary/Conclusion: V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13 for both pediatric and adult participants. Despite the immunocompromised status of the participants, the study vaccines induced serotype-specific immunogenicity and V114 induced generally comparable responses to PCV13 by IgG GMCs and OPA for the 13 shared serotypes at Day 90. In addition, V114 induced higher antibody responses than PCV13 for serotypes unique to V114 (22F and 33F). Study results support the use of V114 in allo-HCT recipients.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BackgroundChildren with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children.MethodsA cohort born in 2001–2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100.ResultsA total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9–97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6–88.9) against all-cause IPD.ConclusionThis is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

ENT/Audiology Department of Samoa welcomes the introduction of the Pneumococcal Conjugate Vaccine (PCV) into the national childhood immunisation program.

In October 2021, the pneumococcal conjugate vaccine (PCV) was introduced into the national immunisation program of Samoa, a Polynesian nation of the Pacific Islands [1]. The immunisation schedule is three doses of PCV for infants (6, 10, and 14 weeks of age), or two catch-up doses with an eight-week interval for toddlers (12-24 months of […]