Pneumococcal Immunization Research Articles

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Risk of pneumonia-related hospitalization after initiating angiotensin-converting enzyme inhibitors compared with angiotensin II receptor blockers: a retrospective cohort study using LIFE Study data.

There is insufficient evidence that angiotensin-converting enzyme inhibitors (ACEIs) can reduce pneumonia by inducing a dry cough that confers a protective effect on the airway. To increase the evidence base on the clinical use of ACEIs for pneumonia prevention, this retrospective cohort study aimed to comparatively examine the risk of pneumonia-related hospitalization between ACEI initiators and angiotensin II receptor blocker (ARB) initiators using claims data from two Japanese municipalities. We identified persons who were newly prescribed any ACEI or ARB as their first antihypertensive agent between April 2016 and March 2020. The Fine-Gray method was applied to a Cox proportional hazards model to estimate the subdistribution hazard ratio (HR) of ACEI use (reference: ARB use) for pneumonia-related hospitalization, with death treated as a competing risk. Sex, age, comorbidities, medications, and pneumococcal immunization were included as covariates. The analysis was conducted on 1421 ACEI initiators and 9040 ARB initiators, and the adjusted subdistribution HR of ACEI use was estimated to be 1.21 (95% confidence interval: 0.89-1.65; P = 0.22). ACEI initiation did not demonstrate any significant preventive effect against pneumonia-related hospitalization relative to ARB initiation. There remains a lack of strong evidence on the protective effects of ACEIs, and further research is needed to ascertain the benefits of their use in preventing pneumonia. We conducted a large-scale retrospective cohort study using real-world healthcare data from a Japanese population. In this study, ACEI initiation did not indicate a significant preventive effect against pneumonia-related hospitalization.

Pneumococcal Colonization in Children With Persistent Asthma: A Retrospective Cohort.

Asthma is the most common chronic medical condition among children ≥5 years of age with invasive pneumococcal disease. How asthma or its management affects pneumococcal colonization is not fully understood. Our objective was to compare pneumococcal colonization rates between children with persistent asthma and children without asthma, and to characterize the pneumococcal serotype distribution. We used nasal mid-turbinate samples obtained per routine care from 5- to 18-year-old children with upper respiratory symptoms from November to April (respiratory seasons) of 2017 to 2018 and 2018 to 2019 in Kansas City, United States. Pneumococcal immunization status, prior antibiotic use and other clinical data were collected. Samples were tested for pneumococcal colonization by real-time polymerase chain reaction targeting lytA gene. Positive samples underwent multiplex serotype-specific polymerase chain reaction assays to determine the serotype. Of 363 children (120 with persistent asthma and 243 without asthma), 87.6% were 5 to 10 years old, 50.1% were female and 74.1% received ≥3 doses of a pneumococcal conjugate vaccine. The pneumococcal colonization rate was lower in children with persistent asthma than in children without asthma (10% versus 18.9%, P = 0.03). The odds of colonization were lower in children with persistent asthma [OR 0.4 (95% confidence interval: 0.2-0.9)] after adjusting for demographic and clinical data. Pneumococcal serotype was confirmed in 77.6% of positive samples; 35.6% of those samples corresponded to PCV13 serotypes and 64.4% to non-PCV13 serotypes. The most common serotypes were 19F (15%), 3 (13%) and 6C/6D (11%). Children with persistent asthma had lower rates of pneumococcal colonization than children without asthma when seeking care for respiratory symptoms.

Pneumococcal carriage and serotype distribution in children with nephrotic syndrome

BackgroundPatients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS.MethodsPneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR.ResultsThe pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all).ConclusionsThe pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

Immunogenicity, Immunological Memory and Monitoring of Disease Activity Following an Anamnestic Immunization With the 13-Valent Pneumococcal Conjugate Vaccine in Children With Idiopathic Nephrotic Syndrome.

Anamnestic 13-valent pneumococcal conjugate vaccine immunization did not affect the relapse risk in pediatric idiopathic nephrotic syndrome. Pneumococcal serotype (PS)-specific antibody titers increased significantly in all groups. Children receiving immunomodulatory treatments (IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids.

Peer education as a strategy to promote vaccine acceptance: A randomized controlled trial within New York community healthcare practices

BackgroundEffective strategies are needed to improve vaccine acceptance. This study sought to determine if a peer-led vaccine education intervention embedded within community medical practices increases parental acceptance of pediatric pneumococcal conjugate vaccination. MethodsFrom March 2022-July 2023, we conducted a randomized trial at three pediatric health practices in predominantly Hasidic Jewish neighborhoods in New York, where vaccine deferral is common. Parents of children up to 18 months due/overdue for routine pneumococcal vaccination were randomized (1:1) to receive routine care alone or routine care plus a peer educational intervention. Peer educators trained in motivational interviewing and vaccine science provided counseling at enrollment and follow-up telephone engagement in the intervention arm at day 30 and 60. Primary outcome was child’s pneumococcal immunization status by allocation arm expressed as at least one dose received between enrollment and 90 days post-enrollment. Results144 parent–child dyads were eligible for outcome analysis. Participants in the group receiving routine care along with peer-led vaccine counseling were significantly more likely to have their child receive at least 1 vaccine dose between enrollment and 90 days compared to the group who received routine care alone (28.4 % vs 12.9 %, risk ratio [RR] 2.21, confidence interval [CI] 1.09–4.49, p = 0.022). The effect of peer education was greatest in dyads with children less than 1 year old at enrollment (34 % vs 12.7 %, RR 2.67, CI (1.22–5.86), p = 0.009). ConclusionsPeer vaccine education can increase vaccine acceptance compared to routine care alone and may be particularly valuable in decreasing vaccination delays for younger infants. (Funded by EGL Charitable Foundation, ClinicalTrials.gov NCT05875779).

B cells in the pneumococcus-infected lung are heterogeneous and require CD4+ T cell help including CD40L to become resident memory B cells.

Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (BRM) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4+ T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4+ cells, and CD40 ligand (CD40L) signaling were all needed for lung BRM cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung BRM cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4+ T cells in the infected lung is critical to establishment of local BRM cells, which subsequently protect the airways and parenchyma against future potential infections.

State of pneumococcal vaccine immunity.

Like the other invasive encapsulated bacteria, Streptococcus pneumoniae is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive diseases caused by S. pneumoniae. Although antibodies against polysaccharide capsule are efficient in eliminating S. pneumoniae, the T cell independent nature of the immune response against polysaccharide vaccines renders them weakly antigenic. The introduction of protein conjugated capsular polysaccharide vaccines helped overcome the weak immunogenicity of pneumococcal polysaccharides and decreased the incidence of pneumococcal diseases, especially in pediatric population. Conjugate vaccines elicit T cell dependent response which involve the interaction of specialized CD4+ T cells, called follicular helper T cells (Tfh) with germinal center B cells in secondary lymphoid organs. Despite their improved immunogenicity, conjugate vaccines still need to be administered three to four times in infants during the first 15 month of their life because they mount poor Tfh response. Recent studies revealed fundamental differences in the generation of Tfh cells between neonates and adults. As the portfolio of pneumococcal conjugate vaccines continues to increase, better understanding of the mechanisms of antibody development in different age groups will help in the development of pneumococcal vaccines tailored for different ages.

A randomized, blind, parallel controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of 23-valent pneumococcal polysaccharide vaccine in healthy people aged 2 years and older

BackgroundDespite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. MethodsAll subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0–7 days and 8–28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). ResultsThe most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. ConclusionThis clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

Isolated Tubercular Splenic Abscess: A Case Report

Tuberculosis is one of the deadliest infectious illnesses in the world. Splenic tuberculosis is typically a component of miliary TB, ranks third after lung and liver, and is more prevalent in people with weakened immune systems. An extremely uncommon variant of abdominal tuberculosis is splenic TB in immune-competent people with no extra splenic involvement. In individuals without pulmonary disease and without symptoms, splenic TB diagnosis is challenging. There are frequently no diagnostic standards for isolated TB. A definitive diagnosis is rarely reached by preoperative testing. When other potential causes of fever and splenomegaly have been ruled out in endemic areas, splenic TB should be suspected. The typical treatment for splenic TB without abscess is medical management (ATT). For splenectomy, a single TB splenic abscess in a healthy patient is recommended. Here we report the case of a 33-year-old patient, who complained of left-sided stomach pain that had been bothering him for four years but was unrelated to radiation or food consumption. It has been linked to several high-grade fever bouts and frequent hospitalizations for the same during the past three years. With standard preoperative pneumococcal immunization, the patient is scheduled for a routine open splenectomy.

Effectiveness of a Program to Raise Awareness About Pneumococcal Vaccination Among Physicians and Patients with Chronic Respiratory Diseases: A Multicenter Cohort Study.

There is a need to increase patient and clinician awareness on the effectiveness of pneumococcal vaccination in at-risk groups. The aim of the study was to evaluate the effect of reminders for physicians and patients using the vaccination tracking system created in the hospital information management system (HIMS) on the vaccination rate, and the effect of pneumococcal vaccination on pneumonia-related hospitalization and mortality over a 12-month period. This prospective observational cohort study was undertaken during a 2-year period in 3 tertiary care centers. Patients were followed up for 12 months following vaccination, and hospital admissions and mortality were recorded via HIMS. During the campaign, HIMS transmitted pneumococcal immunization reminder messages in accordance with guideline recommendations to physicians' computers and patients' mobile phones. Educational posters on pneumococcal vaccination were posted in outpatient clinics. Regular seminars on the evidence for pneumococcal vaccination were organized. All patients who were hospitalized during the follow-up period for chronic obstructive pulmonary disease (COPD), asthma, lung cancer, or pneumonia were analyzed in relation to their vaccination history regarding clinical outcomes. A total of 29530 patients were included in the study. During the study period, the annual vaccination rate increased by 74.4% and reached 4.8% in 3 hospitals (P = .001). The rates were 3.9% in patients older than 65 years without comorbidities and 5.2% in those with COPD and asthma (P = .002). In pneumococcal vaccine recipients, pneumonia-related hospital mortality was lower (relative risk (RR) = 0.19, CI 0.09-0.35, P < .001). It is possible to raise the rate of pneumococcal vaccination through awareness campaigns. Individuals with COPD and asthma are more willing to receive pneumococcal vaccination. Among patients hospitalized for pneumonia, prior pneumococcal vaccination is associated with lower mortalit.

Invasive pneumococcal disease 3 years after introduction of a reduced 1 + 1 infant 13-valent pneumococcal conjugate vaccine immunisation schedule in England: a prospective national observational surveillance study

The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23. We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD. There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules. Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring. None.

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae among healthy children under 5 years of age in Hainan Province, China

BackgroundThe thirteen-valent pneumococcal conjugate vaccine (PCV13) is not included in the national immunization program and is administered voluntarily with informed consent in China. In preparation for assessing the impact of pilot introduction in Hainan Province, we conducted a carriage study among children under 5 years of age from four locations in Hainan Province, China.MethodsFrom March to June 2022, nasopharyngeal (NP) swabs, collected from healthy children aged younger than 59 months who lived in the 4 different locations (Haikou, Wanning, Baisha and Qiongzhong) in Hainan Province, were tested for pneumococcus using conventional culture. Pneumococcal isolates were serotyped using the Quellung reaction. Risk factors associated with pneumococcal colonization were assessed using univariate analysis and multivariable logistic regression adjusting for age, daycare attendance and other factors.ResultsPneumococcus was isolated in 710 (30.4%) of the 2333 children enrolled. Of 737 pneumococci, 29 serotypes were identified; 60.9% were PCV13 serotypes; the most common vaccine serotypes were 6B (20.4%), 19F (13.0%), 6A (11.9%) and 23F (6.1%); and the most common nonvaccine serotypes were 23A (12.9%), 34 (6.1%) and nontypeable (NT) pneumococci (5.6%). Children vaccinated with PCV13 had lower carriage (17.7% vs 32.5%; P = 0.0001) and fewer PCV13 serotypes (41.9% vs 62.7%; P = 0.0017) compared to unimmunized children. After adjustment, NP carriage was higher among children attending daycare (aOR = 2.3, 95% CI: 1.7–3.2), living in rural areas (aOR = 1.4, 95% CI: 1.1–1.8), living with siblings (aOR = 1.3, 95% CI: 1.0–1.6) and whose mothers had completed senior high/technical secondary school (aOR = 1.5, 95% CI: 1.1–2.0). In contrast, completion of 3–4 doses of PCV13 were associated with a lower carriage rate (aOR = 0.6, 95% CI: 0.4–0.9).ConclusionsWe established the baseline of pneumococcal carriage, serotype distribution and PCV13 immunization rates among healthy children under 5 years of age in Hainan Province, prior to the introduction of PCV13 into the national immunization program. The high proportion of PCV13 serotypes suggests that PCV13 introduction will likely have a substantial impact on pneumococcal carriage in Hainan Province.Graphical

Multifaktorska etiologija atipičnog hemolitičko uremijskog sindroma - prikaz slučaja

Abstract: Introduction: Hemolytic uremic syndromes are characterized by the simultaneous occurrence of hemolytic anemia, microangiopathy, thrombocytopenia, and acute renal insufficiency. In terms of the clinical prodrome, they can be classified as typical, which is more common and occurs in 90% of cases, often preceded by diarrheal syndrome induced by enterohemorrhagic Escherichia coli. Alternatively, there is an atypical and rarer form associated with pneumococcal infection, dysregulation of the alternative complement pathway, and cases involving the use of cyclosporine. Hemolytic anemia is confirmed in laboratory analyses (presence of fragmented red blood cells, decreased hemoglobin, undetectable haptoglobin values, and elevated LDH values), along with thrombocytopenia and an increase in nitrogenous substances (urea and creatinine). Case report: The report details the case of an 18-month-old girl who experienced acute renal insufficiency subsequent to a respiratory infection. Ten days preceding admission, the patient exhibited nasal discharge, and during the seven days leading up to hospitalization, she presented with fever. Furthermore, two days prior to admission, the onset of persistent vomiting and abdominal pain occurred. Suspected of bowel intussusception, the patient underwent a surgical assessment where acute surgical pathology was ruled out. The absence of urination, coupled with heightened urea and creatinine levels, prompted consideration of hemolytic-uremic syndrome, later confirmed as atypical during hospitalization. This was grounded in the clinical presentation, devoid of diarrhea syndrome but marked by nasal discharge over the preceding ten days. The administration of fresh frozen plasma yielded no improvement, and there were decreased values of the C3 complement component, H factor, and reduced ADAMTS13 activity. The lack of verotoxins from enterohemorrhagic Escherichia coli further supported the diagnosis of atypical hemolytic-uremic syndrome. After the first dose of eculizumab, a terminal complement C5 component inhibitor, the girl recovered renal function and established diuresis. Conclusion: The prompt diagnosis of atypical hemolytic-uremic syndrome is challenging due to nonspecific symptoms like nasal discharge, vomiting, fatigue, and abdominal pain. Laboratory analyses, lacking specific criteria, make it difficult to conclusively identify aHUS at the disease's onset. In Serbia, pneumococcal immunization is recommended as a preventive measure, administered through a conjugated vaccine in three doses starting from the second month of life. Rapid and accurate differentiation between typical and atypical HUS is crucial for effective treatment and prognosis. Typical HUS requires hemodialysis and plasmapheresis, whereas atypical HUS is managed with plasmapheresis, immunosuppressive therapy, and eculizumab. Administering eculizumab heightens the risk of meningococcal infection by inhibiting the C5 complement component. Therefore, it is crucial not to disregard the importance of meningococcal immunization.

Assessing vaccine-induced immunity against pneumococcus, hepatitis A and B over a 9-year follow-up in pediatric liver transplant recipients: A nationwide retrospective study

Pediatric liver transplant recipients are particularly at risk of infections. The most cost-effective way to prevent infectious complications is through vaccination, which can potentially prevent infections due to hepatitis B (HBV) virus, hepatitis A virus (HAV), and invasive pneumococcal diseases. Here, we performed a retrospective analysis of HBV, HAV, and pneumococcal immunity in pediatric liver transplant recipients between January 1, 2009, and December 31, 2020, to collect data on immunization and vaccine serology. A total of 94% (58/62) patients had available vaccination records. At transplant, 90% (45/50) were seroprotected against HBV, 63% (19/30) against HAV, and 78% (18/23) had pneumococcal immunity, but immunity against these 3 pathogens remained suboptimal during the 9-year follow-up. A booster vaccine was administered to only 20% to 40% of patients. Children who had received >4 doses of HBV vaccine and > 2 doses of HAV vaccine pretransplant displayed a higher overall seroprotection over time post-solid organ transplant. Our findings suggest that a serology-based approach should be accompanied by a more systematic follow-up of vaccination, with special attention paid to patients with an incomplete vaccination status at time of transplant.

1725. Differences in serotype 3 antibody response and antibody functionality compared to serotype 19A following 13-valent pneumococcal conjugate immunization in children

Abstract Background Background. 13-valent pneumococcal conjugate vaccine (PCV13) includes serotype 3 and 19A. However, prevention of infections with PCV13 may be less effective against serotype 3 than 19A. In young children, determine differences in IgG antibody levels, functionality of antibody by OPA and antibody avidity for serotype 3 compared to 19A following PCV13 immunization; determine IgG antibody levels following natural immunization for serotype 3 and 19A; reassess effectiveness of PCV13 against serotype 3 and 19A in prevention of acute otitis media (AOM) and colonization. Methods Samples were secured during a prospective longitudinal study conducted in Rochester NY of children age 6-36 months old. Pneumococcal detection was determined by culture. 713 serum samples were tested for antibody levels by ELISA, 68 serum for functional antibody by OPA, and 47 serum for antibody avidity by thiocyanate bond disruption. Age effects on antibody levels was modeled by generalized estimating equations. PCV13 effectiveness was assessed compared to pre-PCV13. Results The proportion children who did not reach protective threshold against IPD (&amp;lt; 0.35 µg/ml) after PCV13 immunization was higher for serotype 3 antibody compared to 19A. PCV13-induced antibody levels to serotype 3 were1.4 to 3.4 fold lower than 19A. OPA titers were not significantly different for serotype 3 compared to 19A, but antibody avidity at child age 6 and 15 months was significantly lower. Serotype 3 natural- immunized children showed a positive trend of increase in antibody level as children got older. In contrast, PCV13-immunized children showed a negative trend of antibody levels with age. For serotype 19A, both natural immunization and PCV13 immunization showed a positive trend in antibody levels over age. PCV13 effectiveness was not identified in preventing AOM or colonization for serotype 3 but effectiveness of 19A was re-confirmed. Conclusion Conclusions: PCV13 elicits lower antibody levels and lower avidity antibody to serotype 3 than 19A. PCV13 does not elicit antibody levels that increase over age despite a booster dose for serotype 3, as occurs for serotype 19A. Post PCV13-induced antibody levels for serotype 3 may be insufficient to prevent AOM and colonization in young children. Disclosures All Authors: No reported disclosures

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.

Evaluating clinical effectiveness and safety of pneumococcal immunization of infants

According to WHO, pneumococcal infection (PI) is considered one of the most dangerous of all vaccine-preventable diseases and, before vaccination, led to the death of up to 1.6 million people per year, of which from 0.7 to 1 million were children. In the prevention of PI, specific prevention occupies a special place. For the first time in 2014, vaccination against PI with pneumococcal conjugate vaccine was included in the national calendar of preventive vaccinations. International practice of using pneumococcal vaccine has shown that timely vaccination can produce positive results in the fight against PI. Under observation were 55 children who were vaccinated against PI with the pneumococcal polysaccharide conjugate vaccine (adsorbed), 13 valent according to the national calendar of preventive vaccinations of the Russian Federation. It was revealed that post-vaccination complications after vaccination did not occur in any child. General post-vaccination reactions were observed in the form of a short-term increase in temperature, loss of appetite and sleep disturbances, as well as local reactions in the form of edema, hyperemia, and hardening at the site of vaccine administration. We studied the incidence of community-acquired pneumonia (CAP), acute otitis media and acute respiratory infections among 55 children of the first year of life vaccinated at 2 months and 4.5 months (main group) and 50 children for various reasons not vaccinated against PI (comparison group). A study of the long-term results of 2-fold vaccination in the first year of life and revaccination at 15 months against PV based on observation of children for two years showed that children of the main group, compared with the comparison group, were 3.3 times less likely to suffer from PV, 2.7 times acute otitis and 1.7 times acute respiratory infections, p &lt; 0.05. The data obtained show the high efficiency and safety of vaccinating children against PI with the pneumococcal vaccine.

Pneumonia vaccine response in individuals with Down syndrome at three specialty clinics.

Individuals with Down syndrome (DS) have been particularly impacted by respiratory conditions, such as pneumonia. However, the description of co-occurring recurrent infections, the response to pneumococcal immunization, and the association of these was previously unknown. We screened individuals with DS using an 11-item screener and prospectively collected pneumococcal titers and laboratory results. We found that the screener did not successfully predict which individuals with DS who would have inadequate pneumococcal titers. Thirty four of the 55 individuals with DS (62%) had abnormal pneumococcal titers demonstrating an inadequate response to routine immunization. In the absence of a valid screener, clinicians should consider screening all individuals with DS through the use of pneumococcal titers to 23 serotypes to assess vaccine response.

Outcomes of pediatric community-acquired pneumonia before and after national pneumococcal immunization in Taiwan.

In Taiwan, the incidence of invasive pneumococcal disease (IPD) in children declined after the catch-up primary vaccination programs and the full national immunization program (NIP) with PCV13. The objective of the study was to investigate the clinical outcomes of pediatric community-acquired pneumonia (CAP) before and after the NIP. The study included patients aged 3 months to 17 years who were diagnosed with CAP and treated at the National Taiwan University Hospital between 2007 and 2019. Patients were assigned to three birth cohorts according to their birth years and vaccination eligibility: non-NIP, catch-up, and full NIP. We compared the rates of severe outcomes, including case fatality and pathogens. A total of 6557 patients who met the CAP criteria were enrolled during the study period. The case-fatality rate decreased from 3.2% (94/2984) in the non-NIP cohort to 0.3% (7/2176) in the catch-up cohort and 0.8% (11/1397) in the full NIP cohort (p < 0.001). Furthermore, there was a significant decrease in invasive ventilation from the non-NIP (17.9%) to both catch-up (6.8%) and full NIP cohorts (9.1%). The rate of IPD declined from the non-NIP cohort to the catch-up cohort (1.8% vs. 0.6%, p < 0.001) and from the catch-up to the full NIP cohort (0.6% vs. 0.07%, p = 0.014). In contrast, the rates of infections with other pathogens increased after NIP. The introduction of PCV13 showed significant reduction in case-fatality and IPD rates. The increasing rates of other pathogens warrant further surveillance for their clinical significance.