Efficacy Of Pneumococcal Vaccine Research Articles

Genome sequences of 36 Streptococcus pneumoniae strains optimized for the multiplexed opsonophagocytosis killing assay.

A multiplexed opsonophagocytosis assay (MOPA) was developed as a cost-effective, high-throughput biological assay to evaluate the efficacy of pneumococcal vaccines by in vitro measurement of opsonophagocytic activity of anti-capsular antibodies. Here, we report draft genomes of the 36 strains of Streptococcus pneumoniae developed for use in the reference pneumococcal MOPA.

Experience with 23-valent pneumococcal polysaccharide vaccine in patients with ankylosing spondylitis and psoriatic arthritis

Pneumococcus plays a primary role as a causative agent of pneumonia both in the general population and in patients with immuno-inflammatory rheumatic diseases (IVRS), including spondylarthritis (SpA). However, data on the immunogenicity, efficacy and safety of pneumococcal vaccines in patients with SpA are limited.The aim of the study. To study the immunogenicity, efficacy and safety of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), observed at the V.A. Nasonova Research Institute (Moscow, Russia).Materials and methods. 145 people were included in the study: 51 patients with AS, 25 with PsA, 69 in control group (СG) without IVR. The majority of patients (65.8%) received immunosuppressive therapy. PPV-23 was administered in an amount of one dose (0.5 ml) subcutaneously against the background of antirheumatic therapy, regardless of the activity of the main IVR. The level of antibodies (AT) to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clinical Diagnostics, Czech Republic) before vaccination and 1, 3 and 12 months after it. The clinical efficacy and safety of PPV-23 were also evaluated, including the effect on the activity of AS and PsA according to the dynamics of BASDAI and DAPSA indices.Results. After 1, 3 and 12 months after vaccination, the concentration of pneumococcal AT was significantly higher compared to baseline values, which indicates sufficient immunogenicity of PPV-23. The clinical efficacy of PPV-23 in patients with AS and PsA was 98.7%. In general, there was no negative effect of vaccination on the activity of the underlying disease. The frequency of postvaccinal reactions in patients and in СG was comparable.Conclusions. The obtained results of the study indicate sufficient immunogenicity, clinical efficacy and safety of PPV-23 in patients with AS and Ps A.

Efficacy of Pediatric Pneumococcal Conjugate Vaccines in Preventing Complex Otitis Media

Efficacy of Pediatric Pneumococcal Conjugate Vaccines in Preventing Complex Otitis Media

Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study

The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage. We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed. Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci. This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination. Wellcome Trust.

Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults.

New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle-Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: -4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults.

Efficacy of Pneumococcal Vaccine on Otitis Media: A Systematic Review and Meta-Analysis.

To assess the effect of the pneumococcal vaccine (PCV) towardthe surgical management and complications of otitis media. MEDLINE, EMBASE, PubMed, Scopus, and clinicaltrial.gov. A systematic search was performed using a combination of keywords and standardized terms about PCV and surgical management or complications of otitis media. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies were screened by 3 independent reviewers. Risk of bias assessment, followed by meta-analysis in only randomized-controlled trials was conducted. Vaccine efficacy (VE) and 95% confidence interval (CI) were reported. Of the 2649 abstracts reviewed, 27 studies were included in the qualitative analysis and were categorized into 6 outcomes: tympanostomy tube insertion, otitis media with effusion (OME), mastoiditis, spontaneous tympanic membrane (TM) perforation, recurrent acute otitis media (AOM), and severe AOM. Fifteen studies were included in the meta-analysis to evaluate the rate of tympanostomy tube insertion, OME, and recurrent AOM. PCV was significantly more effective in lowering the rate of tympanostomy tube insertion (VE, 22.2%; 95% CI, 14.6-29.8) and recurrent AOM (VE, 10.06%; 95% CI, 7.46-12.65) when compared with the control group, with no significant difference in reducing the incidence of OME. The qualitative analysis revealed that PCV had efficacy in preventing severe AOM and spontaneous TM perforation but the effect on mastoiditis remained unclear. The PCV was effective in reducing the rate of tympanostomy tube insertion and the incidence of recurrent AOM with a nonsignificant effect in preventing OME in children.

Противопневмококковая иммунизация у детей раннего возраста с хронической сердечной недостаточностью

Aim: To determine the coverage, efficacy and tolerability of pneumococcal vaccination in young children with cardiovascular disease associated with chronic heart failure. Design: Retro- and prospective randomized comparative study. Materials and methods. The study included 250 patients at the age of 2 months to 5 years with confirmed chronic cardiac failure caused by cardiomyopathy or congenital heart disorder. Within the scope of a specialised laboratory and instrumental examination, all children underwent an assessment of specific immunoglobulin (Ig) levels to the most common pneumococcal serotypes (1-5, 6B, 7F, 8, 9N, 9V, 10A, 11A,12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F) using VaccZyme Anti-PCP IgG test system. During consultations and vaccination schedule development, pneumococcal vaccination coverage and the reasons for long-term medical exemptions or refusals were analysed. Provided the primary disease was stable, there were no contraindications and a parent gave their consent, patients were vaccinated with 13-valent pneumococcal conjugate vaccine (PCV13). Results. When questioning the parents of patients, it was revealed that before admission to the department, only 97 (38.8%) patients received at least 1 dose of pneumococcal vaccine, while the remaining 153 (61.2%) were not vaccinated. During hospitalization, 65 (42.5%) of 153 unvaccinated patients under 5 years of age who had not received a single pneumococcal vaccine received the first dose (V1) of PCV13; of 97 children vaccinated, 20 (20.6%) received a second dose, 18 (18.6%) — pneumococcal booster. There was a significant difference in the levels of antibodies to Streptococcus pneumoniae between the group of patients who received a full course of immunization according to age and the group of unvaccinated children: 108.1 ± 58.4 vs. 12.14 ± 7.8 mg/l (p < 0.05). In children with an incomplete course of vaccination, the levels of specific IgG to pneumococcal serotypes were lower. In groups of children who received only one dose of the vaccine in the first or second year of life, they amounted to 42.2 ± 11.7 and 40.2 ± 16.2 mg/l, respectively. Children who received at least two doses of vaccine without revaccination (starting before 12 months) had a relatively higher level of 68.2 ± 6.3 mg/L. But, despite a clear trend, there was no significant difference between these groups in our study. In the post-vaccination period, no serious complications were recorded in the examined children. Conclusion. Vaccination against pneumococcal infection in children with chronic heart failure is effective, safe and should be carried out as close as possible to the schedule of the national vaccination calendar, with a limited set of contraindications. Keywords: vaccination, 13-valent pneumococcal conjugate vaccine, immunoglobulin G, chronic heart failure.

Effects of the 23-Valent Pneumococcal Polysaccharide Vaccine on the Mortality of Pneumonia among Elderly over 70 Years Old after the Great East Japan Earthquake—PPV Vaccination Program in Iwate Prefecture, Japan

Objective: To estimate the efficacy of 23-valent pneumococcal polysaccharide vaccine (PPSV23) among the elderly, we analyzed the relationship between the mortality of the elderly for pneumonia and the vaccination rate of PPSV23 from 2008 to 2016 in Iwate Prefecture, Japan. Study Design: The present study was a retrospective, observational, database study adopting an ecological design. The mortality for pneumonia among the elderly over 70 years old from 2006 to 2016 in Iwate Prefecture was calculated based on the data from the Japanese Vital Statistics. We compared the mortality rate (MR) of pneumonia among the elderly over 70 years old between the low-vaccinated period (LVP) (2006-2010) and high-vaccinated period (HVP) (2012-2016) using a Poisson regression model. Results: While the vaccination rate of PPSV23 among the elderly over 65 years old was 3.3% in 2010, it increased rapidly up to 40.7% in 2012 and reached 66.4% in 2016. The MR ratio of the total population during HVP to the average MR during LVP was 0.749. The MR of the total population during HVP was significantly lower than that during LVP (p < 0.001). Notably, the MRs of both men and women during HVP were significantly lower than those during LVP (p < 0.001). The significant decrease in MR during HVP started in 2012 and continued up to 2016. Conclusion: The increase in vaccination rate of PPSV23 during HVP (2012-2016) may contribute to the decrease in mortality for pneumonia among the elderly over 70 years old in Iwate Prefecture.

S779 Efficacy of Pneumococcal Vaccine in Patients With Inflammatory Bowel Disease - A Propensity-Matched Analysis

S779 Efficacy of Pneumococcal Vaccine in Patients With Inflammatory Bowel Disease - A Propensity-Matched Analysis

Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown. To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD. This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included. PCV13 implementation. Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes. Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period. PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA).

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group study

Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

21. Systematic Review and Meta-Analysis of Pneumococcal Vaccine Effectiveness against Invasive Pneumococcal Disease among Adults

Abstract Background Two new pneumococcal conjugate vaccines (PCVs), PCV15 and PCV20, are anticipated to be licensed for use in U.S. adults in 2021. To help inform the U.S. Advisory Committee on Immunization Practices’ discussions on pneumococcal vaccine use among adults, we conducted a systematic review and meta-analysis. We specifically looked at efficacy or effectiveness of PCV13 and pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) in adults. Methods We conducted a search of English literature published from 1998 – February 2021 on PCV13 and PPSV23 efficacy or effectiveness studies using eight major databases. Studies targeting adults with immunocompromising conditions were excluded. Title and abstract screening of identified studies and data abstraction were performed by two reviewers. Results were stratified by vaccine product, outcome evaluated (vaccine type (VT) or all IPD), study design, and effect measure. Random effects models were used to pool estimates by stratum. Results Of 3,422 citations reviewed, we identified 26 IPD studies; 4 on PCV13, 22 on PPSV23, 18 with all IPD, and 17 with VT-IPD (Table) as an outcome. Only one randomized-controlled trial (RCT) was identified for PCV13 with an efficacy of 52% (95% CI: 22%, 77%) against all IPD and 75% (95% CI: 41%, 91%) against VT-IPD. A pooled vaccine effectiveness (VE) estimate from three observational studies evaluating PCV13 was 56% (95% CI: 32%, 71%; I2 =12.8) against VT-IPD. Two RCTs evaluating PPSV23 reported efficacies against all IPD ranging between 79-86%; an additional RCT reported no IPD cases during RCT. Vaccine effectiveness estimates from 14 observational studies evaluating PPSV23 ranged between 29-76% against all IPD. Pooled VE estimates from 12 observational studies showed PPSV23 effectiveness against VT-IPD was 38% (95% CI: 28% to 46%; I2 =40.8). Table. Efficacy and effectiveness studies against vaccine-type invasive pneumococcal disease Conclusion Evidence suggests both pneumococcal vaccines are effective against VT-IPD in adults. Given that PCV15 and PCV20 are expected to be licensed based on immunogenicity data and no clinical efficacy data are available for these new vaccines, the findings from this review will help inform policy discussions on use of the new PCVs among adults. Disclosures All Authors: No reported disclosures

13. The Efficacy and Effectiveness of Pneumococcal Vaccines against Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis

BackgroundTwo pneumococcal vaccines are currently recommended for use in U.S. adults: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). Recommendations for adult PCV13 use were supported by a large randomized-controlled trial (RCT) demonstrating PCV13 efficacy against pneumococcal pneumonia (PnPn) and vaccine-type (VT) PnPn in older adults. New pneumococcal conjugate vaccines are expected to be licensed for adults in late 2021 and recommendations for use among adults will be reviewed and revised, as needed. We conducted a systematic review to summarize evidence on the vaccine efficacy and effectiveness (VE) of PPSV23 and PCV13 against PnPn among adults.MethodsWe conducted a search of literature published from 1998 to February 2021 on PCV13 and PPSV23 VE studies using eight reference databases. Studies targeting adults with immunocompromising conditions were excluded. VE results with 95% confidence intervals (CI) were abstracted and stratified by vaccine product, outcome evaluated (PnPn and VT PnPn), study design, and effect measure. When applicable, random effects models were used to estimate pooled VE and I-squared statistic was reported to assess heterogeneity.ResultsOf 3,422 screened studies, we included 15 studies: three on PCV13 and 12 on PPSV23 (Table 1). In addition to the RCT, we identified two observational studies for PCV13 (Table 1); however, pooled VE of the observational studies was not estimated due to differences in methods for reporting results. Pooled PPSV23 VE against PnPn from two RCTs was 63% (95% CI: 31, 80 I2=0%). Pooled VE of PPSV23 against VT PnPn from three observational studies was 18% (95% CI: -35, 35 I2=38%). PPSV23 effectiveness against PnPn was limited with a pooled VE of 25% (95% CI: 7, 39 I2=78%) from nine observational studies. ConclusionFindings from observational studies supported PCV13 VE against VT PnPn reported in the RCT. Differences in the study design made the magnitude of PPSV23 effectiveness against PnPn and VT PnPn difficult to assess; however, findings from recent observational studies suggest PPSV23 provides limited protection against VT PnPn.Disclosures All Authors: No reported disclosures

1712P Safety and efficacy of influenza and pneumococcal vaccines in cancer patients on active therapy: A prospective study

Influenza virus and S. pneumoniae infections in cancer patients (pts) are responsible of a higher morbidity and mortality rates. Limited data are available about safety, efficacy, immunogenicity and timing of influenza (I) and pneumococcal (P) vaccine (vax) in pts receiving active treatment. However, I and P vax in cancer pts and their family members (FMs) are reccomended.

Immunogenicity, safety and efficacy of 23-valent pneumococcal polysaccharide vaccine in patients with inflammatory joint diseases (preliminary data)

Intoduction.Currently, for the treatment of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), basic anti-inflammatory drugs and biological drugs are widely used to effectively control the activity of the disease. However, the use of these drugs is associated with an increased risk of developing comorbid infections, some of which can be prevented by vaccination. Objective. To evaluate the immunogenicity, safety, and clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with RA and SpA.Materials and methods. The study included 122 patients: 79 - with RA, 43-with SpA. Most patients had a history of two or more cases of lower respiratory tract infections, 2 patients reported a monthly exacerbation of chronic sinusitis, one patient reported the development of otitis media every 2-3 months. At the time of inclusion in the study, most patients received immunosuppressive therapy. PPV-23 was administered in an amount of 1 dose (0.5 ml) subcutaneously against the background of anti-rheumatic therapy. The level of antibodies to pneumococcal capsular polysaccharide was determined using the EIA PCP IgG kit (TestLine Clin-ical Diagnostics s.r.o., Czech Republic) before vaccination, 1, 3 and 12 months after vaccination. In addition, the tolerance of PPV-23, the frequency of pneumonia, and the effect on the activity of RA and SpA were evaluated (according to the dynamics of DAS28 and BASDAI).Results.At 1, 3, and 12 months after vaccination, the concentration of antibodies to pneumococcal capsular polysaccharide was significantly higher than the baseline values, which indicates sufficient immunogenicity of PPV-23. There was no negative effect of vaccination on the activity of the underlying disease and the occurrence of new autoimmune disorders. In the majority of patients (67% - RA, 81.4% - SpA), the tolerance of the vaccine was good. During the follow-up period, none of the patients developed pneumonia. Patients suffering from frequent sinusitis and otitis media reported the absence of these infections after vaccination.Conclusion.Preliminary results of the study indicate sufficient immunogenicity, safety, and clinical efficacy of PPV-23 in patients with RA and SpA.

Incidence of febrile seizures and associated factors in children in Soweto, South Africa.

Febrile seizures (FSs) are a common cause of paediatric emergencies, but there is limited research on the aetiology and epidemiology of FSs, especially in Africa. To determine the incidence of FS hospitalisations in children aged 6 - 59 months in Soweto, South Africa, and factors associated with FS hospitalisations. In a secondary data analysis using a cohort of children enrolled in a 9-valent pneumococcal conjugate vaccine efficacy trial conducted in Soweto during 1998 - 2005, the incidence of FS hospitalisation was calculated and stratified by age group. Regression analysis was used to investigate factors associated with FS at the time of hospitalisation. Influenza A, influenza B, respiratory syncytial virus (RSV), adenovirus and parainfluenza were investigated for among those with respiratory symptoms using immunofluorescent assays. FSs accounted for 780 (11.0%) of 7 126 hospitalisations during the study period. The overall incidence of FSs was 4.4 (95% confidence interval (CI) 4.10 - 4.97) per 1 000 person-years, with the highest incidence in children aged 12 - 23 months (7.25; 95% CI6.44- 8.14). Among hospitalised children, FS hospitalisation was associated with HIV-negative status (odds ratio (OR) 6.25; 95% CI 4.34 - 8.99), body temperature ≥39ºC (OR 2.03; 95% CI 1.56 - 2.64) and concurrent diagnosis of acute otitis media (OR 2.16; 95% CI 1.74 - 2.67). Influenza A was identified in 44/515 FS hospitalisations (8.5%) compared with 123/3 794 non-FS hospitalisations (3.2%) (OR 2.22; 95% CI1.56 - 3.16). In contrast, RSV detection was less commonly identified in children with FSs (21; 4.1%) than without (419; 11.0%) (OR0.36; 95% CI 0.24 - 0.54). FSs contributed significantly to the burden of paediatric hospitalisations in Soweto, and were strongly associated with influenza A virus infection.

Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically, and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.

BackgroundVaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes.MethodsWe performed a systematic review of efficacy trials for several vaccines (1997–2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).ResultsAmong 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5–3.0), and 3.7 (1.0–10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2–10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (−6.0 to 9.1) and with vaccine serotype–confirmed pneumonia was 2.9 (.5–7.8).ConclusionsWhile there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine’s public health value.

Safety and efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with systemic lupus erythematosus

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy &gt; 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs &lt;1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated &lt;1 year before immunization. Further long-term prospective studies in large patient cohorts are required.

Thirteen-Valent Pneumococcal Conjugate Vaccine-Induced Immunoglobulin G (IgG) Responses in Serum Associated With Serotype-Specific IgG in the Lung.

Pneumococcal conjugate vaccine (PCV) efficacy is lower for noninvasive pneumonia than invasive disease. In this study, participants were immunized with 13-valent PCV (PCV13) or hepatitis A vaccine (control). Bronchoalveolar lavage samples were taken between 2 and 6 months and serum at 4 and 7 weeks postvaccination. In the lung, anti-capsular immunoglobulin G (IgG) levels were higher in the PCV13 group compared to controls for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV13 group at 4 weeks for all serotypes, except serotype 3. IgG in bronchoalveolar lavage and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical Trials Registration. ISRCTN 45340436.