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Total shoulder arthroplasty (TSA) is a common orthopedic procedure that can be performed as an anatomic total shoulder arthroplasty (aTSA) or reverse total shoulder arthroplasty (rTSA). These are effective procedures that are being performed with increasing frequency. Understanding the overall 90-day reimbursement variability and their drivers may help the health care systems better understand related considerations to reduce health-care expenditure. The current study predicts there will be large variability in reimbursement highlighting the need for further understanding. Using the 2015-2021 Q1 M151 PearlDiver dataset, patients who underwent aTSA or rTSA were isolated. Patients were excluded if they were aged less than 18 years, had an indication of traumatic, infectious, or oncologic diagnoses within 90-days of surgery, or were not in the dataset for at least 90 days before and after surgery. Patient demographics, comorbidities, 90-day postoperative events, insurance type, and geographic region were abstracted. The overall 90-day reimbursements were then assessed and correlated with these variables having multivariable linear regression. A total of 112,188 TSA patients (aTSA: 36,164 [32.2%]; rTSA: 76,024 [67.8%]) were identified. The average ± standard deviation 90-day overall postoperative reimbursement for aTSA was $6714.26 ± 9587.46 and rTSA was $6246.45 ± 9506.59. The total reimbursement for aTSA was $242,814,515 and for rTSA was $474,836,301. Variables independently associated with greater 90-day overall reimbursement were mostly related to 90-day postoperative events, including hospital readmission [+$6694.51], emergency department visit [+$2129.89], and adverse events [+$2055.84]), geographic region of the country where the procedure was performed (relative to West, South [+$4302.88], Midwest [+$3428.84], and Northeast [+$530.92]), and insurance plan (relative to commercial, Medicare [-$1268.01], and Medicaid [-$901.79]) (P <.0001 for each). Lesser factors included male sex (relative to female +$207.30), Elixhauser-Comorbidity Index (+$51.93 per point increase), age (-$77.16 per year increase), and rTSA surgery type (relative to aTSA -$556.17). The current study leveraged a large, administrative database to evaluate over 100,000 TSA patients and found large variations in 90-day overall reimbursements. The variables mostly associated with increased reimbursement were related to 90-day postoperative events (as might be expected and underscoring the need to minimize such events) and geographic regions and insurance plan (highlighting differences that might be able to be addressed). Interestingly, while patient demographics, comorbidities, and anatomic vs. reverse total shoulder were associated with reimbursements, these were to lesser extents. Understanding these results may help health-care systems further target variables associated with greater cost/reimbursement to the system. [ABSTRACT FROM AUTHOR]

Lumbar discectomy is a commonly performed surgery following which surgical site infection (SSI) may occur. Prior literature has suggested that, following SSI related to lumbar fusion, the rate of subsequent lumbar surgeries is increased over prolonged periods of time. This has not been studied specifically for lumbar discectomy. To define factors associated with SSI following lumbar discectomy and determine if subsequently matched cohorts with and without SSI have differential rates of subsequent lumbar surgery beyond irrigation and debridement (I&Ds) over time. Retrospective cohort study. Adult patients undergoing isolated primary lumbar laminotomy/discectomy were identified from the 2010-2021 M157 PearlDiver database. Exclusion criteria included: age<18 years, preoperative diagnosis of infection, neoplastic, or traumatic diagnoses within 90 days prior to index surgery, additional spinal surgeries on the same day as lumbar discectomy, and not being active in the database for at least 90 days postoperative. From this study population, those who developed SSI were identified based on undergoing I&D within 90 days after surgery. Those with versus without SSI were then matched 1:4 based on age, sex, Elixhauser Comorbidity Index (ECI), and obesity. Following initial I&D, incidence of revision lumbar surgery (revision lumbar discectomy, lumbar laminectomy, lumbar fusion) out to 5 years after lumbar discectomy. Following index isolated lumbar discectomy, those with versus without SSI requiring I&D were matched and compared for incidence of secondary surgery in defined time intervals (0–6 months, 6–12 months, 1–2 years, 2–5 years) using multivariable logistic regression, controlling for patient age, sex, ECI, and obesity status. Of 323,025 isolated lumbar discectomy patients, SSI requiring I&D was identified for 583 (0.18%). Multivariable analysis revealed several independent predictors of these SSIs: younger age (odds ratio [OR] 0.85 per decade increase), ECI (OR 1.22 per 2-point increase), and obesity (OR 1.30). Following matching of those with versus without SSI requiring I&D, rates of subsequent surgery beyond I&D were compared. Those with SSI had significantly increased odds of lumbar revision in the first six months (OR 5.26, p<.001), but not 6–12 months (p=.462), 1–2 years (p=.515), or 2–5 years (p=.677). Overall, SSI requiring I&D is a rare postoperative complication following lumbar discectomy. If occurring, subsequent surgery beyond I&D was higher in the first 6 months, but then not increased at subsequent time points out to five years. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is an inherited disorder of red blood cells caused by mutation in the hemoglobin beta chain and is the most common inherited genetic disorder in the United States. Postoperative outcomes following single-level posterior lumbar interbody fusion (PLIF) in patients with SCD are not well characterized. To examine 90-day postoperative outcomes among a matched cohort of patients with and without SCD who underwent single level PLIF utilizing a national administrative database. Retrospective database study. Adult patients without and with SCD who underwent single level PLIF from 2010 to 2021 Q1 were identified and matched 10:1 based on age, sex and ECI. Exclusion criteria included: age <18 years old, recent history of infection, neoplasm, or trauma, as well as not being active in the database for 90 days following their procedure. Ninety-day postoperative adverse events and emergency department (ED) visits. The matched cohorts were defined, and 90-day adverse event and ED visit rates were compared with univariable analyses and multivariable logistic regression, controlling for age, sex, and Elixhauser comorbidity index (ECI). Overall, 191,765 PLIF patients were identified, of which SCD was noted for 76 (0.04%). On multivariable analysis of the matched populations, patients with SCD were at increased odds ratio (OR) of the following (in decreasing OR order): transfusion (OR 17.69), pneumonia (OR 6.30), sepsis (OR 4.86), aggregated minor adverse events (OR 4.65), aggregated all adverse events (OR 3.87), ED visits (OR 3.53), and aggregated severe adverse events (OR 2.80) (p<.05 for all). The current study examined a relatively small, but largest to date, cohort of SCD patients undergoing PLIF. Patients with this condition were at greater odds of several perioperative adverse events, and these findings may be helpful for patient counselling and surgical planning. [ABSTRACT FROM AUTHOR]

Total shoulder arthroplasty (TSA) is a common orthopedic procedure for which there are anatomic TSA (aTSA) and reverse TSA (rTSA) options. The current study aimed to characterize the 2011-2020 utilization trends of aTSA and rTSA as well as assess and compare perioperative outcomes using a large, national, multi-insurance administrative data set. Data were utilized from the 2011 through 2020 M151 PearlDiver database. Trends in usage of aTSA relative to rTSA were characterized. For the more recent years (2015 through 2020), after 1:1 matching of patients based on age, sex, and Elixhauser Comorbidity Index, perioperative outcomes and surgeon volume were compared for the two procedures with univariable and multivariable analyses. From 2011 through 2020, a total of 148,231 TSAs were identified (aTSA 57,680 [38.9%]; rTSA 90,551 [61.1%]). Over this period, the yearly overall incidence of TSAs being performed increased from 5890 to 23,215 (an increase of 394.1%) and the percent of TSA being performed with rTSA increased from 31.4% to 74.9%. The increased percentage of rTSA was accounted for by increased numbers of rTSA, as opposed to decreased aTHA. When assessing patients from the more recent years (2015-2020), those undergoing rTSA were older, more female, and had a higher Elixhauser Comorbidity Index (P <.0001 for each). After matching for these criteria, 33,582 were available from each of the subcohorts for comparing perioperative outcomes. Of these matched patients, those undergoing rTSA (compared to aTSA) were of independently greater odds for: transfusion (odds ratio [OR] 1.92), wound dehiscence (OR 1.54), any adverse event (OR 1.29), sepsis (OR 1.46), acute kidney infection (OR 1.35), pneumonia (OR 1.30), urinary tract infection (OR 1.28), and severe adverse events (OR 1.16). For surgeon volume, there was a long right-tail where the average ± standard deviation was more than twice the median for both rTSA (average: 40.7 ± 78.9; median: 16 [39]) and aTSA (average: 39.2 ± 56.3; median: 18 [39]). From 2011 to 2020, the number of TSAs performed yearly increased by 394.1%, of which rTSA increased from 31.4% to 74.9%. This shows that rTSA has been a disruptive technology in TSA because it has expanded the TSA patient population. There were increased perioperative adverse events associated with rTSA vs. aTSA, which is not explained by patient demographics or comorbidities. Given the rapid adoption of rTSA and the low average annual volume of this procedure performed per surgeon (<7), the effect of surgeon volume on perioperative outcome following rTSA merits further investigation. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is commonly considered to address symptomatically limiting knee osteoarthritis. With increasing utilization, understanding the variability and related drivers may help the healthcare system optimize delivery to the large numbers of patient to whom it is offered. A total of 1,066,327 TKA patients who underwent primary TKA were isolated from a 2010 to 2021 PearlDiver national dataset. Exclusion criteria included patients less than 18 years old and traumatic, infectious, or oncologic indications. Overall, 90-day reimbursements and variables associated with the patient, surgical procedure, region, and perioperative period were abstracted. Multivariable linear regressions were performed to determine independent drivers of reimbursement. The 90-day postoperative reimbursements had an average (standard deviation) of $11,212.99 ($15,000.62), a median (interquartile range) of $4,472.00 ($13,101.00), and a total of $11,946,962,912. Variables independently associated with the greatest increase in overall 90-day reimbursement were related to admission (in-patient index-procedure [+$5,695.26] or hospital readmission [+$18,495.03]). Further drivers were region (Midwest +$8,826.21, West +$4,578.55, South +$3,709.40; relative to Northeast), insurance (commercial +$4,492.34, Medicaid +$1,187.65; relative to Medicare), postoperative emergency department visits (+$3,574.57), postoperative adverse events (+$1,309.35), (P <.0001 for each). The current study assessed over a million TKA patients and found large variations in reimbursement/cost. The largest increases in reimbursement were associated with admission (readmission or index procedure). This was followed by region, insurance, and other postoperative events. These results underscore the necessity to balance performing out-patient surgeries in appropriate patients versus the risk of readmissions and defined other areas for cost containment strategies. [ABSTRACT FROM AUTHOR]

Following total hip arthroplasty (THA), readmissions and emergency department (ED) visits have been studied. Urgent care utilization is not well-characterized and may represent an overlooked avenue to facilitate lesser acuity patient needs. Primary THAs performed for osteoarthritis indications were identified from 2010 to April of 2021 from a large national database. The incidence and timing of 90-day postoperative ED and urgent care visits were determined. Univariable and multivariable analyses assessed factors associated with urgent care relative to ED utilization. Reasons and acuity of diagnoses for these visits were determined. For 213,189 THA patients, 90-day ED visits were identified for 37,692 (17.7%) and urgent care visits for 2,083 (1.0%). The greatest incidence of both ED and urgent care visits were in the first two postoperative weeks. Independent predictors of urgent care utilization relative to ED utilization were: procedures being performed in the Northeast or South, insurance plan being Commercial, women, and lesser comorbidity burden (P <.0001). Reason for visits to the ED was directly related to the surgical site for 25.6% but for urgent care were just 4.8% (P <.0001). Reasons for visits to the ED were classified as low-acuity for 57.4% and for urgent care 96.9% (P <.0001). Following THA, patients may need urgent evaluation. While many issues can be addressed through the office, urgent care visits may represent a viable and underused resource relative to the ED for a large percentage of patients who have lower acuity diagnoses. [ABSTRACT FROM AUTHOR]

Morbid obesity (MO) has been associated with increased risk of adverse events following procedures such as posterior lumbar fusion (PLF). While preemptive bariatric surgery (BS) has been considered for those with MO (body mass index [BMI] ≥35 kg/m2), not all undergoing such intervention have significant weight loss, and the impact of BS has been shown to correlate with weight loss after different related procedures. To examine outcomes following isolated single level PLF among patients with history of BS who subsequently did and did not transition out of the morbidly obese category. Retrospective case-control study. The PearlDiver 2010-Q1 2020 MSpine database was used to identify adult patients undergoing elective isolated PLF. Patients were excluded if they had a history of infection, neoplasm, or trauma in the 90-days prior to their PLF and if they were not active in the database for at least 90 days following their surgery. Three sub-cohorts were defined: 1) MO controls without a history of BS (-BS+MO), 2) patients with prior BS procedure who remained MO (+BS+MO), and 3) patients with prior BS who were no longer MO at the time of PLF (+BS-MO). Matched 1:1:1 populations were created for these three sub-cohorts based on age, sex and Elixhauser Comorbidity Index (ECI). Ninety-day adverse events and readmission rates were assessed and compared between the three sub-cohorts (-BS+MO, +BS+MO, +BS-MO). Univariable analyses and multivariable logistic regression were performed on the matched population to compare 90-day adverse events and readmission rates controlling for age, sex, and ECI. The current study identified PLF patients who were MO at the time of surgery but did not have a history of BS (-BS+MO, n=34,236), those who had BS and remained MO (+BS+MO, n=564), and those who had MS and were no longer MO (+BS-MO, n=209 which was only 27% of those who had BS). On multivariable analysis of the matched populations, those that had BS but remained MO (+BS+MO) were not at reduced odds of 90-day adverse events. However, those that had BS and were no longer MO (+BS-MO) were at reduced odds of 90-day any, severe, and minor adverse events (OR 0.41, 0.51, and 0.37, respectively with p<0.05 for all). Only 27% of those with a history of BS prior to PLF transitioned out of the MO category. Compared to those who were morbidly obese without BS, those who had BS were only at reduced risk of 90-day adverse events if they actually lost weight sufficient to drop out of morbidly obesity. These findings should be taken into account when counseling patients and interpreting prior studies. [ABSTRACT FROM AUTHOR]

• Toddlers in a randomized maternal Tdap immunization trial received a DTaP-HepB-IPV/Hib booster. • Response to pertussis and to other antigens were similarly high in toddlers from vaccinated and unvaccinated mothers. • Antibody concentrations for two pertussis antigens and diphtheria were lower in toddlers from vaccinated mothers. • The clinical significance of this immune interference needs long-term monitoring. Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7–366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11–18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/ Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4–1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. Clinical Trial Registration. ClinicalTrials.gov: NCT02853929. [ABSTRACT FROM AUTHOR]

• A 3-component Tdap vaccine was administered during the third trimester of pregnancy. • This resulted in high levels of pertussis antibodies in newborns' cord blood. • The Tdap vaccine had a clinically acceptable safety profile in mothers and their fetuses/newborns. • These data support routine maternal Tdap vaccination to prevent newborn pertussis disease. Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. Clinical Trial Registration. ClinicalTrials.gov: NCT02377349. [ABSTRACT FROM AUTHOR]

• Infants of mothers who participated in a phase IV maternal pertussis immunization trial (NCT02377349) received hexavalent DTaP and PCV13 primary series. • High levels of maternally transferred pertussis antibodies persisted in infants from Tdap-vaccinated mothers until 2–3 months after birth. • These maternally transferred pertussis antibodies interfered with the infant immune response to the pertussis components of the primary DTaP series. • The clinical significance of this interference remains unknown. Pertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization. This phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (270/7–366/7 weeks' gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination. 601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related. Pertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant's ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience. Clinical Trial Registration: ClinicalTrials.gov: NCT02422264. [ABSTRACT FROM AUTHOR]

• In a randomized controlled first-in-humans trial in seronegative adults a candidate Cytomegalovirus (CMV)vaccine had mild to moderate reactogenicity, with no safety signals. • Dose-dependent increase in CMV glycoprotein (gB) binding, avidity and neutralizing antibody titers were observed after dose 2 and 3. • Of 3 vaccine formulations compared to placebo, the highest immunogenicity was seen in the alum-adjuvanted 2.0 µg gB dose recipients after the third dose. • This phase 1 trial supports further development of this eVLP CMV vaccine candidate. Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate. [ABSTRACT FROM AUTHOR]

Objectives: The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM197. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera.Methods: Maternal and cord sera collected at baseline and at delivery from vaccine and placebo recipients during a double-blind placebo-controlled Phase II study (www.clinicaltrials.gov, NCT01446289) were tested in an opsono-phagocytic bacterial killing assay. Cord sera from vaccine recipients were also passively transferred to newborn mice to investigate conferred protection against bacterial challenge.Results: Antibody-mediated GBS phagocytic killing was significantly increased in maternal serum at delivery and in cord sera from the investigational vaccine group as compared to the placebo group. Anti-capsular IgG concentrations above 1 µg/mL mediated in vitro killing against GBS strains belonging to all three serotypes and IgG levels correlated with functional titers. Passively administered cord sera elicited a dose-dependent protective response against all GBS serotypes in the in vivo model.Conclusions: The maternal vaccine elicited functional antibodies that were placentally transferred. Anti-capsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model. [ABSTRACT FROM AUTHOR]

Background Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. Objective We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. Methods In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV 1 during 10 days after inoculation. Results In asthmatic patients (n = 63) CNTO3157 provided no protection against FEV 1 decrease (least squares mean: CNTO3157 [n = 30] = −7.08% [SE, 8.15%]; placebo [n = 25] = −5.98% [SE, 8.56%]) or symptoms after inoculation. In healthy subjects (n = 12) CNTO3157 versus placebo significantly attenuated upper ( P = .03) and lower ( P = .02) airway symptom scores, with area-under-the-curve increases of 9.1 (15.1) versus 34.9 (17.6) and 13.0 (18.4) versus 50.4 (25.9) for the CNTO3157 (n = 8) and placebo (n = 4) groups, respectively, after inoculation. All of the severe and 4 of the nonserious asthma exacerbations occurred while receiving CNTO3157. Conclusion In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought for this high unmet medical need. [ABSTRACT FROM AUTHOR]

On November 18–19, 2019, the Immunity of Canadians and Risk of Epidemics (iCARE) Network convened a workshop in Toronto, Ontario, Canada. The objectives of the workshop were to raise the profile of sero-epidemiology in Canada, discuss best practice and methodological innovations, and strategize on the future direction of sero-epidemiology work in Canada. In this conference report, we describe the presentations and discussions from the workshop, and comment on the impact of the COVID-19 pandemic on serosurveillance initiatives, both in Canada and abroad. [ABSTRACT FROM AUTHOR]

• Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants in humans. • Serum PFAS concentrations may reduce antibody response after vaccination. • We conducted a systematic review and meta -analysis of antibody response and PFAS. • An inverse association was found, e.g, −5% per doubling of perfluorooctanoate. • The association was present across antibodies to multiple different antigens. Epidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear. The goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in log e antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA). We conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022. We included studies conducted in humans, including mother–child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine. Study appraisal and synthesis methods: We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data. The 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in log e [antibody concentration] per doubling of serum PFAS) with 95% confidence intervals that excluded zero ("statistical support"), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, −0.06 (-0.10, −0.01; moderate) and in children, −0.10 (-0.16, −0.03; moderate); for Diphtheria in children, −0.12 (-0.23, −0.00; high); for Rubella in all ages, −0.09 (-0.17, −0.01; moderate), and for Tetanus in children, −0.12 (-0.24, −0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, −0.06 (-0.11, −0.01; moderate) and in children, −0.10 (-0.18, −0.03; moderate); for Rubella in all ages, −0.09 (-0.15, −0.03; high) and in children, −0.12 (-0.20, −0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, −0.03 (-0.06, −0.00; moderate) and in children, −0.05 (-0.09, −0.00; low); and for Rubella in children, −0.07 (-0.11, −0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations. Epidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias. [ABSTRACT FROM AUTHOR]

Extracytoplasmic thiol-disulfide oxidoreductases (TDORs) catalyze the oxidation, reduction, and isomerization of protein disulfide bonds. Although these processes have been characterized in Gram-negative bacteria, the majority of Gram-positive TDORs have only recently been discovered. Results from recent studies have revealed distinct trends in the types of TDOR used by different groups of Gram-positive bacteria, and in their biological functions. Actinobacteria TDORs can be essential for viability, while Firmicute TDORs influence various physiological processes, including protein stability, oxidative stress resistance, bacteriocin production, and virulence. In this review we discuss the diverse extracytoplasmic TDORs used by Gram-positive bacteria, with a focus on Gram-positive Firmicutes. [ABSTRACT FROM AUTHOR]

Following spine surgery, postoperative surgical site infection (SSI) is a rare but potentially devastating complication. Previous studies have assessed risk factors for spine SSI and one aimed to develop risk stratification tool to assess management options, but this tool has not been externally validated or regularly used. The current study aimed to investigate the rate of SSI following elective spine surgery, surgical management pursued, and success of traditionally utilized one-stage of irrigation and debridement (I&D) with closure over drains. Retrospective case-control study. Adult, elective spine surgeries performed at a single academic institution between 2013 and 2021 were evaluated. Patients who developed SSI requiring surgical intervention were identified. Those who underwent initial management with I&D and closure over drains were assessed for need of subsequent I&D (considered failure of initial infection management). Of spine surgeries meeting inclusion criteria, those with SSI were identified and management was characterized. For those who did and did not fail attempted one stage I&D with closure over drains, pre-operative and surgical variables from the index procedure as well as infection characteristics were assessed and compared with univariable and multivariable analyses. Of 11,023 elective spine surgeries, SSI was identified for 76 (0.7%). For initial management, I&D with closure over drains was used for 66 (86.8%) while I&D and wound vacuum management was used 10 (13.2%). Failure of attempted one stage I&D (requiring subsequent I&D procedure) was identified for 18 (27% of those undergoing I&D and closure over drains). Of multiple patient, surgical, and infection characteristics, the only factor identified as independently predictive of one stage I&D failure was presence of bacteremia (odds ratio [OR] 38.3, p=0.0007). Within the sub-cohort of patients with bacteremia, failure of attempted one stage I&D was noted for 80%. Less than one percent of a large cohort of patients undergoing spine surgery were found to develop SSIs. Of those undergoing attempted one stage I&D, most patient, surgical, and infection variables did not influence outcome of the intervention. However, those with bacteremia were at 38.3 times greater odds of failing attempted one-stage I&D. These results suggest considering delayed closure approaches in these cases. [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous studies have shown that two doses of an investigational hepatitis B vaccine consisting of hepatitis B surface antigen combined with an immunostimulatory phosphorothioate oligodeoxyribonucleotide adjuvant (HBV-ISS) given 8 weeks apart provides seroprotection sooner than 3 doses of a licensed hepatitis B vaccine over 24 weeks. A more rapid schedule with a 4-week interval could provide earlier protection and potentially greater compliance. Methods: In this randomized, double-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 or 0 and 8 weeks; saline placebo was given at week 8 for the 0–4 schedule and at week 4 for the 0–8 schedule). Adverse events were collected after each dose. Antibodies were measured at 0, 4, 8, 12, and 32 weeks. Results: Participants were randomized to the 0–4 (n =18) or 0–8 (n =23) weeks schedule. Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections. By 4 weeks post-dose-2, 94.1% of 0–4 and 100% of 0–8 recipients had protective antibody levels; geometric mean concentrations were 244mIU/mL and 3217mIU/mL respectively. By 32 weeks, the difference in antibody concentration had decreased (GMC 439mIU/mL vs. 863mIU/mL, respectively; p =0.04). Conclusions: A 0–4 weeks, two-dose regimen of HBV-ISS was well-tolerated and induced an antibody response that was similar to a 0–8 weeks schedule. [Copyright &y& Elsevier]

Abstract: Background: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). Methods: In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody≥10mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. Results: A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n =1809) and HBV-Eng (n =606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. Conclusions: A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated. [Copyright &y& Elsevier]

Abstract: Background: Although decennial adult boosters of tetanus and diphtheria toxoids are recommended in Canada and the United States, a second dose of pertussis vaccine during adulthood is not currently recommended. Methods: This open-label, multicenter study compared the safety and immunogenicity of a first dose of an adult formulation of tetanus, diphtheria, and acelluar pertussis vaccine (Tdap) with a repeat dose of Tdap in adults who had received Tdap 10 years previously. Results: A total of 769 participants ranging in age from 20 to 72 years took part in this study; 92.3% of naïve and 92.7% of repeat-dose participants had at least one solicited adverse event. Injection-site pain (84.4% and 87.8%), erythema (29.7% and 23.1%), and swelling (23.3% and 20.5%), and myalgia (53.5% and 60.1%), headache (37.6% and 40.6%), malaise (29.0% and 29.4%), and fever (4.9% and 4.2%) were the most common solicited adverse events reported in the naïve and repeat-dose groups, respectively. Postvaccination antibody levels ≥0.1IU/mL were achieved by 99.7% of the naïve-group participants and all of the repeat-dose participants for tetanus and 96.1% of the naïve group and 98.5% of the repeat-dose group for diphtheria, both meeting the predefined noninferiority criteria. For pertussis antibodies, anti-PT (89.2EU/mL vs. 116EU/mL) was higher in the repeat-dose group, anti-FHA (249 vs. 214) and anti-PRN (216 vs. 266) were similar, and anti-FIM (1015 vs. 779) was higher in the naïve group. Noninferiority criteria were met for all antigens except for anti-FIM. Conclusion: A repeat dose of Tdap vaccine 10 years after the first dose was well tolerated and immunogenic in adults (ClinicalTrials.gov identifier: NCT00712959). [Copyright &y& Elsevier]

Abstract: Background: Although decennial adult boosters of tetanus and diphtheria toxoids are recommended in Canada and the United States, a second dose of pertussis vaccine is not currently recommended for adults. Methods: This open-label, postmarketing, multicenter study evaluated the tolerability and immunogenicity of a second dose of an adult formulation of tetanus, diphtheria, and pertussis vaccine (Tdap) in adolescents and adults 5 years after a first dose. Results: A total of 545 participants from previous Tdap vaccine studies, ranging in age from 15 to 69 years, participated in this study. Of these participants, 94.2% had at least one solicited adverse event after the booster dose such as injection-site erythema (28.6%), swelling (25.6%), or pain (87.6%) or a systemic adverse event such as myalgia (61.0%), headache (53.2%), malaise (38.2%), or fever (6.5%). These adverse events were slightly more frequent than after the initial dose. Postvaccination, 100% of participants had a tetanus antibody level ≥0.10IU/mL and 95% had a diphtheria antibody level ≥0.10IU/mL. For pertussis, 82.1% (pertussis toxoid), 96.7% (filamentous hemagglutinin), 95.6% (pertactin), and 99.8% (fimbriae) had a postvaccination antibody threshold of ≥50EU/mL. Conclusion: A second dose of Tdap vaccine 5 years after the initial dose was well tolerated and immunogenic in adolescents and adults. [Copyright &y& Elsevier]

Abstract: The current recommended infant vaccination schedules require many injections at multiple sites, which increase stress for infants and parents and may create challenges to vaccination compliance. Therefore, combination vaccines, which reduce the number of injections at each medical visit, can be an essential method to improve compliance. The objective of this study was to assess the safety and immunogenicity of an investigational, liquid, hexavalent, pediatric vaccine at 2, 4, 6, and 12–14 months of age. In this multicenter, open-label controlled study, 756 infants were randomized in approximately equal numbers to receive 0.5mL intramuscular dose of diptheria–tetanus–pertussis–polio–Haemophilus influenzae type b+hepatitis B vaccine, or 1 of 3 double-blind investigational formulations. All formulations included a hepatitis B surface antigen (HBsAg) concentration of 10μg/0.5mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus toxoid [PRP–T, 12μg] or Neisseria meningitidis outer membrane protein complex [PRP–OPMC, 3μg or 6μg]): a minimum acceptable postdose 3 antibody response rate for each antigen was defined by the lower limit of a 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited vaccine-related injection-site reactions (pain, erythema, swelling) with increasing PRP–OMPC dose. No serious vaccine-related AEs were reported in the investigational groups. Both PRP–OMPC formulations met prespecified acceptability criteria for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and poliovirus. The PRP–T formulation met the acceptability criterion for antibody responses to all antigens other than PRP at postdose 3. Postdose 4 responses were adequate for all antigens in all formulations. All vaccine formulations were well-tolerated. Both PRP–OMPC formulations met prespecified immunogenicity criteria of PRP–OMPC evaluation. [Copyright &y& Elsevier]

Abstract: Background: Routine administration of quadrivalent meningococcal conjugate vaccine to adolescents and certain high risk groups is recommended in the United States and Canada. We compared the immunogenicity and safety of an investigational quadrivalent meningococcal vaccine conjugated to CRM-197 (MenACWY-CRM) with a licensed quadrivalent vaccine conjugated to diphtheria toxoid (MCV4) in children aged 2–10 years. Methods: Eligible 2–5-year-olds were randomized 1:2:2 to receive either 2 doses of MenACWY-CRM, or 1 dose of MenACWY-CRM or MCV4; 6–10-year-olds were randomized 1:1 to receive a single dose of MenACWY-CRM or MCV4. The primary immunogenicity assessment was seroresponse separately for the two age cohorts 28 days following a single dose of MenACWY-CRM or MCV4. Noninferiority and superiority criteria were predefined. Solicited injection-site and systemic reactions were collected for the 7 days postvaccination. Results: A total of 2907 children were randomized to receive study vaccine. MenACWY-CRM met statistical superiority criteria vs. MCV4 for groups W and Y and was noninferior for group C in both age strata. For group A, noninferiority criteria were not met; the group A seroresponse rates for MenACWY-CRM and MCV4, respectively were 72% (95% confidence interval 68–75%) and 77% (73–80%) in 2–5-year-olds and 77% (73–80%) and 83% (79–86%) in 6–10-year-olds. When the two age strata were combined (2–10-year-old children), MenACWY-CRM was noninferior to MCV4 for all four groups, and statistically superior for groups C, W, and Y. Safety parameters were similar across age cohorts and vaccines groups. Conclusions: MenACWY-CRM and MCV4 were immunogenic and well tolerated in children aged 2–10 years. Seroresponse to MenACWY-CRM was statistically noninferior to MCV4 for all groups, and statistically superior for groups C, W, and Y. Trial registration: Clinicaltrials.gov identifier: NCT00616421. [Copyright &y& Elsevier]

Abstract: Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N =390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR+varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR+varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p =0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly. [Copyright &y& Elsevier]

Abstract: Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae b conjugate–hepatitis B virus (DTaP–IPV–Hib–HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12–14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12μg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3μg or 6μg]), and in hepatitis B surface antigen (HBsAg, 10μg or 15μg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity. [Copyright &y& Elsevier]

Abstract: Background: Neisserial surface protein A (NspA) is a highly conserved, surface-exposed outer membrane protein of Neisseria meningitidis that has been shown to induce a bactericidal immune response in animals against all pathogenic Neisserial serogroups. Methods: Healthy 18–50-year-old adults were assigned to receive, in a dose escalating manner, 3 doses of 1 of 5 formulations of an experimental, unfolded, recombinant NspA (rNspA) vaccine or placebo, or 1 dose of commercially available quadravalent (A, C, Y, W-135) meningococcal polysaccharide vaccine (Menomune®). Adverse events were collected during the first week post-immunization, prior to the next dose and 1 month after the last dose. Serum for measurement of hematological and biochemical parameters and antibodies by enzyme immunoassay and bactericidal assay were measured before the first dose, prior to the second dose and 1 month after the last dose of vaccine. Results: The rNspA vaccine was well tolerated by recipients. Injection-site pain was reported more frequently by recipients of the three highest doses of rNspA compared to placebo but at similar rates to the licensed meningococcal polysaccharide vaccine. Adverse events were reported less frequently after subsequent doses in the three-dose series. An antibody rise measured by enzyme immunoassay was elicited with a dose-related increase that reached a maximum with the 125μg dose. Prolongation of the dosing interval between the second and third dose appeared to be associated with increased antibody levels. No bactericidal antibodies were detected after any of the rNspA formulations. Conclusions: The unfolded rNspA meningococcal vaccine was well tolerated and immunogenic in healthy adult volunteers but did not elicit bactericidal antibodies. [Copyright &y& Elsevier]

Abstract: Background: Since 1998, all children in Canada have been immunized with a pentavalent diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib) produced by one manufacturer (Pentacel™). Recently, another DTaP-IPV-Hib (Infanrix™-IPV-Hib) became available. Data on the interchangeability of these products was lacking. Methods: In this multicentered, observer-blind study, healthy 15–20-month-old children previously immunized with three doses of Pentacel™ were randomly allocated to receive a single dose of Pentacel™ or Infanrix™-IPV-Hib. Adverse events were documented by diary for 7 days post-immunization and unsolicited adverse events were documented for 30 days. Results: 433 participants were enrolled (mean age 17.1 months). Rates of fever, anorexia and irritability were similar in both groups. Injection-site redness >20mm (11.5% versus 5.6%; p =0.038), injection-site pain (52.1% versus 39.4%; p =0.009) and moderate or greater drowsiness (13.8% versus 7.4%; p =0.042) were more common after Pentacel™ than Infanrix™-IPV-Hib. The proportions of participants who were seroprotected or who seroresponded were similar for all antigens. Geometric mean titers or concentrations were similar for antibodies against diphtheria toxoid and poliovirus type 3. Geometric mean concentrations or titers were higher in the Infanrix™-IPV-Hib group against pertussis toxin (88.5EU/mL versus 65.6EU/mL), filamentous hemagglutinin (207.3EU/mL versus 132.1EU/mL), pertactin (251.9EU/mL versus 166.9EU/mL) and poliovirus type 1 (1293.7 versus 976.2 reciprocal dilution). Geometric mean titers or concentrations were higher in the Pentacel™ group against H. influenzae type b (29μg/mL versus 19μg/mL), tetanus toxoid (5.6IU/mL versus 4.7IU/mL) and poliovirus type 2 (1437.3 versus 1134.2 reciprocal dilution). Conclusions: A booster dose of Infanrix™-IPV-Hib after three priming doses of Pentacel™ is well-tolerated and immunogenic in 15–20-month-old toddlers and can be used interchangeably. [Copyright &y& Elsevier]

Abstract: This study assessed compatibility of concurrently administered 7-valent pneumococcal conjugate (PCV7), hepatitis B (HB) and DTaP.IPV/Hib vaccines. Infants were given DTaP.IPV/Hib and HB at 2, 4, 6 months and randomly assigned (2:1) to receive PCV7 concurrently or sequentially (at 3, 5, 7 months). Antibody levels were compared in 246 concurrent and 122 sequential vaccinees. Responses to PCV7, DTaP.IPV/Hib and HB were generally unaltered with concurrent administration except that Hib responses were increased (p =0.008) and HB responses were reduced (p =0.006) with concurrent dosing, the latter possibly from same thigh injection with DTaP.IPV/Hib. We conclude that PCV7, DTaP.IPV/Hib and HB are compatible with concurrent, separate injections. [Copyright &y& Elsevier]

Abstract: We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome™) in normal, healthy adults. In a randomized, double-blind trial participants (n =78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45μg of each of the three HA antigens, or two nasal doses containing 30μg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule. A shallow vaccine reactogenicity dose-response was seen. The most common local reaction was nasal congestion, which occurred in up to 48.3% of vaccine recipients in days 0–6 after vaccine but was mild and self-limiting; this reaction was not significantly more common among active vaccine recipients than placebo recipients. Mild to moderate headache was the most commonly reported systemic reactogenicity complaint in all treatment groups, and was the only solicited complaint to increase significantly in frequency after a second active dose. No severe systemic reactions occurred. A positive and statistically significant antibody response was observed, in serum and in nasal secretions, to increasing dose for all three antigens. Serum HAI titre responses and nasal secretory IgA immune responses were elicited against all three antigens. Further testing of this nasal influenza vaccine is warranted to determine its safety and immunogenicity in these populations and its efficacy in the prevention of clinical illness. [Copyright &y& Elsevier]

Abstract: Background: Many individuals do not respond to a three-dose series of hepatitis B vaccine (HBV) and most do not achieve a protective antibody response until after dose 2 or 3. Methods: Healthy, seronegative 18–28 year old adults were randomly assigned in equal numbers to receive two doses of the experimental vaccine (HBV-ISS without alum) (0, 8 weeks) and placebo (24 weeks) or Engerix-B® (0, 8, 24 weeks). Adverse events were collected during the first week and at 4 weeks after each injection. Antibodies were measured 4 weeks after dose 1; before, 1 and 4 weeks after dose 2, and before, 1 and 4 weeks after dose 3 and at 1 year. Results: Ninety-nine participants were enrolled (65% female; mean age 22.6 years). 79% of HBV-ISS and 12% of Engerix-B® recipients had a protective antibody response 4 weeks post dose 1 (geometric mean concentration [GMC] 23.0 and 1.87mIU/mL, respectively). By 1 week post dose 2, 100% of HBV-ISS and 18% Engerix-B® recipients had protective levels (GMC 1603 versus 2.40mIU/mL). Rates of adverse events were low and similar in both groups; headache and fatigue were the most common systemic adverse events in up to 1/3 of both groups. Mild injection-site tenderness was more common after HBV-ISS than Engerix-B® after both doses (74–77% compared to 34–58%; p ≤0.029). Conclusions: Protective levels are achieved more quickly and after fewer doses of HBV-ISS than Engerix-B®. HBV-ISS is well tolerated but associated with more mild injection-site tenderness than Engerix-B®. [Copyright &y& Elsevier]

We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria–tetanus toxoid–acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or toddlers enrolling in a RCT of a Meningococcal C conjugate vaccine. Nurses interviewed parents to collect demographic data and parents self-administered the Spielberger Self-evaluation Questionnaire (State Anxiety STAI-Y-I) [Manual for the State-Trait Anxiety Inventory (Form Y) (Self-evaluation Questionnaire), Consulting Psychologists Press Inc., Palo Alto, 1983], a validated instrument measuring the temporary condition of “state anxiety.” A regression tree (CART) (S-Plus) was used to identify factors associated with higher anxiety scores. Parents of 97 children enrolled. Anxiety scores ranged from 22.75 (lower anxiety) to 36.43 (higher anxiety). The regression tree identified a structured tree with six branches. The highest anxiety scores occurred in fathers with education less then grade 8, mothers with education less than high school, birth order of the child less then the third, previous serious illness in the family, or lack of experience with research. In a group of parents agreeing to enroll their infant or toddler in a vaccine study, certain attributes and experiences were associated with higher anxiety at the time of immunization in the context of a RCT. These factors should be considered by vaccine researchers in the recruitment process of clinical trials. [Copyright &y& Elsevier]

Certain oligodeoxynuclotides with CpG motifs provide enhanced immune response to co-delivered antigens. We performed a phase I, observer-blinded, randomized study in healthy anti-hepatitis B surface antigen (anti-HBsAg) antibody negative adults to explore safety and immunogenicity of co-injection of recombinant HBsAg combined with an immunostimulatory DNA sequence (ISS) 1018 ISS. Four ISS dosage groups (N=12 per group) were used: 300, 650, 1000 or 3000 μg. For each group, two controls received 20 μg HBsAg alone, two controls received ISS alone, and eight subjects received ISS+20 μg HBsAg. Subjects received two doses 8 weeks apart. Injection site reactions (tenderness and pain on limb movement) were more frequent at higher ISS+HBsAg doses but were mainly mild and of short duration. Higher anti-HBsAg antibody levels were associated with higher ISS doses. Four weeks after the first dose, a seroprotective titer (≥10 mIU/ml) was noted for 0, 25, 75, and 87.5% of subjects by increasing ISS dose group (P<0.05) for those who received ISS+HBsAg; 1 month after the second dose this increased to 62.5, 100, 100, and 100%, respectively. Geometric mean anti-HBsAg antibody levels by increasing ISS+HBsAg dose were 1.22, 5.78, 24.75, and 206.5 mIU/ml after the first dose and 65.37, 877.6, 1545, and 3045 mIU/ml after the second dose. We conclude that 1018 ISS+HBsAg was well tolerated and immunogenic in this phase I study in healthy adults and may offer the potential for enhancement of hepatitis B virus (HBV) immunization and protection after one or two doses or in individuals who fail to respond to the standard vaccine regimen. [Copyright &y& Elsevier]

We performed a randomized, controlled clinical trial to characterize the evolution of the adverse events associated with the fifth consecutive dose of an acellular pertussis vaccine, and to assess the level of discomfort associated with the injection and the attitude of parents concerning these events. A total of 505 children who had received either four doses of acellular pertussis vaccine or whole-cell pertussis vaccine were given a fifth dose of one of the two vaccines. Adverse events were monitored by parents and collected by telephone or home visit at 4, 8, 12, 24, 48 and 72 h, and 7 and 28 days after immunization. Rates of injection site redness ≥50 mm were similar in recipients of five doses of acellular pertussis vaccine (32.8%) or five doses of whole-cell pertussis vaccine (43.3%). Injection site swelling, tenderness, and decreased arm movement were all more frequent in children who received five doses of whole-cell pertussis vaccine. Antibody levels before or after immunization did not predict those children who had increased injection site reactions. The children rated the injection site reactions as significantly more severe after five consecutive doses of whole-cell vaccine. Parent satisfaction was higher after the acellular vaccine. We conclude that a fifth consecutive dose of a whole-cell pertussis vaccine is associated with high rates of tender redness and swelling at the injection site, in contrast to a fifth consecutive dose of an acellular pertussis vaccine which is associated with high rates of non-painful redness. However, parents will still need to be aware of the high rates of injection site reactions expected after a fifth dose of acellular pertussis vaccine. [Copyright &y& Elsevier]

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19–50 years), children (3–12 years) and the elderly (≥65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors. [Copyright &y& Elsevier]

Streptococci secrete small peptides with important biological functions. These peptides are not amenable to standard immunoblotting, and are often detected indirectly using activity assays, or by alternative approaches that may be expensive and laborious. Here we describe an immunoblotting method that enables reproducible detection of these small streptococcal peptides. [ABSTRACT FROM AUTHOR]

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation. [ABSTRACT FROM AUTHOR]

• 91.2% of Canadian MenB isolates tested expressed fHbp at levels predicted to be susceptible to the MenB-FHbp vaccine. • Peptide 15 (B44, 1.15) was most prevalent and had the highest levels of fHbp surface expression. • fHbp variant type and expression varied by age and region. Invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) remains a health risk in Canada and globally. Two MenB vaccines are now approved for use. An understanding of the genotype of Canadian strains and the potential strain coverage conferred by the MenB-FHbp vaccine is needed to inform immunization policies. Serogroup B Neisseria meningitidis strains responsible for meningococcal disease in Canada from 2006 to 2012 were collected as part of the Canadian Immunization Monitoring Program Active surveillance network. Genotypic analysis was done on MenB isolates from 2006 to 2012 with determination of fHbp surface expression for a subset of isolates: those occurring from 2010 to 2012. Two clonal complexes (cc269 and cc41/44) were observed in 68.8% of the 276 isolates. A total of 50 different fHbp peptides were identified among isolates from 2006 to 2012. Surface expression of fHbp was detected on 95% of MenB isolates from 2010 to 2012 and 91% of isolates expressed fHbp at levels that are predicted to be susceptible to the bactericidal immune response elicited by the MenB-FHbp vaccine. Some regional differences were observed, particularly in isolates from British Columbia and Quebec. The majority of MenB isolates responsible for meningococcal disease in Canada expressed fHbp at levels predicted to be sufficient for complement mediated bactericidal activity in the presence of MenB-FHbp induced serum antibodies. [ABSTRACT FROM AUTHOR]

Pertussis causes significant morbidity and mortality in infants aged <6 months. Maternal pertussis vaccination during pregnancy has been recommended in Canada since 2018 to reduce these negative outcomes. In the absence of routine immunization coverage data, our objective was to evaluate uptake in Toronto, Canada. We recruited mother-infant pairs at The Hospital for Sick Children, Toronto, between 2018 and 2020. We performed logistic regression to examine associations between demographics and self-reported pertussis vaccination. 76/243 mothers (31.3 %) reported receiving pertussis vaccination during their most recent pregnancy. Odds of receiving vaccination more than doubled with each 1-year increase in year of pregnancy (aOR: 2.2; 95 % CI: 1.3, 3.6; p < 0.01) and among those born in Canada as compared to those not (aOR: 2.0; 95 % CI: 1.1, 3.6; p = 0.02) Uptake of pertussis vaccination during pregnancy in Ontario has increased in recent years, however coverage remains lower than desirable. [ABSTRACT FROM AUTHOR]

In 2019, the 3 + 1 schedule for children's vaccination (2–4–6–18 months old) was changed for a reduced 2 + 1 schedule (2–4–12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. We conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children's blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. A total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65–0.90), 0.66 (0.55–0.79), 0.72 (0.52–0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. Infant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children's protection. [ABSTRACT FROM AUTHOR]

• Concerns about vaccine safety may arise after adverse events following immunization. • Exploring factors of revaccination may improve confidence of vaccine safety. • Adverse event type and impact may support clinical recommendation for revaccination. • Adverse event impact may inform patients' intentions to be revaccinated. Individuals and healthcare providers may be uncertain about the safety of revaccination after an adverse event following immunization (AEFI). We identified factors associated with physician recommendation for revaccination and participant intention to be revaccinated among patients with adverse events following immunization (AEFIs) assessed in the Canadian Special Immunization Clinic (SIC) Network from 2013 to 2019. This prospective observational study included patients assessed in the Canadian Special Immunization Clinic Network from 2013 to 2019 for an AEFI who required additional doses of the vaccine temporally associated with their AEFI. Participants underwent standardized assessment and data collection. Physician recommendations regarding revaccination and participant intent for revaccination were recorded. AEFI impact on daily activities and need for medical attention was captured as low, moderate, high impact and serious (e.g., requiring hospitalization). Multivariable logistic regression analysis identified factors associated with physician recommendation and participant intention for revaccination, controlling for province of assessment. Physician recommendation was significantly associated with the type of AEFI and AEFI impact. Compared to large local reaction, physician recommendation for revaccination was reduced for immediate hypersensitivity (aOR: 0.24 [95% CI: 0.08–0.76]) and new onset autoimmune disease (aOR: 0.16; 95% CI: 0.04–0.69). Compared to low impact AEFIs, physician recommendation was reduced for moderate (aOR: 0.22 [95% CI: 0.07–0.65]), high impact (aOR: 0.08 [95% CI: 0.02–0.30]), and serious AEFIs (aOR: 0.11 [95% CI: 0.03–0.37]). Participant intention for revaccination was significantly associated with AEFI impact, with reduced odds for high versus low impact AEFIs (aOR: 0.12 [95% CI: 0.04–0.42]). Physicians appear to use AEFI type and impact to guide recommendations while patients use primarily AEFI impact to form intentions for revaccination. The findings may help inform counselling for patients with AEFIs. [ABSTRACT FROM AUTHOR]

To evaluate immunocompromising conditions and subgroups of immunocompromise as risk factors for severe outcomes among children admitted for influenza. We performed active surveillance for laboratory-confirmed influenza hospitalizations among children ≤16 years old at the 12 Canadian Immunization Monitoring Program Active hospitals, during 2010–2021. Logistic regression analyses were used to compare outcomes between immunocompromised and non-immunocompromised children, and for different subgroups of immunocompromise. The primary outcome was intensive care unit (ICU) admission; the secondary outcomes were mechanical ventilation and death. Among 8982 children, 892 (9.9%) were immunocompromised; these patients were older (median, 5.6 (IQR, 3.1–10.0) vs. 2.4 (1–6) years; p < 0.001) than non-immunocompromised children, had a similar frequency of comorbidities, excluding immunocompromise and/or malignancy (38% (340/892) vs. 40% (3272/8090); p 0.2), but fewer respiratory symptoms, such as respiratory distress (20% (177/892) vs. 42% (3424/8090), p < 0.001). In multivariable analyses, immunocompromise (adjusted odds ratio (aOR), 0.19; 95% CI, 0.14–0.25) and its subcategories immunodeficiency (aOR, 0.16; 95% CI, 0.10–0.23), immunosuppression (aOR, 0.17; 95% CI, 0.12–0.23), chemotherapy (aOR, 0.07; 95% CI, 0.03–0.13), and solid organ transplantation (aOR, 0.17; 95% CI, 0.06–0.37) were associated with decreased probability of ICU admission in children admitted for influenza. Immunocompromise was also associated with a decreased probability of mechanical ventilation (aOR, 0.26; 95% CI, 0.16–0.38) or death (aOR, 0.22; 95% CI, 0.03–0.72). Immunocompromised children are overrepresented among hospitalizations for influenza, but have a decreased probability of ICU admission, mechanical ventilation, and mortality following admission. Admission bias precludes generalizability beyond the hospital setting. [ABSTRACT FROM AUTHOR]

Background We evaluated the immunogenicity and safety of 1 and 2 doses of quadrivalent meningococcal serogroup A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT) given alone or co-administered with 13-valent pneumococcal conjugate vaccine (PCV13) in toddlers. Methods In this phase III, open-label, controlled, multicentre study (NCT01939158), healthy toddlers aged 12–14 months were randomised into 4 groups to receive 1 dose of MenACWY-TT at month (M) 0 (ACWY_1), 2 doses of MenACWY-TT at M0 and M2 (ACWY_2), MenACWY-TT and PCV13 at M0 (Co-ad), or PCV13 at M0 and MenACWY-TT at M2 (PCV13/ACWY). Immune responses were assessed 1 month post-each vaccination. Solicited and unsolicited symptoms were recorded for 4 and 31 days post-each vaccination, respectively; serious adverse events (SAEs) and new onset of chronic illnesses (NOCIs) up to M9 from first vaccination. Results 802 toddlers were vaccinated. Post-dose 1 of MenACWY-TT, ≥92.8% of toddlers had rSBA titres ≥1:8, and ≥62.5% had hSBA titres ≥1:4 for each meningococcal serogroup. Post-dose 2 of MenACWY-TT, rSBA titres ≥1:8 were observed in ≥98.0% and hSBA titres ≥1:4 in ≥95.3% of toddlers. Percentages of toddlers with hSBA titres ≥1:4 were higher after 2 doses versus 1 dose of MenACWY-TT for MenW (97.1% versus 62.5–68.9%) and MenY (95.3% versus 64.3–67.6%). Non-inferiority of immune responses to co-administered MenACWY-TT and PCV13 over their separate administration was demonstrated. AEs incidence was comparable among groups. SAEs were reported for 4.9%, 5.1%, 5.5% and 7.5%, and NOCIs for 2.0%, 3.0%, 0.5% and 3.5% of toddlers in the ACWY_1, ACWY_2, Co-ad and PCV13/ACWY groups, respectively; 4 SAEs reported in 3 toddlers were vaccine-related. Two fatal vaccine-unrelated SAEs were reported. Conclusion MenACWY-TT was immunogenic when administered as a single dose at 12–14 months of age. A second dose in toddlers increased hSBA responses against MenW and MenY. MenACWY-TT and PCV13 can be co-administered without impairing the immunogenicity or safety profile of either vaccine. [ABSTRACT FROM AUTHOR]

• Vaccination of pregnant women is recommended to reduce pertussis in infants. • A novel agent-based mathematical model was developed to examine several phenomena. • Maternal vaccination results in reduction in future pertussis cases in infants. • Immunological blunting has moderate effect on maternal vaccination effectiveness. • Interruption of exposure pathways reduces pertussis disease in infants. The re-emergence of pertussis has occurred in the past two decades in developed countries. The highest morbidity and mortality is seen among infants. Vaccination in pregnancy is recommended to reduce the pertussis burden in infants. We developed and validated an agent-based model to characterize pertussis epidemiology in Alberta. We computed programmatic effectiveness of pertussis vaccination during pregnancy (PVE) in relation to maternal vaccine coverage and pertussis disease reporting thresholds. We estimated the population preventable fraction (PFP) of different levels of maternal vaccine coverage against counterfactual "no-vaccination" scenario. We modeled the effect of immunological blunting and measured protection through interruption of exposure pathways. PVE was inversely related to duration of passive immunity from maternal immunization across most simulations. In the scenario of 50% maternal vaccine coverage, PVE was 87% (95% quantiles 82–91%), with PFP of 44% (95% quantiles 41–45%). For monthly age intervals of 0–2, 2–4, 4–6 and 6–12, PVE ranged between 82 and 99%, and PFP ranged between 41 and 49%. At 75% maternal vaccine coverage, PVE and PFP were 90% (95% quantiles 86–92%) and 68% (95% quantiles 65–69%), respectively. At 50% maternal vaccine coverage and 10% blunting, PVE and PFP were 86% (95% quantiles 77–87%) and 43% (95% quantiles 39–44%), respectively, while at 50% blunting, the corresponding values of PVE and PFP were 76% (95% quantiles 70–81%) and 38% (95% quantiles 35–40%). PVE attributable to interruption of exposure pathways was 54–57%. Our model predicts significant reduction in future pertussis cases in infants due to maternal vaccination, with immunological blunting slightly moderating its effectiveness. The model is most sensitive to maternal vaccination coverage. The interruption of exposure pathways plays a role in the reduction of pertussis burden in infants due to maternal immunization. The effect of maternal immunization on population other than infants remains to be elucidated. [ABSTRACT FROM AUTHOR]

The epidemiology of invasive meningococcal disease continues to change rapidly, even in the three years since the first Meningococcal Exchange Meeting in 2008. Control of disease caused by serogroup C has been achieved in countries that have implemented meningococcal C or quadrivalent meningococcal ACWY conjugate vaccines. Initiation of mass immunization programs with meningococcal A conjugate vaccines across the meningitis belt of Africa may lead to the interruption of cyclical meningococcal epidemics. A meningococcal B vaccination program in New Zealand has led to a decreased incidence of high rates of endemic serogroup B disease. Increases in serogroup Y disease have been observed in certain Nordic countries which, if they persist, may require consideration of use of a multiple serogroup vaccine. The imminent availability of recombinant broadly protective serogroup B vaccines may provide the tools for further control of invasive meningococcal disease in areas where serogroup B disease predominates. Continued surveillance of meningococcal disease is essential; ongoing global efforts to improve the completeness of reporting are required. [ABSTRACT FROM AUTHOR]