Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype.

OBJECTIVES: Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis. METHODS: A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response. RESULTS: Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV. CONCLUSIONS: Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis.

Systematic review of the free thoracodorsal artery perforator flap for head and neck reconstruction.

BACKGROUND: The thoracodorsal artery perforator (TDAP) flap has gained interest as a option for reconstruction of head and neck defects while minimizing donor site morbidity as compared to traditional workhorse flaps. The primary aim of this systematic review is to assess the postoperative outcomes and efficacy of this flap. METHODS: Several databases were screened for relevant citations. The quality of studies and risk of bias were evaluated using the MINORS scoring system. RESULTS: Twenty articles containing 168 patients undergoing at least one TDAP flap reconstruction met the inclusion criteria. There were no incidences of total flap failure and only 10 incidences of partial flap failure (5.95 %). Flap complications and donor site morbidity was low. The average MINORS score of the studies suggested a moderately high amount of bias. CONCLUSIONS: Based on limited quality evidence, this review suggests that TDAP flap is a safe and feasible option for head and neck reconstruction with comparable success rates as other commonly used flaps, with low complication rate and donor site morbidity. Further large-scale studies are warranted.

[Unilateral secondary breast reconstruction using a pedicled dorsal flap sparing the latissimus dorsi (TDAP and MSLD) in patients with a history of total mastectomy for breast cancer. Monocentric observational study]. / Reconstruction mammaire secondaire unilatérale par lambeau dorsal pédiculé épargnant le muscle grand dorsal (TDAP et MSLD) chez les patientes aux antécédents de mastectomie totale pour cancer du sein. Étude observationnelle monocentrique.

INTRODUCTION: The use of pedicled dorsal flaps sparing the latissimus dorsi muscle (TDAP and MSLD flap) is a well-described reconstruction method in breast reconstruction after breast cancer. However, little data exists regarding patient satisfaction after this surgery. The main objective of this study was to evaluate patient satisfaction after unilateral total secondary breast reconstruction using a TDAP or MSLD flap. The secondary objectives corresponded to the evaluation of postoperative complications following this surgery, the evaluation of the duration of the reconstruction and the nature of additional interventions, the evaluation of the functional after-effects, and the evaluation of the chest size when the reconstruction is completed. MATERIAL AND METHOD: This is a monocentric, retrospective cohort study, including 22 patients who underwent unilateral secondary total breast reconstruction using a TDAP or MSLD flap between January 1, 2018 and December 31, 2022. Patient satisfaction was assessed using three questionnaires validated in breast reconstruction: the Reconstruction module of the BREAST-Q, the MBROS-S and the MBROS-BI. RESULTS: The MBROS-S satisfaction score is 71.4%. The MBROS-BI body image score is 62%. With the BREAST-Q, the Satisfaction with Breast score is estimated at 53.1; the Satisfaction with Back score is estimated at 75.5; the physical well-being score regarding the chest is evaluated at 71.7; the physical well-being score concerning the shoulder and back is evaluated at 67.4; the psychosocial well-being score is assessed at 67.4; the sexual well-being score is estimated at 48.7; and for women who have benefited from reconstruction associated with a prosthesis, the satisfaction score regarding the implant is 71.6. CONCLUSION: Unilateral total secondary breast reconstruction with a dorsal pedicled flap sparing the latissimus dorsi muscle is an elegant, reliable, and respectful way to reconstruct a breast, and appears to give high levels of satisfaction.

Half-life Estimation of Pertussis-Specific Maternal Antibodies in (Pre)Term Infants After In-Pregnancy Tetanus, Diphtheria, Acellular Pertussis Vaccination.

BACKGROUND: To reduce the risk of pertussis-related morbidity and mortality in early life, an increasing number of countries recommend maternal pertussis vaccination. However, there is limited knowledge about half-lives of vaccine-induced pertussis-specific maternal antibodies, especially in preterm infants, and factors potentially influencing them. METHODS: We compared 2 different approaches to provide estimates of the half-lives of pertussis-specific maternal antibodies in infants and explored potential effects on the half-life in 2 studies. In the first approach, we estimated the half-lives per child and used these estimates as responses in linear models. In the second approach, we used linear mixed effect models on a log2 transformed scale of the longitudinal data to use the inverse of the time parameter as an estimate for the half-lives. RESULTS: Both approaches provided similar results. The identified covariates partly explain differences in half-life estimates. The strongest evidence we observed was a difference between term and preterm infants, with the preterm infants showing a longer half-life. Among others, a longer interval between vaccination and delivery increases the half-life. CONCLUSIONS: Several variables influence the decay speed of maternal antibodies. Both approaches have advantages and disadvantages, while the choice is secondary when assessing the half-life of pertussis-specific antibodies. CLINICAL TRIALS REGISTRATION: NCT02408926 and NCT02511327.

Maternal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination During Pregnancy: Impact on Infant Anti-Pertussis Antibody Concentrations by Maternal Pertussis Priming Series.

BACKGROUND: Acellular pertussis (aP) vaccines replaced whole-cell pertussis (wP) vaccines for the US childhood primary series in 1997. As women primed with aP vaccines enter childbearing age, protection of infants through tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination during pregnancy may be impacted. METHODS: Term infants born to women vaccinated with Tdap during pregnancy were included. Geometric mean concentrations (GMCs) of pertussis-specific immunoglobulin G antibodies (international units per milliliter) in cord blood of infants born to women born after 1997 (aP-primed) were compared with those born to women born before 1992 (wP-primed). RESULTS: 253 and 506 infants born to aP- and wP-primed women, respectively, were included. Compared with wP-primed women, aP-primed women were younger, more likely to be Hispanic or non-Hispanic Black, and had lower-birthweight infants (P < .01 for all). Antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were lower among infants born to aP-primed vs wP-primed women (PT, 17.3 vs 36.4; GMC ratio, .475; 95% confidence interval [CI], .408-.552 and FHA, 104.6 vs 121.4; GMC ratio, 0.861; 95% CI, .776-.958). No differences were observed for anti-fimbriae or anti-pertactin antibodies. CONCLUSIONS: Transplacental anti-pertussis antibody concentrations in infants of women vaccinated with Tdap during pregnancy differed by type of childhood vaccine the women received. Notably, anti-PT antibody levels, considered most important in preventing severe infant disease, were lower in infants born to aP-primed vs wP-primed women. Maternal Tdap vaccination may confer less protection against pertussis in infants born to aP-primed vs those born to wP-primed women.

Impact of national recommendations for routine pertussis vaccination during pregnancy on infant pertussis in Ontario, Canada: a population-based time-series study.

BACKGROUND: In February 2018, Canada's National Advisory Committee on Immunization (NACI) recommended antenatal tetanus-diphtheria-acellular pertussis (Tdap) immunization in every pregnancy regardless of previous Tdap immunization history. We examined the impact of the NACI recommendation on rates of infant pertussis in Ontario, Canada. METHODS: We conducted a population-based time-series study of all live births in Ontario between August 1, 2011 and February 28, 2020. We used interventional autoregressive integrated moving average models to examine the impact of the NACI recommendation on monthly rates of pertussis among infants ≤ 3 months of age. RESULTS: We observed 675 incident cases of pertussis among 1,368,024 infants 3 months of age or less between August 2011 and February 2020. The average monthly percent change in infant pertussis during the period up to and including publication of the NACI guidance and the period following publication were 0.0% (95% CI: -0.4-0.3%) and - 0.8% (95% CI -2.3% to -0.1%), respectively. Following interventional ARIMA modelling, publication of the NACI guidance was not associated with a statistically significant decrease in the monthly pertussis incidence trend (-0.67 cases per 100,000 infants; p = 0.73). CONCLUSION: Publication of national recommendations for antenatal Tdap immunization in every pregnancy did not significantly reduce infant pertussis rates. This may reflect the persistently low rate of antenatal vaccination following publication of the recommendations. Expanding the scope of practice of allied health care providers to include antenatal Tdap immunization and patient education regarding antenatal pertussis immunization should be considered to further optimize uptake of vaccination.

Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis Vaccine.

BACKGROUND: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age. METHODS: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed. RESULTS: Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses. CONCLUSIONS: RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis. CLINICAL TRIALS REGISTRATION: NCT04071158.

Free Thoracodorsal Artery Perforator Flap for Head and Neck Reconstruction: An Indian Experience.

Background We describe our experience with use of free thoracodorsal artery perforator (TDAP) flap for head and neck (H&N) cancer reconstruction, with respect to the patient and disease profile, suitable defect characteristics, the reconstructive technique, and complications. Methods Consecutive patients ( N = 26) undergoing free TDAP flap for H&N onco-reconstruction, in a single center, were included from January 2015 to December 2018 and the data were analyzed. Results Perforator(s) were reliably predicted preoperatively, using handheld Doppler. Lateral position was comfortable for the harvest. Twenty flaps were harvested on a single perforator, more commonly musculocutaneous ( n = 16). The thoracodorsal nerve and latissimus dorsi muscle could be preserved, completely in almost all cases. The skin paddle was horizontally ( n = 5) or vertically ( n = 21) oriented, both giving a satisfactory scar. The flap was used as a single island or two islands by de-epithelializing intervening skin. Pedicle length was sufficient in all cases. Four cases were explored for suspected venous insufficiency. Two had thrombosis, of which one was salvaged, while the other necrosed. One flap had minimal partial necrosis, which was managed with secondary suturing. The 5-year follow-up showed good oral competence, mouth opening, and cosmetic satisfaction among patients. Conclusion TDAP flap provides all the advantages of a perforator-based free flap and of back as a donor site with close color match to the face, relatively hairless, and thickness in between the thigh and the forearm. It can be a useful tool to provide an ideal functional and aesthetic outcome, with a hidden donor site and minimal donor site morbidity in selected cases.

Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm-Born Infants.

BACKGROUND: Limited data exist on the impact of maternal tetanus, diphtheria, acellular pertussis (Tdap) vaccination for preterm born infants. We report its effect at birth and on antibody-mediated immune responses to a DTaP-IPV-HB-PRP~T vaccine in preterm compared with term infants. METHODS: Women delivering at term or prematurely were either vaccinated with a Tdap vaccine (Boostrix; GSK) during pregnancy or not vaccinated in the last 5 years. Cord and maternal blood were collected at delivery. Infants were vaccinated with DTaP-IPV-HB-PRP~T vaccine (Hexyon; Sanofi Pasteur) and blood collected before and 1 month after primary (8-12-16 weeks) and before and 1 month after booster vaccination (13 or 15 months for preterm and term, respectively). Immunoglobulin G antibodies against all antigens included in DTaP-IPV-HB-PRP~T vaccine were measured (NCT02511327). RESULTS: Cord blood geometric mean concentrations (GMCs) in preterm infants from Tdap-vaccinated women were significantly higher than in term and preterm infants from unvaccinated women. A longer time interval between maternal vaccination and delivery resulted in higher cord blood GMCs in preterm infants. Equal GMCs in term and preterm infants from Tdap-vaccinated women were observed after primary vaccination. After boosting, significantly lower GMCs were seen for pertussis toxin, filamentous hemagglutinin, and tetanus toxoid in preterm compared with term infants from Tdap-vaccinated women, yet still comparable to GMCs in both term and preterm infants from unvaccinated women. CONCLUSIONS: Preterm infants profit from maternal Tdap vaccination. Prematurity did not influence primary immune responses in the presence of maternal antibodies but was associated with a lower booster immune response.

Impact of Maternal Pertussis Antibodies on the Infants' Cellular Immune Responses.

INTRODUCTION: Maternal antibody interference of the infant's humoral immune responses raises some concern to the strategy of maternal Tdap (tetanus, diphtheria, acellular pertussis [aP]) vaccination. This study assessed the impact of maternal Tdap antibodies on the infant's pertussis-specific T lymphocyte responses following infant vaccination with an aP containing vaccine, in a term and preterm born cohort. METHODS: Heparin samples (±0.5 mL) were conveniently drawn from infants of a Belgian prospective cohort study (N = 79, NCT02511327), including Tdap vaccinated (Boostrix®) and nonvaccinated women (no Tdap vaccine in the last 5 years) that delivered at term or prematurely. Sampling was performed before and 1 month after primary (8-12-16 weeks) and booster vaccination (13 or 15 months) with DTaP-IPV-HB-PRP~T vaccine (Hexyon®). Pertussis toxin (PT)-specific CD3+, CD3+ CD4+ and CD3+ CD8+ lymphoblasts and their cytokine secretions were measured using a flow cytometric assay on whole blood (FASCIA) and multiplex technology (Meso Scale Discovery), respectively. RESULTS: In total, 57% of all infants were considered PT-specific CD3+ CD4+ lymphoblasts responders after primary and booster vaccination, whereas 17% were CD3+ CD8+ lymphoblast responders. Interferon (IFN)-γ, interleukin (IL)-13, IL-17A, and IL-5 cytokine secretions after primary and booster vaccination were indicative of a mixed T helper (Th) 1/Th2/Th17 cell profile. Lymphoblast and cytokine levels were comparable between term and preterm infants. Nonresponders for IL-13 after booster vaccination had higher maternal PT immunoglobulin G (IgG) levels at birth when compared to responders. CONCLUSIONS: Term and preterm born infants are capable of inducing Th1, Th2, and Th17 responses after aP vaccination, yet maternal vaccination modulate these responses. Evaluation of this effect in larger trials is needed.

Tdap-HPV vaccination bundling in the USA: Trends, predictors, and implications for vaccine series completion.

The Centers for Disease Control and Prevention (CDC) promotes taking a 'bundling approach' (i.e., administering Tetanus, diphtheria toxoids, and acellular pertussis [Tdap] and human papillomavirus [HPV] vaccines in the same way and on the same day) for adolescent vaccinations. Recent trends and patterns in Tdap-HPV vaccination bundling in the USA remain undocumented. In addition, the implications of bundling Tdap-HPV vaccination for HPV vaccine series completion remain unknown. To address these critical knowledge gaps, we performed a retrospective study using a nationwide sample of privately insured adolescents (Optum's de-identified Clinformatics® Data Mart Database). Tdap-HPV vaccination bundling (per 100 Tdap vaccination encounters) during 2014-2018 was estimated overall, for 50 states, and by adolescents' age, sex, and provider specialties. Survival model estimated the likelihood of series completion among 9-14-year-old adolescents. From 2014 to 2018, 560,806 adolescents received a Tdap vaccine of which 172,604 (30.8%) received the HPV vaccines on the same day. Tdap-HPV vaccination bundling (per 100 Tdap vaccinations) increased nationally, from 22.9 in 2014 to 39.1 in 2018 (Ptrend < 0.001); bundling was lowest in New York and New Jersey. The likelihood of receiving the Tdap and HPV vaccines bundled was higher for young and female adolescents. Adolescents who received their first HPV vaccine bundled with the Tdap vaccine were more likely to complete the series compared to those who received it alone (Hazards Ratio = 1.45; 1.43-1.48). HPV vaccination bundling has increased in recent years in the USA. The increased likelihood of HPV vaccine series completion provides important evidence supporting the adoption of same-day Tdap-HPV vaccine administration in clinical practice to boost HPV vaccination coverage.

Improving vaccination rates in older adults and at-risk groups: focus on pertussis.

Despite the implementation of effective paediatric vaccination programmes, pertussis remains a global health problem. Disease epidemiology has changed over time, shifting towards the adolescent and adult populations. In adults, the true burden of pertussis is greatly underestimated and pertussis vaccine coverage rates are suboptimal, including individuals with chronic conditions. Here, we report the outcomes of a virtual international scientific workshop to assess the evidence on the burden of pertussis in older adults and identify potential solutions to improve uptake of pertussis vaccines. In adults, pertussis is underdiagnosed in part due to atypical or milder clinical presentation and the lack of testing and case confirmation. However, contemporary epidemiological data denoted an increase in the burden of pertussis among adolescents and adults. This might be related to a variety of reasons including the waning of immunity over time, the lack of booster vaccination, and the improved diagnostic methods that led to increased recognition of the disease in adults. Pertussis sequelae can be severe in older adults, particularly those with existing chronic medical conditions, and the vulnerability of these groups is further enhanced by low pertussis vaccine coverage. Possible measures to increase vaccine uptake include strengthening and harmonisation of immunisation guidelines, healthcare professionals taking a more active role in recommending pertussis vaccination, involvement of vaccination centres and pharmacies in the vaccination process, and improving knowledge of pertussis burden and vaccine efficacy among the general population.

Factors Influencing Maternal Antepartum Tdap Vaccination.

INTRODUCTION: Antepartum Tdap remains low despite national recommendations. This prospective observational study aims to identify factors associated with lower antepartum Tdap rates. METHODS: Maternal demographics, personal health beliefs, Tdap vaccination status, and recall of in-office obstetric provider actions were collected from a convenience sample of postpartum women in a New York metropolitan hospital. Bivariate and multivariable logistic regression were used to identify significant factors and adjusted odds ratios (OR) for recorded Tdap; OR > 1 reflects elements with increased odds of not receiving antepartum Tdap, while OR < 1 demonstrates increased odds of receipt. RESULTS: Surveys were collected (n = 1682) from a study population demographically similar to New York City and more diverse in race/ethnicity than the national population. Demographic analysis showed Hispanic women less likely than white, non-Hispanic women to vaccinate (OR 2.44, CI 1.54-3.88). Health beliefs associated with non-receipt of antepartum Tdap included "It is dangerous for pregnant women to get vaccines" (OR 1.68, CI 1.01-2.77), and "I worry about the safety of the Tdap vaccine" (OR 1.59, CI 1.12-2.24). Obstetric provider actions associated with vaccination included receiving an OB recommendation (OR 0.39, CI 0.23-0.65), getting written information about Tdap (OR 0.44, CI 0.30-0.64), and having Tdap offered in office (OR 0.24, CI 0.15-0.37). Health beliefs associated with antepartum Tdap included "I generally do what my OB/GYN provider recommends" (OR 0.49, CI 0.30-0.80), and "Pregnant women should get the Tdap (pertussis) vaccine" (OR 0.17, CI 0.09-0.33). DISCUSSION: Maternal race/ethnicity, personal health beliefs, and obstetric provider actions predict antepartum Tdap.

Pertussis Infections Among Pregnant Women in the United States, 2012-2017.

BACKGROUND: Little is known about pertussis among pregnant women, a population at increased risk for severe morbidity from respiratory infections such as influenza. We used the Centers for Disease Control and Prevention's Enhanced Pertussis Surveillance (EPS) system to describe pertussis epidemiology among pregnant and nonpregnant women of childbearing age. METHODS: Pertussis cases in women aged 18-44 years with cough onset between 1 January 2012 and 31 December 2017 were identified in 7 EPS states. Surveillance data were collected through patient and provider interviews and immunization registries. Bridged-race, intercensal population data and live birth estimates were used as denominators. RESULTS: We identified 1582 pertussis cases among women aged 18-44 years; 5.1% (76/1499) of patients with a known pregnancy status were pregnant at cough onset. Of the pregnant patients with complete information, 81.7% (49/60) reported onset during the second or third trimester. The median ages of pregnant and nonpregnant patients were 29.0 and 33.0 years, respectively. Most pregnant and nonpregnant patients were White (78.3% vs. 86.4%, respectively; P = .09) and non-Hispanic (72.6% vs. 77.3%, respectively; P = .35). The average annual incidence of pertussis was 7.7/100000 among pregnancy women and 7/3/100000 among nonpregnant women. Compared to nonpregnant patients, more pregnant patients reported whoop (41.9% vs. 31.3%, respectively), posttussive vomiting (58.1% vs. 47.9%, respectively), and apnea (37.3% vs. 29.0%, respectively); however, these differences were not statistically significant (P values > .05 for all). A similar proportion of pregnant and nonpregnant patients reported ever having received Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; 31.6% vs. 32.7%, respectively; P = .84). CONCLUSIONS: Our analysis suggests that incidence of pertussis and clinical characteristics of disease are similar among pregnant and nonpregnant women. Continued monitoring is important to further define pertussis epidemiology in pregnant women.

Breast Milk Antibody Levels in Tdap-Vaccinated Women After Preterm Delivery.

BACKGROUND: Enrichment of breast milk (BM) with immunoglobulin (Ig) A and IgG through maternal vaccination could help infants combat targeted pathogens. However, evidence on this effect after preterm delivery is lacking. In this study, we investigated the total and anti-pertussis toxin (anti-PT)-specific IgA and IgG production in BM after term and preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination. METHODS: Serum and BM samples of lactating women who delivered at term or prematurely and did or did not receive Tdap vaccine (Boostrix, GSK Biologicals) during pregnancy were collected as part of a clinical study (N = 234). Anti-PT IgA/IgG (IBL assay; Meso Scale Discovery assay) and total IgA/IgG (Thermofisher, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours and 4, 8, and 12 weeks postpartum. RESULTS: BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (eg, colostrum anti-PT IgA, 5.39 IU/mL vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMCs in colostrum of vaccinated compared with unvaccinated women who delivered at term (0.110 IU/mL vs 0.027 IU/mL, P = .009). Anti-PT antibodies persisted up to 12 weeks postpartum. CONCLUSIONS: This study provides evidence that maternal Tdap vaccination induces high Ig levels in BM after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life. CLINICAL TRIAL REGISTRATION: NCT02511327.

Maternal Self-Report of Tetanus Diphtheria Pertussis Vaccination during Pregnancy Correlates with Patient-Specific Electronic Medical Records.

OBJECTIVES: To evaluate the concordance between maternal report of antepartum tetanus, diphtheria, pertussis (Tdap) vaccination and vaccination status documented in the electronic medical record (EMR), as well as factors associated with discordance. STUDY DESIGN: A survey was completed by a convenience sample of postpartum patients in a New York metropolitan hospital. The survey collected patients' demographic information, health beliefs, and whether they received Tdap vaccine during this pregnancy. The patient's Tdap vaccination status was abstracted from the EMR, a combination of data gathered from the obstetrician and patient's hospital record. Kappa statistics measured the agreement between maternal report and EMR on antepartum Tdap vaccination. Univariate and multivariable logistic regression analyses were performed to identify maternal characteristics associated with discordance. RESULTS: Of the 1571 patients with Tdap status available in the EMR, 1549 patients (92%) reported on receipt status for Tdap vaccination during pregnancy; 1328 maternal reports (86%) agreed with the EMR for Tdap status (kappa = 0.72, 95% CI 0.68-0.75). Several factors were statistically significant in multivariable analyses: lower income was associated with greater discordance (ie, overreporting; P = .02), as well as certain health beliefs including "Pregnant women should be concerned about the possibility of pertussis in their babies" (aOR 2.86, 95% CI 1.02-8.04) and "My friends would probably think getting a Tdap vaccine is a good idea" (aOR 2.36, 95% CI 1.11-4.99). CONCLUSIONS: Maternal recall of Tdap vaccination during pregnancy is consistent with the EMR. This supports the value of maternal report in determining Tdap vaccination status, which is especially important when vaccination records are not available.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

BACKGROUND: Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. OBJECTIVE: To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. CONCLUSIONS: jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.

Vaccination in pregnancy against pertussis and seasonal influenza: key learnings and components from high-performing vaccine programmes in three countries: the United Kingdom, the United States and Spain.

BACKGROUND: Pertussis and seasonal influenza are responsible for significant maternal, neonatal, and infant morbidity and mortality, but vaccine coverage rates (VCR) for both pertussis (administered as a tetanus, diphtheria, acellular pertussis [Tdap] vaccination) and seasonal influenza in pregnancy remain generally low. Only a small number of countries, including Spain, the United Kingdom (UK), and the United States (US), have high Tdap and seasonal influenza VCRs in pregnancy. The purpose of this study was to identify the key factors that contributed to the high VCRs observed in these countries. METHODS: The experience from both Tdap and seasonal influenza vaccination programmes during pregnancy were documented in Spain, the UK, and the US using a three-step approach. A literature review yielded 157 publications, and a further 117 documents were selected through desk research. A published five-pillar VCR framework for influenza was amended to evaluate the specific contributing factors leading to high Tdap and seasonal influenza VCRs among pregnant women. RESULTS: The analysis identified components that contributed to higher VCR in pregnant women across three different healthcare systems in Spain, UK, and US. The combination of several key interventions in each country led to a rapid increase in VCR that reached near-optimal levels (i.e. 75% for seasonal influenza) within a few years. As well as inclusion in national immunisation programme and vaccine reimbursement, key components that were identified included the mobilisation of health authorities, prenatal care Healthcare Professionals (HCP) and scientific societies, the inclusion of vaccination in antenatal medical guidance, the provision of educational material to HCPs, and a strong disease awareness driven by recent pertussis outbreaks in each country. CONCLUSIONS: Although there is no simple, universal solution to improving sub-optimal VCRs, the list of components identified in this study from three countries with high-performing Tdap and seasonal influenza vaccination programmes provides a basis for public health and medical stakeholders in other countries to define strategies to successfully implement national vaccination programmes for pregnant women.

Pertussis in infants in Nordic countries.

AIM: A life-course immunisation approach is required to prevent and control pertussis. We aimed at reviewing pertussis incidence among infants in Denmark, Finland, Norway and Sweden, and at putting these data in the context of national surveillance systems and vaccination schedules. METHODS: We collected 2014-2018 data on pertussis incidence, on pertussis vaccination schedules and on coverage of the third dose of the diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine from publicly available sources. We gathered opinions on national surveillance systems from public health and paediatrics experts of the relevant countries. RESULTS: The pertussis vaccination schedules and coverage in infancy were similar across countries. All countries except Denmark recommended an additional booster vaccine dose for adolescents. None of the countries had maternal immunisation recommendation. Mean pertussis incidence in Denmark, Sweden and Finland was 168, 76 and 35 per 100,000 infant-years, respectively. Data were insufficient to derive a mean incidence in Norway. There were no systematic differences in the national surveillance systems across the countries. CONCLUSION: The higher mean pertussis incidence in Denmark may be explained by the lack of recommendations for adolescent pertussis booster vaccination. Further investigations are warranted.

Dysautonomia Following Tetanus, Diphtheria, and Pertussis Vaccine (Tdap): The First Case of Extreme Cachexia Caused by Autoimmune/Inflammatory Syndrome Induced by Adjuvants (ASIA Syndrome) in a Human.

Autoimmune/inflammatory Syndrome Induced by Adjuvants (ASIA; Shoenfeld's syndrome) comprehends a group of autoimmune conditions that flourish in genetically predisposed individuals, following an external stimulus by the so-called adjuvants. Many adjuvants were described, such as vaccines, aluminum and other metals, silicone, tattoos, among others. Those conditions entail defined diseases, such as sarcoidosis and Sjogren's syndrome, and generalized complex symptoms, for example, fatigue, sleep disturbance, orthostatic intolerance, and other dysautonomic manifestations. Those complaints were previously associated with autoantibodies against nervous system autonomic receptors, especially antibeta 1 adrenergic receptor antibodies, suggesting the autoimmune component of the condition. Here we report on a case of an 18-year-old woman who presented with extreme cachexia due to severe dysautonomia caused by the ASIA syndrome induced by the tetanus, diphtheria, and pertussis vaccine (Tdap).