Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study.

BACKGROUND: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. METHODS: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 µg vaccination 12-18 months after first vaccination. RESULTS: The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. CONCLUSIONS: This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. CLINICAL TRIALS REGISTRATION: NCT04138056.

Immunogenicity of tetanus, diphtheria and acellular pertussis vaccination among pregnant women living with and without HIV.

OBJECTIVE: Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity of data on immune responses to Tdap in pregnant women with HIV (PWWH), and its impact on the protection of their infants has not been described. METHODS: In an open label phase IV clinical trial in South Africa, we evaluated the immunogenicity and safety of Tdap in PWWH compared with HIV-uninfected women. Antigen-specific immunoglobulin G (IgG) to pertussis toxoid, filamentous haemagglutinin, pertactin, fimbriae, diphtheria and tetanus were measured by electrochemiluminescence-based multiplex assay. RESULTS: Overall, 91 PWWH and 136 HIV-uninfected pregnant women were enrolled. All PWWH were on antiretroviral treatment and 94.5% had HIV viral loads <40 copies per millilitre. Antibody levels prevaccination were lower among PWWH compared with HIV-uninfected women for all antigens. At 1 month postvaccination PWWH compared with HIV-uninfected women had lower fold-increase and antibody concentrations for all epitopes. Also, a lower proportion of PWWH achieved ≥4-fold increase from pre to postvaccination for pertussis toxoid and pertactin, or diphtheria IgG levels ≥0.1 IU/ml and ≥1 IU/ml postvaccination. Adverse events postvaccination were similar in PWWH and HIV-uninfected. CONCLUSION: Tdap vaccination was safe and immunogenic. PWHW had, however, attenuated humoral immune responses, which could affect the effectiveness of protecting their infants against pertussis compared with those born to women without HIV.ClinicalTrials.gov identifier: NCT05264662.

Surveillance of adverse events following immunisation in Australia annual report, 2020.

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2020, reported to the Therapeutic Goods Administration (TGA), and describes reporting trends over the 21-year period from 1 January 2000 to 31 December 2020. There were 3,827 AEFI records for vaccines administered in 2020, an annual AEFI reporting rate of 14.9 per 100,000 population. There was a slight (3.8%) decrease in the overall AEFI reporting rate in 2020 compared with 2019 (15.5 per 100,000 population). This decrease in the AEFI reporting rate in 2020 is potentially due to the impact of coronavirus disease 2019 (COVID-19) and was mainly from a decline in reported adverse events related to HPV, dTpa, and seasonal influenza vaccines. AEFI reporting rates for most individual vaccines in 2020 were similar to 2019. The most commonly reported adverse events were injection site reaction (37.1%); pyrexia (18.1%); rash (15.8%); vomiting (7.6%); pain (7.4%); headache (5.7%); and urticaria (5.1%). There were six deaths reported to the TGA. In one of the reports, the timing and clinical findings were consistent with a causal association with vaccination. In the remaining five reports, no clear causal relationship with vaccination was found.

Severe immune thrombocytopenia following diphtheria, tetanus, pertussis and polio vaccination in a 36-year-old Caucasian woman: a case report.

BACKGROUND: Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts and increased bleeding risk. The disease may be induced by other disorders, including malignancies, autoimmune diseases, infectious agents or drugs. However, ITP has also been described following vaccinations, such as the measles-mumps-rubella vaccination. In rare cases, ITP may occur in children who received a DTaP-IP (diphtheria, tetanus, acellular pertussis vaccine and inactivated poliovirus) vaccine. Hereinafter, we report the first well-documented cases of ITP in an adult patient in the temporal context of a DTaP-IP vaccination. CASE PRESENTATION: This case report attempts to capture the life-threatening picture of a 36-year-old otherwise healthy Caucasian woman with newly diagnosed severe immune thrombocytopenia in the temporal context of a DTaP-IP vaccination. Four days after receiving the vaccine, the women presented to her primary care physician with malaise, fever and recurrent epistaxis. Clinical examination revealed oral petechiae, ecchymoses, and non-palpable petechiae on both legs. The patient was immediately referred to a local hematology unit where she developed hematuria and an intestinal bleeding (WHO Bleeding Grade III) requiring multiple transfusions. After receiving oral corticosteroids and intravenous immunoglobulins, her platelets gradually recovered. Common causes of secondary ITP were ruled out by laboratory investigations, bone marrow and peripheral blood examinations. This raises the possibility of a (secondary) vaccination-associated thrombocytopenia. To the best of our knowledge, this is the first well-documented case of a DTaP-IP vaccination-related ITP in an adult patient in the English literature. CONCLUSION: Although a causal connection between both entities may not be established, we would like to raise awareness in clinicians that ITP following DTaP-IP vaccinations is potentially not limited to children, but may also occur in adults. Users of DTaP-IP booster vaccines should be alert of the possibility of such adverse reactions.

A decade of data: Adolescent vaccination in the vaccine safety datalink, 2007 through 2016.

BACKGROUND: Between May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines. METHODS: This was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007-2010 and 2011-2016. RESULTS: The number of 11-18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33-61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32-48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods. CONCLUSIONS: The high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns.

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

BACKGROUND AND OBJECTIVES: Maternal immunization with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is routinely recommended in many countries as a strategy to protect young infants against severe pertussis infection; few studies have assessed whether prenatal exposure to the vaccine is associated with any longer-term adverse health effects in children. We evaluated the long-term safety of exposure to Tdap vaccination during pregnancy. METHODS: Population-based retrospective cohort study conducted in Ontario, Canada using multiple linked province-wide health administrative databases. All live births between April 2012 and March 2017 were included, and children were followed for up to 6 years to ascertain study outcomes. Children exposed to prenatal Tdap were propensity score matched to unexposed children at a 1:5 ratio. Tdap vaccination during pregnancy was ascertained by using vaccine-specific fee codes. Immune-related (infectious diseases, asthma) and nonimmune-related (neoplasm, sensory disorders) outcomes and a nonspecific morbidity outcome (urgent or inpatient health service use) were evaluated from birth to end of follow-up. RESULTS: Of 625 643 live births, 12 045 (1.9%) were exposed to Tdap in utero. There were no significant increased risks of adverse childhood outcomes and prenatal Tdap exposure; however, we observed inverse associations (adjusted incidence rate ratio [95% confidence interval]) with upper respiratory infections (0.94 [0.90-0.99]), gastrointestinal infections (0.85 [0.79-0.91]), and urgent and inpatient health service use (0.93 [0.91-0.96]). CONCLUSIONS: Exposure to Tdap vaccination in pregnancy was not associated with any increased risk of adverse health outcomes in early childhood, supporting the long-term safety of Tdap administration in pregnancy.

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic.

INTRODUCTION: The response to vaccines in juvenile idiopathic arthritis (JIA) patients on and off anti-tumor necrosis factor (anti-TNF) agents remains highly discussed. There are no published studies on the immune response following a Tdap booster dose in JIA patients so far. OBJECTIVE: To evaluate the immune response and safety after a Tdap booster in JIA patients and in healthy adolescents. METHODS: Nineteen adolescents with JIA according to the ILAR criteria on anti-TNF medication, 19 adolescents with JIA off anti-TNF medication, and 27 healthy adolescents (control group) were compared after a Tdap booster. 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: The three groups showed a similar frequency of adverse events. There was no disease reactivation after the Tdap booster. Tetanus, diphtheria and pertussis antibodies showed a significant response when D0 and D14 concentrations were compared in both JIA groups and controls. Over time, a different pattern of response to the Tdap booster was observed among the groups for tetanus antibodies (p = 0.005) but not for diphtheria and pertussis antibodies. In contrast to the protection attained for tetanus and diphtheria, in the three groups, not all individuals showed pertussis seroconversion at either D14 or D28. In addition, the seroconversion of three subjects with JIA on anti-TNF medication was not maintained at D28. JIA patients off anti-TNF showed a higher percentage of naive CD8 + T cells (p = 0.007) and central memory CD8 + cells (p = 0.003) and a lower percentage of effector CD8 + T cells (p = 0.003) and NK cell numbers (p = 0.018) than the control group. The JIA group off anti-TNF medication had fewer B lymphocytes than both the JIA group on anti-TNF medication and the control group (p = 0.016). Cellular immunity to Bordetella pertussis showed that IFNγ levels were significantly lower in both JIA groups than in the control group (p = 0.003), IL10 levels were higher in the JIA off anti-TNF group (p = 0.009), IL17A and IL5 levels were lower in the JIA on anti-TNF group than in the control group (p = 0.018 and p = 0.016, respectively); however, an increase in IFNγ (p = 0.008), IL17A (p = 0.030) and TNFα (p = 0.041) levels was observed at D14 in both patient groups. Both JIA groups showed higher levels of IL21 than the control group (p = 0.023). CONCLUSION: We conclude that individuals with JIA on or off anti-TNF agents showed a good response to a booster dose for the three antigens studied in the absence of major adverse events and without the reactivation of the disease.

Ocorrência de eventos adversos após o uso da vacina adsorvida difteria, tétano e pertussis (acelular) - dTpa -, São Paulo, SP, 2015-2016 / Aparecimiento de eventos adversos después del uso de la vacuna adsorbida difteria, tétanos y tosferina (acelular) - dTpa -, São Paulo, SP, Brasil, 2015-2016 / Adverse event occurrence following use of tetanus, diphtheria and acellular pertussis adsorbed vaccine - Tdap -, São Paulo, SP, Brazil, 2015-2016

Objetivo: descrever a ocorrência de eventos adversos pós-vacinação (EAPV) com a vacina dTpa durante a gestação. Métodos: estudo descritivo, com dados de relatos das participantes de estudo de efetividade e imunogenicidade realizado em dois hospitais de São Paulo, SP, Brasil, entre 2015 e 2016. Resultados: das 201 mães incluídas no estudo, 48 (23,9%) apresentaram pelo menos um EAPV; foram identificados 60 sintomas relacionados ao uso da dTpa - dor (22,4%), inchaço (2,5%), febre (1,5%), sono (1,0%), vermelhidão (0,5%), vômito (0,5%), dor de cabeça (0,5%), reação local (0,5%) e cansaço (0,5%); não foram registrados eventos adversos raros, muito raros ou extremamente raros; todos os eventos foram considerados esperados e estão descritos em bula; todos tiveram desfecho para cura sem sequelas. Conclusão: a dTpa, na forma adotada pelo Programa Nacional de Imunizações (PNI), é segura; não foram identificados eventos adversos inesperados entre as gestantes imunizadas com a vacina.

Objetivo: describir el aparecimiento de eventos adversos posvacunación (EAPV) con la vacuna dTpa durante el embarazo. Métodos: estudio descriptivo con datos de relatos de las participantes del estudio de efectividad e inmunogenicidad realizado en dos hospitales de São Paulo, SP, Brasil, entre 2015 y 2106. Resultados: de las 201 madres del estudio, 48 (23,9%) tuvieron al menos un EAPV; se identificaron 60 síntomas relacionados al uso de dTpa - dolor (22.4%), hinchazón (2.5%), fiebre (1.5%), somnolencia (1.0%), enrojecimiento (0.5%), vómitos (0.5 %), dolor de cabeza (0.5%), reacción local (0.5%) y cansancio (0.5%) -; no se informaron eventos adversos raros, muy raros o extremadamente raros; todos los eventos se consideraron esperados y se describen en el prospecto; todos tuvieron resultados curativos sin secuelas. Conclusión: el estudio mostró que la vacuna dTpa utilizada por el Programa Nacional de Inmunización (PNI) es segura y no se identificaron eventos adversos inesperados entre las mujeres embarazadas vacunadas.

Objective: to describe occurrence of adverse events following immunization (AEFI) with Tdap vaccine during pregnancy. Methods: this was a descriptive study using data from reports by participants in an effectiveness and immunogenicity study conducted in two hospitals in São Paulo, SP, Brazil, from 2015 to 2016. Results: of the 201 mothers included in the study, 48 (23.9%) had at least one AEFI; 60 symptoms related to Tdap use were identified - pain (22.4%), swelling (2.5%), fever (1.5%), somnolence (1.0%), redness (0.5%), vomiting (0.5%), headache (0.5%), local reaction (0.5%), and fatigue (0.5%); no rare, very rare, or extremely rare adverse events were reported; all events were considered to be expected, as they are described in the vaccine package insert; outcome of all events was recovery without sequelae. Conclusion: Tdap vaccine in the form adopted by the National Immunization Program is safe; no unexpected adverse events were identified among vaccinated pregnant women.

Vaccine Allergy? Skin Testing and Challenge at a Tertiary Pediatric Hospital in Melbourne, Australia.

BACKGROUND: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. OBJECTIVE: We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy. METHODS: A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented. RESULTS: There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis. CONCLUSIONS: The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI.

Aluminum granuloma in a child secondary to DTaP-IPV vaccination: A case report.

Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum-containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP-IPV vaccine. We present the case of a 6-year-old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum-containing DTaP-IPV (Kinrix) vaccine. The nodule was eventually excised 14 months after its initial appearance, after which her symptoms resolved. Histologic inspection demonstrated a dense, deep dermal and subcutaneous nodular mixed infiltrate of lymphocytes, histiocytes, and eosinophils, with germinal center formation. The bluish, amphophilic granular cytoplasm found in most of the histiocytes is a characteristic feature of "aluminum granulomas." This adverse reaction should be considered in any patient presenting with similar findings in the weeks following a DTaP-IPV vaccination or other aluminum-containing vaccines. Furthermore, the self-limiting tendency of these nodules should not preclude affected patients from any future vaccinations, though vaccines without aluminum should be preferentially selected when possible.

Primary Ovarian Insufficiency and Adolescent Vaccination.

BACKGROUND: Published case series have suggested a potential association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency (POI). We describe POI incidence and estimate POI risk after HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap); inactivated influenza (II); and meningococcal conjugate (MenACWY) vaccination. METHODS: We searched Kaiser Permanente Northwest electronic health records for outpatient diagnoses suggestive of POI in female patients aged 11 to 34 years between 2006 and 2014. We reviewed and adjudicated the medical record to confirm diagnoses and estimate symptom onset dates. We excluded cases with known causes and calculated the incidence of idiopathic POI. We estimated risk by calculating hazard ratios and 95% confidence intervals (CIs). RESULTS: From a cohort of 199 078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1 000 000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio was 0.30 (95% CI: 0.07-1.36) after HPV, 0.88 (95% CI: 0.37-2.10) after Tdap, 1.42 (95% CI: 0.59-3.41) after II, and 0.94 (95% CI: 0.27-3.23) after MenACWY vaccination. CONCLUSIONS: We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination.

Development of Kasabach-Merritt phenomenon following vaccination: More than a coincidence?

Kasabach-Merritt phenomenon (KMP) occurred uniquely in patients with kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). We report the clinical characteristics of two patients with KHE involving the right upper arm. The patients demonstrated rapid enlargement of the lesion with severe KMP shortly after vaccination. Sirolimus was used to treat the KHE with KMP. The patients showed a quick normalization of the platelet level. The follow-up examination revealed that the size of the mass was significantly decreased. This report raises the intriguing possibility that extrinsic factors may contribute to the development of KMP in the context of an already existing KHE.

No pain no gain? Adjuvant effects of alum and monophosphoryl lipid A in pertussis and HPV vaccines.

Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccine's reactogencicity are predictive of successful immunization outcomes. Recent clinical studies of pertussis and human papillomavirus vaccines adjuvanted with alum or the TLR4 agonist monophosphoryl lipid A can be used to advance understanding of the relationship between vaccine side effects and immunization outcomes.

Randomized clinical trial of the safety and immunogenicity of the Tdap vaccine in pregnant Mexican women.

Immunization with the tetanus, diphtheria, and pertussis (Tdap) vaccine raises controversies on immunogenicity and possible antibody interference. We performed an experimental, double-blind, parallel group controlled clinical trial to evaluate the safety and immunogenicity of the Tdap vaccine in 204 pregnant women and their children and to determine its interference in antibody production. Pregnant women 18 to 38 y of age with 12 to 24 weeks gestation, a low obstetric risk, and without serious disease were randomly selected. The experimental group received 0.5 mL IM of Tdap and the control group normal saline. Six blood samples were drawn before and after solution application, and from the umbilical cord of the infants and at 2, 4, and 6 months of age. Pertactin and Pertussis toxin antibodies and possible interference of maternal antibodies with the vaccine were determined. In the experimental group, antibodies against Bordetella pertussis pertactin (anti-PRN) (112 E/mL 95% CI 89.9-139.9) and antibodies against pertussis toxin (anti-PT) (24.0 E/mL, 95% CI 18.3-31.4) were elevated in the mother before vaccination. These were higher in the umbilical cord and descended in the infant at 2 months (71.4 (95% CI 56.8-89.7 and 10.9; 95% CI 8.7-13.7, respectively). Anti-PT showed a delay in production. Tdap safety was confirmed with only mild local pain at 24 and 48 hours. Anti-PRN and anti-PT antibodies in the infant descend at 2 months of age. There is a delay in anti-PT in children of immunized mothers. Further studies are needed to elucidate its clinical significance.

Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis.

BACKGROUND: Case reports have suggested that vaccines may trigger transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM), but the evidence for a causal association is inconclusive. We analyzed the association of immunization and subsequent development of TM or ADEM. METHODS: We identified all cases of TM and ADEM in the Vaccine Safety Datalink population. Using a case-centered method, we compared vaccination of each case to vaccination of all matched persons in the study population, who received the same type of vaccine, with respect to whether or not their vaccination occurred during a predetermined exposure interval. We calculated a risk difference (excess risk) of TM and ADEM for each vaccine. RESULTS: Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5-28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the odds ratio for Tdap exposure 5-28 days prior to ADEM onset was 15.8 (95% confidence interval [CI], 1.2-471.6; P = .04), and the estimated excess risk was 0.385 (95% CI, -.04 to 1.16) cases per million doses. CONCLUSIONS: We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered.

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System.

BACKGROUND: In October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010-2012 found a small but statistically significant increased risk of chorioamnionitis. OBJECTIVE: We conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines. METHODS: We searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014. RESULTS: VAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported. CONCLUSION: Chorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.

How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study.

UNLABELLED: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. CONCLUSION: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.

Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination.

UNLABELLED: Persistent itching subcutaneous nodules and aluminium (Al) allergy have been described after vaccination with Al-adsorbed vaccines but are considered rare. Little is known about the prognosis. Sixty-four children with itching nodules following vaccination with diphtheria-tetanus-pertussis (DTP) vaccines currently used in Sweden (Infanrix® and Pentavac®) were spontaneously reported to the authors from 1999 and followed for up to 12 years. The median duration of itching was 5 years in the 44 children who were free or almost free from symptoms at the latest follow-up. Typical findings were a long interval between vaccination and onset of symptoms (months or years) and intensified itching during intercurrent infections. Contact allergy to aluminium was demonstrated in 60/63 children (95 %). Neither the incidence nor differences between the two vaccines can be estimated from this study, but vaccine-induced itching nodules are probably more common than hitherto realised. The median interval between onset of symptoms and diagnosis was 8 months in a region where nurses were educated to recognise the condition compared to 2 years in other regions. Booster vaccination with DTP-polio was postponed or declined by 15/40 families in fear for new problems. Out of 25 children who received a booster dose, only two had new itching nodules. CONCLUSION: Intensely itching subcutaneous nodules (vaccination granulomas) and contact allergy to aluminium may occur after primary vaccination with the two most commonly used DTP vaccines in Europe. The condition is probably underreported. Symptoms may last for at least 4-5 years but eventually seem to subside.

Complex regional pain syndrome following immunisation.

Complex regional pain syndrome type 1 (CRPS-1) is a clinical syndrome that affects one or more extremities and is characterised by persistent pain disproportionate to any inciting event, and at least one sign of autonomic dysfunction in the affected limb(s). The pathogenesis of this syndrome is poorly understood, but its onset is often precipitated by a physical injury, such as minor trauma, fracture, infection or a surgical procedure. In the literature, there are reports of CRPS-1 following immunisation with rubella and hepatitis B vaccines. Here we present a case series of CRPS-1 following immunisation in adolescents, with either diphtheria-tetanus-acellular pertussis (1 case), or human papillomavirus vaccines (4 cases). Enhanced awareness of this syndrome and its potential to occur following immunisation in the paediatric population is vital to the prompt and effective management of this condition.

Local vaccine site reactions and contact allergy to aluminum.

Childhood vaccines are a routine part of pediatric care in the United States; clinicians must be able to recognize and interpret associated localized adverse reactions. Redness and induration at the site of injection are commonly reported and are considered to be the result of local inflammation or hematoma formation, although other atypical reactions can occur. We report the case of a 6-month-old infant who developed subcutaneous nodules at the sites of his 4- and 6-month Pentacel (DTaP/Hib/IPV, diphtheria, tetanus, acellular pertussis, Haemophilus b conjugate, and inactivated poliovirus vaccine) and 6-month Prevnar (heptavalent pneumococcal vaccine) injections. Infectious disease and immunodeficiency examinations were unremarkable. Aluminum contact allergy was considered, and contact allergy testing confirmed sensitivity to aluminum. Although rare, aluminum contact allergy after routine immunization can occur and should be considered in the differential diagnosis of persistent subcutaneous nodules after vaccination.