Adverse events following immunization of co- and separate administration of DTaP-IPV/Hib vaccines: A real-world comparative study.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

BACKGROUND: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. METHODS AND FINDINGS: OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). CONCLUSIONS: Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. TRIAL REGISTRATION: Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.

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.

Do Pentavalent (DTwP-Hib-HBV) vaccines have sex-differential nonspecific effects? An observational study.

Vaccines may alter the ability to combat infections unrelated to the target disease, i.e. have "nonspecific effects." The non-live Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for females. In 2008, the DTP-containing Pentavalent vaccine replaced DTP vaccine in Guinea-Bissau. We investigate female relative to male mortality after Penta vaccination. In Guinea-Bissau, Bandim Health Project (BHP) registered children's vaccination and vital status at biannual village visits and provided vaccines. Among children Penta-vaccinated by BHP, we compared mortality of males and females in Cox proportional hazards models. Children aged 6 weeks to 8 months entered the analysis at the date of vaccination and were followed for up to 6 months. Between September 2008 and December 2017, 33,989 children aged 6 weeks to 8 months were under surveillance. Of these 12,753 (females: 6,363; males: 6,390) received Penta by the BHP and entered the study contributing with 19,667 observations. The mortality rate following Penta vaccination was 25.2 per 1,000 person years for females and 26.6 for males, resulting in an adjusted Female/Male mortality rate ratio of (F/M aMRR) 1.01 (0.82-1.25). The association between sex and mortality differed by timeliness of vaccination, F/M aMRR: 0.62 (0.41-0.93) for children vaccinated below median age, and F/M aMRR: 1.38 (0.90-2.13) for children vaccinated above median age. We did not find higher overall mortality in females than males after Penta vaccination. Our findings suggest that mortality differences between males and females following Penta vaccination may depend on timeliness of Penta vaccination.

Guillain Barré syndrome after combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine: A rare pediatric case report and review of literature.

A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl's GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.

Safety and immunogenicity of a new formulation of a pentavalent DTwP-HepB-Hib vaccine in healthy Indian infants-A randomized study.

BACKGROUND: Pentavalent vaccines (DTP-HepB-Hib) have been introduced in many countries in their routine public immunization programmes to protect against diphtheria (D), tetanus (T), pertussis (P), hepatitis B (Hep B) and Hemophilus influenzae type b (Hib) diseases. This study compared the safety and immunogenicity of a new formulation of a whole-cell Bordetella pertussis (wP) based pentavalent vaccine (DTwP-HepB-Hib). The new formulation was developed using well-characterized hepatitis B and pertussis whole cell vaccine components. METHODS: This was a phase III, observer-blind, randomized, non-inferiority, multi-center study conducted in India among 460 infants who were followed up for safety and immunogenicity for 28 days after administration of three doses of either investigational or licensed comparator formulations at 6-8, 10-12 and 14-16 weeks of age. RESULTS: The investigational formulation of DTwP-HepB-Hib vaccine was non-inferior to the licensed formulation in terms of hepatitis B seroprotection rate (% of subjects with HepB antibodies ≥10mIU/mL were 99.1% versus 99.0%, respectively, corresponding to a difference of 0.1% (95% CI, -2.47 to 2.68)) and pertussis immune responses (adjusted geometric mean concentrations of antibodies for anti-PT were 76.7 EU/mL versus 63.3 EU/mL, with a ratio of aGMTs of 1.21 (95% CI, 0.89-1.64), and for anti-FIM were 1079 EU/mL versus 1129 EU/mL, with a ratio of aGMTs of 0.95 (95% CI, 0.73-1.24), respectively). The immune responses to other valences (D, T, and Hib) in the two formulations were also similar. The safety profile of both formulations was found to be similar and were well tolerated. CONCLUSIONS: The investigational DTwP-HepB-Hib vaccine formulation was immunogenic and well-tolerated when administered as three dose primary series in infants. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry India number: CTRI/2018/12/016692.

Differential impacts of vaccine scandal by ethnic and socioeconomic factors: Evidence from China.

Widespread vaccination against important diseases plays a key role for global health security, particularly in the context of the COVID-19 pandemic. However, building and maintaining trust in immunization services remains challenging because of doubts about quality and safety of vaccines. China has periodically faced mounting pressure and even public outrage triggered by incidents of poor-quality vaccines. We aimed to evaluate the impact of the diphtheria, pertussis, and tetanus (DPT) vaccine scandal of 2018 in China and the ensuing misinformation on vaccination, and investigate differential responses to the scandal by ethnic and socioeconomic factors. With data from January 2017 to December 2018 in Sichuan province, China, we used a difference-in-differences (DID) method to compare the changes in the county-level monthly DPT vaccinations against the hepatitis B vaccinations, both before and after the DPT vaccine scandal. We found that the number of DPT vaccinations decreased by 14.0 percent in response to the vaccine scandal and ensuing misinformation. The number of vaccinations in minority regions, under-developed regions, and regions with poor medical resources decreased more than in non-minority regions, developed regions, and regions with good medical resources (24.5 versus 10.1 percent, 17.3 versus 8.3 percent, and 17.0 versus 8.7 percent, respectively). People did more online searching for "Substandard vaccine" and "DPT vaccine" after the scandal, with the socioeconomically advantaged group searching more compared with the socioeconomically disadvantaged group. The results suggest the urgent need to make true information about the vaccine easily accessible over the internet, especially for the socioeconomically disadvantaged groups. Our findings for China can also have implications for immunization service planning for better safeguarding public health in other countries, particularly developing ones.

Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) - a protocol for two parallel, open-label, randomised controlled trials.

BACKGROUND: Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines. METHODS: The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety. DISCUSSION: These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood. TRIAL REGISTRATIONS: ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

Postmarketing Safety Surveillance of a Hexavalent Vaccine in the Vaccine Adverse Event Reporting System.

We assessed the safety of hexavalent vaccine diphtheria and tetanus toxoids and acellular pertussis, inactivated poliovirus, hepatitis b, and haemophilus influenzae b conjugate vaccine in the Vaccine Adverse Event Reporting System. Five hundred-one reports of adverse events (AEs) were identified; 21 (4.2%) were serious. Most frequently reported AEs were fever (10.2%) and injection site erythema (5.4%). AEs reported were consistent with findings from prelicensure studies.

Acute adverse events following immunization with DTP-HB-Hib pentavalent vaccine in the first year of life.

Background: Since November 2014, the pentavalent (Diptheria+Tetanus+Pertussis and Hepatitis B and Hib or DTP-HBHib) vaccine has been integrated into the Iranian national vaccination programme. Aims: We conducted a prospective study in Zahedan in the southeast of the Islamic Republic of Iran to determine the incidence of adverse events following immunization (AEFI) with the pentavalent vaccine in children aged under one year. Methods: Using cluster sampling, 1119 children aged 2-10 months at 15 public health clinics were invited, through their parents, to participate in the study. The parents were trained to register and report any AEFIs in a questionnaire. They were instructed to return the child to the clinic for further examination by a physician if they observed any complications within 3 days of vaccination. Results: The most commonly reported AEFIs were fever (50.94%), mild (41.46%) and severe (1.70%) injection site complications, persistent crying for 3 hours or more (1.88%), hypotonic hyporesponsive episode (0.36%), vomiting (1.88%), diarrhoea (2.95%), and sterile abscess (0.62%). There were no cases of convulsion, purulent abscess or rash. The work experience of vaccinators (OR = 1.85; 95% CI: 1.4-2.46) showed a significant statistical association with the incidence of mild local complications at the injection site. Those with a history of Bacillus Calmette-Guérin (BCG) lymphadenitis (OR = 3.89; 95% CI:1.04-14.49) had a higher risk of severe local complications at the injection site. Conclusions: The observed incidence of serious AEFIs following pentavalent vaccine injection in the study population was within the expected range. However, some of the relationships observed in this study require further research.

Vaccination in children with congenital heart disease: an observational study in a Beijing hospital.

INTRODUCTION: Underimmunization of CHD children is a public health concern in China. This study aimed to analyze the vaccination status of CHD children to provide additional evidence on optimal vaccination strategies and to make suggestions to promote appropriate vaccination services for these children. METHODS: This cross-sectional study evaluated 155 CHD children who received at least one vaccine at Peking University First Hospital. Vaccine-specific immunization rates were calculated. A telephone questionnaire survey was conducted that covered the following: the prognosis, reasons for delayed vaccinations and getting vaccination in the hospital. All statistical analyses were performed using the SPSS version 22 software. RESULTS: The left-to-right shunt group involved 138 children, while the other type CHD group involved 17. The vaccination rate was the highest for MPSV-AC (87.1%) and the lowest for DTaP (40.1%). The most frequent reason for vaccination in the hospital was refusal from community health centers (61.5%). No participant reported vaccine-related adverse effects. CONCLUSIONS: The age-appropriate vaccine-specific immunization rates in CHD children are low, with the lowest for DTaP. Refusal of community health centers was the primary reason. Our findings support that clinically stable CHD children may be safely vaccinated on a schedule similar to that of ordinary children in China. IMPACT: From our investigation, we found that the age-appropriate vaccine-specific immunization rates in children with CHD in China are low, with the lowest for diphtheria and tetanus toxoid and acellular pertussis. Refusal of community health centers to vaccinate was the primary reason for the low rates. We believe our study provides additional evidence on optimal vaccination strategies for children with CHD and it can be used to develop strategies to promote appropriate vaccination services for these children.

A combined DTaP-IPV vaccine (Tetraxim®/Tetravac®) used as school-entry booster: a review of more than 20 years of clinical and post-marketing experience.

INTRODUCTION: Routine infant primary series and toddler booster vaccination are associated with waning of antibody levels over time, which can lead to an increased incidence of vaccine-preventable diseases. A diphtheria-tetanus-pertussis (DTP) booster vaccination at school-entry (aged 4-7 years) allows continued protection against these diseases and is included in many national immunization programs. AREAS COVERED: The available immunogenicity and safety data from 6 clinical studies of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (DTaP-IPV [Tetraxim®]) used as a school-entry booster vaccination were identified using a PubMed search or on file at Sanofi. The studies spanned a 15-year period (1995-2010) and were performed in different populations using different study designs, so all data were reviewed descriptively (no meta-analyses were conducted). Additionally, post-marketing experience was reviewed. EXPERT OPINION: Each vaccine antigen is highly immunogenic, and the safety profile of the vaccine is satisfactory. Post-marketing evaluations have shown the effectiveness of a school-age booster, particularly against increased pertussis disease incidence around the time of school entry and the associated risk of spreading the disease through contact with younger vulnerable infants. School-entry provides an ideal opportunity to implement DTaP-IPV vaccination to close the gap between waning immunity from the previous infant/toddler vaccination and future adolescent vaccination.

Non-specific effects of BCG and DTP vaccination on infant mortality: An analysis of birth cohorts in Ghana and Tanzania.

BACKGROUND: Vaccines may induce non-specific effects on survival and health outcomes, in addition to protection against targeted pathogens or disease. Observational evidence suggests that infant Baccillus Calmette-Guérin (BCG) vaccination may provide non-specific survival benefits, while diphtheria-tetanus-pertussis (DTP) vaccination may increase the risk of mortality. Non-specific vaccine effects have been hypothesized to modify the effect of neonatal vitamin A supplementation (NVAS) on mortality. METHODS: 22,955 newborns in Ghana and 31,999 newborns in Tanzania were enrolled in two parallel, randomized, double-blind, placebo-controlled trials of neonatal vitamin A supplementation from 2010 to 2014 and followed until 1-year of age. Cox proportional hazard models were used to estimate associations of BCG and DTP vaccination with infant survival. RESULTS: BCG vaccination was associated with a decreased risk of infant mortality after controlling for confounders in both countries (Ghana adjusted hazard ratio (aHR): 0.51, 95% CI: 0.38-0.68; Tanzania aHR: 0.08, 95% CI: 0.07-0.10). Receiving a DTP vaccination was associated with a decreased risk of death (Ghana aHR: 0.39, 95% CI: 0.26-0.59; Tanzania aHR: 0.19, 95% CI: 0.16-0.22). There was no evidence of interaction between BCG or DTP vaccination status and infant sex or NVAS. CONCLUSION: We demonstrated that BCG and DTP vaccination were associated with decreased risk of infant mortality in Ghana and Tanzania with no evidence of interaction between DTP or BCG vaccination, NVAS, and infant sex. Our study supports global recommendations on BCG and DTP vaccination and programmatic efforts to ensure all children have access to timely vaccination. CLINICAL TRIALS REGISTRATION: Ghana (Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000582055) and Tanzania (ANZCTR: ACTRN12610000636055).

Post-vaccination aluminium granulomas in children. / Aluminiumsgranulomer etter barnevaksinasjon.

BACKGROUND: Persistent itching subcutaneous granulomas related to aluminium-containing vaccines are poorly recognised in health care. They are often associated with aluminium hypersensitivity. CASE PRESENTATION: An intensely itching subcutaneous nodule appeared on the left thigh of a 17-month-old girl at the injection site for an aluminium adsorbed diphtheria-tetanus-pertussis-polio-HiB vaccine given at 3, 5 and 12 months. Ultrasound suggested a vascular malformation among other differential diagnoses. An MR investigation under general anaesthesia was planned, but the diagnosis was confirmed prior to this by a positive epicutaneous test with aluminium. INTERPRETATION: Despite a typical history of an itchy vaccination granuloma, the child underwent a thorough hospital workup to rule out malignancy. The diagnosis was delayed for two years. Vaccination granulomas have a good prognosis but can persist for many years. It is important to recognise the condition early in primary health care to avoid unnecessary anxiety and investigations.

Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study.

OBJECTIVE: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. METHODS: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. RESULTS: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. CONCLUSIONS: The study vaccine  had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs.

Safety evaluation of the DTaP5-IPV-Hib-HepB vaccine: a review.

INTRODUCTION: The DTaP5-IPV-Hib-HepB vaccine is the most recently approved combination hexavalent vaccine. In Europe, it is licensed since 2016 for primary and booster vaccination in infants and toddlers above the age of 6 weeks to provide active immunization against diphtheria, tetanus, pertussis, poliomyelitis, invasive diseases caused by Haemophilus influenzae type b and hepatitis B. In the US, DTaP5-IPV-Hib-HepB is approved since 2018 in children 6 weeks through 4 years of age. Its safety profile has been extensively documented in infants and children born at term, and also data in preterm infants are made available. AREAS COVERED: In this article, we conducted a safety evaluation of the DTaP5-IPV-Hib-HepB vaccine in infants and toddlers considering evidence from clinical trials and post-marketing use, also with regard to data on special populations e.g. preterm infants. EXPERT OPINION: Based on the available data, the DTaP5-IPV-Hib-HepB vaccine has demonstrated a good safety profile, similar to that of other approved penta- and hexavalent vaccines. Rather, post-marketing data are limited and are frequently reported in combination with other hexavalent vaccines or are not adjusted for shares of vaccines use. Neither relevant interferences with other co-administered pediatric vaccines nor safety issues in premature infants have been shown.

How were DTP-related adverse events reduced after the introduction of an acellular pertussis vaccine in Chile?

OBJECTIVES: To describe the trend in the frequency of adverse events (AE) records associated to pertussis component vaccines between January 1st, 2015 and June 30th, 2020 in infants younger than 2-years-old in Chile, by reviewing the records submitted to the AEFI NIP, stratified by DTP-vaccine type, wP or aP. MATERIALS AND METHODS: This was a retrospective observational study including all AEFI records of DTP (either aP or wP)-containing vaccines in the described sample. A descriptive analysis was performed according to vaccine type and AEFI, using MedDRA terminology. RESULTS: The total number of AEFI reports was 1,697: 815 corresponding to wP vaccines, 417 to aP vaccines, and 465 with unknown type. The reporting rates for the years 2015 to 2020 were 40.1, 56.2, 37.1, 24.7, 19.1, and 12.2 per 100,000 doses administered, respectively. The most reported AEFI were injection site erythema (42.9%), pyrexia (35.7%), and pain at the injection site (29.2%). Among all cases, 5.8% were SAEs (n = 98), 5.9% were SAEs for wP vaccines (n = 48) and 5.3% were for aP vaccines (n = 22). DISCUSSION: A significant decrease in AEFI reports was observed as of 2018, the year that the DTaP-IPV-HepB-Hib was introduced in the NIP.

Disproportionality analysis of reported drug adverse events to assess a potential safety signal for pentavalent vaccine in 2019 in El Salvador.

Detection and surveillance of vaccine safety hazards is a public health staple. In the post-marketing phase, when vaccines are used in mass, it is crucial to monitor potential signals of adverse reactions that may have been missed in the pre-marketing phase. We analysed spontaneous reports of drug adverse events in El Salvador to assess a potential safety signal related to an increase in febrile seizures following the pentavalent (diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae Type B) vaccine in 2019. This was a retrospective observational study of adverse event notifications in the national electronic drug safety database from 2011 to 2019. We performed standard disproportionality analysis computing Proportional Reporting Risk (PRR), Reporting Odds Ratio (ROR), Relative Reporting Ratio (RRR), Chi-squared, and Information Component (IC), comparing the pairing of febrile seizures and pentavalent vaccine to all other drugs and adverse events recorded in 2019. The occurrence of febrile seizures following pentavalent vaccination exceeded the WHO expected rate of six cases × 100 000 doses administered from April 2019, with a maximum of 9.2 in September. IC was 4.3, ORR 421.9 (95% Confidence Interval, CI: 123.8-1437.7), PRR 223.5 (95 %CI: 70.2-710.9), RRR was 19.5. The first booster presented the highest rate (14.6 per 100,000 doses) of febrile seizures, more than double than expected. Rates for 2018 remained below expected. Reports of febrile seizures following pentavalent vaccine were also on the increase globally since 2014, with highest rates in 2018 and 2019. There was a disproportion of febrile seizures notifications following pentavalent in El Salvador in 2019, suggesting the existence of a safety signal. This may be due to the change in provider. Further studies should assess the causes of the increase and compute costs and benefits of this vaccination to determine if switching to a less reactogenic vaccine formulation is indicated.