Post-Marketing Safety Surveillance of a Childhood Pentavalent Diphtheria-Tetanus-Acellular Pertussis-Polio and Haemophilus influenzae Type B (DTaP-IPV//Hib) Vaccine in South Korea.

INTRODUCTION: PENTAXIM™ (Sanofi), DTaP-IPV//Hib, a pentavalent combination vaccine for protection against diphtheria, tetanus, pertussis, poliomyelitis, and invasive infections caused by Haemophilus influenzae type b, has been licensed in South Korea by the Ministry of Food and Drug Safety (MFDS) on May 9, 2016, and is currently used in routine vaccination. The aim of this phase IV study, conducted as a post-licensure commitment in South Korea, was to evaluate the safety of the DTaP-IPV//Hib vaccine when administered in infants at 2, 4, and 6 months of age in the real-world clinical practice. METHODS: This multicenter, observational, post-marketing surveillance (PMS) study was conducted in real-world practice in South Korea. Infants aged 2 months or older were enrolled across seven centers from July 31, 2018 to February 11, 2020. The study outcomes included occurrence, time to onset, duration, intensity, and causality assessment (for unsolicited adverse events [AEs] only) for several pre-listed solicited injection-site and systemic reactions, unsolicited AEs, and serious adverse events (SAEs). RESULTS: Data from 619 participants were included in the safety analysis. Overall, 618 AEs were reported by 273 (44.1%) participants consisting of 121 solicited injection-site reactions (15.4%), 344 solicited systemic reactions (24.6%), and 153 unsolicited AEs (15.7%) of which, 124 were unexpected AEs (12.9%) (regardless of intensity). None of the unsolicited AEs were reported to have a causal relationship with the study vaccine. One SAE of pyrexia (solicited reaction) was reported. Most AEs were of mild intensity, and all participants recovered. CONCLUSION: This PMS study of the DTaP-IPV//Hib vaccine confirmed its safety profile in a real-life setting in South Korea and justified that the vaccine is well tolerated when used in infants aged 2 months or older for the primary series.

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.

What is the true burden of diphtheria, tetanus, pertussis and poliovirus in children aged 3-18 years in Asia? A systematic literature review.

OBJECTIVES: In recent years, outbreaks and a rising incidence of diphtheria, tetanus, and pertussis have occurred in Asia, particularly in older children. METHODS: A systematic search of MEDLINE and Embase was conducted from January 2000 to October 2020 to identify the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis in children and adolescents (aged 3-18 years) in Asia. The results were then related to vaccination schedules, booster coverage rates, pertussis source of infection, and booster immunogenicity, as identified by a pragmatic review. The International Prospective Register of Systematic Reviews (PROSPERO) registration: #CRD42020222445. RESULTS: A total of 35 studies were included in this review. Limited data were reported on the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis. Data from studies reporting the incidence of diphtheria and pertussis exemplify the shift in epidemiology to older children/adolescents. Seroprevalence data suggest that immunity to pertussis and diphtheria is below the level of herd immunity in several Asian countries in this population. CONCLUSION: The true burden of diphtheria, pertussis, and tetanus in children aged 3-18 years in Asia is unknown because of weak or absent nationwide surveillance systems. The available evidence highlights the inadequacies in immunity, either by gaps in a recommendation or suboptimal booster coverage, supporting the public health need for booster vaccinations in this population.

Incidence rates of neurotropic-like and viscerotropic-like disease in three dengue-endemic countries: Mexico, Brazil, and Malaysia.

BACKGROUND: The background incidence of viscerotropic- (VLD) and neurotropic-like disease (NLD) unrelated to immunization in dengue-endemic countries is currently unknown. METHODS: This retrospective population-based analysis estimated crude and standardized incidences of VLD and NLD in twelve hospitals in Brazil (n = 3), Mexico (n = 3), and Malaysia (n = 6) over a 1-year period before the introduction of the tetravalent dengue vaccine. Catchment areas were estimated using publicly available population census information and administrative data. The denominator population for incidence rates was calculated, and sensitivity analyses assessed the impact of important assumptions. RESULTS: Total cases adjudicated as definite VLD were 5, 57, and 56 in Brazil, Mexico, and Malaysia, respectively. Total cases adjudicated as definite NLD were 103, 29, and 26 in Brazil, Mexico, and Malaysia, respectively. Crude incidence rates of cases adjudicated as definite VLD in Brazil, Mexico, and Malaysia were 1.17, 2.60, and 1.48 per 100,000 person-years, respectively. Crude incidence rates of cases adjudicated as definite NLD in Brazil, Mexico, and Malaysia were 4.45, 1.32, and 0.69 per 100,000 person-years, respectively. CONCLUSIONS: Background incidence estimates of VLD and NLD obtained in Mexico, Brazil, and Malaysia could provide context for cases occurring after the introduction of the tetravalent dengue vaccine.

Parental occupational exposure and risk of childhood central nervous system tumors: a pooled analysis of case-control studies from Germany, France, and the UK.

PURPOSE: To assess the risk of childhood central nervous system (CNS) tumors associated with parental occupational exposure to polycyclic aromatic hydrocarbons (PAH), diesel motor exhaust (DME), asbestos, crystalline silica, and metals, which are established carcinogens in adults. METHODS: We pooled data from three population-based case-control studies from Germany, France, and the UK. Cases were children aged up to 15 years and diagnosed with CNS tumor, and controls were frequency-matched by age and sex. Socio-demographic data and parental occupation around conception/pregnancy and at diagnosis were collected using standardized interviews, face-to-face or by telephone. A general population job-exposure matrix was used to assign a level of exposure to each job. Logistic regression models were fitted to compute odds ratios and 95 % confidence intervals. RESULTS: Our study included 1,361 cases of CNS tumors and 5,500 controls. Paternal exposure to PAH, asbestos, and metals around conception was associated with an increased moderate risk of CNS tumors, although statistically non-significant. The association with exposure to asbestos around conception and diagnosis was stronger when fathers were exposed to high levels. Paternal exposure to DME and silica, and maternal exposure to PAH, DME, asbestos, silica, and metals, were not associated with an increased risk of CNS tumors. CONCLUSION: Our large pooled study showed weak evidence of a modest association between paternal occupational exposure to PAH and CNS tumor risk. Our findings need further exploration in the future studies.

Incidence of hospital-acquired pneumonia, bacteraemia and urinary tract infections in patients with haematological malignancies, 2004-2010: a surveillance-based study.

OBJECTIVE: This study charted incidence trends of hospital-acquired (HA) pneumonia, bacteraemia and urinary tract infections (UTI) in a haematology department. METHODS: Prospective surveillance of hospital-acquired infections (HAI) was undertaken in a 42-bed haematology department of a university hospital. All patients hospitalized ≥48 hours between 1(st) January 2004 and 31(st) December 2010 were included. Definitions of HAI were based on a standardized protocol. The incidence was the number of events per 1000 patient-days at risk; only the first HAI was counted. Multivariate Poisson regression was fitted to assess temporal trends. RESULTS: Among 3 355 patients (58 063 patient-days at risk) included, 1 055 (31%) had HAI. The incidence of HA pneumonia, HA bacteraemia and HA UTI was respectively 3.3, 12.0 and 2.9 per 1000 patient-days at risk. HA bacteraemia incidence increased by 11% (95% confidence interval: +6%, +15%, P<0.001) per year, independently of neutropenia, central venous catheterization (CVC) and haematological disease. The incidences of HA pneumonia and HA UTI were stable. The most frequently isolated pathogens were Aspergillus spp. (59.2%) for pneumonia, coagulase-negative Staphylococcus (44.2%) for bacteraemia and enterobacteria (60%) for UTI. CONCLUSION: The incidence of bacteraemia increased, indicating that factors other than CVC exposure, including chemotherapy with its impact on the immune system, could explain this trend. Further analytic studies are needed to explore the factors that could explain this trend.