Safety evaluation of adverse events following vaccination with Havrix, Engerix-B or Twinrix during pregnancy.

BACKGROUND: Vaccination of pregnant women against hepatitis A virus (HAV) or hepatitis B virus (HBV) may benefit the mother and the fetus but is not routinely recommended. However, the risk associated with vaccination should be weighed against the risk of HAV or HBV infection. Data on safety profiles after hepatitis A, B or combined AB immunization during pregnancy are limited. METHODS: We searched the GSK Worldwide Safety Database for adverse events (AEs) following immunization of pregnant women with HAV (Havrix, GSK), HBV (Engerix-B, GSK) or the combined hepatitis AB (Twinrix, GSK) vaccine since market authorization through 31 January 2018, covering at least 25 years. AE reports (spontaneous, post-marketing surveillance and clinical trial cases) in the GSK Worldwide Safety Database were identified using a systematic search and were reviewed by clinicians to ascertain pregnancy status at time of vaccination and characterize adverse pregnancy outcomes, including pregnancy-related AEs and AEs in infants regardless of the causality assessment. RESULTS: Overall, 613, 700 and 363 pregnancies with exposure to Havrix, Engerix-B and Twinrix, respectively, were reported. Of these, 378, 339 and 194 were analyzed. The most frequently identified pregnancy outcomes were live infants (288, 223 and 151), spontaneous abortions (43, 57 and 26) and elective terminations (25, 24 and 9). A total of 19, 29 and 10 cases of congenital anomalies were reported. Of these, 17, 20 and 7 were major birth defects. The most commonly reported pregnancy-related AE and AE in infants were premature delivery (28) and jaundice (11), respectively. No maternal deaths were reported. Congenital anomalies were reported in all recorded infant deaths. CONCLUSIONS: This review did not indicate any concerning pattern of adverse pregnancy outcomes following exposure to any of the 3 vaccines during pregnancy.

Brain stones revisited-between a rock and a hard place.

OBJECTIVES AND METHODS: Large intracranial calcifications are occasionally encountered in routine computed tomography (CT) scans of the brain. These calcifications, also known as "brain stones", can be classified according to location and aetiology. Combining imaging findings with relevant clinical history and physical examination can help narrow down the differential diagnosis and may allow confident diagnosis in certain situations. RESULTS: This article provides a pictorial review illustrating various clinical entities resulting in brain stones. DISCUSSION: Based on location, brain stones can be classified as extra- or intra-axial. Extra-axial brain stones comprise tumours and exaggerated physiological calcifications. Intra-axial brain stones can further be classified according to aetiology, namely neoplastic, vascular, infectious, congenital and endocrine/metabolic. Imaging findings combined with essential clinical information can help in narrowing the differential diagnosis, determining disease state and evaluating effect of therapy. TEACHING POINTS: • Based on location, brain stones can be either extra- or intra-axial. • Extra-axial brain stones comprise tumours and exaggerated physiological calcifications. • Intra-axial aetiologies include neoplastic, vascular, infectious, congenital and endocrine/metabolic. • CT scan is the mainstay in identifying and characterising brain stones. • Certain MRI sequences (gradient echo T2* and susceptibility-weighted imaging) are considered adjunctive.

A decennial booster dose of reduced antigen content diphtheria, tetanus, acellular pertussis vaccine (Boostrix™) is immunogenic and well tolerated in adults.

Reduced-antigen-content diphtheria-tetanus-acellular-pertussis (dTpa) vaccines are predominantly recommended for once-in-a-lifetime use. A second dTpa (Boostrix™, GlaxoSmithKline Biologicals) administration in 164 adults previously vaccinated with dTpa 10 years previously was evaluated. Before the decennial booster, 89.4% and 94.8% subjects were seroprotected (antibodies ≥0.1 IU/mL) for diphtheria and tetanus, respectively. One-month post-booster, all subjects were seroprotected/seropositive against all vaccine antigens. Robust GMC increases indicated a booster response similar to the first booster. The decennial booster was well tolerated without serious adverse events, consistent with product experience. This study supports replacing traditional Td boosters with dTpa, and use of Boostrix™ as a decennial booster. This study is registered at www.clinicaltrials.com NCT00548171.

Repeated administration of a reduced-antigen-content diphtheria-tetanus-acellular pertussis and poliomyelitis vaccine (dTpa-IPV; Boostrix™ IPV).

BACKGROUND: The rising incidence of pertussis amongst adults and adolescents in industrialized countries could be reduced by replacing tetanus and diphtheria (Td) boosters with reduced-antigen-content dT-acellular pertussis (dTpa)vaccines. Repeated administration of a dTpa-IPV (dTpa-inactivated poliomyelitis; BoostrixTM Polio, GlaxoSmithKline)booster to adolescents, 5 years after their previous dose was evaluated. RESULTS: Before the second dTpa-IPV booster, the percentage of subjects who were seroprotected/seropositive was: 98.2% (D); 98.5% (T); 40.6% (PT); 99.7% (FHA); 97.0% (PRN); 98.8% (anti-polio 1); 99.7% (anti-polio 2); 97.0% (anti-polio 3). One month after the second dTpa-IPV dose, all subjects were seroprotected against D, T and polio and anti-pertussis booster responses (seroconversion or ≥2-fold increase) were seen in 93.3% (PT), 93.4% (FHA) and 95.2% (PRN) of subjects.During 4-day follow-up, 4.1% subjects recorded grade 3 pain; 4.6% and 3.6% recorded redness or swelling >50 mm, respectively. No serious adverse events were recorded. The incidence of symptoms was not higher than after the previous booster. METHODS: 415 subjects (mean age 11.4 years) who had received either dTpa-IPV or dTpa + IPV at age 4­8 years, all received one dose of dTpa-IPV in this open, phase IV trial. Blood samples were taken before and one-month post-vaccination. Antibody concentrations against D, T, pertussis toxoid (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and polio antigens were determined. Reactogenicity and safety was assessed. CONCLUSIONS: A second dTpa-IPV booster was highly immunogenic and well tolerated in this population of adolescents, supporting the repeated administration of BoostrixTM Polio. This study is registered at www.clinicaltrials.gov NCT00635128.