Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

Background

There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.

Characterization of infections and hypogammaglobulinemia treated with the combination of pertuzumab and trastuzumab

We update a patient series that reported a high incidence of infection with Gram-positive cocci in women treated with the combination of pertuzumab and trastuzumab and further characterize this clinical problem. Treating physicians and advanced practice partners identified women who developed infections while on treatment with pertuzumab and trastuzumab alone or in combination with chemotherapy and enrolled them onto this registry trial. Between March, 2014 and May, 2017, 48 patients with HER2-positive breast cancers were reported to have 59 individual infections. The median age was 48 years. Twenty-four patients received neoadjuvant therapy, 17 were treated for metastatic disease, and 7 were treated in the adjuvant setting. Pertuzumab and trastuzumab were combined with carboplatin and docetaxel in 24 (49%) patients, docetaxel in 10 (21%), nab-paclitaxel in 12 (24%), and without other agents in 2 (4%). Granulocyte growth factors were administered in 24 (49%) patients and no patients were documented to be neutropenic. Folliculitis developed in 25 (52%) patients and was counted as a single infection. Abscesses developed at a number of sites in 24 (49%) patients, including a septic knee requiring total knee replacement. Paronychia occurred in 7 (15%) patients, and 5 (10%) developed cellulitis. When cultures were obtained, Gram-positive cocci were consistently identified. Hypogammaglobulinemia was documented in 14 (36%) of the 33 patients tested. Our data continue to support an increased risk of infections with Gram-positive cocci as a potentially serious adverse event in women treated with pertuzumab and trastuzumab.     

A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero‐posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four‐fold increase with a low thoracic index, r² = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels. Clin. Anat. 28:614–620, 2015. © 2015 Wiley Periodicals, Inc.     

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6–59 months of age: A phase 3, randomized,noninferiority study

Background

In the Southern Hemisphere 2010 influenza season, Seqirus’ split-virion, trivalent inactivated influenza vaccine was associated with increased reports of fevers and febrile reactions in young children. A staged clinical development program of a quadrivalent vaccine (Seqirus IIV4 [S-IIV4]; Afluria® Quadrivalent/Afluria Quad?/Afluria Tetra?), wherein each vaccine strain is split using a higher detergent concentration to reduce lipid content (considered the cause of the increased fevers and febrile reactions), is now complete.