Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

The impact of frost-damage on the quality and quantity of the secreted antigen-specific IgG repertoire

Freezing of alum-based vaccines drastically alters their colloidal composition and leads to irreversible cluster formation. The loss of stability is well described, but the impact of frost damage on the functionality of the induced and secreted antibody repertoire has not been studied in detail. We therefore applied our single-cell measurement platform to extract the frequencies of Immunoglobulin G-secreting cells in combination with individual secretion rates and affinities. We showed that, frost-damaged or not, the tested vaccine was able to generate similar frequencies of total and antigen-affine IgG-secreting cells. Additionally, the frost-damaged vaccine stimulated a similar T-cell cytokine secretion pattern when compared to the regularly stored vaccine. However, frost-damaged vaccines induced no efficient affinity maturation and a complete collapse of the affinity distribution was observed. This study unveiled the impact of frost-damage to alum-based vaccines on the induced secreted antibody repertoire, and illustrated the power of functional single-antibody analysis.     

Evaluation of human antibody responses to diphtheria toxin subunits A and B in various age groups

This study aimed to evaluate human antibody responses to diphtheria toxin subunits in various age groups. Antibodies against the intact diphtheria toxin and the diphtheria toxin subunits A and B were evaluated in 1319 individuals using a double-antigen ELISA. Although high levels of protection (83.6%, 95% CI 79.2-87.4) were found in children and adolescents, the middle-aged adult population was less protected (28.8%, 95% CI 24.3-33.6). An increase in age was associated with a decrease in the frequency of protected individuals in the 0-39-year age group (p <0.001). Anti-subunit B levels correlated well (p <0.01) with levels of antibodies against the intact toxin. In children aged < or =16 years, the intervals at which the peaks in geometric mean titres of anti-subunit B antibodies were observed were found to correlate with the ages at which booster doses are administered. Overall, males appeared to be more protected than females (OR 1.67, 95% CI 1.34-2.08, p <0.001). A small group of individuals had antibody levels of > or =0.1 IU/mL against the intact toxin, but did not have protective antibody against subunit B. Determination of anti-subunit B antibody levels should help in evaluating the effectiveness of diphtheria boosters and other aspects of diphtheria immunity.     

Learning and sexual deficiencies in transgenic mice carrying a chimeric vasoactive intestinal peptide gene

The molecular mechanisms responsible for behavior are largely unknown. A state of the art model, paving the path from genes to behavior, is offered by transgenic animals. Candidate molecules are classic neuropeptides, such as vasoactive intestinal peptide (VIP). Transgenic mice harboring a chimeric VIP gene driven by the polyoma promoter were produced. Behavioral studies revealed learning impairment and prolonged retardation in memory acquisition in the genetically altered animals. Furthermore, reduced performance was observed when the male transgenic mice were tested for sexual activity in the presence of receptive females. Surprisingly, radioimmunoassays showed an approx 20% decrease in the VIP content of the transgenic mice brains. To directly assess genetically reduced VIP content as a cause for learning impairment, transgenic mice carrying diphtheria toxia-encoding sequences driven by the rat VIP promoter were created. These animals had reduced brain VIP and exhibited deficiencies in learning abilities, strongly supporting an important neurobiological function for VIP in vivo.     

Characterization of bacteriophages fromtox-containing, non-toxigenic isolates ofCorynebacterium diphtheriae

Non-toxigenic strains ofCorynebacterium diphtheriaecontinue to cause disease within immunized populations. A subset of these corynebacteria carry the diphtheria toxin gene but in a cryptic form. To determine whether such strains might contribute to the re-emergence of functional toxin genes, the phages andtoxmutations within three clone types were examined.tox-containing, β-related phages were isolated from two of the strain types. The third isolate appeared to harbour a defective prophage. One of thetox⁻phages encoded truncated, yet enzymatically-active, forms of diphtheria toxin, suggesting that it had sustained a point mutation within the latter half of its toxin gene. In contrast, the other mutant phage did not elicit the production of either a cross-reacting material or an ADP-ribosylating activity. Complementation tests employing a series of double lysogens confirmed that the mutations responsible for the non-toxigenic phenotype of all of the phages werecisdominant. Given these findings, it is reasonable to hypothesize thattox⁺genes can arise within human populations by either homologous recombination between two distincttox⁻phages or spontaneous reversion within a single mutant allele.     

A fatal case of necrotizing sinusitis due to toxigenic Corynebacterium ulcerans

A 77-year-old farmer developed cough with sputum production, fever, bloody nasal discharge and a mass in his right maxillary sinus leading to necrotic ulceration of the sinus. Corynebacterium ulcerans, carrying the beta-phage for the diphtheria toxin and secreting the toxin, was detected microscopically and by culture from the sinusoidal and ulcer discharge. Despite immediate antimicrobial chemotherapy the patient died of pulmonary failure associated with the production of large amounts of very viscous sputum. Identification of the causative agent, pathophysiological aspects and risk factors of this unusal infection are discussed.     

两种百白破联合疫苗基础免疫后百日咳凝集抗体和白喉抗体监测分析

为了解无细胞百白破联合疫苗(DTaP)和全细胞百白破联合疫苗(DTwP)接种后的血清学免疫效果,在东莞市随机选取3月龄健康婴儿107名,分两组分别用DTaP和DTwP做基础免疫,在免疫前和免疫后1个月分别采血,用微量凝集试验检测百日咳凝集抗体,采用间接血球凝集试验检测白喉抗体.结果表明:经DTaP基础免疫后,百日咳凝集抗体保护率为95.83%,≥4倍增长率为100.00%,几何平均滴度(GMT)为1:783.43;白喉抗体的保护率为100.00%,≥4倍增长率为100.00%,平均白喉抗毒素含量(DAT)为0.68IU/ml.经DTwP基础免疫后百日咳凝集抗体保护率为98.04%,≥4倍增长率为100.00%,GMT为1:1 634.93;白喉抗体保护率为100.00%,≥4倍增长率为100.00%,DAT为1.28IU/ml.DTaP和DTwP两组免疫前各项指标差异均无显著的统计学意义,但免疫后两组的百日咳凝集抗体GMT的差异有非常显著的统计学意义(t=4.68,P＜0.01).采用DTaP和DTwP作基础免疫均可获得良好的百日咳和白喉的血清学免疫效果.     

Prevention of pertussis across the age spectrum through the use of the combination vaccines PENTACEL™ and ADACEL™

Acellular pertussis-containing combination vaccines are widely used in the developed world for the control of pertussis and have been successful in controlling disease in preschool-aged children. Combination vaccines formulated for use in adolescents and adults have been developed more recently and are increasingly being implemented for the control of pertussis in these age groups. One such family of products is PENTACEL? (Haemophilus influenzae type b conjugate vaccine reconstituted with component pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine, DTaP-IPV-Hib), for use in young children, and ADACEL? (tetanus and diphtheria toxoids adsorbed combined with component pertussis vaccine, dTap) for use in adolescents and adults. These products have been demonstrated to be safe, immunogenic and effective for the control of pertussis and the other included diseases.     

Improving knowledge and trust in vaccines: A survey-based assessment of the potential of the European Union Clinical Trial Regulation No 536/2014 plain language summary to increase health literacy

The European Clinical Trial Regulation No 536/2014 is the first mandate for a non-technical, publicly disclosed, plain language summary (PLS) of clinical trial results. This easy-to-understand summary has the potential to inform the public about clinical trial results and thereby improve health literacy in vaccines.To investigate the utility of the PLS, we undertook 2 online surveys (July/October 2020) in the United Kingdom, the United States and India. Participants were selected by quota sampling to ensure representation of gender, age and parental status. Those lacking interest in vaccine clinical research were excluded. In survey 1, participants were questioned about their interest in and expectations of vaccine trial results. In survey 2, the perceptions of participants to a range of written communication styles used in publicly available PLSs were evaluated.A total of 66 (13%) and 122 (29%) individuals were excluded solely due to lack of interest in vaccine clinical research in surveys 1 and 2, respectively; 450 respondents (150/country) completed survey 1 and 300 (100/country) completed survey 2. In survey 1, there was a correlation (p < 0.01) between claimed knowledge of and trust in vaccines. Healthcare professionals were the most trusted source for vaccine information, while vaccine companies were ranked relatively low. In survey 2, infographic PLS formats were considered easiest to understand, most engaging and the strongest communicators. Emphasizing the main points of the infographics in the text did not improve comprehension or recall. Most respondents (86%) indicated that they would like to see this type of communication in the future.Overall, this research suggests that the PLS, by optimizing content and format, has a potential to increase health literacy, and thereby, as part of a wider integrated communication strategy, build vaccine knowledge and confidence.     

Nasal diphtheria (chronic carriage) caused by nontoxigenic Corynebacterium diphtheriae

Toxigenic strains of Corynebacterium diphtheriae cause the majority of respiratory diphtheria cases. However, nontoxigenic strains of C. diphtheriae can also cause diseases, and have become increasingly common. Infection that is limited to the anterior nares (nasal diphtheria) is a well-described but rare condition, even for toxigenic C. diphtheriae. We report a case involving chronic carriage of nasal diphtheria caused by nontoxigenic C. diphtheriae, as well as a review of other reported nontoxigenic C. diphtheriae cases in Japan. Mild or asymptomatic nasal diphtheria involving nontoxigenic strains, which can be the source of transmission, may be underrecognized. Our case highlights the importance of awareness regarding nontoxigenic diphtheria among clinicians, especially in the era of improved diphtheria vaccination coverage.