MomsTalkShots, tailored educational app, improves vaccine attitudes: a randomized controlled trial.

BACKGROUND: Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. METHODS: MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant's birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. RESULTS: By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23-2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47-2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13-1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15-3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46-4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36-2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17-2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52-31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06-0.98). CONCLUSIONS: MomsTalkShots improved pregnant women's and mothers' knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. TRIAL REGISTRATION: Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

The state of vaccine safety science: systematic reviews of the evidence.

This Review updates the scientific evidence assessing possible causal associations of adverse events following immunisation (AEFI) compiled in the 2012 report from the Institute of Medicine and the 2014 report from the Agency for Healthcare Research and Quality. For 12 of 46 AEFI examined, a causal relationship has been established with at least one vaccine currently routinely recommended to the general USA population: anaphylaxis, arthralgia or arthritis (mild, acute, and transient, not chronic), deltoid bursitis (when vaccine is administered improperly), disseminated varicella infection (in immune deficient individuals for whom the varicella vaccine is contraindicated), encephalitis, febrile seizures, Guillain-Barré syndrome, hepatitis (in immune deficient individuals for whom the varicella vaccine is contraindicated), herpes zoster, immune thrombocytopenic purpura, meningitis, and syncope. Other than mild acute and transient arthralgia or arthritis, which is very common in adult women after rubella vaccine, these adverse reactions are rare or very rare. Vaccines have an excellent safety profile overall and provide protection against infectious diseases to individuals and the general population.

MomsTalkShots: An individually tailored educational application for maternal and infant vaccines.

INTRODUCTION: The development and initial assessment in a clinical setting of a theory-driven, individually tailored educational application (app), MomsTalkShots, focused on increasing uptake of maternal and infant vaccines is described. METHODS: MomsTalkShots algorithmically tailored videos based on parent needs to deliver an intervention that was specifically responsive to individual vaccine attitudes, beliefs and intentions, demographics, and source credibility. MomsTalkShots was evaluated among 1103 pregnant women recruited from 23 geographically and socio-demographically diverse obstetrician-gynecologist offices in Georgia and Colorado in 2017. Self-reported information needs were assessed pre-and post-videos and participants self-reported factors related to usability and analyzed in 2018. RESULTS: The vast majority of women reported MomsTalkShots was helpful (95%), trustworthy (94%), interesting (97%) and clear to understand (99%), none of which varied by demographics or parity. Reported usability was slightly lower among vaccine hesitant women, yet the majority reported MomsTalkShots was helpful (91%), trustworthy (85%), interesting (97%) and clear (99%). The majority of women (72%) who did not have enough vaccine information pre-videos reported enough information post-videos. CONCLUSIONS: MomsTalkShots was designed to provide individually tailored vaccine information to pregnant women from a population with varied vaccine intentions, confidence and vaccine concerns. MomsTalkShots was extremely well-received among pregnant women, even among women who were initially vaccine hesitant and did not intend to vaccinate themselves and their infants according to the recommended immunization schedule. Next steps include evaluation to assess impact on vaccine uptake and expansion to adolescent and adult vaccines.

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination.

BACKGROUND: The timing of host cytokine responses to influenza vaccination is poorly understood. OBJECTIVES: We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV-related side effects. PATIENTS/METHODS: Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14. RESULTS: Serum cytokine responses to TIV were evident as early as 3 hours post-immunization. Compared to baseline, IFN-γ and IP-10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post-vaccination. Although IL-8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL-8 was significantly lower compared to baseline. Interestingly, IL-8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL-6, IL-2, IL-8, IP-10, MCP-1, TNF-α, TARC, and MCP-4. CONCLUSIONS: Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine-induced reductions in IL-8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.

BACKGROUND: Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. METHODS: All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. RESULTS: A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. CONCLUSIONS: The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.

Value of an in-depth analysis of unpublished data on the safety of influenza vaccines in pregnant women.

BACKGROUND: Unpublished data can sometimes provide valuable information on the safety of biologic products. METHODS: We assessed information potentially available from regulatory authorities, manufacturers, and public health agencies. We explored 4 recently established vaccine registries, reviewed package inserts from 99 influenza vaccines, and contacted vaccine manufacturers and regulatory agencies for data on influenza vaccine safety in pregnant women. RESULTS: The vaccine registries did not have sufficient data to analyze and there are problems with the quality of the information. The majority of package inserts provided no product-specific safety information for pregnant women, especially in less developed countries. The majority of available data come from reports gathered from passive adverse event reporting systems in the general population and reports of women enrolled in clinical trials of influenza vaccines who became pregnant at various times before or after receiving influenza vaccine. The information was not collected in a systematic manner, there are inconsistencies in the follow up of pregnant women and the available information about pregnancy outcomes. Considerable resources would be needed to systematically identify all of the information, try to obtain missing follow up information, and conduct analyses. There would be substantial limitations to any attempt to conduct a systematic analysis. CONCLUSIONS: The value of trying to analyze unpublished data on the safety of influenza vaccine in pregnancy is limited and would require considerable resources to thoroughly investigate. Expanding efforts to identify and review unpublished data regarding the safety of influenza vaccines in pregnancy is not likely to produce information of high scientific value or information that could not be identified from publications and other publically available data.

Arm Paralysis After Routine Childhood Vaccinations: Application of Advanced Molecular Methods to the Causality Assessment of an Adverse Event After Immunization.

Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause. This case illustrates the complexity of assessing AEFI causality, and the importance of careful and complete evaluations when determining the most likely cause of an AEFI.

Reflections of a Vaccinologist: Lessons Learned About What We Can Do to Improve Trust in Vaccines and Vaccine Programsa.

Public trust can be improved by learning from past mistakes, by establishing a standing forum for review of new concerns as they arise, and by maintaining a robust vaccine safety system. Developing standard guidelines for reporting causality assessment in case reports would help educate physicians and prevent future unnecessary concerns based on false assumptions of causal relationships.

International Consensus (ICON): allergic reactions to vaccines.

BACKGROUND: Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. METHODS: Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. RESULTS: Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. CONCLUSIONS: This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

Review of prescribing information for influenza vaccines for pregnant and lactating women.

Information provided by most influenza vaccine manufacturers do not reflect the recommendations of WHO and/or national public health advisory groups with regard to the use of influenza vaccines in pregnant or lactating women. The majority of vaccines contain precautionary language which could discourage use in pregnant women and some include stronger language discouraging or contradicting use in pregnant or lactating women. Regulators and manufacturers should regularly assess the language of pregnancy and lactation sections in product information for vaccines and include information from national public health advisory groups regarding use by pregnant or lactating women and data from relevant studies.

Pediatric Invasive Pneumococcal Disease in Guatemala City: Importance of Serotype 2.

INTRODUCTION: To inform estimations of the potential impact of recently introduced pneumococcal conjugate vaccine (PCV), we report results of 11 years of pre-PCV surveillance for invasive pneumococcal disease (IPD) among children in Guatemala City. METHODS: Cases of IPD in children younger than 5 years were identified by active surveillance at 3 referral hospitals in Guatemala City from October 1996 through 2007. Clinical and demographic data were obtained, and isolates of Streptococcus pneumoniae from normally sterile sites were serotyped using latex agglutination and confirmed by Quellung reaction. RESULTS: Four hundred fifty-two cases of IPD were identified with a case fatality rate of 21%. Meningitis was the most common cause of death (77% of all deaths) and occurred more often in infancy (median age 5 months) than other clinical syndromes. Of the 137 isolates serotyped, type 1 (26 cases, 17%), type 2 (25 cases, 16%) and type 5 (18 cases, 12%) were the most common. Serotype 2 was associated with a higher case fatality rate (28%), higher rate of meningitis (68%) and occurred in younger infants (median age, 3.5 months) than other common serotypes. Recently introduced PCV13 includes 73% of observed serotypes in the study. CONCLUSION: Infants with IPD presented at a young age. Serotype 2, rarely reported as a significant cause of IPD and not included in available PCVs, was a common cause of disease in this population. PCV13 introduction in Guatemala, begun in 2013, may not have as great an impact in disease reduction as has been observed in other countries.

Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali.

BACKGROUND: The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the "meningitis belt" of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. METHODS: The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1-29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. RESULTS: An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. CONCLUSIONS: No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries.

Risk Factors for Death and Major Morbidity in Guatemalan Children with Acute Bacterial Meningitis.

BACKGROUND: Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries. Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. METHODS: Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000 to 2007 were analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture, positive latex agglutination or CSF white blood cell greater than 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd score (HTS). RESULTS: Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity and 192 (23.7%) died. Among 383 children with nonmissing data, the most significant multivariate predictors for death or major morbidity were seizure [odds ratio (OR), 101.5; P < 0.001], CSF glucose less than 20 mg/dL (OR, 5.3; P = 0.0004), symptom duration more than 3 days (OR, 3.7; P = 0.003) and coma (OR, 6.3; P = 0.004). Of 221 children with a HTS greater than 5, 204 (92%) died or suffered major morbidity (OR, 10.3; P < 0.0001). CONCLUSION: ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite HTS predicted death or major morbidity. These predictors could help clinicians in low and middle income country guide medical care for ABM and could contribute to the public health impact assessment in preventing meningitis with vaccines.

The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children.

Effect of buffer on the immune response to trivalent oral poliovirus vaccine in Bangladesh: a community based randomized controlled trial.

BACKGROUND: Polio eradication efforts have been hampered by low responses to trivalent oral poliovirus vaccine (tOPV) in some developing countries. Since stomach acidity may neutralize vaccine viruses, we assessed whether administration of a buffer solution could improve the immunogenicity of tOPV. METHODS: Healthy infants 4-6 weeks old in Sylhet, Bangladesh, were randomized to receive tOPV with or without a sodium bicarbonate and sodium citrate buffer at age 6, 10, and 14 weeks. Levels of serum neutralizing antibodies for poliovirus types 1, 2, and 3 were measured before and after vaccination, at 6 and 18 weeks of age, respectively. FINDINGS: Serologic response rates following 3 doses of tOPV for buffer recipients and control infants were 95% and 88% (P=.065), respectively, for type 1 poliovirus; 95% and 97% (P=.543), respectively, for type 2 poliovirus; and 90% and 89% (P=.79), respectively, for type 3 poliovirus. CONCLUSIONS: Administration of a buffer solution prior to vaccination was not associated with statistically significant increases in the immune response to tOPV; however, a marginal 7% increase (P=.065) in serologic response to poliovirus type 1 was observed. CLINICAL TRIALS REGISTRATION: NCT01579825.

Live vaccine use and safety in DiGeorge syndrome.

OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge syndrome (DGS), a congenital disorder characterized by cellular immune deficiency. Vaccine utilization and safety in this population are not well described. This study examined vaccination patterns and adverse events following live immunization (AEFLI) in these individuals. METHODS: A multicenter retrospective cohort study was conducted in subjects with DGS confirmed by fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in the 56-day window after live vaccination were examined. Bivariate and multivariable analyses assessed the impact of demographics medical history, timing of diagnostic confirmation, and preceding immune function on vaccination patterns and AEFLIs. RESULTS: Of 194 subjects, 77% and 75% received measles-mumps-rubella (MMR) and varicella vaccines, respectively; 58% completed recommended vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of MMR and varicella vaccine doses, respectively. Most events were minor, few were serious, and no deaths were reported in post-live vaccination windows. Although early diagnostic confirmation negatively affected live vaccination coverage and timeliness (P < .001), baseline CD4% did not differ between subjects who did or did not receive live vaccines by 12 to 18 months. Among varicella vaccine recipients, those with a subsequent adverse event had a lower preceding CD4% (24.8% ± 7.3%) than those without (35.5% ± 11.7%) (P < .05); no CD4% differences were observed with MMR vaccination. Fourteen unvaccinated subjects experienced live vaccine-preventable illnesses. CONCLUSIONS: Live vaccines were frequently given and generally well-tolerated among patients with DGS with mild-to-moderate immunosuppression.

Physicians' human papillomavirus vaccine recommendations, 2009 and 2011.

BACKGROUND: Physician recommendation is a key predictor of human papillomavirus (HPV) vaccine uptake. Understanding factors associated with recommendation is important for efforts to increase current suboptimal vaccine uptake. PURPOSE: This study aimed to examine physician recommendations to vaccinate female patients aged 11-26 years, in 2009 and 2011, at 3 and 5 years postvaccine licensure, respectively. A second aim was to identify trends in factors associated with vaccine recommendation for ages 11 and 12 years. METHODS: Nationally representative samples of physicians practicing family medicine, pediatrics, and obstetrics and gynecology were randomly selected from the American Medical Association Physician Masterfile (n=1538 in 2009, n=1541 in 2011). A mailed survey asked physicians about patient and clinical practice characteristics; immunization support; and frequency of HPV vaccine recommendation ("always" ≥75% of the time vs other). Analyses were conducted in 2012. RESULTS: Completed surveys were received from 1013 eligible physicians (68% response rate) in 2009 and 928 (63%) in 2011. The proportion of physicians who reported always recommending HPV vaccine increased significantly from 2009 to 2011 for patients aged 11 or 12 years (35% vs 40%, respectively; p=0.03), but not for patients aged 13-17 years (53% vs 55%; p=0.28) or 18-26 years (50% vs 52%; p=0.52). Physician specialty, age, and perceived issues/barriers to vaccination were associated with vaccine recommendation for patients aged 11 or 12 in both years. CONCLUSIONS: Results suggest a modest increase in recommendations for HPV vaccination of girls aged 11 or 12 years over a 2-year period; however, recommendations remain suboptimal for all age groups despite national recommendations for universal immunization.