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).

Primary ovarian insufficiency and human papilloma virus vaccines: a review of the current evidence.

Human papilloma virus is the primary causative agent for cervical cancer, and vaccination is the primary means of preventing anogenital cancers caused by human papilloma virus infection. Despite the availability of human papilloma virus vaccines for more than a decade, coverage rates lag behind those for other vaccines. Public concerns regarding safety of human papilloma virus vaccines have been identified as an important barrier to vaccination, including concerns that the human papilloma virus vaccine may cause primary ovarian insufficiency, driven in part by isolated reports of ovarian failure following the human papilloma virus vaccine. We summarize published peer-reviewed literature on human papilloma virus vaccines and primary ovarian insufficiency, reviewing information contained in the case reports and series. Healthcare providers should address any patient concerns about primary ovarian insufficiency and the human papilloma virus vaccine by acknowledging the case reports but noting the lack of association found in a recently published epidemiologic study of approximately 60,000 female individuals. Current evidence is insufficient to suggest or to support a causal relationship between human papilloma virus vaccination and primary ovarian insufficiency.

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.

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.

United States private schools have higher rates of exemptions to school immunization requirements than public schools.

OBJECTIVE: To compare medical, religious, and personal belief immunization exemption rates between private and public schools in US. STUDY DESIGN: Exemption rates were calculated using the Centers for Disease Control and Prevention School Immunization Assessment Surveys for the 2009-2010 school year excluding states with incomplete survey data. Standardized exemption rates weighted on enrollments in public and private schools were calculated. Differences in exemption rates between public and private schools were tested using Wilcoxon signed rank test. RESULTS: The overall state exemption rate was higher in US private than public schools, 4.25% (SD 4.27) vs 1.91% (1.67), P = .0001 and private schools had higher exemption rates for all types of exemptions; medical 0.58% (0.71) vs 0.34% (0.34) respectively (P = .0004), religious 2.09% (3.14) vs 0.83% (1.05) respectively (P = .0001), and personal belief 6.10% (4.12) vs 2.79% (1.57), respectively (P = .006). Overall exemption rates were significantly higher in states that allowed personal belief exemptions. CONCLUSIONS: Exemption rates were significantly higher in US private than in public schools. Children attending private schools may be at higher risk of vaccine-preventable diseases than public school children.

Gender differences in immediate hypersensitivity reactions to vaccines: a review of the literature.

OBJECTIVE: To examine published studies of immediate hypersensitivity reactions (IHS) following vaccination and to determine whether women are at an increased risk of developing IHS after vaccination. DESIGN AND SAMPLE: PubMed was reviewed for vaccine articles reporting IHS by gender through June 2012. Data were abstracted on type of study, vaccine, hypersensitivity reaction, and statistic reported. MEASURES: Articles were included if they described experimental, quasi-experimental, correlational or descriptive studies and IHS was reported by gender. RESULTS: Of 847 articles found in PubMed, 11 met the inclusion criteria. In eight studies, more women than men reported IHS, in two studies more men than women reported IHS and in one study the count was even. CONCLUSION: Limited data from these studies suggest that women may have higher rates of IHS reactions following vaccination than men. Limitations to the available data include the lack of denominator data and that the definition of IHS was not consistent across the studies. Large-scale population-based studies are indicated to determine if there are differences in rates by gender and biologic basis for these differences.

Review and assessment of poliovirus immunity and transmission: synthesis of knowledge gaps and identification of research needs.

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.

Expert review on poliovirus immunity and transmission.

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Vaccine refusal, mandatory immunization, and the risks of vaccine-preventable diseases.

Vaccines are among the most effective prevention tools available to clinicians. However, the success of an immunization program depends on high rates of acceptance and coverage. There is evidence of an increase in vaccine refusal in the United States and of geographic clustering of refusals that results in outbreaks. Children with exemptions from school immunization requirements (a measure of vaccine refusal) are at increased risk for measles and pertussis and can infect others who are too young to be vaccinated, cannot be vaccinated for medical reasons, or were vaccinated but did not have a sufficient immunologic response. Clinicians can play a crucial role in parental decision making. Health care providers are cited as the most frequent source of immunization information by parents, including parents of unvaccinated children. Although some clinicians have discontinued or have considered discontinuing their provider relationship with patients who refuse vaccines, the American Academy of Pediatrics Committee on Bioethics advises against this and recommends that clinicians address vaccine refusal by respectfully listening to parental concerns and discussing the risks of nonvaccination.

Multi-tiered intervention to increase maternal immunization coverage: A randomized, controlled trial.

OBJECTIVE: To evaluate the impact of a multi-component intervention package of maternal immunization uptake in obstetric care clinics. METHODS: In a multi-level, cluster- and individually-randomized controlled trial we implemented an evidence-based intervention that targeted practice-, provider- and patient-level barriers to vaccine uptake. Obstetric practices were randomized to receive the practice and provider-level interventions or continue their normal standard of care. We enrolled pregnant women at practices in Georgia and Colorado and randomized women into patient-level intervention and control groups, resulting in four study arms. The primary outcomes were receipt of the influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccines during pregnancy. A sample size of 550 women per arm (2200 total) was planned and enrolled to compare the intervention between the four study arms. RESULTS: Between June 2017 and July 2018, 4907 women were screened and 2200 women were randomized, 550 to each of the four study arms. We were unable to follow-up with 108 women, for a final sample size of 2092. Sample characteristics and sample size were similar among study arms. There was no significant increase in Tdap or influenza vaccine uptake overall. Among women who had no intention of or were unsure about receiving the influenza vaccine during pregnancy, those who received just the patient-level intervention were 61% more likely to receive the influenza vaccine than those in the control arm (Relative risk: 1.61; 95% Confidence Interval: 1.18-2.21). There was no significant difference in vaccine uptake for either influenza or tetanus, diphtheria and acellular pertussis between the four arms of the study. CONCLUSIONS: This trial highlights the need for more targeted interventions to improve vaccine uptake. Future work should focus on clinics with low baseline vaccine uptake and the patient-level intervention should be expanded and targeted towards women with low vaccine confidence.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines.

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21.5 cases of Guillain-Barré syndrome and 5.75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86.3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination.

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.

The science of vaccine safety: Summary of meeting at Wellcome Trust.

Vaccines are everywhere hugely successful but are also under attack. The reason for the latter is the perception by some people that vaccines are unsafe. However that may be, vaccine safety, life any other scientific subject, must be constantly studied. It was from this point of view that a meeting was organized at the Wellcome Trust in London in May 2019 to assess some aspects of vaccine safety as subjects for scientific study. The objective of the meeting was to assess what is known beyond reasonable doubt and conversely what areas need additional studies. Although the meeting could not cover all aspects of vaccine safety science, many of the most important issues were addressed by a group of about 30 experts to determine what is already known and what additional studies are merited to assess the safety of the vaccines currently in use. The meeting began with reviews of the current situation in different parts of the world, followed by reviews of specific controversial areas, including the incidence of certain conditions after vaccination and the safety of certain vaccine components. Lastly, information about the human papillomavirus vaccine was considered because its safety has been particularly challenged by vaccine opponents. The following is a summary of the meeting findings. In addition to this summary, the meeting organizers will explore opportunities to perform studies that would enlarge knowledge of vaccine safety.

High incidence of childhood pneumonia at high altitudes in Pakistan: a longitudinal cohort study.

OBJECTIVE: To determine the incidence of pneumonia and severe pneumonia among children living at high altitudes in Pakistan. METHODS: A longitudinal cohort study was conducted in which 99 female government health workers in Punial and Ishkoman valleys (Ghizer district, Northern Areas of Pakistan) enrolled children at home, conducted home visits every 2 weeks and actively referred sick children to 15 health centres. Health centre staff used Integrated Management of Childhood Illness criteria to screen all sick children aged 2-35 months and identify those with pneumonia or severe pneumonia. FINDINGS: Community health workers enrolled 5204 eligible children at home and followed them over a 14-month period, ending on 31 December 2002. Health centre staff identified 1397 cases of pneumonia and 377 of severe pneumonia in enrolled children aged 2-35 months. Among children reported with pneumonia, 28% had multiple episodes. Incidence rates per 100 child-years of observation were 29.9 for pneumonia and 8.1 for severe pneumonia. Factors associated with a high incidence of pneumonia were younger age, male gender and living at high altitude. CONCLUSION: Pneumonia incidence rates in the Northern Areas of Pakistan are much higher than rates reported at lower altitudes in the country and are similar to those in high-altitude settings in other developing countries. More studies are needed to determine the causes of pneumonia in these high-mountain communities. However, early introduction of the vaccines that are known to prevent pneumonia should be considered.

Safety of influenza vaccination during pregnancy.

The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommends routine influenza vaccination for all women who are or will be pregnant during the influenza season. During seasonal influenza epidemics, during previous pandemics, and with the current influenza A (H1N1) pandemic, pregnancy places otherwise healthy women at increased risk for serious complications from influenza, including death. Inactivated influenza vaccine can be safely and effectively administered during any trimester of pregnancy. No study to date has demonstrated an increased risk of either maternal complications or adverse fetal outcomes associated with inactivated influenza vaccination. Moreover, no scientific evidence exists that thimerosal-containing vaccines are a cause of adverse events among children born to women who received influenza vaccine during pregnancy. In this article, we review the evidentiary basis for the recommendation of vaccination of all women who will be pregnant during the influenza season and safety data of influenza vaccination during pregnancy.

Endemic measles in Karachi, Pakistan and validation of IMCI criteria for measles.

AIM: To estimate the incidence of measles in Karachi, Pakistan and to determine the proportion of children with measles based on the WHO integrated management of childhood illness (IMCI) criteria with a positive IgM for measles or dengue. METHODS: Patients up to 14 years old were screened for febrile rash illnesses at five Karachi hospitals. Active measles cases were classified as measles, measles with eye and mouth complications, or severe complicated measles using IMCI criteria. RESULTS: Screening 1,219,061 patients over a 39-month period identified 3503 qualified children. Most (76.8%) measles cases occurred in children under five years of age. The average annual incidence rate was 0.68 per 1000 in year 1; 0.19 in year 2 and 0.08 in year 3 of surveillance. Pneumonia and diarrhoea were the most common complications. Of 18.1% hospitalized, 1.6% died. Of 2286 children tested, 1599 (69.9%) were measles IgM positive. Of 542 measles IgM negative children, 66 (12%) were dengue IgM positive. The predictive positive value for the IMCI case definition was 75%. CONCLUSION: The IMCI case definitions for measles is reasonable but may overestimate measles incidence. Measles continues to be a public health problem in Pakistan; increased efforts to control measles are urgently needed.

Disparities in preschool immunization coverage associated with maternal age.

Associations between maternal age and preschool immunization coverage are unclear. This study aimed to determine if maternal age is associated with preschool immunization coverage and the importance of maternal age compared with other factors affecting vaccination coverage. Data from the 2001-2003 National Immunization Survey (NIS) were used to estimate vaccine coverage. Children were considered up-to-date (UTD) if they received > or =4 doses of DTaP, > or =3 doses of polio, > or =1 doses of MMR, > or =3 doses of Hib and > or =3 doses of Hep B. Bivariate and multivariate relationships between UTD coverage and maternal, child and household factors were evaluated. Classification tree analysis assessed complex interactions between maternal, child and household factors associated with UTD coverage and isolated the most important factors in predicting UTD coverage. UTD coverage was significantly associated with maternal age: coverage increased as maternal age increased. Coverage among children with 17 year old mothers was 64%; coverage among children of mothers 17-26 years old increased by 16.3% overall (approximately 1.8% per year). After 26 years of age, coverage did not increase significantly as maternal age increased. The relationship between maternal age and UTD coverage remained statistically significant after adjusting for a broad range of maternal, child and household factors. Classification tree analysis suggested that maternal age is the most important factor associated with vaccine coverage. More research is needed to determine the reasons for underimmunization of children born to young mothers.