Stroke Risk After COVID-19 Bivalent Vaccination Among US Older Adults.

Importance: In January 2023, the US Centers for Disease Control and Prevention and the US Food and Drug Administration noted a safety concern for ischemic stroke among adults aged 65 years or older who received the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. Objective: To evaluate stroke risk after administration of (1) either brand of the COVID-19 bivalent vaccine, (2) either brand of the COVID-19 bivalent plus a high-dose or adjuvanted influenza vaccine on the same day (concomitant administration), and (3) a high-dose or adjuvanted influenza vaccine. Design, Setting, and Participants: Self-controlled case series including 11 001 Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine (among 5 397 278 vaccinated individuals). The study period was August 31, 2022, through February 4, 2023. Exposures: Receipt of (1) either brand of the COVID-19 bivalent vaccine (primary) or (2) a high-dose or adjuvanted influenza vaccine (secondary). Main Outcomes and Measures: Stroke risk (nonhemorrhagic stroke, transient ischemic attack, combined outcome of nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day risk window after vaccination vs the 43- to 90-day control window. Results: There were 5 397 278 Medicare beneficiaries who received either brand of the COVID-19 bivalent vaccine (median age, 74 years [IQR, 70-80 years]; 56% were women). Among the 11 001 beneficiaries who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there were no statistically significant associations between either brand of the COVID-19 bivalent vaccine and the outcomes of nonhemorrhagic stroke, transient ischemic attack, nonhemorrhagic stroke or transient ischemic attack, or hemorrhagic stroke during the 1- to 21-day or 22- to 42-day risk window vs the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12). Among the 4596 beneficiaries who experienced stroke after concomitant administration of either brand of the COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window for the Pfizer-BioNTech BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine (IRR, 1.20 [95% CI, 1.01-1.42]; risk difference/100 000 doses, 3.13 [95% CI, 0.05-6.22]) and a statistically significant association between vaccination and transient ischemic attack during the 1- to 21-day risk window for the Moderna mRNA-1273.222 COVID-19 bivalent vaccine (IRR, 1.35 [95% CI, 1.06-1.74]; risk difference/100 000 doses, 3.33 [95% CI, 0.46-6.20]). Among the 21 345 beneficiaries who experienced stroke after administration of a high-dose or adjuvanted influenza vaccine, there was a statistically significant association between vaccination and nonhemorrhagic stroke during the 22- to 42-day risk window (IRR, 1.09 [95% CI, 1.02-1.17]; risk difference/100 000 doses, 1.65 [95% CI, 0.43-2.87]). Conclusions and Relevance: Among Medicare beneficiaries aged 65 years or older who experienced stroke after receiving either brand of the COVID-19 bivalent vaccine, there was no evidence of a significantly elevated risk for stroke during the days immediately after vaccination.

Vaccination Status and Associated Factors among Street Children 9-24 Months Old in Sidama Region, Ethiopia.

Background: Childhood non-vaccination can have different short-and long-term negative outcomes on their health. In Ethiopia, in addition to low coverage of full vaccination, street children were among the neglected part of the community who were missed during planning and reporting vaccination coverage. Moreover, there is no related research conducted on this title specifically. Objective: The objective of the study was to assess the vaccination status and its associated factors among street children 9-24 months old in Sidama zone. Methods: Community-based cross-sectional study design was conducted in four selected towns of Sidama region, southern Ethiopia. The convenience sampling method was applied to involve mothers of street children younger than two years during the study period. Data entry was done with EpiData version 3.1 and exported to SPSS22 for analysis. Bivariate and multivariable logistic regression analysis were performed to identify factors associated with immunization status of street children. Results: A significant number (26 [24.3%]) of the street children younger than two years were not vaccinated. Those mothers who are ≤20 years old (P = 0.014, AOR = 0.216, 95% CI: 0.064-0.732) and who gave birth at home (P = 0.029, AOR = 0.292, 95% CI: 0.097-0.879) had less odds of vaccinating their child than those older than 20 and who gave birth at health facility respectively. Conclusion: A significant number of the street children in this study are not fully vaccinated. Mothers aged <20 years and home births were significantly associated with non-vaccination status.

Chickenpox: An update.

Despite its benign characteristics, chickenpox is a childhood disease responsible for complications and deaths, particularly in the high-risk population. VariZIG®, not commercialized in France, is a good alternative for seronegative individuals exposed to the virus and not eligible for vaccination. The efficacy of routine vaccination has been demonstrated with a decrease in chickenpox incidence and with the development of herd immunity. Over time, the protective antibody titer of vaccinated people decreases and can be maintained by two doses of the vaccine. A tetravalent measles-mumps-rubella-chickenpox vaccine, used in the United States, has a good tolerability in spite of the occurrence of fever and febrile seizures. Routine vaccination would contribute to make savings in France, by reducing direct and indirect costs of chickenpox.

Public health impact of Infanrix hexa™ (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 2: Evolution of the acceptability of infants' vaccination against hepatitis B in general and pediatric practices - the PRALINE study.

BACKGROUND: The reimbursement of the hexavalent vaccine (Infanrix hexa™), comprising the DTPa-IPV-Hib components and the hepatitis B recombinant in a single vaccine, was approved in France in March of 2008. The impact of its reimbursement on physicians' decisions to vaccinate infants against hepatitis B was assessed in a study conducted with general practitioners and pediatricians. METHODS: The PRALINE study (NCT01777074) was a national, cross-sectional, repeated study with two measurement periods (T1 and T2) that measured the changes in physicians' acceptance of hepatitis B vaccination of infants before and for the 3 years after the approval of the hexavalent vaccine reimbursement. Two patient registers were created for each measurement period to enroll the first 15 12- to 15-month-old infants and the first 15 24- to 27-month-old children seen by the practitioners. The proportion of eligible children receiving a hepatitis B vaccine for each physician's practice was calculated. Practitioners also answered a vaccination practice questionnaire via telephone interviews. RESULTS: Across the two study periods, 418 general practitioners and 463 pediatricians were recruited and responded to the telephone interview on their vaccination practices. The overall number of children included in the study in both study periods reached almost 20,000. In the general practitioners group, there was a significant increase in the proportion of physicians "practicing hepatitis B vaccination" (i.e., at least 50% of eligible children receiving the initial hepatitis B vaccination) in children 24-27 months old (79% T2 versus 47% T1, P-value [P]<0.001). Similarly, the proportion of pediatricians initiating hepatitis B vaccination increased from 51% (T1) to 94% (T2) (P<0.0001). General practitioners offered hepatitis B vaccination to infants more systematically in the second study period (87% T2 versus 73% T1, P<0.001) and also suggested the use of the hexavalent vaccine to more patients after reimbursement (92% T2 versus 78% T1, P<0.0001). The proportion of pediatricians offering vaccination to every infant was high at T1 (94%) and remained steady (97%) with a high use of the hexavalent vaccine (94% T1 and 96% T2). CONCLUSION: The PRALINE study shows a significant and immediate change in the hepatitis B vaccination practices of general practitioners and pediatricians following hexavalent vaccine reimbursement with a significant increase in hepatitis B vaccine coverage in infants.

Public health impact of Infanrix hexa (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 1: Evolution of hepatitis B vaccine coverage rates in infants aged less than 27 months, in the general population - the PopCorn study.

BACKGROUND: Reimbursement of the hexavalent vaccine (Infanrix hexa) comprising the DTPa-IPV-Hib components and the hepatitis B valence in a single vaccine was decided in March 2008 in France. The impact of its reimbursement on the hepatitis B vaccine coverage rate was assessed in a study conducted in the general population prior to and after implementation of the reimbursement policy. METHODS: The PopCorn study (NCT01782794) was a national, cross-sectional and repeated study, with four assessment periods over 3 years, from 2009 to 2012, to assess the hepatitis B vaccine coverage in 12- to 15- and 24- to 27-month-old children, vaccinated between 2007 and 2011 and selected by the quota sampling method. Face-to-face interviews were conducted at their homes and vaccination status was collected using their child's health record. Parents were also interviewed on their perceptions and acceptance of hepatitis B vaccination. Three indicators were calculated to assess hepatitis B vaccination coverage: proportions of infants with at least one dose before 6 months of age, with at least two doses before 6 months of age and with a complete schedule at 24 months of age. RESULTS: A total of 4903 children were enrolled in the study. An overall significant increase (P-value [P<0.05]) of the three indicators of interest over the four periods of time was observed for both age groups. The proportion of children receiving hepatitis B vaccination before 6 months increased from 21% at baseline (before vaccine reimbursement) to almost 75% at the last assessment period in 2012. More than 60% of 24- to 27-month-old children received a complete schedule in 2012 compared to 33% at baseline. No significant increases in the proportions of parents "favourable" and "moderately in favour" of hepatitis B vaccination were observed across the four evaluation periods (respectively, 17-22% and 48-50%, P=0.09). CONCLUSION: The rapid increase of hepatitis B vaccination coverage suggests a significant change in hepatitis B vaccination practice related to the hexavalent vaccine's reimbursement. This change was observed in a context of stability regarding parents' perceptions and acceptance of hepatitis B vaccination and of coverage rates for other infant vaccinations.

The relationship between pediatric combination vaccines and market effects.

We explored market factors that affect pediatric combination vaccine uptake in the US public-sector pediatric vaccine market. We specifically examined how Pediarix and Pentacel earned a place in the 2009-2012 lowest overall cost formulary. Direct competition between Pediarix and Pentacel is driven by the indirect presence of the Merck Haemophilus influenzae type b vaccine and the Recommended Childhood Immunization Schedule requirement for a hepatitis B birth dose. The resulting analysis suggests that Pentacel would never have earned a place in the lowest overall cost formulary for 2009-2012 federal contract prices for any cost of an injection unless the Merck H influenzae type b advantage was ignored and the hepatitis B birth dose administration cost was recognized by health care providers in designing the lowest overall cost formularies.

Rotavirus live, oral, pentavalent vaccine.

BACKGROUND: On February 3, 2006, the US Food and Drug Administration (FDA) approved a live, oral, pentavalent (G1-G4, P1[8]) human-bovine reassortant rotavirus vaccine for the prevention of rotavirus gastroenteritis (RVGE) in infants in the United States. The Advisory Committee of Immunization Practices of the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) recommended routine immunization of infants using 3 doses of the oral pentavalent rotavirus vaccine (PRV) at 8, 12, and 24 months of age, with the first dose administered between 6 and 12 weeks of age and subsequent doses administered at 4- to 10-week intervals. OBJECTIVE: This article reviews the composition, clinical efficacy, adverse events, and cost-effectiveness associated with its use. METHODS: Relevant literature was identified through searches of MEDLINE (1990-June 2007) and International Pharmaceutical Abstracts (1990-July 2007). Search terms included, but were not limited to, RotaTeq, PRV, intussusception, rotavirus infection, and cost-effectiveness. Further publications were selected from the reference lists of identified articles. Guidelines for use were identified from the Web sites of the CDC and the AAP. RESULTS: Two published Phase III clinical trials involving the PRV were identified. The Rotavirus Efficacy and Safety Trial (REST) and the Concomitant Use Study, a subanalysis of REST, found that PRV was efficacious and well tolerated. The vaccine was associated with preventing RVGE of any severity in 74% of patients and severe RVGE in 98%. The combined prevalence of hospitalizations and emergency department (ED) visits was reduced by 94.5% (95% CI, 91.2%-96.6%), including a decrease in hospitalizations of 95.8% (95% CI, 90.5%-98.2%) and a decrease in ED visits 93.7% (95% CI, 88.8%-96.5%), with vaccine administration compared with placebo. There were also reductions in physician's office visits of 86% (95% CI, 73.9%-92.5%) and the number of workdays lost for parents (65 vs 487). There were no confirmed cases of intussusception due to the vaccine. The prevalences of fever, diarrhea, and vomiting were not significantly different between the vaccine and placebo groups. Overall, the vaccine was well tolerated. The second study, a multicenter, randomized, placebo-controlled trial, found that PRV was efficacious, well tolerated, and immunogenic at the end of the vaccine's shelf-life. The vaccine was associated with preventing RVGE of any severity in 72.5% of cases and severe RVGE in 100% of cases. No cases of intussusception were reported. The Concomitant Use Study found that PRV could be administered concomitantly with other routine vaccinations during the first 24 weeks of life. Recently, the FDA's Vaccine Adverse Event Reporting System (VAERS) received 28 reports of cases that occurred after the first, second, and third doses. Approximately 50% of cases occurred 1 to 21 days after vaccination. Sixteen of the infants required hospitalization, while the remaining 12 required contrast or air enema intervention to reduce the intussusception. CONCLUSIONS: Based on the results from published studies, PRV appears effective in decreasing the prevalence of RVGE in the United States. Despite evidence from the large trial and no reported cases of intussusception, this event has been reported to VAERS. Continued postmarketing surveillance by the manufacturer, together with the VAERS and the CDC, will confirm whether use of the vaccine increases the risk for intussusception.

Global reduction of Hib disease: what are the next steps? Proceedings of the meeting Scottsdale, Arizona, September 22-25, 2002.

On September 22 to 25, 2002, a group of infectious disease specialists, public health officials, and vaccine experts from 33 countries gathered in Scottsdale, Arizona, to discuss the epidemiology and control of disease caused by Haemophilus influenzae type b (Hib) in the era of Hib conjugate vaccines. This supplement is a synthesis of the major themes and key lessons identified at the meeting. The objectives of the conference were to review the 10-year experience with Hib conjugate vaccines, discuss strategies to reduce Hib disease rates to lowest possible levels in industrialized countries, review impediments to the introduction of Hib vaccine in developing countries, and discuss strategies for disseminating lessons learned from countries using to those not using Hib conjugate vaccines. Over 10 years of international experience with Hib conjugate vaccines has demonstrated that they are safe and effective. Routine use of Hib conjugate vaccine has consistently led to decreases in the incidence of invasive Hib disease of 90% or more across a wide range of epidemiologic situations in industrialized countries. In some countries, the vaccine has caused a near-disappearance of invasive Hib disease through a combination of direct protection and herd immunity. Developing countries that have implemented routine vaccination (eg, The Gambia, Chile) have also had substantial disease reduction. In countries where Hib conjugate vaccine is being used, reducing Hib disease incidence to the lowest possible level will depend on maintaining high vaccine coverage levels, conducting surveillance for Hib disease, and investigating Hib disease cases. The optimal Hib vaccination strategy will depend on many factors, including local epidemiology and programmatic considerations. In countries that are not using Hib conjugate vaccine, information on the local burden of Hib disease will be essential for leaders considering vaccine introduction. Where disease burden is high, a multifaceted approach is urgently needed to evaluate and overcome barriers to vaccine introduction. In areas where Hib disease burden is not well characterized, additional work will be needed to understand the epidemiology of Hib disease and to communicate the value of Hib conjugate vaccine.

Issues in selection of DTwP-based combination vaccines.

This study examines regulatory, supply, acceptance and financing issues of combinations based on diphtheria-tetanus-pertussis (whole cell) vaccines (DTwP). These combination vaccines are currently produced in Europe mostly for export. Future regulatory oversight issues could have an impact on their availability. Before use of acellular pertussis-containing vaccines, the number of doses of DTwP vaccines offered in response to United Nations agency procurement tenders far exceeded the projected demand. Current demand and supply are converging. Most of that supply comes from developing country manufacturers, a potential new source of combination vaccines as well. The expected development and use of DTwP-based combination vaccines raises antigen allocation issues that could further affect supply. These combination vaccines have strong programmatic advantages, but pose complex selection issues involving disease burden, presentation, and availability of long-term financing. Vaccine price is not the major driving factor. A model examining important selection factors for regional country groupings provides predictions that have been validated by decisions on use of DTwP-based combination vaccines. This model may be useful in providing long-term uptake projections for other combination vaccines.

Current status and future trends in vaccine regulation--USA.

In regulating vaccines, the US Food and Drug Administration (FDA) is governed by the Code of Federal Regulations. These regulations serve as the framework for product characterization, as well as preclinical and clinical testing strategies. Novel vaccine approaches such as combination vaccines, vectored vaccines, new adjuvants, and novel delivery systems pose unique regulatory challenges for the FDA. If US licensure is sought, communication with the FDA throughout the clinical development of a product is essential to identify and implement the appropriate strategies for demonstrating the safety and effectiveness of a new product.