Agency Updates
Department of Defense (DoD) Written report provided:
DoD continues due diligence in managing Yellow-Fever vaccine requests during manufacturer shortage. No changes from June 2017 report.
The Adenovirus Vaccine Program was successfully instituted into an Officer Candidate School in January 2018 following an outbreak of Adenovirus among these trainees. This is the first application of the Adenovirus Vaccine Program outside of DoD’s enlisted recruitment population. Surveillance and serological studies are in process.
DoD has completed all of Japanese Encephalitis vaccine FDA-required post-licensure studies and is awaiting FDA comment. Significant interest in intramural immunization projects with a focus on military-relevance/readiness continues to occur throughout the field.
Vaccine redistribution continues to be a widely successful program. Individual DoD immunization sites have the capability to communicate near-expiring vaccine surplus or a vaccine deficit through personnel at the Immunization Healthcare Branch (IHB) at the Defense Health Agency. IHB staff then can reach out to other immunization site to redistribute vaccine as needed. In Fiscal Year 2017, $771,000 worth of vaccine was successfully redistributed.
Tracking of vaccine loss due to temperature compromise has continued to evolve. Potential vaccine loss, which vaccines were ultimately cleared vs discarded, etiology for potential vaccine loss (example: power failure, human error, etc.) and trends are identified. These metrics not only provide valuable information to the services with regard to lessons learned, but present an opportunity to standardize best practices across the DoD.
Publications:
Authored by IHB Staff:
McClenathan BM, Stewart DA, Spooner CE, et al. Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance
metabolomics. Vaccine. 2017 Mar 1:35(9):1238-1245.
Dumas EK, Gross T, Larabee J, Pate L, Cuthbertson H, Charlton S, Hallis B, Engler RJM, Collins LC Jr, Spooner CE, Chen H, Ballard J, James JA, Farris AD.. Anthrax Vaccine Precipitated induces Edema Toxin-neutralizing, Edema Factor-specific antibodies in human recipients. Clin Vaccine Immunol. 2017 Sep 6.
Funded by IHB Intramural Studies Program:
Khodr ZG, Bukowinski AT, Gumbs GR, Conlin AMS. Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections. Vaccine. 2017;35(42):5603-5610. Intramural Studies Program funded.
Hang J, Zavaljevski N, Yang Y, et al. Composition and variation of respiratory microbiota in healthy military personnel. PLoS ONE. 2017;12(12):e0188461. Intramural Studies Program funded.
Conlin AMS, Sevick CJ, Gumbs GR, Khodr ZG, Bukowinski AT. Safety of inadvertent anthrax vaccination during pregnancy: An analysis of birth defects in the U.S. military population, 2003-2010. Vaccine. 2017;35(34):4414-4420. Intramural Studies Program funded.
Khodr ZG, Bukowinski AT, Gumbs GR, Conlin AMS. Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections. Vaccine. 2017;35(42):5603-5610. Intramural Studies Program funded.
Pittman PR, Barrera-Oro JG, Xiaofei, et al. Time course of the early antibody response to the priming doses of anthrax vaccine adsorbed. Under review at Military Medicine.
Intramural Studies Program funded.
Food and Drug Administration (FDA)
Dr. Sun reported that since the last ACIP meeting in October 2017, FDA approved the HEPLISAV-B™ vaccine using the novel adjuvant CpG, which is a novel TLR9 agonist for persons 19 years of age and older. In addition, FDA approved Fluarix® Quadrivalent for
children 6 through 35 months of age. As mentioned earlier, FDA convened a VRBPAC meeting in November 2017 specifically addressing the issue of the Pfizer S. aureus vaccine and how safety and efficacy for a specific population could be generalizable to all elective orthopedic surgeries. The VRBPAC Northern Hemisphere 2018-2019 strain selection meeting will be convened on March 1, 2018.
Health Resources and Services Administration (HRSA)
Dr. Nair reported that HRSA is continuing to see a number of claims in the National Vaccine Injury Compensation Program (VICP) for the fiscal year (FY) ending September 30, 2017.
There were 1243 claims filed, with $252 million awarded to petitioners and nearly $30 million awarded to attorneys for fees and costs that were compensated and claims that were
dismissed. For FY2018 he had data that were current as of November 29, 2017. At that point,
$31 million had been awarded to petitioners and $5.7 million had been awarded to attorneys.
Detailed information is posted on the HRSA website.
Indian Health Service (IHS) Written report provided:
1. Influenza Vaccine Coverage: IHS conducts weekly surveillance for influenza-like-illness and influenza vaccine coverage. As of 2/3/2018, 321,317 doses of influenza vaccine were
administered to patients seen at an IHS/Tribal/Urban health facility. Influenza-like-illness (ILI) activity in IHS is decreasing but remains elevated at 4.3%, above the IHS baseline of 1.67%. Eleven IHS regions are reporting elevated ILI activity. Influenza vaccine coverage among children 6 months – 17 was 34.4%; coverage among adults 18 years and older was 32.9%.
2. IHS Pharmacy Survey: The IHS Immunization program, in partnership with the IHS
Pharmacy program, is conducting a survey of pharmacies located in IHS healthcare facilities to assess the role of pharmacists in the provision of adult and adolescent immunizations, and the implementation of the Standards for Adult Immunization Practice in IHS pharmacies.
Information will be used to identify best practices and strategies to increase pharmacy—
based immunization activities in IHS facilities.
3. HHS Region VI National Adult Immunization Plan-Stakeholder Engagement Meeting, Jan.
18th, 2018, Irving, Texas: IHS participated in this meeting and presented information on IHS efforts to implement the NVAC/CDC Standards for Adult Immunization Practice in
IHS/Tribal/Urban health facilities and current initiatives to improve access to adult immunizations in American Indian/Alaska Native communities.
National Institutes of Health (NIH) No report provided.
National Vaccine Program Office (NVPO) / National Vaccine Advisory Committee (NVAC) No report provided.
US Department of Veterans Affairs (DVA)
Dr. Kim reported that VA released a policy in September 2017 that requires HCP to participate in the influenza prevention program by getting an influenza vaccine or declining vaccination and wearing a mask throughout the influenza season. VA is currently implementing this policy.
More than 211,000 VA employees are documented as having received the influenza vaccine as of February 3, 2018. More than 1.7 million influenza vaccinations have been administered in outpatient settings within Veterans Health Administration (VHA) facilities since August 2017. In addition, VA is continuing its partnership with Walgreen’s. There are more than 100,000
enrolled veterans who are documented to have received an influenza vaccine from Walgreen’s this influenza season. VA is updating its Clinical Preventive Guidance on Herpes Zoster Administration to align with the recently published ACIP recommendation. The recombinant adjuvanted zoster vaccine was added to the VA formulary late last year.
Discussion Points
Dr. Fryhofer (ACP) indicated that they have had difficulty ordering the shingles vaccines, as two of the websites are down. There is one available source, but it is 20% higher. She said it is a surprise that this happened.
Introduction
Grace Lee, MD, MPH
Pneumococcal Vaccines WG Chair
Advisory Committee on Immunization Practices
Dr. Lee reminded everyone that the Pneumococcal Vaccines WG’s terms of reference are to:
Review current data on efficacy, effectiveness, immunogenicity, and cost-effectiveness of pneumococcal vaccines;
Review current recommendations considering up-to-date (UTD) evidence, including
epidemiological studies conducted post-licensure, and assess strength of the evidence; and
Revise or update recommendations for pneumococcal vaccine use, as needed.
Pneumococcal Vaccines
As a reminder, ACIP recommended PCV13 for use routinely in adults ≥65 years of age in August 2014. At that time, the short-term thought was that the recommendation for universal PCV13 use in this age group was warranted. There was a recognition that the long-term, continued herd effects from the childhood vaccination program might limit the utility of a universal recommendation for older adults. There was uncertainty about the magnitude of indirect effects as well as the burden of vaccine-preventable non-bacteremic pneumococcal pneumonia and that additional work was needed. The recommendation was to re-evaluate the decision to routinely use PCV13 among adults ≥65 years of age.
A research agenda was laid out that focused on monitoring invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) among adults ≥65 years of age;
examine the impact of indirect effects on pneumococcal disease trends in PCV13-naïve adults 19 through 64 years old without PCV13 indications; and evaluate the impact of direct and indirect effects on pneumococcal disease among adults ≥65 years of age.
During the October 2017 ACIP meeting, the WG updated ACIP on changes in carriage and IPD among adults ≥65 years of age. Carriage rates were documented to be very low at 1.8% overall and 0.2% for PCV13 serotypes. IPD caused by PCV13 serotypes declined by 40% after PCV13 was introduced in children and annual incidence rates plateaued from 2014 through 2016. At that time, the outline of the research agenda was presented to inform potential policy change.
Dr. Lee indicated that during the February 2018 pneumococcal session, presentations would focus on the following topics:
PCV13 effectiveness against IPD among adults ≥65 years old
PCV13 direct and indirect effects among adults ≥65 years old
PCV13 effectiveness against pneumococcal pneumonia among US adults and coverage estimates
Estimating burden of pneumococcal pneumonia among U.S. adults and progress of the research agenda to inform potential policy change
In conclusion, Dr. Lee posed the following question for ACIP’s consideration:
What additional information will the committee need to help determine whether continued PCV13 use in adults ≥65 years is warranted?
Pneumococcal VE against Invasive Disease among Adults ≥65 Years of Age Tamara Pilishvili, PhD, MPH
Respiratory Diseases Branch
National Center for Immunization & Respiratory Diseases Centers for Disease Control and Prevention
Dr. Pilishvili shared the results of studies evaluating PCV13 effectiveness against IPD among adults. PCV13 efficacy against IPD was demonstrated in a large clinical trial, Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), in which the efficacy was
measured at 75% with a 41% to 91% confidence interval against PCV13-type IPD among adults 65 years or older. Effectiveness of PCV13 alone or PCV13 given in series with PPSV23 in the
general population of US adults 65 years or older has not been demonstrated. Therefore, evaluation of the effectiveness is crucial to inform future policy decisions.
With this in mind, two case-control evaluations were conducted in parallel using slightly different methodologies. Dr. Pilishvili outlined the methodologies and shared the results of each, in addition to comparing the results across both studies. The objective was to evaluate PCV13 effectiveness against PCV13-type IPD among adults ≥65 years of age. For Study 1, population-based controls were selected and vaccination and medical histories for cases and controls were assessed through provider record review. Study 2 was conducted in collaboration with CMS.
Controls were selected from Medicare part B beneficiaries and vaccination and medical
histories for both cases and controls were obtained through CMS records. As a reminder of the timeline of the vaccine introduction as it relates to the reference period for which the vaccination histories are being obtained, PCV13 was introduced for children in 2010, the PCV13
recommendation was made for adults ≥19 years of age with immunocompromising conditions in 2012, and PCV13 was recommended for adults ≥65 years of age in 2014.
Regarding the methods for Study 1, IPD cases among adults ≥65 years of age were identified through Active Bacterial Core Surveillance (ABCs). Those with pneumococcal isolates available for serotyping were eligible for enrollment. Controls were identified using the commercial
database ReferenceUSAGov. The goal was to enroll 4 controls per case matched on age group and Zip Code of residence. Phone interviews were conducted for cases and controls in which all medical care encounters in the last 6 years were identified, as well as their current and past medical care providers. Information was assessed through interviews on the presence of underlying conditions, previous hospitalizations, and household exposures to smoking. For medical and vaccination history, contact was made with all providers identified through the case and control interview process, including pharmacies and vaccine registries when available.
Vaccine doses received within 14 days of the case culture date were excluded from analysis.
For the analysis, underlying medical conditions were grouped as Chronic Medical Conditions (diabetes; chronic heart, lung, or liver disease; alcoholism; cigarette smoking) and
Immunocompromising Conditions (HIV, hematologic cancer, generalized malignancy,
immunosuppressive therapy, sickle cell disease, asplenia). VE was measured using conditional logistics regression adjusted for the presence of underlying conditions and race. VE was
estimated as one minus the odds ratio. VE was measured against various groups of serotypes, but VE against PCV13 types as a group was the primary objective.
In terms of the characteristics of cases and controls, 267 cases and over 1000 matched controls have been enrolled to date. Enrollment began in October 2015 and is still ongoing. The median age of cases and controls is approximately 75 years. There was a higher proportion of black and other races among cases than controls, and there was similar distribution of gender
between cases and controls. One or more chronic medical conditions were present among 83%
of cases versus 60% of controls, and 60% of cases versus 32% of controls had at least one immunocompromising condition. Regarding vaccination status, a higher proportion of controls (29%) than cases (23%) received a single dose of PCV13 only. PPSV23 alone was received by a higher portion of cases (22%) than controls (20%), and both vaccines were received by a higher proportion of cases (27%) than controls (25%).
Looking at the distribution of serotypes of enrolled cases compared to the same timeframe for ABCs cases identified, there is a similar distribution of serotypes. Serotype 3 is the single most common PCV13-type at 16% for enrolled cases versus 13% for ABCs cases. Other PCV13 serotypes (19A, 7F, 19F) were identified among enrolled and ABCs cases at 7% each.
Serotype 06C was identified in about 4% of enrolled cases compared to 3% of ABCs cases. In some of the analyses, Serotype 06C was grouped with PCV13 serotypes, given that it has shown some cross-protection with the 6A antigen in PCV13.
The following table presents effectiveness by vaccine type and serotype group:
The cells that are highlighted in white is where any effectiveness would be expected and VE in bold are the ones for which the confidence intervals do not cross the null value. VE against all IPD was measured at 37% against all IPD types and 65% against PCV13 types. When
serotype 06C was included, the estimate did not change, and the confidence intervals are slightly narrower. Effectiveness was 44% against all PPSV serotypes. PCV13 types are included in the PPSV serotypes with the exception of 6A, so there is some effect expected because PCV13 types are contained in that group. There is no effectiveness against serotypes that are unique to the polysaccharide vaccine for PCV13 and against non-vaccine serotypes.
Looking at VE for any PCV13 dose received (with or without PPSV23), the results were similar though slightly lower VE estimates, and the confidence intervals overlapped.
For Study 2, the starting point was again cases of IPD among adults ≥65 years old identified through ABCs. These cases were linked to CMS Medicare Part B data based on demographic, geographic, and clinical variables. After creating a linkage and identifying these cases, controls were identified from CMS Medicare Part B beneficiaries. Controls were matched on age group, Census tract of residence, and length of enrollment in Medicare Part B. All eligible controls within Census tract of the case were included in the analyses. Vaccinations and medical
records were obtained through CMS data and doses received within 14 days of the case culture date were excluded from analysis.
Again, underlying medical conditions were classified as Chronic Medical Conditions (diabetes;
chronic heart, lung, or liver disease, alcoholism, cigarette smoking); and Immunocompromising Conditions (HIV, hematologic cancer, generalized malignancy, immunosuppressive therapy, sickle cell disease, asplenia). Conditional logistics regression was used to estimate VE, adjusted for presence of underlying conditions and race. Again, VE was estimated as one minus the odds ratio. VE against PCV13-type IPD was the primary objective.
For this analysis, it was possible to include retrospective data, so the enrollment started with the cases with culture dates from January 2015. The investigators were able to include 2 years of cases from ABCs and link them to CMS Medicare Part B beneficiaries. A total of 699 cases and over 10,000 matched controls were included. The median age was somewhat higher than in Study 1 at about 78 years. As in the previous study, there is a higher number of cases than controls of black or other races and a similar distribution of gender. There also was a higher proportion of cases with chronic conditions at 88% compared to 58% among controls, while 54% of cases versus 32% of controls had at least one immunocompromising condition. For vaccination status, overall coverage based on Medicare Part B data was lower. As far as the differences between cases and controls, the pattern was similar in that a high proportion of controls and cases had received a single dose of PCV13 and no difference was observed between cases and controls in terms of the percentage receiving both PCV13 and PPSV23.
The distribution of serotypes also was compared for cases that were included in the analysis versus cases that were identified through ABCs during the same time period. There is a very similar distribution, so there is no selection in terms of which cases were included in the analysis versus identified through surveillance. Again, Serotype 3 is the most prevalent vaccine
serotype. Effectiveness against all IPD was measured at 24% and the confidence intervals did not cross the null. Effectiveness was 36% for PCV13-types as a group, but the confidence interval includes the null value. When serotype 06C was included, effectiveness was 47% with a significant confidence interval. Against all PPSV types combined (PCV13 types included), effectiveness was 26% and the confidence interval was not significant.
The following table compares the Study 1 and 2 evaluations side-by-side:
Overall, the results were similar for the two studies. The point estimates for CMS analyses were lower but the confidence intervals do overlap, with the exception of VE against PPSV Serotypes which was much lower for CMS study, and not significant.
In conclusion, PCV13 was shown to be moderately effective in preventing IPD caused by PCV13-types in Study 1 with 65% VE (16, 86%), which was significant, and Study 2 with 36%
VE (-18, 65%), which was not significant. VE estimated similar when Serotype 6C IPD was included, which offers evidence of cross-protection. PCV13 was not effective against PPSV23-unique and non-vaccine type IPD, but had no reason to be effective. Estimates in both studies were slightly lower compared to VE from the clinical trial of 75% efficacy (95% CI 41, 91%).
However, the populations are different. As a reminder, the immunocompromised individuals were excluded from the CAPiTA study. Also, Study 1 and Study 2 had a higher proportion of adults with chronic conditions compared to the trial. At this point, it is not possible to evaluate VE estimates for PPSV23 or for PCV13 and PPSV23 given in series. Enrollment and analyses are ongoing, so those secondary objectives will be addressed. There are plans to assess VE for PCV13 and PPSV23 given in series, VE for PPSV23 against PPSV23-type IPD, and age group-specific VE to determine whether there is any difference among adults 65 through 75 years of age versus adults 75 years or older.
Estimating PCV13 Direct and Indirect Effects on IPD among Adults >65 Years of Age Tamara Pilishvili, PhD, MPH
Respiratory Diseases Branch
National Center for Immunization & Respiratory Diseases Centers for Disease Control and Prevention
Dr. Pilishvili indicated that this study was proposed at the time the recommendation was made.
Dr. Pilishvili indicated that this study was proposed at the time the recommendation was made.